• exacerbate renal disease (above)
• be potentiated by accumulation due to failure of renal excretion
• be ineffective, e.g. thiazide diuretics in moderate or severe renal failure; uricosurics.
Problems of safety arise especially in patients with impaired renal function who must be treated with drugs that are potentially toxic and that are wholly or largely eliminated by the kidney.
A knowledge of, or at least access to, sources of pharmacokinetic data is essential for safe therapy for such patients.4 The profound influence of impaired renal function on the elimination of some drugs is illustrated in Table 26.1.
The tj/ of other drugs, whose activity is terminated by metabolism, is unaltered by renal impairment. Many such drugs, however, produce pharmacologically active metabolites which tend to be more water-soluble than the parent drug, are dependent on the kidney for their elimination, and
4 e.g. manufacturers' data, formularies and specialist journals.
accumulate in renal failure, e.g. acebutolol, diazepam, warfarin, pethidine.
The majority of drugs fall into an intermediate class and are partly metabolised and partly eliminated unchanged by the kidney.
Administering the correct dose to a patient with renal disease must therefore take into account both the extent to which the drug normally relies on renal elimination, and the degree of renal impairment; the most convenient and useful guide to the latter is the creatinine clearance. These issues are now discussed.
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