Pets Pharmacology and Theraputics

Pharmacology is the study of the properties of chemicals used as drugs for therapeutic purposes. It is divided into the study of pharmacokinetics and pharmacodynamics. Veterinary pharmacology focuses on drugs that are used in domestic animals. Pharmacokinetics is the study of drug absorption, distribution, biotransformation (metabolism), and excretion. Pharmacokinetic processes affect the route of administration, doses, dose intervals, and toxicities of drugs given to animals. Pharmacodynamics is the study of cell/tissue responses and selective receptor effects. In this chapter, we introduce standard concepts of pharmacokinetics and pharmacodynamics and comment on the need to be aware of species variation when considering principles of veterinary pharmacology. There are about 1,600 drugs specifically labeled for veterinary use, compared to about 20,000 drugs approved for people. In fact, for many animal species, there are diseases and conditions for which no suitable veterinary drug is available. Veterinarians, like physicians, may legally prescribe human drugs for conditions (and species) not approved by the Food and Drug Administration (FDA). In the veterinary community, off-label prescriptions are called “extra label”. The basic principles of drug action are identical across veterinary and human pharmacology . But estimating the optimal dosing regimen for an animal using a human drug is often little more than guesswork. Each animal species (and breed) may respond with different pharmacokinetics, pharmacodynamics, and adverse effects. Elimination half-life values are highly correlated between dogs and cats for the non-metabolized drugs, and poorly correlated for the metabolized (oxidized and/or conjugated) drugs. Human elimination half-life data were poorly predictive of dog and cat elimination half-life data for most of the drugs evaluated. Cats are deficient in a number of drug conjugation pathways that can lead to relatively slow elimination of certain drugs, and the need for dose adjustment or alternative therapies to avoid serious adverse effects. The most well understood conjugation defect in cats causes reduced glucuronidation of phenolic drugs, such as acetaminophen and propofol. Cats lack UGT1A6 and UGT1A9, which glucuronidate these drugs in other species. Slower clearance of carprofen might also result from deficient glucuronidation, although direct evidence for this is lacking. On the other hand, slower aspirin clearance does not appear to result from deficient glucuronidation, and is more likely a consequence of poor glycine conjugation. Cats are also deficient in several other conjugation pathways, including N-acetylation by NAT2 and S-methylation by TMPT. NAT deficiency may be the reason cats (and dogs) are more prone to acetaminophen-induced methemoglobinemia rather than hepatotoxicity. TMPT deficiency likely results in sensitivity to azathioprine toxicity. No evidence was found for slower clearance of drugs that are eliminated by oxidation or unchanged into urine or bile. The ultimate goal of this book is to provide to both the veterinary students and practitioners the information on pharmacology that is applicable and easily retrievable in cats and dogs.