General Principles of Pharmacology II Flashcards
Where does biotransformation of drugs occur?
Primarily in the liver
Can also occur in kidney, lung, nerve tissue, plasma, or GI tract
What are the results of biotransformation?
Active -> inactive
Inactive -> active
Convert active drug to active metabolite
Convert active drug to toxic metabolite
What is a metabolite?
Product of biotransformation of a drug
Generally more polar, more water soluble, and excreted faster than parent drug
What are general classes of biotransformation reactions?
Phase I - Oxidation, reduction, hydrolysis
Phase II - Conjugation
What are microsomal enzymes?
Located in SER
Oxidative enzymes known as mixed function oxidases (MFO)
Cyt P450 is the terminal oxidase of MFO
Require substrates to be lipid soluble
Activity is inducible
What is the danger of taking acetaminophen after drinking alcohol?
Ethanol activated 2E1 enzyme which is responsible for converting acetaminophen to a toxic metabolite
What is the most common conjugation reaction in the body?
Glucuronide formation
What are non-microsomal enzymes?
Located in cytosol and mitochondria
Non-inducible
What factors affect the rate of biotransformation?
Enzyme inducers and inhibitors
Age
Liver function/disease
Nutritional State
Genetics
Gender
What are the primary routes of drug excretion?
Biliary and renal
Other routes include sweat, saliva, breast milk and exhalation
What generally determines whether a drug undergoes biliary excretion or urinary excretion?
Molecular weight
> 300 -> biliary
What is enterohepatic cycling?
If a drug has a favorable partition coefficient for reabsorption in the GI tract, then it will be reabsorbed and returned to the liver, where it will be excreted again in the bile
What three processes occur in renal excretion of drugs?
Filtration through glomerulus
Non-ionic back diffusion in distal portion (weak acids are prononated and unionized)
Active transport of anionic and cationic forms of drugs in the proximal portion of the nephron
