Drugs Information Center(DIC)

“Gatifloxacin can cause severe hyperglycemia”

2011-11-29T09:54:00.000+05:30

A 65-year-old woman with no history of diabetes, developed hyperglycemia, after taking Gatifloxacin. She was admitted to the hospital with a one day history of abdominal cramps, nausea, and vomiting. Her blood glucose was 1,121 mg/dL (normal range 70 to 100 mg/ dL). She had a history of high BP, transient ischemic attacks, hyperlipidemia and renal failure. The patient was receiving Gatifloxacin 200 mg daily for 9 days empirically for bronchitis, which was started during a prior hospitalization. After admission, she responded well to an insulin infusion combined with subcutaneous doses of regular insulin. (Ann Pharmacother.2005; 39(7):1349–1352)

Reports of hypoglycemia with other fluoroquinolones have been documented, but only Gatifloxacin is reported to cause severe hyperglycemia

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Omeprazole+ Sodium bicarbonate

2009-12-25T23:33:00.001+05:30

FDA Approved OTC Version Of Heartburn Drug Zegerid (omeprazole and sodium bicarbonate) on December 2, 2009.

Omeprazole is sensitive to acidic environment, so it is destroyed partly is stomach. Sodium bicarbonate saves it from destruction and increases the bioavailability by its acid neutralisation capacity.

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Dexmedetomidine

2009-12-08T20:48:00.002+05:30

Dexmedetomidine is a sedative medication used by intensive care units and anesthesiologists. It is relatively unique in its ability to provide sedation without causing respiratory depression. Like clonidine, its mechanism of action is agonism of alpha-2 receptors in certain parts of the brain.

Dexmedetomidine has sedative, analgesic, sympatholytic, and anxiolytic effects that blunt many of the cardiovascular responses in the perioperative period. It reduces the volatile anesthetic, sedative and analgesic requirements of the patient without causing significant respiratory depression.

Recent research has suggested dexmedetomidine to be an effective treatment for the dangerous cardiovascular symptoms of cocaine intoxication and overdose. It also seemed to be superior to lorazepam for ventilated patients in the intensive care unit. Compared to midazolam, dexmedetomidine was similarly effective for sedation, but shortened the time to extubation, was associated with less delirium, and experience more bradycardia and less tachycardiaand hypertension.

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FDA Warns of Drug Interactions between Clopidogrel and Omeprazole

2009-11-19T19:15:00.003+05:30

FDA notified healthcare professionals of new safety information concerning an interaction between clopidogrel (Plavix), an anti-clotting medication, and omeprazole (Prilosec/Prilosec OTC), a proton pump inhibitor (PPI) used to reduce stomach acid. New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole. Separating the dose of clopidogrel and omeprazole in time will not reduce this drug interaction.

Other drugs that are expected to have a similar effect and should be avoided in combination with clopidogrel include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine.

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RANOLAZINE

2009-11-17T19:30:00.002+05:30

Dosing Information

Adult: In Angina pectoris, chronic, initial, 500 mg orally twice daily; increase to the maximum recommended dose of 1000 mg orally twice daily as needed based on clinical symptoms.

Pediatric: Safety and efficacy not established in pediatric patients.

Contraindications

• Concurrent use of potent and moderately potent CYP3A inhibitors, including diltiazem, verapamil, macrolide antibiotics, HIV protease inhibitors, ketoconazole and other azole antifungals, and grapefruit juice or grapefruit-containing products; increased ranolazine levels and QTc prolongation.

• Concurrent use of QT prolonging drugs (such as Class Ia and Class III antiarrhythmics, and certain antipsychotic).

• Hepatic impairment, Child-Pugh Classes A, B or C; QTc prolongation is increased approximately 3-fold.

• QT prolongation, pre-existing, including congenital long QT syndrome and uncorrected hypokalemia.

Precautions

• Concurrent use of CYP3A and P-glycoprotein inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin, St John’s Wort) should be avoided; decreased ranolazine concentrations.

• Doses greater than 1,000 mg twice daily should be avoided; increased risk of QTc interval prolongation.

• QTc interval prolongation; dose-related prolongation may occur, possibly leading to torsades de pointes-type arrhythmias and sudden death.

• Renal impairment, severe; increases blood pressure by approximately 15 mmHg.

• Ventricular tachycardia, history.

Adverse Effects

• Prolonged QT interval

• Serum blood urea nitrogen raised

• Syncope

Pharmacokinetics

Onset and Duration of action: Initial Response in stable angina, Oral: 2.5 hours (single doses; reflects time of efficacy measurements after dosing).

Drug Concentration Levels

A) Therapeutic Drug Concentration: In stable Angina Pectoris 500 ng/mL suggested in single-dose study.

B) Peak Concentration

1) Oral, extended-release: 2569 ng/mL.

2) Steady state peak and trough plasma concentrations for ranolazine and its metabolites were generally higher in renally impaired subjects compared to healthy subjects. Patients received a ranolazine extended-release loading dose of 875 mg orally, followed by 500 mg every 12 hours for a total of 4 maintenance doses.

C) Time to Peak Concentration: Oral, extended-release: 2 to 5 hours.

Mechanism of Action

1) Ranolazine is a piperazine derivative and the mechanism of action of its anti-anginal and anti-ischemic effect is unknown. The anti-anginal and anti-ischemic action of ranolazine is not dependent upon heart rate or blood pressure reduction and does not increase myocardial workload. At therapeutic levels, ranolazine can inhibit the inactivating component of the sodium current (I(Na)) although its relationship to angina symptoms is uncertain. It also inhibits the rapid inward rectifying current (I(Kr)), thereby prolonging the ventricular action potential.

2) Ranolazine has also been postulated to modulate myocardial metabolism by partially inhibiting fatty acid oxidation, thereby increasing glucose oxidation and generating more adenosine triphosphate (ATP) per molecule of oxygen consumed (i.e., cardiac muscle cell substrate utilization is shifted towards carbohydrates and away from fatty acids). The anti-anginal and anti-ischemic action of ranolazine is not dependent upon heart rate or blood pressure reduction and does not increase myocardial workload.

3) Action unlike beta-blockers and calcium antagonists, ranolazine lacks effects on hemodynamics, contractile/ conduction parameters.

4) Ranolazine has renal transplant preservation potential.

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Pharmacotherapy of Asthma

2009-11-17T19:18:00.002+05:30

Asthma is a long-term illness that causes the airways of the lungs to be irritated, make mucus, and to swell. You may have some airway swelling all the time, even when you feel OK. Your airways may also become smaller causing you to have breathing problems or to wheeze. Wheezing is a loud noise you hear when you breathe in or out. An asthma attack happens when your airways narrow making it hard to breathe. Asthma attacks are also called flare-ups, exacerbations, or episodes.

Causes: The following may be possible causes of an asthma attack.

􀁺 Air pollution.

􀁺 Animals.

􀁺 Cold weather.

􀁺 Dust.

􀁺 Exercise.

Foods.

􀁺 Lung infections.

􀁺 Molds.

􀁺 Pollens.

􀁺 Smoke.

􀁺 Stress.

Signs and Symptoms:

Breathing faster than normal.
􀁺 Breathing trouble.
􀁺 Cough which may be worse at night or early morning.
􀁺 Drop in peak flow reading.
􀁺 Fast heartbeat.
􀁺 Head "stopped up."
􀁺 Itchy, scratchy, or sore throat.
􀁺 Short of breath.
􀁺 Tight feeling in the chest.
􀁺 Tired.
􀁺 Wheezing.

Grades of asthma
􀁺 Intermittent: This is the least serious level of asthma. At this level a person has asthma symptoms no more than 2 times a week. He will also not be awakened at night with asthma symptoms more than 2 times a month. An asthma attack may last from a few hours to a few days. A person at this level will not have symptoms between asthma attacks. Between asthma attacks the peak expiratory flow or "PEF" is normal. The PEF is a measure of airflow to your lungs. A peak flow meter is used to get a PEF reading. The PEF reading will vary by less than 20%.
􀁺 Mild persistent : A person at this level has asthma symptoms more than 2 times a week but not every day. He will have nightime asthma symptoms more than 2 times a month. An asthma attack may slow his daily activities. The PEF reading will vary by 20% to 30%.
􀁺 Moderate persistent: A person at this level has asthma symptoms every day. He will use a shortacting inhaled asthma medicine every day. He will have nightime asthma symptoms about once a week. Asthma attacks may happen at least 2 times a week and last for many days. At this level, asthma attacks get in the way of a person's daily activities. The PEF reading may vary by more than 30%.
􀁺 Severe persistent: This is the most serious level of asthma. A person at this level has asthma symptoms all the time. These symptoms limit a person's physical activity. Asthma attacks are common as well as nighttime symptoms. The PEF reading may vary by more than 30%.

Pharmacotherapy. Following are the 2 groups of asthma medicines.
􀁻 Long-term control medicines. These medicines are taken every day to control persistent
asthma by decreasing inflammation . Inflammation is when your airways swell and tighten. This group of medicines may also keep airway swelling from starting. Inhaled steroid medicine is used to decrease the inflammation. This medicine is put into an inhaler through which you breathe.
􀁻 Quick-relief medicines. These medicines are taken to quickly open your airways and to treat other symptoms. These symptoms may be cough, chest tightness, wheezing, or shortness of breath. Quick-relief medicines are bronchodilators . Bronchodilators relax muscles that have tightened around the airways. This opens the airways to help you breathe easier.

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MEMANTINE

2009-11-17T18:41:00.003+05:30

Treats symptoms of Alzheimer's disease, such as problems with memory, concentration, and

judgment.

How to Use This Medicine:

Tablet

􀁺 Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to. Most people need to wait at least one week between dose changes.

􀁺 You may take this medicine with or without food.

If a dose is missed:

􀁺 If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.

Warnings While Using This Medicine:

􀁺 Make sure your doctor knows if you are pregnant or breast feeding, or if you have epilepsy or liver disease. Tell your doctor if you have any problems with your kidneys or bladder.

􀁺 Call your doctor if you get a urinary tract infection. This includes any infection in your bladder or kidneys. Your dose of this medicine might need to be changed while you have an infection.

Possible Side Effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or
throat, chest tightness, trouble breathing.
􀁺 Chest pain.
􀁺 Dizziness, fainting.
􀁺 Severe sleepiness, restlessness, seeing or hearing things that are not there.
􀁺 Sudden or severe headache.

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FEXOFENADINE may interact with GRAPEFRUIT JUICE

2009-09-20T00:27:00.001+05:30

Grapefruit juice can decrease the absorption of fexofenadine from the stomach into the bloodstream. This could make fexofenadine less effective. To avoid this interaction, take fexofenadine with water or liquids other than fruit juices. Do not take fexofenadine with grapefruit juice or grapefruit itself. Also avoid taking fexofenadine with apple juice and orange juice.Discuss this potential interaction with your healthcare provider at your next appointment, or sooner if you think you are having problems.

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Maraviroc, CCR5 Co- Receptor Antagonists

2009-09-19T18:00:00.003+05:30

Clinical Use

:Ø ART experienced patients with CCR5 tropic HIV-1 virus and withdetectable viral resistance to multiple ARTs

Ø Should not be used in treatment naïve patient

Failure:• Tropism for conversion from CCR 5 to CXCR 4 or dual or mixedtropism of HIV-1

• v3 loop mutation in gp120

Recommended Maraviroc Dose:1) 150mg oral BD in combination with CYP3A inhibitors (proteaseinhibitors,azole itraconazol/ ketoconazol, clarithromycin).2) 300mg oral BD in combination with ritonavir boosted tipranavir, NRTI,enfuvirtide, nevirapine or other drugs without CYP3A effect.3) 600mg oral BD with CYP 3A inducers efavirenz, entravirin, rifampicin,st. jone`s wart.Metabolism :Primarily by liverToxicities: Diarrhoea, nausea, fatigue, headache and derangement ofliver function testVicriviroc:Plasma half life markedly increased by CYP 3A4 inhibitorsPlasma half life >24 hrsNo food effectDurable antiretroviral activity in CCR5 tropic strainUnder Phase III trialAlpraviroc: Hepatotoxic, so trial was terminated.Apretinant: neurokinin 1 receptor antagonistApproved antiemetic, downregulates CCR5 expression on macrophages invitro- under investigation.

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The First HIV Integrase Inhibitor: Raltegravir

2009-08-03T22:27:00.001+05:30

Raltegravir is the first integraseinhibitor to be approved by the US Food and Drug Administration for use in antiretroviral treatment–experienced adult patients with viral resistance. Raltegravir blocks HIV replication by inhibitingessential strand-transfer activities of integrase. Raltegravir is rapidly absorbed, with a median Tmax of~4 hours in the fasting state. No dose adjustment is recommended in patients with moderate renal or hepaticinsufficiency, and raltegravir may be taken withoutregard to meals.

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Vaccination against Typhoid Fever

2009-07-23T09:12:00.001+05:30

Outbreaks of chloramphenicol-resistant typhoid stimulated a search for alternative oral antibiotic therapies and accelerated efforts to develop a new generation of better-tolerated, efficacious typhoid vaccines. The efforts bore fruit when live oral S. Typhi vaccine strain Ty21a and parenteral Vi polysaccharide vaccine were licensed in the late 1980s and early 1990s. Despite extensive data documenting the safety, efficacy, and practicality of the Vi and Ty21a vaccines, these preparations have not been widely applied programmatically in developing countries. The limited use of the Vi vaccine has been partly due to doubts about the programmatic feasibility and effect of Vi vaccination in public health programs, as well as questions about whether the vaccine is protective in children between the ages of 2 and 5 years and whether it can confer herd immunity.

According to the Sur et al. report, the Vi vaccine conferred an adjusted vaccine effectiveness in preschool children of 80% after two years follow-up; but vaccine effectiveness was lower in older children and adults (56% in children between the ages of 5 and 14 years and 46% in persons 15 years of age or older). Among unvaccinated members of the Vi-vaccine clusters, the level of protection was 44%, giving an overall level of protection among all residents of Vi-vaccine clusters of 57%.

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Propylthiouracil (PTU) side effects

2009-06-16T10:24:00.000+05:30

The FDA warned prescribers about the risk of serious liver injury associated with the use of the anti-thyroid drug propylthiouracil (PTU).
FDA’s warning highlights:
There is an increased risk of liver injury with propylthiouracil (PTU) when compared to methimazole.
Monitor for symptoms and signs of liver injury when propylthiouracil is chosen as anti-thyroid therapy. This should be emphasized during the first six months after initiating therapy.

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Injecting Insulin

2009-06-08T15:22:00.002+05:30

Insulin is injected into the fatty tissue. The body areas that can be used for injections are shown in the picture below. Insulin absorption varies with the body area that is used. The abdomen has the fastest rate of absorption followed by the arms, legs and buttocks. Randomly changing the body areas used for injections may result in variability in blood sugar levels. It is best that injection sites be changed within one body area instead of between body areas. The body area used for each routine injection (for example, before breakfast) should be the same every day.
Abdomen - stay 2 inches away from the navel (belly button) or scars and go sideways to the hips. You can go above or below the waist if there is good tissue.
Arms - measure one hand width down from the shoulder and one hand width up from the elbow. Use the fleshy outer surface.
Legs - measure one hand width down from the groin and one hand width up from the knee. Use the top and outer part of the leg staying away from the inner part of the thigh.
Buttocks - use the upper outer area. * Do Not Inject In The Same Place. Keep Changing Your Injection Sites In A Body Area.
Injecting
Wipe the injection site with alcohol or clean with soap and water.
Gently pinch up the skin at the injection site with your free hand to pull the fat away from the muscle.
Holding the syringe like a pencil, quickly push the needle into the injection site. The needle can be inserted at an angle of 45° or 90°. Be sure the needle is all the way in.
Push the plunger in at a steady rate all the way down.
Pull the needle straight out quickly. Hold the alcohol wipe over the injection site for a few seconds. Do not rub the area. Disposal of Needles and Syringes Dispose of the needles and syringes properly. It is recommended that they be disposed of in a container that is used only for that purpose. A coffee can or hard plastic bottle, such as an empty bleach or liquid detergent bottle, can be used. Do not use a container that will be returned to a store or recycled. Do not use glass or clear plastic containers. When the container is full, seal the lid with heavy-duty tape. Check with your local community waste disposal agency for the proper way to dispose of the container. Make sure that sharps are kept out of the reach of children.
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DANGEROUS DRUGS THAT HAVE BEEN GLOBALLY DISCARDED

2009-06-06T03:06:00.002+05:30

India has become a dumping ground for banned drugs; also the business for production of banned drugs is booming. Plz make sure that u buy drugs, only if prescribed by a doctor (Also, ask which company manufactures it, this would help to ensure that u get what is prescribed at the Drug Store) and that also from a reputed drug store. Not many people know about these banned drugs and consume them causing a lot of damage to themselves.
1. PHENYLPROPANOLAMINE: cold and cough. Reason for ban : stroke.
Brand name : Vicks A
2. ANALGIN: This is a pain-killer. Reason for ban: Bone marrow depression.
Brand name: Novalgin
3. CISAPRIDE: Acidity, constipation. Reason for ban : irregular heartbeat
Brand name : Ciza, Syspride
4. DROPERIDOL: Anti-depressant. Reason for ban : Irregular heartbeat.
Brand name : Droperol
5. FURAZOLIDONE: Antidiarrhoeal. Reason for ban : Cancer.
Brand name : Furoxone, Lomofen
6. NIMESULIDE: Painkiller, fever. Reason for ban : Liver failure.
Brand name : Nise, Nimulid
7. NITROFURAZONE: Antibacterial cream. Reason for ban : Cancer.
Brand name : Furacin
8. PHENOLPHTHALEIN: Laxative.. Reason for ban : Cancer.
Brand name : Agarol
9. OXYPHENBUTAZONE: Non-steroidal anti-inflammatory drug.
Reason for ban : Bone marrow depression.
Brand name : Sioril
10. PIPERAZINE: Anti-worms. Reason for ban : Nerve damage.
Brand name : Piperazine
11. QUINIODOCHLOR: Anti-diarrhoeal. Reason for ban : Damage to sight.
Brand name: Enteroquinol

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Treatment Guidelines for Malaria Contd...

2009-03-16T11:24:00.005+05:30

Treatment regimens for uncomplicated malaria in adults

_ Oral quinine sulphate 600 mg/8 h for 5e7 days plus doxycycline 200 mg daily (or clindamycin 450 mg/8 h for pregnant women) for 7 days

_ Atovaquoneeproguanil (Malarone_): 4 ‘standard’ tablets daily for 3 days or

_ Co-artem ((artemetherelumefantrine_): if weight > 35 kg, 4 tablets then 4 tablets at 8, 24, 36, 48 and 60 h

Child Initial dose 10 mg/kg/base then 5 mg/kg base 6e8 h later and on days 2 and 3

However, both of these newer regimens need to be taken for only 3 days. In contrast, quinine needs to be taken for 5e7 days and is often associated with ‘‘cinchonism’’ (nausea, deafness and ringing in the ears), which often results in poor adherence. Although international recommendations suggest that quinine should be taken for 7 days in endemic areas,2 UK experience suggests that 5 days treatment is adequate for the vast majority of cases. Quinine should be combined with a second drug (doxycycline for adults or clindamycin in pregnant women and young children) to ensure complete eradication of parasites.

Drug treatment of severe or complicated malaria

_ Quinine: loading dose of 20 mg/kg quinine dihydrochloride in 5% dextrose or dextrose saline over 4 h. Followed by 10 mg/kg every 8 h for first 48 h (or until patient can swallow). Frequency of dosing should be reduced to 12 hourly if intravenous quinine continues for more than 48 h.

_ Alternative rapid quinine loading regimen (adults only) 7 mg/kg quinine dihydrochloride over 30 min using an infusion pump followed by 10 mg/kg over 4 h.

_ Parenteral quinine therapy should be continued until the patient can take oral therapy when quinine sulphate 600 mg should be given 3 times a day to complete 5e7 days of quinine in total.

_ Quinine treatment should always be accompanied by a second drug: doxycycline 200 mg (or clindamycin 450 mg 3 times a day for pregnant women, 7e13 mg/kg 3 times a day for children), given orally for total of 7 days from when the patient can swallow.

_ Artesunate regimen: appropriate for adults only on expert advice. 2.4 mg/kg given as an intravenous injection at 0, 12 and 24 h then daily thereafter. A 7-day course of doxycycline should also be given.

Intensive care management of severe or complicated malaria

_ Careful management of fluid balance to optimise oxygen delivery and reduce acidosis

_ Monitoring of central venous pressure to keep right atrial pressure <>

_ Regular monitoring for hypoglycaemia

_ Consider broad spectrum antibiotics if evidence of shock or secondary bacterial infection

_ Haemofiltration for renal failure or control of acidosis or fluid/electrolyte imbalance

_ Consider medication to control seizures

_ Consideration of exchange transfusion in patients with hyperparasitaemia

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Treatment Guidelines for Malaria Contd...

2009-03-16T11:24:00.004+05:30

Treatment regimens for uncomplicated malaria in adults

_ Oral quinine sulphate 600 mg/8 h for 5e7 days plus doxycycline 200 mg daily (or clindamycin 450 mg/8 h for pregnant women) for 7 days

_ Atovaquoneeproguanil (Malarone_): 4 ‘standard’ tablets daily for 3 days or

_ Co-artem ((artemetherelumefantrine_): if weight > 35 kg, 4 tablets then 4 tablets at 8, 24, 36, 48 and 60 h

Child Initial dose 10 mg/kg/base then 5 mg/kg base 6e8 h later and on days 2 and 3

Drug treatment of severe or complicated malaria

_ Alternative rapid quinine loading regimen (adults only) 7 mg/kg quinine dihydrochloride over 30 min using an infusion pump followed by 10 mg/kg over 4 h.

_ Parenteral quinine therapy should be continued until the patient can take oral therapy when quinine sulphate 600 mg should be given 3 times a day to complete 5e7 days of quinine in total.

Intensive care management of severe or complicated malaria

_ Careful management of fluid balance to optimise oxygen delivery and reduce acidosis

_ Monitoring of central venous pressure to keep right atrial pressure <>

_ Regular monitoring for hypoglycaemia

_ Consider broad spectrum antibiotics if evidence of shock or secondary bacterial infection

_ Haemofiltration for renal failure or control of acidosis or fluid/electrolyte imbalance

_ Consider medication to control seizures

_ Consideration of exchange transfusion in patients with hyperparasitaemia

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Treatment Guidelines for Malaria

2009-03-16T11:24:00.003+05:30

The treatment of choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which only a limited proportion of P. vivax strains have gained resistance. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine. This must be avoided or given with caution under expert supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone _) or co-artemether (Riamet_); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline.

ALL patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h, since patients can deteriorate suddenly, especially early in the course of treatment. Intravenous artesunate reduces high parasite loads more rapidly than quinine and is more effective in treating severe malaria in selected situations.

Falciparum malaria in pregnancy is more likely to be severe and complicated: the placenta contains high levels of parasites. Stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. The treatment of choice for falciparum malaria in pregnancy is quinine; doxycycline is contraindicated in pregnancy but clindamycin can be substituted for it, and is equally effective. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy; after treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery when hypnozoite eradication can be considered.

There are no specific symptoms of malaria: most patients complain of fever, headache and general malaise.6 Gastrointestinal disturbances, jaundice or respiratory symptoms occasionally occur and are often responsible for misdiagnosis. Most missed malaria infections are erroneously diagnosed as non-specific viral infections, influenza, gastroenteritis or hepatitis.

If there is clinical suspicion of malaria, but initial blood films are negative, repeat films should be examined after 12e24 h and again after a further 24 h. Thrombocytopenia, in particular, is highly suggestive of malaria in non-immune adults and children, both in falciparum and non-falciparum malaria.

Major features of severe or complicated falciparum malaria in adults

Impaired consciousness or seizures
Renal impairment (oliguria <> 265mmol/l)
Acidosis (pH <>
Hypoglycaemia (<2.2>
Pulmonary oedema or acute respiratory distress syndrome (ARDS)
Haemoglobin _ 8 g/dL
Spontaneous bleeding/disseminated intravascular coagulation
Shock (algid malaria e BP <>
Haemoglobinuria (without G6PD deficiency)

Assessment of the patient should include careful clinical evaluation and review of investigations for the features of severe malaria detailed below. A full blood count, urea and electrolytes, liver function tests and blood glucose should be done routinely. In ill patients, blood gases, blood culture, lactate and clotting studies should also be performed. Urine dipstick and culture, stool culture and chest X-ray may be appropriate. Lumbar puncture to exclude meningitis should be considered in febrile patients with impaired consciousness or repeated seizures.

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DARPins (designed ankyrin repeat proteins)

2009-02-19T11:14:00.000+05:30

DARPins (designed ankyrin repeat proteins) are a novel class of binding molecules with the potential to overcome limitations of monoclonal antibodies, hence allowing novel therapeutic approaches. DARPins are small, single domain proteins (14 kDa) which can be selected to bind any given target protein with high affinity and specificity. These characteristics make them ideal agonistic, antagonistic or inhibitory drug candidates. Furthermore, DARPins can be engineered to carry various effector functions or combine multiple binding specificities, enabling completely new drug formats. Taken together, DARPins are a prominent member of the next generation of protein therapeutics with the potential to surpass existing antibody drugs.

For details visit http://www.drugdiscoverytoday.com/echoice/feb2009/Stumpp.pdf

Cortesy

Dr. Tariq Salman

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Clopidogrel bisulfate

2009-01-30T10:49:00.002+05:30

Cardiovascular healthcare professionals, Pharmacists agreed to work with FDA to conduct studies to obtain additional information that will allow a better understanding and characterization of the effects of genetic factors and other drugs (especially the proton pump inhibitors (PPIs)) on the effectiveness of clopidogrel. FDA is aware of published reports that clopidogrel (marketed as Plavix) is less effective in some patients than it is in others. Differences in effectiveness may be due to genetic differences in the way the body metabolizes clopidogrel or that using certain other drugs with clopidogrel can interfere with how the body metabolizes clopidogrel. These studies should lead to a better understanding about how to optimize the use of clopidogrel. Until further information is available FDA recommends the following:

Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke.
Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec OTC, in patients taking clopidogrel.
Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec OTC.

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Side Effects of Statin Drugs

2009-01-21T11:36:00.002+05:30

Statins work by blocking the action of the liver enzyme that is responsible for producing cholesterol. Too much cholesterol in the blood can cause a buildup of plaque on the walls of the arteries. That buildup can eventually cause the arteries to narrow or harden. Sudden blood clots in these narrowed arteries can cause a heart attack or stroke.

Statins lower LDL (“bad”) cholesterol and total cholesterol levels. At the same time, they lower triglycerides and raise HDL (“good”) cholesterol levels. Statins may also tend to stabilize plaques in the arteries. That makes sudden blood clots less likely.

Maintaining a healthy lifestyle while taking statins can improve the effectiveness of this drug. Be sure to:

eat a balanced, heart-healthy diet
get regular physical activity
limit alcohol intake
avoid smoking

Most people who take statins tolerate them very well. But some people experience statin side effects.

The most common statin side effects include:

headache
difficulty sleeping
flushing of the skin
muscle aches, tenderness, or weakness
drowsiness/ weakness
dizziness
nausea and/or vomiting
abdominal cramping and/or pain
bloating and/or gas
diarrhea
constipation
rash

Myositis, which is inflammation of the muscles, can occur with statins. The risk of muscle injury increases when certain other medications are coupled with statin use. For example, if you take a combination of a statin and a fibrate -- another cholesterol-reducing drug -- the risk of muscle damage increases greatly compared to someone who takes a statin alone.

Other dangers of statins include other muscle conditions, which can be serious in rare cases. First, there can be statin muscle pain. Known as myalgia, this pain can generally be resolved quickly by discontinuing the medication. Myalgias may be uncomfortable, but, medically speaking, they’re harmless.

Statins can also cause your CPK levels to be mildly elevated. CPK or creatine kinase is a muscle enzyme that can be measured in the bloodstream. Muscle pain, mild inflammation, and possibly weakness are also seen. This condition, though uncommon, can take a long while to resolve.

The third and most severe serious side effect of statins is called rhabdomyolysis. Muscles all over the body become painful and weakened because of extreme muscle inflammation and damage. CPK levels are extremely elevated as well. The kidneys can become overworked trying to eliminate a large amount of muscle breakdown caused by statin use. The severely damaged muscles release proteins into the blood that collect in the kidneys, thereby causing damage. This can ultimately lead to kidney failure or even death. Fortunately, rhabdomyolysis is extremely rare. It occurs in less than one in 10,000 cases.

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Sulfasalazine

2009-01-15T11:35:00.003+05:30

Category: Aminosalicylates

Sulfasalazine is a combination of 5-aminosalicylic acid (‘5-ASA') and sulfapyridine; sulfapyridine acts only as a carrier to the colonic site of action but still causes side-effects. In the newer aminosalicylates, mesalazine (5-aminosalicylic acid), balsalazide (a prodrug of 5-aminosalicylic acid) and olsalazine (a dimer of 5-aminosalicylic acid which cleaves in the lower bowel), the sulphonamide-related side-effects of sulfasalazine are avoided, but 5-aminosalicylic acid alone can still cause side-effects including blood disorders (see recommendation below) and lupus-like syndrome also seen with sulfasalazine.
Cautions

Aminosalicylates should be used with caution in renal impairment, during pregnancy and breast-feeding; blood disorders can occur.
Blood disorders: Patients receiving aminosalicylates should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasia.

Side-effects
Side-effects of the aminosalicylates include diarrhoea, nausea, vomiting, abdominal pain, exacerbation of symptoms of colitis, headache, hypersensitivity reactions (including rash and urticaria); side-effects that occur rarely include acute pancreatitis, hepatitis, myocarditis, pericarditis, lung disorders (including eosinophilia and fibrosing alveolitis), peripheral neuropathy, blood disorders (including agranulocytosis, aplastic anaemia, leucopenia, methaemoglobinaemia, neutropenia, and thrombocytopenia—see also recommendation above), renal dysfunction (interstitial nephritis, nephrotic syndrome), myalgia, arthralgia, skin reactions (including lupus erythematosus-like syndrome, Stevens-Johnson syndrome), alopecia.

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Antibiotic-associated colitis

2009-01-15T11:21:00.000+05:30

Antibiotic-associated colitis (pseudomembranous colitis) is caused by colonisation of the colon with Clostridium difficile which may follow antibiotic therapy. It is usually of acute onset, but may run a chronic course; it is a particular hazard of clindamycin but few antibiotics are free of this side-effect. Oral vancomycin or metronidazole are used as specific treatment; vancomycin may be preferred for very sick patients.

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ISPAGHULA HUSK

2009-01-12T16:22:00.004+05:30

Indications: Constipation

Category: Bulk forming Laxative.

Cautions Adequate fluid intake should be maintained to avoid intestinal obstruction—it may be necessary to supervise elderly or debilitated patients or those with intestinal narrowing or decreased motility.

Contra-indications: difficulty in swallowing, intestinal obstruction, colonic atony, faecal impaction

Side-effects Flatulence, abdominal distension, gastro-intestinal obstruction or impaction; hypersensitivity reported

Counseling Preparations that swell in contact with liquid should always be carefully swallowed with water and should not be taken immediately before going to bed.

Innohep (tinzaparin sodium injection)

2009-01-02T15:53:00.000+05:30

Celgene has issued a Dear Healthcare Professional letter describing a controlled clinical study suggesting that Innohep may increase the risk for death, compared to unfractionated heparin when used to treat elderly patients with renal insufficiency. It recommended consideration of alternatives to Innohep when treating these patients for deep vein thrombosis with or without pulmonary embolism.

Read the complete MedWatch 2008 Safety summary, at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#Innohep

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Drugs That Induce Bronchospasm

2009-01-01T14:10:00.002+05:30

Anaphylaxis (IgE-mediated)
Penicillins F
Sulfonamides F
Serum F
Cephalosporins F
Bromelin R
Cimetidine R
Papain F
Pancreatic extract I
Psyllium I
Subtilase I
Tetracyclines I
Allergen extracts I
Ll-Asparaginase F
Pyrazolone analgesics I
Cyclooxygenase inhibition
Aspirin/nonsteroidal antiinflammatory drugs F
Phenylbutazone I
Acetaminophen R
Anaphylactoid mast-cell degranulation
Narcotic analgesics I
Ethylenediamine R
Iodinated-radiocontrast media F
Platinum R
Local anesthetics I
Steroidal anesthetics I
Iron–dextran complex I
Pancuronium bromide R
Benzalkonium chloride I
Direct airway irritation
Acetate R
Bisulfite F
Cromolyn R
Smoke F
N-acetylcysteine F
Inhaled steroids I

F, frequent; I, infrequent; R, rare.

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Rosuvastatin

2008-12-29T16:08:00.002+05:30

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.

Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%.

Thus in apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.

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JUPITER trial stopped early

2008-12-29T16:03:00.000+05:30

The JUPITER (Justification for the Use of Statins in Primary Prevention Intervention) trial has shown that rosuvastatin reduces the risk of cardiovascular events by 54% in people who do not have high cholesterol level but have raised high sensitive C reactive protein. The trial was scheduled for a follow up of 4 years, but after nearly two years as there was a significant reduction in the primary end point at two years tyhe trial was stopped. The original research article and an editorial was recently published in NEJM. There are two important issues regarding the results of this trial 1. Long term safety of rosuvastatin is not yet established. If we are going to start rosuvastatin for a low risk subject without any clinical disease for primary prevention, he will be taking it for a long period say 20 years. In such case without long term safety being established, it should not be advised. 2. Secondly the patency of rosuvastatin is now held by Astra Zeneca and the drug is very costly now. If this protective effect is a class effect then the cheaper statins which have become generic can be substituted.

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New Drug Approvals

2008-12-24T14:18:00.003+05:30

Vasovist (gadofosveset trisodium) - formerly MS-325
Date of Approval: December 22, 2008
Company: EPIX Pharmaceuticals, Inc.
Treatment for: Diagnostic
Vasovist (gadofosveset trisodium) is a blood pool magnetic resonance angiography (MRA) agent used to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease.
ZolpiMist (zolpidem tartrate) Oral Spray
Date of Approval: December 22, 2008
Company: NovaDel Pharma, Inc.
Treatment for: Insomnia
ZolpiMist is an oral spray formulation of zolpidem, the drug contained in Ambien. ZolpiMist is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation.
Oral Fludarabine (fludarabine phosphate) Tablets
Date of Approval: December 19, 2008
Company: Antisoma plc
Treatment for: Chronic Lymphocytic Leukemia
Oral fludarabine (fludarabine phosphate) is an oral nucleoside analogue approved as a single agent for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL).
Mozobil (plerixafor)
Date of Approval: December 15, 2008
Company: Genzyme Corporation
Treatment for: Bone Marrow Transplantation
Mozobil (plerixafor) is a small molecule CXCR4 chemokine receptor antagonist used in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.
Trilipix (fenofibric acid) Delayed-Release Capsules
Date of Approval: December 15, 2008
Company: Abbott
Treatment for: Hypertriglyceridemia, Hyperlipidemia
Trilipix (fenofibric acid) is a peroxisome proliferator receptor alpha (PPARα) activator indicated for use along with diet to help lower triglycerides and LDL cholesterol, and to raise HDL cholesterol in patients with lipid problems. Trilipix is the first and only fibrate to be approved for use in combination with a statin.
Lusedra (fospropofol disodium) Injection - formerly Aquavan
Date of Approval: December 12, 2008
Company: Eisai Corporation of North America
Treatment for: Sedation
Lusedra (fospropofol disodium) is an intravenous sedative-hypnotic agent for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures.
Tapentadol Immediate Release Tablets
Date of Approval: November 20, 2008
Company: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Treatment for: Pain
Tapentadol is a centrally acting oral analgesic indicated for the relief of moderate to severe acute pain.
Toviaz (fesoterodine fumarate) Extended Release Tablets
Date of Approval: October 31, 2008
Company: Pfizer Inc.
Treatment for: Urinary Frequency
Toviaz (fesoterodine fumarate) is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
Vimpat (lacosamide) Tablets and Injection
Date of Approval: October 28, 2008
Company: UCB
Treatment for: Seizures
Vimpat (lacosamide) is an anti-convulsant drug for the treatment of partial onset seizures in adults with epilepsy.

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Ramipril

2008-12-24T12:22:00.003+05:30

Therapeutic Class
ACE Inhibitor
Antihypertensive

Mechanism of Action

Ramipril, an angiotensin-converting enzyme (ACE) inhibitor, is metabolized to a more potent ramiprilat (active drug). Both prevent the conversion of angiotensin I to angiotensin II, a vasoconstrictor agent, which decreases vasopressor activity and aldosterone secretion .

Mechanism of Action - Pharmacokinetics

Ramipril (prodrug), Protein binding: about 73%
Ramipril (prodrug)-Hepatic; almost completely metabolized
Ramipril (prodrug): time to peak concentration, within 1 h
Ramiprilat (active drug): greater than 50 h
Active metabolite: ramiprilat (active drug)
Ramipril (prodrug), Bioavailability: 28%

Ramiprilat (active drug), Protein binding: about 56%
Ramipril (prodrug), Effect of food: reduces rate of absorption

Clinical Advice

Patient should avoid activities requiring mental alertness or coordination until drug effects are realized, as drug may cause dizziness.
Advise patient to rise slowly from a sitting or lying position.
This drug may cause nausea, vomiting, persistent cough, and fatigue.
Tell patient to report signs/symptoms of angioedema (deep swelling around eyes and lips and sometimes hands and feet), intestinal angioedema (abdominal pain), unusual bleeding, or infection.
Instruct patient to maintain adequate hydration to prevent volume depletion and symptomatic hypotension.
Patient should avoid using potassium-containing supplements or salts while taking this drug.
Dosing - Adult
withdraw concurrent diuretic therapy 2 to 3 days before initiating ramipril if possible; if a diuretic cannot be discontinued, use an initial dose of 1.25 mg orally once daily; reinstate diuretic therapy if blood pressure is not controlled by ramipril alone
observe patients following the initial dose of ramipril for at least 2 hours and until blood pressure has stabilized for at least an additional hour
Cardiovascular event risk, Reduction: initial, 2.5 mg ORALLY once daily for 1 wk followed by 5 mg ORALLY once daily for 3 weeks
Cardiovascular event risk, Reduction: maintenance, 10 mg (if tolerated) ORALLY once daily or in 2 divided doses
Congestive heart failure - Myocardial infarction: initial, 1.25 to 2.5 mg ORALLY twice daily for 1 wk; maintenance, 5 mg (if tolerated) ORALLY twice daily; dose titration at 3 wk intervals
Hypertension: (in patients not receiving a diuretic) initial, 2.5 mg ORALLY once daily; maintenance, 2.5 to 20 mg ORALLY once daily or in 2 divided doses
Hypertension: lower initial dose to 1.25 mg daily if given with a diuretic

Dosing - Dose Adjustment
CrCl less than 40 mL/min/1.73 m(2): use 25% of normal dose
renal impairment in hypertensive patients: starting dose, 1.25 mg ORALLY once daily, titrate to effect, MAX 5 mg daily
renal impairment in heart failure patients: starting dose, 1.25 mg ORALLY once daily; increase to 1.25 mg twice daily; titrate to effect, MAX 2.5 mg twice daily
volume depletion (eg, past and current diuretic use) or renal artery stenosis: use initial starting dose of 1.25 mg ORALLY once daily

Contraindications

angioedema related to prior therapy with an ACE inhibitor
hypersensitivity to ramipril/other ACE inhibitors
Warnings - Precautions
pregnancy, second and third trimesters; can cause fetal and neonatal morbidity and death; discontinue ramipril therapy
agranulocytosis, neutropenia, and pancytopenia have been reported
anaphylactoid reactions have been reported
anaphylaxis during lipid apheresis with dextran sulfate membranes and hemodialysis with high flux membranes has been reported
angioedema, history of; increased risk of head and neck angioedema; discontinue therapy
congestive heart failure, history of, with or without renal impairment; risk for excessive hypotension sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death
collagen vascular disease; increased risk of agranulocytosis, neutropenia, and pancytopenia concomitant diuretic therapy; increased risk for symptomatic hypotension and increases in blood urea nitrogen and serum creatinine may occur
cough (nonproductive) has been reported with all ACE inhibitors
hepatic failure, potentially fatal, has occurred; discontinue therapy in patients who develop jaundice or have marked elevations in hepatic enzymes
hepatic impairment; increased plasma levels of ramipril
hyperkalemia has been reported; increased risk with renal disease, diabetes, and concomitant use of potassium supplements, potassium containing salt substitutes, and potassium-sparing diuretics
insect venom allergy, hymenoptera venom immunotherapy; may exacerbate the allergic response
intestinal angioedema has been reported
renal artery stenosis, unilateral or bilateral; increases in blood urea nitrogen and serum creatinine may occur; may consider dosage reduction or discontinuation of therapy if warranted
renal impairment; risk for excessive hypotension sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death
renal impairment; increased risk of agranulocytosis, neutropenia, and pancytopenia
surgery/anesthesia; excessive hypotension has been reported
volume and/or salt depletion, presence of; increased risk for symptomatic hypotension

Adverse Effects - Serious
Gastrointestinal: Intestinal angioedema
Hepatic: Liver failure, starting with cholestatic jaundice (rare)
Other: Angioedema, Face, lips, throat; more frequent in Black patients (rare)
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Amlodipine Besylate/Benazepril Hydrochloride

2008-12-23T12:04:00.003+05:30

Therapeutic Class
ACE Inhibitor/Calcium Channel Blocker Combination
Clinical Teaching
Patient should avoid activities requiring coordination until drug effects are realized, as drug may cause dizziness.
This drug may cause edema, headache, or angioedema (deep swelling around eyes and lips and sometimes hands and feet).
Instruct patient to report signs/symptoms of peripheral edema, hypotension, or hepatic dysfunction.
Advise patient against sudden discontinuation of drug, as this may cause rebound hypertension.
Patient should avoid use of potassium-containing supplements or salt substitutes unless approved by healthcare professional.
Dosing - Adult
Hypertension, Second-line therapy: initial, amlodipine 2.5 mg/benazepril 10 mg ORALLY once daily; may titrate dose up to amlodipine 10 mg/benazepril 40 mg ORALLY once daily, based on clinical response
Dosing - Dose Adjustment
renal impairment: NOT recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73m(2) or serum creatinine greater than or equal to 3 mg/dL)
hepatic impairment: initial dose, amlodipine 2.5 mg/benazepril 10 mg
geriatric: initial dose, amlodipine 2.5 mg/benazepril 10 mg
Dosing - FDA Labeled
Hypertension, Second-line therapy: Adult: yes
Hypertension, Second-line therapy: Pediatric: no
Dosing - Pediatric
safety and efficacy not established in pediatric patients
Contraindications
hypersensitivity to amlodipine or benazepril or to any component of the product
hypersensitivity to ACE inhibitors
Warnings - Precautions

angioedema of the head and neck; fatal laryngeal stridor, edema, and angioedema of the face, tongue, or glottis reported.
concomitant peripheral vasodilators; acute hypotension reported.
congestive heart failure, with or without renal insufficiency; acute hypotension may occur, associated with oliguria, azotemia, and rarely acute renal failure, and death
hemodialysis with high flux membranes; anaphylactoid reactions reported
hepatic failure/dysfunction; cholestatic jaundice, fulminant hepatic necrosis, and death reported
insect venom allergy; may exacerbate the allergic response
hymenoptera desensitization; anaphylactoid reactions reported
intestinal angioedema
obstructive coronary artery disease; exacerbation of angina or myocardial infarction during initial therapy or with dose increases
pregnancy; risk of fetal and neonatal morbidity and death
renal artery stenosis, unilateral or bilateral; increases in BUN and serum creatinine reported
renal disease, severe
renal impairment with concomitant collagen-vascular disease; increased risk of agranulocytosis and neutropenia
surgery/anesthesia; increased risk of hypotension
volume and/or salt depleted patients; hypotension more likely

Adverse Effects - Common
Cardiovascular: Edema
Neurologic: Dizziness, Headache
Respiratory: Cough (3.3%)
Adverse Effects - Serious
Gastrointestinal: Intestinal angioedema
Other: Angioedema, Face, lips, throat; more frequent in Black patients (rare)
Mechanism of Action
Systemic: Amlodipine is a dihydropyridine calcium channel blocking agent. Like the other dihydropyridine agents, amlodipine selectively inhibits calcium influx across cell membranes in cardiac and vascular smooth muscle, with a greater effect on vascular smooth muscle. Amlodipine is a peripheral arteriolar vasodilator; thus it reduces afterload.
Benazepril is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor and a prodrug for benazeprilat, the active metabolite. Both benazepril and benazeprilat inhibit ACE. ACE catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II. Angiotensin II normally stimulates secretion of aldosterone and inhibits the release of renin through a negative feedback mechanism. When ACE activity is inhibited, angiotensin II formation is decreased and the interruption of the negative feedback mechanism results in increased plasma renin concentrations. The reduction of angiotensin II formation also decreases aldosterone secretion and vasoconstriction. The decrease in aldosterone secretion causes a small increase in serum potassium concentrations. Suppression of the renin-angiotensin-aldosterone system is thought to be the primary mechanism through which ACE inhibitors lower blood pressure.
ACE is also known as kininase, an enzyme that degrades bradykinin. Benazepril may increase concentrations of bradykinin, a potent vasodepressor peptide, but its role in the therapeutic effects of this drug combination has not been determined.
Amlodipine exhibits negative inotropic effects in vivo , but appears to have no significant effect on the sinoatrial (SA) or atrioventricular (AV) node in humans.

Clinical Effects - Treatment
ACE INHIBITORS: Decontamination: Consider activated charcoal after a potentially toxic ingestion and if the patient is able to maintain airway or if airway is protected.
ACE INHIBITORS: Hypotensive episode: IV 0.9% NaCl 10-20 ml/kg, dopamine, norepinephrine. Naloxone effective in animal models and several case reports. Angiotensin Amide - IV infusion 8.5 to 18 mcg/min effective in several case reports.
ACE INHIBITORS: Monitoring of patient: Monitor BP, continuous cardiac monitoring, electrolytes, renal function, ECG and urinalysis in symptomatic patients.
CALCIUM ANTAGONISTS: Decontamination: Activated charcoal, gastric lavage; consider late gastric lavage and/or whole bowel irrigation with sustained release.
CALCIUM ANTAGONISTS: Hypotensive episode: IV 0.9% NaCl 10-20 ml/kg. CaCl adult dose 1 g IV over 5 min repeat every 10-20 min up to 4 or 5 (total) doses if needed. Insulin/dextrose: Insulin bolus of 1 unit/kg along with 25 to 50 mL D50W. Begin an insulin infusion of 0.1 to 1 unit/kg/hour and administer sufficient intravenous dextrose to maintain a blood glucose between 100 to 200 mg/dL. Vasopressors such as dopamine, epinephrine, isoproterenol, norepinephrine may be used but are often less effective than insulin/dextrose. Phosphodiesterase inhibitors (inamrinone, milrinone) may also be useful.
CALCIUM ANTAGONISTS: Bradycardia: Administer CaCl, glucagon and pacemaker as necessary. Atropine is usually not effective in this setting.
CALCIUM ANTAGONISTS: Seizure: IV benzodiazepines, barbiturates.
CALCIUM ANTAGONISTS: Acute lung injury: Maintain adequate ventilation and oxygenation; monitor ABGs; PEEP as needed.
CALCIUM ANTAGONISTS: Monitoring of patient: Obtain serial ECGs, continuous cardiac monitoring, BP, electrolytes, renal function, urine output and ABGs.

Toxicology - Clinical Effects
ACE INHIBITORS: OVERDOSE: Hypotension most common overdose effect; acute renal failure is rare. Onset of hypotension is generally within 6 hours of ingestion. ADVERSE EFFECTS: Hypotension, bradycardia, bronchospasm, cough, renal insufficiency, nephrotic syndrome, hyperkalemia, and neutropenia can develop.
CALCIUM ANTAGONISTS: MILD/MODERATE: hypotension, bradycardia, nausea & vomiting common. SEVERE: dysrhythmias, AV conduction delays, metabolic acidosis, hypokalemia, hyperglycemia, syncope, CNS depression, pulmonary edema, acidosis, acute renal failure, rhabdomyolysis, bowel ischemia. ONSET: Usually within 5 hrs, delayed with sustained release.

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Polypharmacy

2008-12-11T00:15:00.001+05:30

Our most complex patients are at highest risk for Drug-Drug Interactions. Polypharmacy, narrow therapeutic range of the medication, decreased hepatic and/or renal function of the patient each may increase the risk for DDIs. Each may be identified prior to coadministration. One should consider the potential for DDIs at all steps of the drug-delivery process. In a retrospective review of patients admitted to the emergency department, patients taking 3 or more medications or patients who were 50 years or older taking 2 or more medications had a considerable risk for DDIs. Furthermore, an increasing number of medications administered further increased the risk for adverse effects. Patients taking 2 medications had a 13% risk while patients taking 5 medications had a 38% risk for DDIs. Patients taking 7 or more medications had an 82% risk of developing adverse drug interactions.
Advanced age is an additional risk factor for DDIs. Aparasu and colleagues found that the risk for DDIs increases significantly after 44 years of age and is greatest for patients over 74 years of age. The need for multiple medications often arises with advancing age that may further the risk for DDIs. Almost 25% of the elderly outpatients referred to a diagnostic clinic in The Netherlands for decreased cognition, functional dependence, or both who were taking more than 1 medication were found to have potential adverse effects or decreased drug effect possibly due to a DDI. In general, when multiple medications are prescribed in the elderly population, the risk for DDIs increases exponentially.
Other patient-related risks for DDIs noted below, include very young age, female sex, genetics, decreased organ function, use of a medication having a narrow therapeutic range (eg, warfarin, digoxin, and cyclosporine), major organ impairment, metabolic or endocrine risk conditions (eg, hypothyroidism, hypoproteinemia), and acute medical issues (eg, dehydration).

Patient-Related Risks for Drug-Drug Interactions

Acute medical condition (eg, dehydration, infection);
Age extremes (ie, the very young and the elderly);
Decreased renal/ hepatic function;
Female sex;
Metabolic or endocrine condition (eg, obesity, hypothyroidism);
Multiple medication use;
Narrow therapeutic range of medication; and
Pharmacogenetics.

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Ceftriaxone Sodium

2008-12-05T14:58:00.002+05:30

Therapeutic Class
3rd Generation Cephalosporin Antibiotic

Clinical Teaching
Advise patient to report severe diarrhea and consult healthcare professional prior to taking anti-diarrhea medicine. Other superinfection signs/symptoms should be reported as well.
Dosing - Adult
Acute otitis media: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Bacterial endocarditis; Prophylaxis: (high-risk patients; dental, respiratory, or infected skin/skin structure or musculoskeletal tissue procedures) 1 g IV or IM 30 to 60 minutes prior to procedure.
Bacterial musculoskeletal infection: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Chancroid: 250 mg IM as a single dose
Epididymitis: 250 mg IM as a single dose plus doxycycline 100 mg ORALLY twice a day for 10 days
Gonorrhea: uncomplicated, 125 mg to 250 mg IM as a single dose
Gonorrhea: conjunctivitis, 1 g IM as a single dose
Gonorrhea: disseminated, 1 g IV/IM every 24 hr for 24-48 hr after improvement begins then switch to appropriate oral therapy to complete at least 1 week of therapy
Gonorrhea: meningitis and endocarditis, 1 to 2 g IV every 12 hr, for 10-14 days (meningitis) or at least 4 weeks (endocarditis)
Infection of skin AND/OR subcutaneous tissue: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Infectious disease of abdomen: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Infective proctitis: 125 mg IM as a single dose plus doxycycline 100 mg ORALLY twice a day for 7 days
Lower respiratory tract infection: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Lyme disease: 2 g IV once daily for 14 days (range, 10 to 28 days) for early Lyme disease with acute neurological disease manifested by meningitis or radiculopathy, or patients with seventh-cranial-nerve palsy with CNS involvement; for 14 to 21 days for the initial treatment of hospitalized patients with Lyme carditis; for 14 to 28 days for Lyme arthritis with neurological involvement, including those refractory to oral therapy, or late neurologic Lyme disease
Meningitis: 4 g/day IV/IM divided every 12-24 hr; maximum 4 g/day
Pelvic inflammatory disease: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day
Pelvic inflammatory disease: 250 mg IM as a single dose plus doxycycline 100 mg ORALLY twice daily for 14 days, with or without metronidazole 500 mg ORALLY twice daily for 14 days
Postoperative infection; Prophylaxis: 1 g IV 0.5 to 2 hr prior to surgery
Septicemia: 1 to 2 g IV every 24 hr or in divided doses twice a day; maximum 4 g/day
Sexually transmitted infectious disease; Prophylaxis - Victim of sexual aggression: 125 mg IM as a single dose plus metronidazole 2 g ORALLY as a single dose plus either azithromycin 1 g ORALLY as a single dose or doxycycline 100 mg ORALLY twice a day for 7 days
Urinary tract infectious disease: 1 to 2 g IV/IM every 24 hr or in divided doses twice a day; maximum 4 g/day

Dosing - Dose Adjustment
renal impairment: no dose adjustment needed
hepatic impairment: no dose adjustment needed
combined renal and hepatic impairment: doses should not exceed 2 g/day

Dosing - Pediatric
Acute otitis media: 50 mg/kg IM as a single dose; maximum 1 g/dose
Bacterial endocarditis; Prophylaxis: (high-risk patients; dental, respiratory, or infected skin/skin structure or musculoskeletal tissue procedures) 50 mg/kg IV or IM 30 to 60 minutes prior to procedure
Bacterial musculoskeletal infection: 50 to 75 mg/kg/day IV/IM in divided doses every 12 hr; maximum 2 g/day
Gonorrhea: uncomplicated (45 kg or less), 125 mg IM as a single dose
Gonorrhea: concomitant bacteremia or arthritis (45 kg or less), 50 mg/kg IM or IV in a single daily dose for 7 days; max 1 g/dose
Gonorrhea: concomitant bacteremia or arthritis (greater than 45 kg), 50 mg/kg IM or IV in a single daily dose for 7 days
Gonorrhea: disseminated and scalp abscesses (newborns), 25 to 50 mg/kg IV/IM once daily for 7 days; treat 10-14 days for meningitis
Gonorrhea: ophthalmia neonatorum, 25 to 50 mg/kg IV/IM as a single dose; max 125 mg dose
Gonorrhea: prophylaxis for newborn (maternal gonococcal infection), 25 to 50 mg/kg IV/IM as a single dose; max 125 mg dose
Infection of skin AND/OR subcutaneous tissue: 50 to 75 mg/kg/day IV/IM once daily or in divided doses every 12 hr; maximum 2 g/day
Infectious disease of abdomen: 50 to 75 mg/kg/day IV/IM in divided doses every 12 hr; maximum 2 g/day
Lower respiratory tract infection: 50 to 75 mg/kg/day IV/IM in divided doses every 12 hr; maximum 2 g/day
Lyme disease: 50 to 75 mg/kg/day in a single daily IV dose for 14 days (range, 10 to 28 days) for early Lyme disease for acute neurological disease manifested by meningitis or radiculopathy, or patients with seventh-cranial-nerve palsy with CNS involvement; for 14 to 21 days for the initial treatment of hospitalized patients with Lyme carditis; for 14 to 28 days for Lyme arthritis with neurological involvement, including those refractory to oral therapy, or late neurologic Lyme disease; maximum daily dose, 2 g
Meningitis: 80 to 100 mg/kg/day IV/IM divided every 12-24 hr; maximum 4 g/day
Septicemia: 50 to 75 mg/kg/day IV in divided doses every 12 hr; maximum 2 g/day
Urinary tract infectious disease: 50 to 75 mg/kg/day IV/IM in divided doses every 12 hr; maximum 2 g/day
Warnings - Contraindications

concurrent administration of calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition, in neonates (aged 28 days or less); risk of fatal salt precipitation in lungs and kidneys
hypersensitivity to cephalosporins
neonates, hyperbilirubinemic; increased risk of bilirubin encephalopathy (kernicterus), especially in premature neonates

Warnings - Precautions

administration of calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, within 48 hours of ceftriaxone use; has caused fatal salt precipitation in lungs and kidneys of neonates
allergy, history (particularly allergy to any drug); increased risk of acute hypersensitivity reaction
concurrent calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, even via different infusion lines, must not be administered within 48 hours
gastrointestinal disease, history of; particularly colitis
hepatic dysfunction with significant renal disease; increased risk of drug toxicity
hypersensitivity to penicillins
malnutrition; increased risk of altered prothrombin time due to low vitamin K stores
biliary stasis and biliary sludge risk factors (preceding major therapy, severe illness, total parenteral nutrition); increased risk of pancreatitis, possibly secondary to biliary obstruction
prolonged treatment; may result in overgrowth of nonsusceptible organisms (superinfection)
renal failure; increased risk of drug toxicity
sonographic abnormalities in gallbladder; ceftriaxone-calcium salt precipitate may be misinterpreted as gallstones
vitamin K synthesis, impaired or low vitamin K stores; risk of prothrombin time alteration (rare)

Adverse Effects - Serious
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis
Hematologic: Hemolysis, Immune-mediated (rare)
Hepatic: Disorder of gallbladder, Reversible
Immunologic: Immune hypersensitivity reaction (2.7% to 3.3% )
Neurologic: Kernicterus of newborn
Renal: Kidney finding
Respiratory: Lung finding
Mechanism of Action
Ceftriaxone sodium is a semisynthetic, broad-spectrum cephalosporin antibiotic. Its bactericidal activity results from inhibition of cell-wall synthesis and it is highly stable in the presence of penicillinases and cephalosporinases of gram-negative and gram-positive bacteria .
Mechanism of Action - Pharmacokinetics
5.8 h to 8.7 h
Fecal via bile: remaining amount after renal excretion as inactive compounds
Intramuscular: time to peak concentration, 2 h to 3 h
Vd: 5.78 L to 13.5 L
Pediatric patients with bacterial meningitis, Vd: 373 mL/k to 338 mL/kg
Pediatric patients with bacterial meningitis: 4.3 h to 4.6 h
Renal: 33% to 67% unchanged
Dialysis: no (hemodialysis); no (peritoneal dialysis)
Patients with otitis media: 25 h (middle ear fluid)
Protein binding: 85% (300 mcg/mL) to 95% (less than 25 mcg/mL), reversibly bound

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Cefixime

2008-12-05T14:38:00.002+05:30

Therapeutic Class
3rd Generation Cephalosporin Antibiotic

Clinical Teaching

This drug may cause abdominal pain or nausea.
Instruct patient to report signs/symptoms serum-sickness-like reactions (rash, urticaria, arthralgia, fever, malaise, enlarged lymph nodes).
Advise patient to report severe diarrhea and consult healthcare professional prior to taking anti-diarrhea medicine. Other superinfection signs/symptoms should be reported as well.

Dosing - Adult
Acute infective exacerbation of chronic obstructive pulmonary disease: 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Bronchitis, acute: 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Gonorrhea: uncomplicated, 400 mg ORALLY as one-time dose
Gonorrhea: disseminated (after parenteral therapy), 400 mg ORALLY twice a day to complete at least one week of therapy
Otitis media: 400 mg ORALLY once a day or divided twice a day, depending on type and severity of infection
Pharyngitis: 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Tonsillitis: 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Urinary tract infectious disease, Uncomplicated: 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection

Dosing - Pediatric
Acute infective exacerbation of chronic obstructive pulmonary disease: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Acute infective exacerbation of chronic obstructive pulmonary disease: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Bronchitis, acute: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Bronchitis, acute: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Gonorrhea: uncomplicated (greater than 45 kg), 400 mg ORALLY as one-time dose
Otitis media: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Otitis media: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Pharyngitis: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Pharyngitis: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Tonsillitis: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Tonsillitis: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection
Urinary tract infectious disease, Uncomplicated: (6 months to 12 years of age) 8 mg/kg/day ORALLY once a day or divided twice a day; depending on type and severity of infection
Urinary tract infectious disease, Uncomplicated: (over 50 kg or over 12 years of age) 400 mg ORALLY once a day or divided twice a day; depending on type and severity of infection.

Adverse Effects - Common
Dermatologic: Pruritus, Rash, Urticaria
Gastrointestinal: Abdominal pain, Diarrhea, Nausea
Mechanism of Action
Cefixime, a semisynthetic cephalosporin, is a broad-spectrum bactericidal agent that inhibits cell-wall synthesis and is highly stable in the presence of beta lactamases .
Mechanism of Action - Pharmacokinetics
3 h to 4 h but may range up to 9 h
Oral: time to peak concentration, 2 h to 6 h
Protein binding: approximately 65%
Renal: approximately 50% unchanged
Bioavailability: about 40% to 50%
Dialyzable: no (hemodialysis), no (peritoneal dialysis)
moderate renal impairment (creatinine clearance of 20 mL/min to 40 mL/min): prolonged to 6.4 h
Effect of food: increases maximal absorption by approximately 0.8 h
severe renal impairment (creatinine clearance of 5 mL/min to 20 mL/min): increases to 11.5 h

Toxicology - Clinical Effects
CEPHALOSPORINS: OVERDOSE: Acute ingestion of large doses of cephalosporins may result in nausea, vomiting, diarrhea, and abdominal pain. Seizures have developed after parenteral overdose. ADVERSE EFFECTS: COMMON: Hypersensitivity reactions, including anaphylaxis, may commonly occur with therapy; oral exposures are less likely to cause severe allergic reactions than parenteral exposures. Seizures have also been reported following therapeutic administration. Prolonged prothrombin times, thrombocytopenia, and coagulopathies associated with a qualitative platelet defect and aggregation abnormalities have been reported following IV cephalosporin therapy. Pseudocholelithiasis may follow intravenous administration of ceftriaxone. Several cases of fatal hemolytic reactions following intravenous ceftriaxone therapy have been reported in children with serious hematologic abnormalities.

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Acetaminophen

2008-12-03T11:55:00.002+05:30

Advise patient it is unsafe to take more than 4 grams of acetaminophen in a 24-hour period.
Instruct patient that many non-prescription combination products may contain acetaminophen.
Instruct patient to report signs/symptoms of gastrointestinal hemorrhage, hepatotoxicity, or nephrotoxicity.
Patient should take with a full glass of water.
Patient should not drink alcohol while taking this drug. Advise patients who drink more than 3 alcoholic drinks a day to consult a healthcare professional prior to taking acetaminophen.

Dosing - Adult
Dysmenorrhea: 650 to 1000 mg ORALLY every 4 h as needed, maximum 4 g/day
Dysmenorrhea: 650 mg RECTALLY every 4 to 6 h; maximum 6 suppositories/24 h
Fever: 650 to 1000 mg ORALLY every 4 h as needed, maximum 4 g/day
Fever: 650 mg RECTALLY every 4 to 6 h; maximum 6 suppositories/24 h
Headache: 650 to 1000 mg ORALLY every 4 h as needed, maximum 4 g/day
Headache: 650 mg RECTALLY every 4 to 6 h; maximum 6 suppositories/24 h
Pain (Mild to Moderate): 650 to 1000 mg ORALLY every 4 h as needed, maximum 4 g/day
Pain (Mild to Moderate): 650 mg RECTALLY every 4 to 6 h; maximum 6 suppositories/24 h

Dosing - Pediatric
Dysmenorrhea: 10 to 15 mg/kg/dose ORALLY every 4 to 6 h, maximum 5 doses/day
Dysmenorrhea: age 12 y and older, 650 mg ORALLY every 4 to 6 h, maximum 3.9 g/24 h
Dysmenorrhea: age 6 to 11 y, 325 mg ORALLY every 4 to 6 h, maximum 2.6 g/24 h
Fever: 10 to 15 mg/kg/dose ORALLY every 4 to 6 h, maximum 5 doses/day
Fever: age 6 to 12 y, 325 mg ORALLY every 4 to 6 h, maximum 2.6 g/24 h
Fever: age 3 to 6 y, 120 to 125 mg RECTALLY every 4 to 6 h; maximum 720 mg/24 h
Fever: age 1 to 3 y, 80 mg RECTALLY every 4 h
Fever: age 3 to 11 months, 80 mg RECTALLY every 6 h
Headache: 10 to 15 mg/kg/dose ORALLY every 4 to 6 h, maximum 5 doses/day
Headache: age 6 to 12 y, 325 mg ORALLY every 4 to 6 h, maximum 2.6 g/24 h
Headache: age 3 to 6 y, 120 to 125 mg RECTALLY every 4 to 6 h; maximum 720 mg/24 h
Headache: age 1 to 3 y, 80 mg RECTALLY every 4 h
Headache: age 3 to 11 months, 80 mg RECTALLY every 6 h
Pain (Mild to Moderate): 10 to 15 mg/kg/dose ORALLY every 4 to 6 h, maximum 5 doses/day
Pain (Mild to Moderate): age 6 to 12 y, 325 mg ORALLY every 4 to 6 h, maximum 2.6 g/24 h
Pain (Mild to Moderate): age 3 to 6 y, 120 to 125 mg RECTALLY every 4 to 6 h; maximum 720 mg/24 h
Pain (Mild to Moderate): age 1 to 3 y, 80 mg RECTALLY every 4 h
Pain (Mild to Moderate): age 3 to 11 months, 80 mg RECTALLY every 6 h

Warnings - Precautions
Acetaminophen-induced liver disease: pts who drink greater than 3 alcoholic drinks every day.

Adverse Effects - Common
Dermatologic: Rash
Adverse Effects - Serious
Gastrointestinal: Gastrointestinal hemorrhage
Hepatic: Hepatotoxicity
Renal: Nephrotoxicity
Respiratory: Pneumonitis
Mechanism of Action
Systemic: For acetaminophen:
Analgesic: The mechanism of analgesic action has not been fully determined. Acetaminophen may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and, to a lesser extent, through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation.
Antipyretic: Acetaminophen probably produces antipyresis by acting centrally on the hypothalamic heat-regulating center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating, and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
Antipyretic: Caffeine is a mild CNS stimulant. Caffeine-induced constriction of cerebral blood vessels, which leads to a decrease in cerebral blood flow and in the oxygen tension of the brain, may contribute to relief of some types of headache.
It has been suggested that the addition of caffeine to acetaminophen may provide a more rapid onset of action and/or enhanced pain relief with lower doses of the analgesic. However, the FDA has determined that studies performed to date have not demonstrated that caffeine is an effective analgesic adjuvant or that it does not interfere with acetaminophen"s efficacy as an antipyretic.

Mechanism of Action - Pharmacokinetics
Systemic: 1 to 4 h
Systemic: Approximately 90 to 95% of a dose is metabolized in the liver, primarily by conjugation with glucuronic acid, sulfuric acid, and cysteine. An intermediate metabolite, which may accumulate in overdosage after the primary metabolic pathways become saturated, is .
Systemic: Oral: Rapid; Rectal: varies
Systemic: Renal: 3% unchanged; Metabolites: primarily conjugates
Systemic: Hepatic: 90 to 95%

Clinical Effects - Treatment
ACETAMINOPHEN-ACUTE: Decontamination: Activated charcoal. Ipecac could interfere with NAC administration.
ACETAMINOPHEN-ACUTE: Acetylcysteine: N-ACETYLCYSTEINE (NAC): Administer if toxic plasma level, or toxic dose ingested and APAP level not readily available. ORAL NAC DOSE - 140 mg/kg load, 70 mg/kg Q 4 hrs for 72 hrs maintenance.
ACETAMINOPHEN-ACUTE: Intravenous infusion: 150 mg/kg NAC in 200 mL D5W over 60 min, followed by 50 mg/kg in 500 mL D5W over next 4 hrs, then 100 mg/kg in 1000 mL D5W over next 16 hrs. Standard intravenous dosing can cause hyponatremia and seizures secondary to large amounts of free water in young children; use of a NAC solution of 40 mg/mL is recommended.
ACETAMINOPHEN-ACUTE: Monitoring of patient: Obtain APAP level 4 hrs postingestion and plot on nomogram. Follow LFTs, renal function, PT or INR in patients with toxic APAP levels.
ACETAMINOPHEN-REPEATED SUPRATHERAPEUTIC: Decontamination: Generally NOT indicated. Consider activated charcoal if recent substantial dose.
ACETAMINOPHEN-REPEATED SUPRATHERAPEUTIC: Acetylcysteine: N-ACETYLCYSTEINE (NAC): Give if initial APAP serum level greater than 10 mcg/mL (greater than 66.16 S.I. Units (micromole/L)) or evidence of liver injury. NAC DOSE - Oral - 140 mg/kg load, 70 mg/kg Q 4 hrs maintenance; IV - 150 mg/kg in 200 ml D5W over 60 min, then 50 mg/kg in 500 ml D5W over 4 hr then 100 mg/kg in 1 L D5W over 16 hr. Standard intravenous dosing can cause hyponatremia and seizures secondary to large amounts of free water in young children; use of a NAC solution of 40 mg/mL is recommended.
ACETAMINOPHEN-REPEATED SUPRATHERAPEUTIC: Monitoring of patient: Obtain serum acetaminophen level, AST, ALT, and PT or INR.

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Ranexa

2008-12-01T12:01:00.002+05:30

Ranexa is an anti-anginal medication. It works by improving blood flow to help the heart work more efficiently.
Ranexa is used to chronic treat angina (chronic chest pain) when other medications have not helped the condition. It should be used in combination with another medicine (eg, amlodipine, beta-blockers, nitrates).

You should not take Ranexa if you have liver disease, hypokalemia (low levels of potassium in your blood), or a personal or family history of "Long QT syndrome." Ranexa should not be taken together with certain medicines to treat heart rhythm disorders, malaria, infections, mental illness, pain, cancer, or stomach disorders. Before you take Ranexa, tell your doctor about all other medications you are using.
Ranexa is not for use during an acute (emergency) attack of angina. Continue using any other medicines prescribed by your doctor (such as nitroglycerin) to treat acute angina.
Chronic angina is often treated with a combination of different drugs. To best treat your condition, use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor.Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

Before taking Ranexa

You should not take Ranexa if you have liver disease, hypokalemia (low levels of potassium in your blood), or a personal or family history of "Long QT syndrome." Ranexa should not be taken together with certain medicines to treat heart rhythm disorders, malaria, infections, mental illness, pain, cancer, or stomach disorders. Before you take Ranexa, tell your doctor about all other medications you are using.
Ranexa is not for use during an acute (emergency) attack of angina. Continue using any other medicines prescribed by your doctor (such as nitroglycerin) to treat acute angina.FDA pregnancy category C. Ranexa may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known if Ranexa passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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Memantine

2008-11-09T23:10:00.002+05:30

Treats symptoms of Alzheimer's disease, such as problems with memory, concentration, and judgment.

How to Use This Medicine:
Tablet
􀁺 Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to. Most people need to wait at least one week between dose changes.
􀁺 You may take this medicine with or without food.
If a dose is missed:
􀁺 If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.
How to Store and Dispose of This Medicine:
􀁺 Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.
􀁺 Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any outdated medicine or medicine no longer needed.
􀁺 Keep all medicine away from children and never share your medicine with anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.
􀁺 Make sure your doctor knows if you are also using amantadine (Symmetrel®), ketamine (Ketalar®), cimetidine (Tagamet®), ranitidine (Zantac®), or quinidine (Cardioquin®, Quinaglute®, Quinidex®).
􀁺 Your doctor needs to know if you are using a diuretic or "water pill," such as acetazolamide, hydrochlorothiazide (HCTZ), methazolamide, triamterene, Diamox®, Dyazide®, Dyrenium®, Maxzide®, Neptazane®. Make sure your doctor knows if you are also using an antacid or laxative that contains sodium bicarbonate, such as Alka-Seltzer®. Sodium bicarbonate is the same thing as baking soda or bicarbonate of soda.
􀁺 Talk to your doctor before using a cold or cough medicine that contains dextromethorphan. Some brand names are DayQuil®, NyQuil®, Robitussin® DM, or TheraFlu®.
Tell your doctor if you smoke or if you are using a stop-smoking aid that contains nicotine (such as Nicoderm®, Nicotrol®, or Nicorette®).

Warnings While Using This Medicine:
􀁺 Make sure your doctor knows if you are pregnant or breast feeding, or if you have epilepsy or liver disease. Tell your doctor if you have any problems with your kidneys or bladder.
􀁺 Call your doctor if you get a urinary tract infection. This includes any infection in your bladder or kidneys. Your dose of this medicine might need to be changed while you have an infection.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
􀁺 Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
􀁺 Chest pain.
􀁺 Dizziness, fainting.
􀁺 Severe sleepiness, restlessness, seeing or hearing things that are not there.
􀁺 Sudden or severe headache.
If you notice these less serious side effects, talk with your doctor:
􀁺 Constipation.
􀁺 Headache.

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Methotrexate

2008-11-08T09:26:00.002+05:30

Methotrexate is a folic acid antagonist derived from aminopterin. It inhibits dihydrofolate reductase, the enzyme required in the pathway supplying methyl donor groups for DNA, RNA and protein synthesis. Methotrexate has been used for the treatment of diseases characterised by inflammation or cellular proliferation. In 1985 the first randomised, placebo-controlled trials were published that demonstrated the short-term efficacy of low-dose weekly methotrexate in rheumatoid arthritis (RA). Methotrexate is now the most widely used disease-modifying antirheumatoid drug (DMARD) in the developed world. It was first used in the treatment of psoriatic arthritis (PsA) in 1951, and has been shown to be of clinical benefit in this condition.

However, methotrexate toxicity remains an important issue when considering its use, and is one of the main reasons for discontinuation. The most common adverse effects are gastrointestinal, such as anorexia, nausea, stomatitis and diarrhoea. CNS toxicity including headache, dizziness, fatigue and mood disturbance may occur. Haematological toxicity is not common, and although all types of cytopenia have been documented, an identifiable risk factor can usually be found, such as untreated folate deficiency, renal insufficiency or superimposed infection.

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Amlodipine Besylate

2008-11-05T15:19:00.004+05:30

Therapeutic Class

Calcium Channel Blocker
Cardiovascular Agent
Dihydropyridine

Mechanism of Action
Amlodipine besylate is a long-acting dihydropyridine calcium channel blocker that exerts its effect by blocking the transmembrane influx of calcium ions into cardiac and vascular smooth muscles. It also reduces peripheral vascular resistance and lowers blood pressure by causing a direct vasodilation in the peripheral arteries of the vascular smooth muscle. Its therapeutic effect on vasospastic angina is through inhibition of coronary spasm .

Pharmacokinetics
about 30 h to 50 h
Hepatic
Oral: time to peak concentration, 6 h to 12 h
Protein binding: approximately 93%
Renal: 60% as metabolites, 10% unchanged
Bioavailability: 64% to 90%
Impaired hepatic function: 56 h
Effect of food: bioavailability not altered

Patient Advice

Patient should avoid activities requiring coordination until drug effects are realized, as drug may cause dizziness.
This drug may cause palpitations, peripheral edema, fatigue, skin-flushing, angina, or myocardial infarction.
Instruct patient to report signs/symptoms of hypotension or exacerbation of angina with initial dosing and dose changes.
Advise patient against sudden discontinuation of drug.
Patient should not drink alcohol while taking drug.

Dosing - Adult

Hypertension: initial, 5 mg ORALLY once daily; maintenance 5-10 mg ORALLY once daily
Stable angina: 5-10 mg ORALLY once daily
Variant angina: 5 to 10 mg ORALLY once daily

Dosing - Dose Adjustment

liver disease and hypertension: starting dose 2.5 mg once daily
elderly, fragile, or small: for hypertension, or when adding to other antihypertensive therapy starting dose 2.5 mg once daily

Warnings - Precautions

aortic stenosis
CHF
exacerbation of angina during initiation of therapy, after dose increases, or withdrawal of beta blocker therapy
hypotension (initially or after dose increases)
liver impairment
persistent progressive dermatologic reactions

Adverse Effects - Common

Cardiovascular: Palpitations, Peripheral edema
Dermatologic: Flushing
Neurologic: Dizziness, Headache
Other: Fatigue

Adverse Effects - Serious
Cardiovascular: Angina, Cardiac dysrhythmia (rare), Myocardial infarction

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Alprazolam

2008-10-23T12:35:00.002+05:30

Indications:

Treating anxiety and panic disorder.

Do NOT use Alprazolam if:

you are allergic to any ingredient in Alprazolam or other benzodiazepines (eg, diazepam)
you have acute narrow-angle glaucoma, severe liver disease, or a mental state where contact with reality is lost (psychosis)
you are taking an azole antifungal (eg, itraconazole, ketoconazole), delavirdine, or sodium oxybate (GHB)

Before using Alprazolam :
Some medical conditions may interact with Alprazolam . Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, plan to become pregnant, or are breast-feeding
if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
if you have allergies to medicines or other substances
if you have glaucoma or a predisposition for glaucoma, liver problems, lung problems or chronic obstructive pulmonary disease (COPD), muscle problems, depression, suicidal tendencies, a blood disorder known as porphyria, or a history of substance abuse or dependence

Drug Interactions:

Rifampin or St. John's wort because the effectiveness of Alprazolam may be decreased
Azole antifungals (eg, itraconazole, ketoconazole), cimetidine, clozapine, delavirdine, fluvoxamine, HIV protease inhibitors (eg, ritonavir), fluoxetine, macrolides and ketolides (eg, erythromycin, azithromycin), nefazodone, omeprazole, propoxyphene, sodium oxybate (GHB), or valproic acid because side effects such as increased sedation or heart problems may occur.
Clozapine, hydantoins (eg, phenytoin), or valproic acid because the actions and side effects of these medicines may be increased.

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Arthritis Drug May be Helpful in Type-2 Diabetes

2008-10-01T23:13:00.003+05:30

Doctors have rediscovered that salsalate, a drug used to treat arthritis, may be beneficial for type 2 diabetes as well. Rediscovered? Well, dial back to 1876 -- a medical journal reported on a patient who was successfully treated with salicylate (a simple form of salsalate) for diabetes. Salicylates are a subset of NSAIDs (nonsteroidal anti-inflammatory drugs).
Now, researchers from the Joslin Diabetes Center in Boston report that using salsalate for short time periods can lower blood sugar before people eat and after they eat -- and affect average blood sugar measurements over time. It may turn out to be that one drug benefits both conditions -- arthritis and diabetes.
Salsalate is reportedly safe and inexpensive. Results from a broad study carried out in 13 states, that evaluated salsalate as a treatment for type 2 diabetes, are expected to be released in a couple of months. A larger study will begin later in the year at 20 U.S. sites. More than 15 million people in the U.S. have type 2 diabetes and over 46 million have doctor-diagnosed arthritis. Some of those patients have both conditions. Salsalate may prove to be a good treatment option for that population of patients.

Source: About.com

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ZEFTERA

2008-09-15T12:57:00.001+05:30

ZEFTERA the only approved antibiotic in its class (cephalosporin) by Health Canada to demonstrate efficacy against Methicillin-resistant Staphylococcus aureus (MRSA), a growing public health concern in both hospital and community settings.ZEFTERA is specially designed to tightly bind to and inhibit targets in both gram-positive (including MRSA) and gram-negative bacteria. The approval of ZEFTERA for the treatment of complicated skin and skin structure infections, including non-limb threatening diabetic foot infections without concomitant osteomyelitis, was based on results of two Phase III, double-blind, randomized, multi-centre, global trials involving 817 patients with cSSSI 2,3. The second Phase III trial included patients with non-limb threatening diabetic foot infections (mild, moderate or severe)3. Pathogens identified at baseline in this subpopulation included MSSA (38 per cent), MRSA (13 per cent), E. cloacae (9 per cent), and P.mirabilis (7 per cent). The results demonstrated the non-inferiority of ceftobiprole versus vancomycin plus ceftazidime in the treatment of diabetic foot infections. In both studies, ZEFTERA was well tolerated. The most common treatment-emergent adverse reactions were nausea (9 per cent) taste disturbance (6 per cent), diarrhea (5 per cent) and vomiting (5 per cent).

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Alvimopan

2008-09-03T13:40:00.002+05:30

A peripherally acting mu-opioid receptor antagonist, wasapproved by the US FDA to accelerate thetime to gastrointestinal recovery followingbowel resection surgery. It is the firstpharmacotherapy to be approved for thisapplication.

Ileus — a temporary impairment ofgastrointestinal function — is a complicationthat affects almost all patients that undergomajor bowel surgery. It results in abdominaldiscomfort, nausea and vomiting, and is amajor reason for prolonged hospitalization.

The pathophysiology of post-operative ileus(POI) is complex. An important contributoryfactor is the activation of m-opioid receptors in the gastrointestinal tract by endogenous opioidsthat are released in response to the stress causedby surgery, as well as by opioid analgesics thatare the most common treatment for pain inpatients undergoing surgery1,2. Activation ofthese peripheral m-opioid receptors leads to anincrease in colonic muscle tone and a reductionin propulsive activity in the gastrointestinaltract. Consequently, opioid treatmentto provide pain relief following surgery isthought to prolong POI. The adverse effects of opioids on thegastrointestinal tract can be reversed bym-opioid-receptor antagonists such as naloxoneand nalmefene, but these drugs are also activein the central nervous system, and so inhibitthe analgesic effects of systemic opioids.To overcome this issue, efforts have beendirected at identifying m-opioid receptorantagonists with peripherally restrictedactivity. One such research programmeresulted in the discovery of alvimopan.

Drug properties

Alvimopan is a potent and selective antagonistof the human m-opioid receptor4 –6. It is orallyavailable, but its activity is peripherallyrestricted because its moderately large,zwitterionic form and polarity limitgastrointestinal absorption and preventpassage through the blood–brain barrier4 –6.Preclinical and small-scale clinical studiesdemonstrated that alvimopan administeredorally can selectively antagonize thegastrointestinal effects of opioid agonists suchas morphine without affecting analgesia.

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Thiazolidinediones (Rosiglitazone)

2008-08-16T22:44:00.002+05:30

WARNINGS AND PRECAUTIONS-

Cardiac Failure
Myocardial Ischemia
Myocardial Ischemic Events in Large Long-Term Prospective Randomized Controlled Trials
Congestive Heart Failure and Myocardial Ischemia During Coadministration With Insulin
Weight Gain

Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients.
After initiation of Thiazolidinediones, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction must be considered.

Limitations of Use:

It should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Coadministration with insulin is not recommended.
Use with nitrates is not recommended.

DOSAGE AND ADMINISTRATION

Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.
• Dose increases should be accompanied by careful monitoring for adverse events related to fluid retention.
• Do not initiate AVANDIA if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels.

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Amlodipine and Valsartan

2008-08-16T22:37:00.002+05:30

WARNINGS AND PRECAUTIONS-

Avoid use in pregnancy.
Fetal/Neonatal Morbidity and Mortality - can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Drugs that act on the renin angiotensin system can cause fetal and neonatal morbidity and mortality when used in pregnancy. In several dozen published cases, ACE inhibitor use during the second and third trimesters of pregnancy was associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death.
Hypotension- Volume depletion should be corrected prior to administration .
Impaired Renal Function - Hypertension

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Stop your NSAID medicine if you have any of the following symptoms

2008-07-28T16:27:00.001+05:30

nausea
more tired or weaker than usual
itching
your skin or eyes look yellow
stomach pain
flu-like symptoms
vomit blood
there is blood in your bowel movement or it is black and sticky like tar
unusual weight gain
skin rash or blisters with fever
swelling of the arms and legs, hands and feet

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Get emergency help right away if you have any of the following symptoms

2008-07-28T16:24:00.000+05:30

Shortness of breath or trouble breathing
Chest pain
Weakness in one part or side of your body
Slurred speech
Swelling of the face or throat

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Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Side Effects

2008-07-28T16:19:00.003+05:30

Serious side effects include:

heart attack
stroke
high blood pressure
heart failure from body swelling (fluid retention)
kidney problems including kidney failure
bleeding and ulcers in the stomach and intestine
low red blood cells (anemia)
life-threatening skin reactions
life-threatening allergic reactions
liver problems including liver failure
asthma attacks in people who have asthma

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Naproxen

2008-07-28T15:15:00.001+05:30

Naproxen is a proprionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs.
Indications:
Rheumatoid arthritis
Osteoarthritis
Ankylosing spondylitis
Juvenile Arthritis
Immediate ReleaseAfter administration of NAPROSYN tablets, peak plasma levels are attained in 2 to 4 hours. After oral administration of ANAPROX, peak plasma levels are attained in 1 to 2 hours
Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance < 30 mL/min)
Naproxen has been studied in patients with rheumatoid arthritis, osteoarthritis, juvenile arthritis, ankylosing spondylitis, tendonitis and bursitis, and acute gout. Improvement in patients treated for rheumatoid arthritis was demonstrated by a reduction in joint swelling, a reduction in duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and patient, and by increased mobility as demonstrated by a reduction in walking time. Generally, response to naproxen has not been found to be dependent on age, sex, severity or duration of rheumatoid arthritis.In patients with osteoarthritis, the therapeutic action of naproxen has been shown by a reduction in joint pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a reduction in walking time, and improvement in capacity to perform activities of daily living impaired by the disease.
Naproxen has been shown to be comparable to aspirin and indomethacin in controlling the aforementioned measures of disease activity, but the frequency and severity of the milder gastrointestinal adverse effects (nausea, dyspepsia, heartburn) and nervous system adverse effects (tinnitus, dizziness, lightheadedness) were less in naproxen-treated patients than in those treated with aspirin or indomethacin.

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Highly Drug-Resistant HIV

2008-07-24T15:20:00.002+05:30

Integrase is a viral enzyme that is essential for HIV type 1 (HIV-1) replication; it catalyzes the insertion of proviral DNA into the host-cell genome. Raltegravir is an integrase inhibitor and specifically inhibits proviral DNA-strand transfer, with potent in vitro activity against HIV-1.

In most patients with highly drug-resistant HIV, the resistance develops because of sequential exposure to HIV drugs in the context of incomplete virologic suppression. The genetic barrier to drug resistance for several of the most important HIV agents is low, requiring only a single point mutation to confer loss of activity. Drug-resistant virus can also be transmitted from person to person, although the transmission of strains resistant to multiple classes of drugs is rare.

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Desmopressin increases risk for hyponatremia.

2008-07-19T12:30:00.005+05:30

Today i recieve a article from Doctor's Guide regarding Desmopressin and i want to share with healthcare professionals.

Health Canada is informing healthcare professionals that all intranasal formulations of desmopressin (DDAVP) are no longer indicated for the treatment of primary nocturnal enuresis (PNE) due to an increased risk of hyponatremia with the intranasal formulations.· All intranasal formulations of desmopressin are now contraindicated for the treatment of PNE.· All patients using intranasal formulations of desmopressin for treatment of PNE should be reassessed to determine their need for continued treatment and to discuss other options.

If ongoing treatment is considered necessary, patients should be switched to the lowest starting dose of an oral formulation, with the dose increased only if necessary to control symptoms.

Fluid intake and desmopressin dosage should be adjusted carefully in order to reduce the possibility of water retention and hyponatremia, especially in very young and elderly patients or when significant daily variables occur such as hot climate conditions, intense exercise, or other situations where increased water intake can be expected.

Worldwide postmarketing data indicate a higher incidence of hyponatremia in patients being treated with the desmopressin intranasal formulations compared with the oral formulations.

When desmopressin treatment is needed, physicians should discuss with the patient and/or guardian the importance of limiting the amount of fluid intake 1 hour before taking the medication and during the 8 hours postdose.

SOURCE: Health Canada

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Antipsychotics

2008-07-18T12:58:00.002+05:30

FDA is notifying healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics.
Antipsychotics are not indicated for the treatment of dementia-related psychosis.

Antipsychotic drugs are not approved for the treatment of dementia-related psychosis. Furthermore, there is no approved drug for the treatment of dementia-related psychosis. Healthcare professionals should consider other management options.
Physicians who prescribe antipsychotics to elderly patients with dementia-related psychosis should discuss this risk of increased mortality with their patients, patients’ families, and caregivers.

Source

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Fluoroquinolone Antimicrobial Drugs

2008-07-18T12:34:00.002+05:30

FDA notified healthcare professionals that a BOXED WARNING and Medication Guide are to be added to the prescribing information to strengthen existing warnings about the increased risk of developing tendinitis and tendon rupture in patients taking fluoroquinolones for systemic use.Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture. This risk is further increased in those over age 60, in kidney, heart, and lung transplant recipients, and with use of concomitant steroid therapy.

Physicians should advise patients, at the first sign of tendon pain, swelling, or inflammation, to stop taking the fluoroquinolone, to avoid exercise and use of the affected area, and to promptly contact their doctor about changing to a non-fluoroquinolone antimicrobial drug. Selection of a fluoroquinolone for the treatment or prevention of an infection should be limited to those conditions that are proven or strongly suspected to be caused by bacteria.

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Amantadine

2008-07-16T16:49:00.002+05:30

Class of drug: Treatment for Parkinson’s disease, antiviral agent.
Mechanism of action: Anti-Parkinson action: promotes release of dopamine in substantia nigra. Antiviral action: prevents viral penetration of influenza A virus into target host cells.
Indications/dosage/route: Oral only.
Parkinson’s disease
Ð Adults: 100 mg b.i.d., may be titrated up. Maximum: 400 mg/d.
Influenza A: Ð Adults: 200 mg/d, single or divided dose.
Adjustment of dosage:
Kidney disease: reduce dose as follows. Creatinine clearance 30–50 mL/min: initial 200 mg, then 100 mg/d; creatinine clearance 15–29 mL/min: initial 200 mg, then 100 mg q.i.d.; creatinine clearance <15 mL/min: 200 mg q7d.
• Liver disease: None
• Elderly: Dosage should be divided as twice daily administration.
Contraindications: Hypersensitivity to amantadine, untreated angle-closure glaucoma.
Warnings/precautions: Use with caution in patients with the following conditions:
Psychiatric disorders, liver or kidney disease, history of epilepsy, peripheral edema, orthostatic hypotension, severe psychosis, eczematoid dermatitis, exposure to rubella.
• There is a possibility of seizures if given with CNS stimulants or in patients with history of epilepsy.
• Do not stop abruptly when treating Parkinson’s disease.
• Deaths from amantadine overdose have been reported.
Adverse reactions: Common: dizziness, insomnia.
• Serious: CHF, seizures, hallucinations, depression, psychosis, bone marrow depression, livedo reticularis, renal toxicity.

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Drug Errors

2008-07-13T00:46:00.002+05:30

Drug errors contribute to morbidity. They also cost the country's health care system. So, doctors should keep in mind these points while prescribing medicines. Drug errors may involve:

The wrong choice of a drug or a prescription for the wrong dose, frequency, or duration.
An error in reading the prescription by the pharmacist so that the wrong drug or dose is dispensed.
Incorrect instructions to the patient.
Incorrect administration by a health care practitioner or patient.
Incorrect storage of a drug by the pharmacist or patient, altering the drug's potency.
Use of outdated drug, altering the drug's potency.
Confusion of the patient so that the drug is taken incorrectly.
Unscrupulous replacement of a drug with an inferior, diluted, or inactive product.

Errors in prescribing are common, especially for certain populations. The elderly ), women of childbearing age, and children are particularly at risk. Drug interactions particularly affect those taking many drugs. To minimize risk, a physician should know all drugs being taken—including those prescribed by others and OTC drugs—and keep a complete problem list.

Most commonly, drug error results from a patient's confusion about how to take drugs. Patients may take the wrong drug or dose. Dosing instructions for each drug, including why the drug has been prescribed, should be completely explained to patients.

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Most common Drug Interactions

2008-07-11T20:13:00.002+05:30

Aspirin. This common, over-the-counter pain reliever also thins the blood. Aspirin may cause internal bleeding if combined with a prescription blood thinner such as warfarin (Coumadin). It can also decrease the effectiveness of some gout medications and increase the strength of certain diabetes drugs.
Antibiotics. Some forms of these infection-fighting drugs can lose their power if combined with antacids or other products containing calcium. In addition, certain antibiotics can hamper the effectiveness birth control pills and greatly increase the effects of warfarin. Probenecid , a drug used to treat gout, can increase blood levels of several different types of antibiotics. In some cases, doctors may even use this interaction to their advantage: For extra punch against germs, doctors sometimes prescribe this drug along with antibiotics.
Antidepressants. Newer antidepressants known as SSRIs, such as fluoxetine and paroxetine, shouldn't be mixed with older mood-lifters known as MAOIs (such as phenelzine). This combination can send blood pressure soaring. Fluoxetine and similar drugs can also clash with St. John's wort and migraine drugs known as triptans. Potential side effects of such combinations include confusion, fever, high blood pressure, and tremors. Another class of antidepressants called tricyclics (such as Elavil), can also clash with MAOIs, causing confusing dizziness, seizures, and even coma.
Bronchodilators. The popular drug albuterol can cause dangerous spikes in blood pressure if combined with MAOIs or tricyclic antidepressants such as nortriptyline. If albuterol is combined with a beta blocker (used to treat blood pressure), neither drug will work as well as it should.
Diabetes medications. Many drugs can block the effectiveness of glipizide (Glucotrol) and glyburide (Diabeta, Glynase, Micronase). Potential culprits include corticosteroids, hormones, diuretics, and antipsychotics. Several other drugs make the effects of glipizide and glyburide stronger, including blood thinners, insulin, MAOIs, aspirin, and the gout medicine probenecid.
Heart medications. The common heart drug digoxin can lose effectiveness if combined with antacids. On the other hand, its effects can be amplified by several other drugs, including diazepam (Valium) and antiarrhythmia medications. Heart drugs known as nitrates can trigger dangerously low blood pressure if taken with the erectile dysfunction drug sildenafil (Viagra). The combination of the blood pressure medication atenolol (Tenoretic, Tenormin) and reserpine (Serpalan, Serpasil-- another blood pressure medication sometimes prescribed to calm severe agitation) can cause a slow heartbeat and lower than normal blood pressure.

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Immunosuppressive Agents

2008-07-10T01:02:00.002+05:30

Major classes of agents employed in immunosuppressive therapy:

Corticosteroids
Cytotoxic Agents
T-cell suppressive agents
Antibodies

Mechanism of action:

Cytotoxic Agents- suppress bone marrow function

1. Cyclophosphamide:
a. Primarily suppresses B-cell production; lowers humoral immunity
b. Used to treat severe rheumatoid arthritis
c. Not normally used for graft rejection
2. Azathioprine
a. Primarily suppresses T-cell production
b. Used for graft rejection
c. Normally used in combination with corticosteroids
3. Mycophenolate Mofetil (CELLCEPT)
a. Mechanism of action: inhibits inosine monophosphate dehydrogenase; an
enzyme required for de novo purine synthesis
b. Selective because T and B cells rely on de novo pathway
c. Suppresses lymphocyte proliferation and B-cell antibody production
d. Can be used to inhibit transplant rejection

T-Cell Suppressor Agents

1. Cyclosporine and Tacrolimus
a. Mechanism of action: block proliferative response of T-cells to antigen by inhibiting calcineurin activity.
b. Have little myelotoxicity
c. Used in combination with corticosteroids for organ transplants
d. Variable oral absorption
e. Extensively metabolized
f. Metabolite excreted in urine
g. Cause renal toxicity in up to 75% of patients; frequently responsible for stopping therapy.

Antibodies

Selective antibodies against lymphocytes and thymocytes have been used as immunosuppressants.

1. Antithymocyte Globulin
(A) Polyclonal antibody, binds T-lymphocytes
(B) Primary use: graft rejection during acute phase
(C) Side effects: allergic reactions; consequences of immune suppression
b. Muromonoab-CD3
(A) Monoclonal antibody, binds to T-lymphocytes
(B) Primary use: acute graft rejection
(C) Side effects: cytokine release syndrome (can be fatal); allergic reactions; consequences of immune suppression.

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Infliximab

2008-07-09T20:50:00.002+05:30

Infliximab is a chimeric IgG 1K monoclonal antibody. Its approximate molecular weight is 149,100 daltons. It is composed of human constant and murine variable regions. Infliximab binds specifically to human TNF-α.

Biological effects of infliximab

TNF-α induces proinflammatory cytokines that include IL-1 and IL-6. These cytokines enhance leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, and induction of acute phase and other liver proteins.

Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble and transmembrane forms of TNF-α and inhibits binding of TNF-α with its receptors. A related cytokine that utilizes the same receptors as TNF-α, TNF-beta (lymphotoxin α) is not neutralized by infliximab. It has been found to downregulate IL-18 but not IL-12 and IL-13.

It upregulates the expression of CXCchemokine receptor type II and magnifies the proliferative activity of CXCchemokines in human melanocytes. In Crohn’s disease, it decreases levels of IL-10.
Apoptosis of monocytes is not responsible for the therapeutic TNF-alpha Inhibitors. However, some of the therapeutic effects of infliximab may be caused by its ability to downregulate proinflammatory cytokines production by monocytes exposed to bacterial antigens.

Infliximab was first approved by the Food and Drug Administration (FDA) in 1998 as a treatment of moderately to severely active Crohn’s disease. Its initial indication was to reduce the signs and symptoms in patients with Crohn’s. The recommended dose of infliximab for the treatment of severe active Crohn’s disease in refractory patients is 5 mg/kg intravenously as a single dose. In patients with Crohn’s disease with fistula involvement, an initial dose of 5 mg/kg followed by additional 5 mg/kg doses at weeks 2 and 6 is recommended. This dose is often used in other Crohn’s disease patients.

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Dabigatran etexilate

2008-07-06T23:56:00.004+05:30

Dabigatran is a direct thrombin inhibitor, for the prevention of venous thromboembolic events in patients who have undergone total hip- or knee-replacement surgery.

Venous thromboembolism (VTE) — occlusion of veins by blood clots — is the third most common cause of cardiovascular-associated death, after heart attacks and stroke. Without preventive treatment, patients undergoing hip- or knee-replacement surgery are at high risk of developing VTE2. Indeed, many clinical studies have demonstrated the importance of primary thromboprophylaxis in reducing morbidity and mortality for such patients.

The serine protease thrombin is the final mediator in the coagulation cascade that leads to the production of fibrin, the main protein component of blood clots. Thrombin is also a potent activator of platelets. Consequently, thrombin has been a popular target for the development of
novel anticoagulants.

Several peptidic direct thrombin inhibitors (DTIs) have been approved for clinical use in the prevention of thrombosis, such as desirudin1,3. However, these agents still require parenteral administration, limiting their chronic use. An orally available DTI, ximelagatran was approved in Europe in 2004, but was subsequently withdrawn from the market owing to issues with liver toxicity. The development of other DTIs has continued, and dabigatran is the first to receive regulatory approval in a major market.

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Lead Poisoning

2008-07-05T12:33:00.001+05:30

Lead is widespread in the environment, reflecting the many uses we have for it. Exposure to lead has decreased dramatically since its use in house paints and gasoline was banned.
Lead and its compounds are quite toxic. Metallic lead generally converted to Pb2+ in the body. Lead can damage the brain, liver, and kidney. Extreme cases can be fatal.
Lead poisoning is especially harmful to children. Some children develop a craving that causes them to eat unusually things, and children with the syndrome called ‘pica’ eat chips of peeling lead-based paints.
Large amount of Pb2+ in a child’s blood can cause mental retardation, behavior problems, anemia, hearing loss, developmental delays, and other physical and mental problems.
Adults can excrete about 2 mg of lead per day. If intake exceeds excretion, however, lead builds up in the body and chronic irreversible led poisoning results.

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Quicksilver --- Slow Death

2008-07-05T12:31:00.001+05:30

Mercury is the only common metal that is a liquid at room temperature.
Dentists use it to make amalgams for filling teeth, and laboratory workers employ mercury and its compounds in a variety of ways. Farmers use seeds treated with compounds of mercury.
Mercury vapor is quite hazardous when inhaled, particularly when exposure takes place over a long period of time. By some as yet unknown mechanism, the body converts the inhaled mercury to Hg2+ ions. All compounds of mercury, except those that are essentially insoluble in water, are poisonous no matter how they are administered.
Because mercury is cumulative poison (it takes the body about 70 days to rid itself of half of a given dose), chronic poisoning is a threat to those continually exposed.
The antidote for mercury, the compound, a derivative of glycerol, is called British antilewisite (BAL). It acts by chelating (from the Greek chela meaning “claw”) Hg2+ ions. Thus tied up, the mercury cannot attack vital enzymes.
The effects of mercury poisoning may not show up for several weeks. By the time they symptoms – loss of equilibrium, sight, feeling, and hearing – are recognizable, extensive damage has already been done to the brain, and the nervous system. Such damage is largely irreversible. The BAL antidote is effective only when a person knows that he or she has been poisoned and seeks treatment right away.

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Cyanides: Agents of Death

2008-07-05T12:22:00.002+05:30

They act quickly, and it takes only a small amount to kill. The average fatal dose is only 50 or 60 mg of gaseous hydrogen cyanide or of a solid salt containing the cyanide ion.
Cyanide blocks the oxidation of glucose inside the cell by forming a stable complex with iron (III) ions in oxidative enzymes called cytochrome oxidases. These enzymes normally act by providing electrons for the reduction of oxygen in the cell. Cyanide blocks this action and brings an abrupt end to cellular respiration, causing death in minutes.
Any antidote for cyanide poisoning must be administered quickly. Providing 100% oxygen to support respiration can sometimes help. Sodium nitrite is often given intravenously to oxidize iron atoms in the enzymes back to the active Fe3+ form. Sodium thiosulfate is then used if time permits. The thiosulfate ion transfers a sulfur atom to the cyanide ion, converting it to the relatively innocuous thiocyanate ion.

Aminoglycoside Antibiotics

2008-06-30T01:06:00.002+05:30

The aminoglycoside antibiotics have the narrowest therapeutic range of any of the antimicrobial drugs. Their use requires precision of administration; optimal use requires monitoring serum levels. Accumulation of these compounds causes nephrotoxicity and ototoxicity, which can be delayed in onset and from which full recovery may not ensue. All of these compounds demonstrate a slow terminal elimination phase, and drug is excreted in the urine for weeks after discontinuation of therapy. This slow elimination phase contributes to accumulation of any of these compounds.

Penicillins, particularly carbenicillin, piperacillin, and ticarcillin, can physically complex with these agents and, therefore, cannot be mixed in the same intravenous infusion. This same phenomenon occurs in patients with ESRD such that co administration of these penicillins results in a decreased serum level of aminoglycoside.More precise guidelines are offered because of the narrow therapeutic index of aminoglycosides.

Acute migraine treatments

2008-06-30T00:44:00.002+05:30

Acetaminophen and NSAIDS

First of treatment for mild migraines
Time to onset: 1-2 hours
Duration of effect: 2-3 hours, decreases with increasing frequency of use
Side effects: can lead to GI bleeding, liver and renal dysfunction.

Ergotamine Derivatives

Ergotamine are fungal derivatives that are potent vasoconstrictors.
Used for severe migraines.
Time to onset: 15 min to 2 hours depending on route.
Duration of effect: 2-4 hours.
Side effects: increased BP, MI, stroke.

Triptans

Triptans are 5HT1B, 5HT1D agonists.
Sumatriptan was the first to be introduced in 1991.
Sumatriptan is used for severe migraine with 10 min time to onset and 60-70% efficacy with a duration of 2 hours.
2ndgeneration triptans have since been developed with increased efficacy and duration of action.
Side effects are referred to as triptan sensations and include tingling, numbing, anxiety, heaviness or tightness in the chest and throat, and sensations of warmth, burning, cold, or pressure.

Prophylaxis Treatment

Beta-blockers
Antidepressants
Calcium channel blockers
Anti-convulsants
Serotonin antagonists
Natural products
Newer treatments ( BOTOX)

MCQ 1.

2008-06-27T16:27:00.003+05:30

Which one of the following statements is CORRECT?

A. Weak bases are absorbed efficiently across the epithelial cells of the stomach.
B. Coadministration of atropine speeds the absorption of a second drug.
C. Drugs showing large Vd can be efficiently removed by dialysis of the plasma.
D. Stressful emotions can lead to a slowing of drug absorption.
E. If the Vd for a drug is small, most of the drug is in the extraplasmic space.

Answer: Click

Alteplase

2008-06-21T01:57:00.002+05:30

Class of drug: Thrombolytic agent.
Mechanism of action: Converts fibrin-bound plasminogen to plasmin, which initiates local fibrinolysis (clot dissolution).
Indications/dosage/route: IV only.

Acute myocardial infarction: accelerated infusion:
Ð Adults weighing more than 65 kg: Infuse 15 mg over 1–2 minutes; infuse 50 mg over next 30 min. Begin heparin 5000–10,000 units IV bolus followed by continuous infusion of 1000 units/h. Infuse 35 mg alteplase over next hour.
Acute ischemic stroke
Pulmonary embolism

Contraindications:

Patients treated for acute MI, pulmonary embolism, active internal bleeding, history of cerebrovascular accident, recent intracranial or intraspinal surgery or trauma, intracranial neoplasm, arteriovenous malformation or aneurysm, known bleeding diathesis, severe uncontrolled bleeding, severe uncontrolled hypertension.

Warnings/precautions:

Use with caution in patients with the following conditions:
internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, or respiratory tracts), superficial bleeding (venous cutdown sites, arterial punctures), recent major surgery (coronary artery bypass graft, obstetric delivery), cerebrovascular disease, mitral stenosis with atrial fibrillation, acute pericarditis, hemorrhagic ophthalmic conditions, concomitant administration of anticoagulants.
Cardiac and blood pressure monitors are required when using this drug.
Dose should be limited to 100 mg. Doses of 150 mg or greater have been shown to increase intracranial bleeding.
Initiate therapy as soon as possible after stroke symptoms are apparent and no more than 3 hours after onset of stroke symptoms. After MI, therapy should be initiated within 7 hours.
Obtain values for the following parameters before administering this drug: CBC, PT, PTT, creatinine phosphokinase, fibrinogen, cardiac isoenzymes.

Clinically important drug interactions:

The following drugs increase effects/toxicity of alteplase: warfarin, aspirin, ticlopidine, dipyridamole, heparin.

Nsaids

2008-06-15T17:22:00.001+05:30

As with any tightly protein bound drug, Nsaids can displace other protein bound pharmacologic agents causing transient increases in concentrations of free drug in the serum. It is important to point out that all of these anti inflammatory agents are inhibitors of prostaglandin synthesis and in a variety of disease states, particularly congestive heart failure, liver disease, hemorrhage, systemic lupus erythematosus with renal involvement, and chronic renal failure, prostaglandins appear to be important in maintaining renal blood flow. In addition, it is now clear that both COX-1 and COX-2 have physiologic and pathophysiologic roles in renal function. As a consequence, prostaglandin inhibition, either COX-1 or COX-2, can result in decrements in renal function. Therefore, any of the nonsteroidal anti-inflammatory drugs could cause worsening renal function in patients with the aforementioned diseases.

Thus,before prescribing Nsaids it is mandatory to know the Kidney profile of the patient.

Anticonvulsants

2008-06-07T00:30:00.000+05:30

The disposition of phenytoin and valproic acid shows important changes in patients with decreased renal function and hypoalbuminemic conditions.
These changes are a manifestation of decreased protein binding with a concomitant increase in the volumes of distribution of these drugs. This phenomenon has been closely investigated with phenytoin, and it is likely that parallels can be drawn with valproic acid. Both drugs are highly protein bound; so in patients with renal dysfunction or with hypoalbuminemia, displacement from serum proteins occurs with a concomitant increase in the volume of distribution. The clinical importance of this phenomenon is that the patient with renal dysfunction manifests the same concentration of free drug in serum at a lower total blood concentration than does the subject with normal renal function. Since most clinical laboratories measure only total concentration of drug in the blood, the importance of the phenomenon is in the proper interpretation of a blood level for these drugs in such patients. In some circumstances it may be desirable to obtain a measurement of the unbound drug concentration. Fundamentally, clinicians should not misinterpret diminished concentrations of total phenytoin in such patients.
In summary, in a uremic or hypoalbuminemic subject, one should not misinterpret a low serum phenytoin concentration as subtherapeutic. The clinician must depend on clinical measures of end points of response. Phenytoin is readily assessed because patients with therapeutic concentrations often have nystagmus and increasing the dose in such patients would result in toxicity. On the other hand, the dose can be safely increased if there is a lack of efficacious effect and the patient does not have nystagmus. It is also important to note that phenytoin follows dose dependent kinetics. As a consequence, increments in dosing should be small and sufficient time should be allowed for the patient to achieve a new steady state.

Anesthetics

2008-06-04T16:39:00.000+05:30

Many of the neuromuscular blocking agents are eliminated by the kidney and require dose adjustment in patients with renal dysfunction. For some of these drugs no data are available to allow development of guidelines for use in patients. Use of any of these drugs in the patient with renal failure requires caution, and it has been recommended that a peripheral nerve stimulator be employed to assess the degree of neuromuscular blockade. Short of this, the clinician must be aware that a patient with renal dysfunction may have slow recovery from anesthesia owing to both retention of anesthetic agents eliminated by the kidney or to additional factors that again are related to renal function. For example, patients with renal disease who either accumulate aminoglycoside antibiotics to high concentrations or who are potassium depleted may have prolonged respiratory suppression in the face of anesthetic agents as a result of the "curare like" effect that can occur with these antibiotics. The same principles apply to patients with liver disease and to drugs eliminated by hepatic routes.

Fazadinium appears to have only minor changes in pharmacokinetics in patients with end stage renal disease and may, therefore, be a preferred agent in patients with renal dysfunction.

Alfentanil, fentanyl, and propofol have been studied in the elderly. The disposition of the former two drugs was no different than in young patients. However, the pharmacodynamics were clearly altered such that half as much of either drug resulted in the same CNS depression as in young patients. The mechanism of this increased sensitivity is unknown. The initial volume of distribution and the clearance of propofol in elderly patients were about 75% of those in young patients. Thus, with this anesthetic, lower doses should also be used in elderly patients.

Analgesic Agents

2008-06-04T16:32:00.000+05:30

Most of the analgesics are eliminated by the liver and renal dysfunction has little influence on their disposition. It has been noted, though poorly documented, that patients with renal and hepatic dysfunction manifest an increased sensitivity to a variety of the analgesic agents, particularly to narcotics. Whether this increased sensitivity is related to changed distribution to the sites of activity, additive effects of retained endogenous toxins, or to truly increased sensitivity is unclear. Usually, beginning doses of these agents are reduced in patients with renal and liver dysfunction until the individual patient demonstrates his or her own dose response relationship.

Baclofen

2008-06-04T14:45:00.003+05:30

Class of drug: Skeletal muscle relaxant.
Mechanism of action: Inhibits mono- and polysynaptic reflexes within the spinal cord resulting in decreased spasticity.
Indications/dosage/route: Oral only.

Spasticity of multiple sclerosis and spinal cord lesion

Adults: Initial: 15 mg/d, may increase dose every 3 days by 5–15 mg/d. Maximum: 80 mg/d, q8h.
Ð Children 2–7 years: Initial: 10–15 mg/kg/d, may increase dose every 3 days by 5–15 mg/d. Maximum: 40 mg/d.
Ð Children >8 years: Initial: 10–15 mg/d, titrate dose as above. Maximum: 80 mg/d.

Adjustment of dosage

• Kidney disease: reduce dose.
• Liver disease: no reduction required.
• Elderly: reduce dose.

Contraindications: Hypersensitivity to baclofen.
Warnings/precautions

Use with caution in patients with the following conditions:
Seizures, decreased renal function.
• Seizure threshold may be lowered in epileptics.
• Patients requiring spasticity to maintain posture and balance may worsen with treatment.
• Avoid abrupt withdrawal.

Advice to patient

Avoid alcohol and other CNS depressants such as opiate analgesics and sedatives (eg, diazepam) when taking this drug.
Change position slowly, in particular from recumbent to upright, minimizing orthostatic hypotension. Sit at the edge of the bed for several minutes before standing, lie down if feeling faint or dizzy. Avoid hot showers or baths and standing for long periods. Male patients with orthostatic hypotension may be safer urinating while seated on the toilet rather than standing.
Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known.
Do not stop drug abruptly as this may precipitate withdrawal reaction (anxiety, hallucinations, tachycardia, seizures).

Adverse reactions

Common: slurred speech, dizziness, drowsiness.
Serious: psychiatric abnormalities, confusion, syncope, dyspnea, hallucinations, depression.

Clinically important drug interactions

Drugs that increase effects/toxicity of balclofen: antihistamines, sedatives, opioids, CNS depressants, alcohol, MAO inhibitors.

Parameters to monitor

Evaluate patient for orthostasis.
• Monitor for sedation and CNS side effects.
• Signs of hypersensitivity reactions.

Note: Food: Take with food or milk.

Adenosine

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Class of drug: Antiarrhythmic.
Mechanism of action: Vagolytic effect: Slows conduction through AV node; prevents reentry through AV node. Restores normal sinus rhythm in patients with paroxysmal supraventricular tachycardia including Wolff–Parkinson–White syndrome.
Indications/dosage/route: IV only.
Paroxysmal supraventricular tachycardia
Ð Adults: bolus of 6 mg. If no effect after 1–2 min, 12-mg bolus. May repeat 12-mg dose × 2.
Adjustment of dosage•
Kidney disease: None.
Liver disease: None.
Elderly: None.
Contraindications:
Second- or third-degree AV block (without pacemaker), sick sinus syndrome, symptomatic bradycardia.
Warnings/precautions
Use with caution in patients with the following condition:
Stroke, asthma, unstable angina (higher risk of arrythmias, MI).
Cardiac arrest (including fatalities), ventricular tachycardia, and MI have been reported coincident with use.
May produce transient first-, second-, third-degree AV block.
Asystole has been reported in atrial flutter when given with carbamazepine.
Use cautiously in patients receiving digoxin and/or verapamil.
May cause ventricular fibrillation.
Resuscitative equipment should be readily available when adenosine is administered.
May produce hypotension or hypertension as side effects.
May cause bronchoconstriction in patients with asthma or COPD.
Advice to patient

It is necessary to inject adenosine rapidly by peripheral IV route followed by saline bolus because of its short half-life. Solution should be checked for presence of crystals; if present, warm solution. Do not inject if crystals are present.

Adverse reactions
Common: facial flushing (18%), nausea, hyperventilation, thoracic constriction, palpitations.
Serious: hypotension, dyspnea (12%), heart block, ventricular fibrillation, asystole, hypertension.

SYMPATHOMIMETIC DRUG (Epinephrine)

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The smooth muscle of blood vessels that supply skeletal muscles has both beta-2 and alpha receptors; activation of beta-2 receptors causes vasodilation, and stimulation of alpha receptors constricts these vessels.
In such vessels, the threshold concentration for activation of beta-2 receptors by Epinephrine is lower than that for alpha receptors, but when both types of receptors are activated at high concentrations of Epi, the response to a receptors predominates; physiological concentrations of Epi primarily cause vasodilation.
The integrated response of an organ to sympathomimetic amines results not only from their direct effects, but also from reflex homeostatic adjustments.
when a drug (e.g., a beta-2 agonist) lowers mean blood pressure at the mechanoreceptors of the carotid sinus and aortic arch, the baroreceptor reflex works to restore pressure by reducing parasympathetic (vagal) outflow from the CNS to the heart, and increasing sympathetic outflow to the heart and vessels. Conversely occurs when alpha agonist are used.
The baroreceptor reflex effect is of special importance for drugs that have little capacity to activate beta receptors directly. With diseases (e.g., atherosclerosis) that may impair baroreceptor mechanisms, effects of sympathomimetic drugs may be magnified.
Coronary blood flow is enhanced by Epinephrine or by cardiac sympathetic stimulation under physiological conditions. The increased flow, which occurs even with doses that do not increase the aortic blood pressure, is the result of two factors. The first is the increased relative duration of diastole at higher heart rates; this is partially offset by decreased blood flow during systole because of more forceful contraction of the surrounding myocardium and an increase in mechanical compression of the coronary vessels. The increased flow during diastole is further enhanced if aortic blood pressure is elevated by Epi; as a consequence, total coronary flow may be increased. The second factor is a metabolic dilator effect that results from the increased strength of contraction and myocardial O2 consumption due to direct effects of Epi on cardiac myocytes. This vasodilation is mediated in part by adenosine released from cardiac myocytes, which tends to override a direct vasoconstrictor effect of Epi that results from activation of a receptors in coronary vessels.
Epi elevates the concentrations of glucose and lactate in blood , and can inhibit (alpha-2 effect) or stimulate (beta-2 effect) insulin secretion; inhibition is the predominant effect. Glucagon secretion is enhanced via activation of beta receptors of the a cells of pancreatic islets. Epi also decreases the uptake of glucose by peripheral tissues, in part because of its effects on the secretion of insulin, but also possibly due to direct effects on skeletal muscle.
Epi raises the plasma concentration of free fatty acids by stimulating beta receptors in adipocytes, activating triglyceride lipase and accelerating triglyceride breakdown to free fatty acids and glycerol.
Epi injection is available in 1 mg/mL (1:1000), 0.1 mg/mL (1:10,000), and 0.5 mg/mL (1:2000) solutions. The usual adult dose given subcutaneously ranges from 0.3 to 0.5 mg. The intravenous route is used cautiously if an immediate and reliable effect is mandatory. If the solution is given by vein, it must be adequately diluted and injected very slowly. The dose is seldom as much as 0.25 mg, except for cardiac arrest, when larger doses may be required. Epi suspensions are used to slow subcutaneous absorption and must never be injected intravenously.

THERAPEUTIC USES:

Rapid relief of hypersensitivity reactions, including anaphylaxis, to drugs and other allergens.
prolong the action of local anesthetics, presumably by vasoconstriction and a consequent reduction in absorption.
restore cardiac rhythm in patients with cardiac arrest.
topical hemostatic agent on bleeding surfaces such as in the mouth or in bleeding peptic ulcers during endoscopy of the stomach and duodenum.

Beta- ADRENERGIC RECEPTOR ANTAGONISTS

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Effects of beta-adrenergic antagonists may be predicted from the consequences of b receptor stimulation (generally equivalent to the effects of elevated cyclic AMP). Effects of b antagonists at a particular site depend on the level of receptor stimulation, or tone, at that site. Effects of antagonists are more prominent when receptor stimulation by agonist is high.

Beta-Adrenergic antagonists may be classified as

Non-Subtype Selective (First Generation)-( Nadolol ,Penbutolol ,Pindolol ,Propranolol ,Timolol)
Beta 1-Selective (Second Generation), - (
Acebutolol, Atenolol, Bisoprolol, Esmolol, Metoprolol) and
Antagonists with Additional Cardiovascular Actions (Third Generation).

Nonselective b blockers with additional actions: Third generation (Carteolol, Carvedilol, Labetalol)
Beta1-selective b blockers with additional actions: Third generation (Betaxolol, Celiprolol)

Beta-Blockers in Hypertension

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Antagonism of beta-adrenergic receptors affects blood pressure through a number of mechanisms,

Reducing cardiac output
act on the juxtaglomerular complex to reduce renin secretion and thereby diminish production of circulating angiotensin II.
alteration of the control of the sympathetic nervous system at the level of the CNS,
altered baroreceptor sensitivity,
altered peripheral adrenergic neuron function, and
increased prostacyclin biosynthesis.

Drugs without intrinsic sympathomimetic activity produce an initial reduction in cardiac output and a reflex-induced rise in peripheral resistance generally with no net change in arterial pressure; peripheral resistance gradually returns to pretreatment values or less.
Drugs with intrinsic sympathomimetic activity produce lesser decreases in resting heart rate and cardiac output; the fall in arterial pressure correlates with a fall in vascular resistance below pretreatment levels, possibly because of stimulation of vascular b2 adrenergic receptors that mediate vasodilation.

ADVERSE EFFECTS AND PRECAUTIONS

The beta adrenergic blocking agents should be avoided in patients with

Asthma
Sinoatrial or atrioventricular (AV) nodal dysfunction, or
in combination with other drugs that inhibit AV conduction, such as verapamil.
Patients with type 1 diabetes mellitus also are better treated with other drugs (e.g., ACE inhibitors).
b Receptor antagonists without intrinsic sympathomimetic activity increase concentrations of triglycerides in plasma and lower those of high-density lipoprotein (HDL) cholesterol.
b Adrenergic blocking agents with intrinsic sympathomimetic activity have little or no effect on blood lipids.
Sudden discontinuation of b adrenergic blockers can produce a withdrawal syndrome that is likely due to up-regulation of b receptors during blockade, causing enhanced tissue sensitivity to endogenous catecholamines; this can exacerbate the symptoms of coronary artery disease. The result, especially in active patients, can be rebound hypertension. Thus, b adrenergic blockers should be tapered over 10–14 days.
NSAIDs such as indomethacin can blunt the antihypertensive effect of propranolol and probably other b receptor antagonists. This effect may relate to inhibition of vascular synthesis of prostacyclin, as well as to Na+ retention.

Acebutolol

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Class of drug: β-Adrenergic receptor blocker.
Mechanism of action: Competitive blocker of β adrenergic receptors in heart and blood vessels.
Indications/dosage/route: Oral only.

Hypertension
Adults: Initial: 400 mg/d. Maintenance: 200–1200 mg/d.
Premature ventricular contractions
Adults: Initial: 200 mg b.i.d. Maintenance: 600–1200 mg/d.

Adjustment of dosage
• Kidney disease: Creatinine clearance 25–50 mL/min: decrease
dose by 50%; creatinine clearance <25 mL/min: decrease dose
by 75%.
• Liver disease: None.
• Elderly: Avoid doses >800 mg/d.
• Pediatric: Safety and efficacy have not been established in children.

Contraindications:

Cardiogenic shock,
CHF unless it is secondary to tachyarrhythmia treated with a β blocker,
sinus bradycardia and AV block greater than first degree,
severe COPD.

Warnings/precautions

Use with caution in patients with the following conditions: diabetes, kidney disease, liver disease, COPD, peripheral vascular disease.
Do not stop drug abruptly as this may precipitate arrhythmias, angina, MI or cause rebound hypertension. If necessary to discontinue, taper as follows: reduce dose and reassess after 1–2 weeks; if status is unchanged, reduce by another 50% and reassess after 1–2 weeks.
Drug may mask the symptoms of hyperthyroidism, mainly tachycardia.
Drug may exacerbate symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease.

Advice to patient

Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known.
Dress warmly in winter and avoid prolonged exposure to cold as drug may cause increased sensitivity to cold.
Avoid drinks that contain xanthines (caffeine, theophylline, theobromine) including colas, tea, and chocolate because they may counteract the effect of the drug.
Restrict dietary sodium to avoid volume expansion.
Drug may blunt response to usual rise in blood pressure and chest pain under stressful conditions such as vigorous exercise and fever.

Adverse reactions

Common: fatigue.
Serious: symptomatic bradycardia, CHF, worsened AV block, hypotension, depression, bone marrow depression, SLE-like condition, bronchospasm, Peyronie’s disease, hepatitis.

Clinically important drug interactions

Drugs that increase effects/toxicity of beta blockers: reserpine, bretylium, calcium channel blockers.
Drugs that decrease effects/toxicity of beta blockers: aluminum salts, calcium salts, cholestyramine, barbiturates, NSAIDs, rifampin.