Drugs Information Center(DIC)

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 clindam...

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 o...

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 treat...

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.

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.