Renal elimination, drugs, effect

Clearance is defined as the fraction of the volume of distribution Vp that is cleared of the drug per unit of time. In the case of elimination from the kidneys, the clearance provides a measure for the effectiveness of renal elimination with respect to the dmg under study. 

Primarily renal elimination of unchanged drug Would not expect hepatic impairment to have an effect (no data) Expect sign, effect of renal impairment and no effect of advanced age (beyond decreased CrCI with age) (no data)... 

The effect of age on the renal elimination of some drugs is shown in Table 2. In general, the dose can be guided by the estimated or measured creatinine clearance. This should be performed in particular... 

The major pathways for its metabolism include ring hydroxylation, with subsequent glucuronide conjugation and A-acetylation. Hydralazine exhibits a first-pass effect in that a large part of an orally administered dose is metabolized before the drug reaches the systemic circulation. The first-pass metabohsm occurs in the intestinal mucosa (mostly A-acetylation) and the hver. The primary excretory route is through renal elimination, and about 80% of an oral dose appears in the urine within 48 hours. About 10% is excreted unchanged in the feces. 

Procainamide INa (primary) and IKr (secondary) blockade Slows conduction velocity and pacemaker rate prolongs action potential duration and dissociates from INa channel with intermediate kinetics direct depressant effects on sinoatrial (SA) and atrioventricular (AV) nodes Most atrial and ventricular arrhythmias drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction Oral, IV, IM eliminated by hepatic metabolism to /V-acetylprocainamide (NAPA see text) and renal elimination NAPA implicated in torsade de pointes in patients with renal failure Toxicity Hypotension long-term therapy produces reversible lupus-related symptoms... 

Tahara H, Kusuhara H, Chida M, et al. Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance Effect of probenecid on the renal elimination of H2 receptor antagonists. J Pharmacol Exp Ther 2006 316 1187-1194. 

All drugs are ultimately removed from the body, either in the form of their metabolites or in their unchanged form, by excretory organs (mainly the kidneys) and excreted in the urine (although in some instances, excretion may be via the biliary route). Compromised renal function may effect the PK of the drugs if urinary excretion is a substantial part of the overall elimination. 

METHOTREXATE ANTIGOUT DRUGS -PROBENECID t methotrexate levels Probenecid 1 elimination of methotrexate renally by interfering with tubular secretion in the proximal tubule and also 1 protein binding of methotrexate (a relatively minor effect). Probenecid competes with methotrexate for renal elimination Avoid co-administration if possible if not possible, 1 dose of methotrexate and monitor FBC closely... 

PROCARBAZINE ANTICANCER AND IMMUNOMODULATING DRUGS - METHOTREXATE t risk of renal impairment if methotrexate infusion is given within 48 hours of procarbazine administration. Also t risk of methotrexate toxicity, particularly to the kidneys Procarbazine has a transient effect on the kidneys, and this will delay the renal elimination of methotrexate Do not start methotrexate infusion less than 72 hours after the last dose of procarbazine. Hydrate patients aggressively (plenty of oral fluids or intravenous fluids), alkalinize the urine to pH>7 and closely monitor renal function, e.g. blood urea and creatinine, before and after methotrexate infusion until methotrexate blood levels are <0.05 p,mol/L... 

PENICILLINS ANTICANCER AND IMMUNOMODULATING DRUGS - METHOTREXATE t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from protein-binding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasias, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

Effects of Liver Disease on the Renal Elimination of Drugs... 

Primaquine is rapidly absorbed, extensively distributed, and predominantly cleared by non-renal elimination. Its principal metabolite is carboxyprimaquine. While primaquine itself is rapidly eliminated from the plasma, the drug is effective when given once daily or even once weekly (SEDA-13, 810). The pharmacokinetics in children, pregnant women, and patients with renal or hepatic dysfunction are unknown. 

Amantadine and rimantadine are chemically related antiviral drugs active against influenza A but not influenza B viruses. Amantadine differs from rimantadine because it is primarily renally eliminated and is associated with more CNS side effects and can potentially lower the seizure threshold. 

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