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→Metabolism
==Metabolism==
==Metabolism==
For drugs to be eliminated from the body in a more water soluble form, most drugs require metabolism. The extent of metabolism varies between species and age. Herbivores metabolise drugs the most efficiently followed by dogs and then cats. This is due to the amount of metabolising enzymes present differ in each species. Old and neonatal animals show reduced hepatic metabolisma and renal excretion. Neonates also have greater absorption via the gastrointestinal tract and have an increased permeability of the blood brain barrier. This means that a neonate has higher plasma levels of a drug than an adult and so are at greater risk to drug toxicity.
In certain drugs the metabolite is in fact the active form. The adminstered inactive form is called a '''pro-drug'''.
Drugs can be metabolised in a variety of sites including the blood, lungs, gastrointestinal tract wall and kidneys. But the main site of drug metabolism is in the '''liver'''.
===Drug Metabolism in the Liver===
For a drug to be metabolised in the liver it must be '''lipophilic''' as it must cross cell membranes to reach the enzymes in the liver microsomes. Metabolism here is a biphasic process.
'''Phase 1''' - involves mitochondrial mixed function oxidase (MFO) enzymes, or cytochrome P-450 enzymes. In phase 1 the reactions convert the molecules into more polar metabolites via oxidation, reduction and hydrolysis.
'''Phase 2''' - the metabolites are conjugated, adding groups such as glucuronic acid, glycine, sulphate and acetyl. This increases the metabolites polarity further and decreases it's lipophilicity and thus enhancing its excretion in urine.
Some species are deficient in certain aspects of this pathway. Cats lack glucuronidation, pigs lack sulphation and dogs lack acetylation. This will affect these animals ability to metabolise certain drugs.
Some drugs a capable of either inducing or inhibiting metabolising liver enzymes. This can effect how long drugs will stay in the systemic circulation if concurrent therapy with another drug is used.
==Excretion==