lecture 3 Flashcards
a drug is terminated by its ____
metabolism
____ are inactive when given, activated in the body
prodrugs
sites of drug metabolism
- skin
- lungs
- kidney
- *liver
rapid metabolism in the liver
first pass metabolism
drugs that highly metabolized in liver
nitroglycerine and morphine
liver cell enzymes or enzyme complexes are called
cytochrome P450 (CYP)
what liver cells contain cytochrome P450?
smooth endoplasmic reticulum cells
most significant CYP?
CYP 3A4
what type of reactions do CYP catalyze?
oxidation
CYPs can be reduced or inhibited by ____
environmental factors
CYP inhibitors
grape fruit juice, some antibacterials, antifungals antihistamines
CYP activators
phenytoin, phenobarbital, st. john’s, rifampin
CYP inhibitors ____ dose in body, CYP activators ____ dose in body
increase, decrease
Phase 1 reactions work to:
make small changes to make drug polar, get inside kidney tubule
Phase 1 CYP450 reactions
- hydroxylation
- N-oxidation
- S-oxidation
- N-dealkylation
- O-dealkylation
Phase 1 non CYP450 reactions
- deamination (remove amine group, maybe to ketone)
- hydrolysis (esterase - ester into alcohol and water)
- peptidase (cleaves peptide bonds)
- phsphatase (removes phosphate)
Phase 2 reactions work to:
- add a moiety to the drug, a large molecule
Phase 2 reactions:
- acetylation
- glucuronidation
- methylation
- sulfation
- glycination
phase 1 is ____, phase 2 is _____
inactivation, detoxification of the drug
drug excretion mechanism
- feces, urine, lung, sweat, breast milk
factors that can alter absorption
- age; older you get the less you metabolize
- environment; other drugs can affect absorption
factors that can alter distribution
- fat
- gender
factors that can alter metabolism
- genetic factors (CYP450 difference, slow acetylation)
- age
- disease, pregnancy, exposure of drugs
slow acetylators
- procainamide and hydralazine
how many stages of testing a new drug
- 4
first part of testing
- animal testing
phase 1
- dose dependent effect in normal human volunteers
phase 2
- in small # of patients with target disease
phase 3
- in larger # of patients
phase 4
- apply for new drug application (NDA)
