Drugs Information Center(DIC)

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.

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

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

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, gastrointesti

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

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

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 antibiotic

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.

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

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

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. Conve