Drug Biotransformation Flashcards
It is the mechanism by which the body terminates the action of some drugs
Drug Metabolism
In some cases, it serves to activate prodrug
Types of Metabolic Reactions
What phase is described by the following:
- Non-synthetic reactions
- Converts the parent drug to a more polar conjugate (water soluble) or more reactive product
- Introducing/inserting/unmasking a polar functional group
- OH, SH, NH2
Phase I
What are the different types of reactions under Phase I?
- Oxidation
- Reduction
- Deamination
- Hydrolysis
What phase is described by the following:
- Synthetic reactions
- Endogenous substrate is conjugated to the parent drug to make it more polar
Phase II
What are the different types of reactions under Phase II?
- Glucoronidation-glucoronic acid
- Acetylation-acetyl CoA
- Sulfation
- Methylation
- Glycine conjugation-glycine
- Glutathione conjugation
- H2O conjugation
True
Most drugs go through Phase I, initially then Phase II
True
What drug is this:
- Maybe metabolized by gastric fluid
- Must be given 2 hours before meals
if given through the oral route
Penicillin
True or False
Penicillin is an example of a Gastric Acid
True
True or False
Insulin is an example of a Gastric and digestive enzyme
True
True or False
Epinephrine is an example of aIntestinal wall enzymes
True
What is the most important organ for drug metabolism
Liver
It contains high concentration of PHASE I enzymes
Activity of these enzymes require
* NADPH (reducing agent)
* Molecular form of oxygen
Smooth Endoplasmic Reticulum (SER)
Determinants of Biotransformation Rate - Genetic Factors
- Its duration of action is 5 minutes
In 1/2500:
- Abnormal form of this enzyme
- Neuromuscular paralysis may last for hours
Hydrolysis of Esters
Determinants of Biotransformation Rate - Genetic Factors
Determinants of Biotransformation Rate - Genetic Factors
- Isoniazid (INH)
- hydralazine, and procainamide
Acetylation of Amines
Determinants of Biotransformation Rate - Genetic Factors
- Individuals deficient in acetylating capacity
- Prolonged or toxic responses to normal doses of this drug
Acetylation of Amines - Slow Acetylators
Determinants of Biotransformation Rate - Genetic Factors
- Dextrometorphan, metoprolol and some tricyclic antidepressants
- Oxidation by P450 isoenzymes are genetically
predetermined
Oxidation
Determinants of Biotransformation Rate - Individual Differences
Examples of this factor are the following:
- Charcoal inhibits the effect of the drug
- Grapefruit juice increases the amount of drug in the body
Diet and environmental factors
Determinants of Biotransformation Rate | True or False
Age and Sex:
Drug metabolites differ in young and old
True
True or False
Males metabolize drugs faster than
females
True
Give on disease that affects drug metabolism
Hyperthyroidism
Determinants of Biotransformation Rate
- It Increase rate of synthesis of the enzyme
- Reduces the rate of degradation of the enzyme
- May also induce self metabolism of the drug
- May also induce metabolism of other drugs and reduce its effects
Enzyme Induction
Give some enzyme inducers
- Enzyme inducers
- Phenobarbital
- Carbamazepine + drug = decreased effects
- Phenytoin
- Rifampicin
Determinants of Biotransformation Rate
- It Inhibits CP450
- Metabolism of the drug is diminished
- Increase effect of the drug
Enzyme Inhibition
Give some enzyme inhibitors
- Amiodarone
- Cimetidine
- Ketoconazole + drug = increased effect
- Ritonavir
- Furanocoumarin
Types of Drug Interaction Mechanism
It affects drug action
Altered metabolism
Types of Drug Interaction Mechanism
This is an example of what absorption:
Cholestyramine inhibits the effect of digoxin when combined with it
Altered absorption
What are the types of Drug Interaction Mechanism?
- Altered Absorption
- Altered Metabolism
- Altered Plasma binding protein
- Altered Excretion
Types of Drug Interaction Mechanism
This is an example of what absorption:
- Probenecid inhibits the secretion of acids
- Penicillin inhibits the excretion of probenecid
Altered Excretion
Drug Interaction
- Its response is elicited by combined drugs is equal to the combined response of the individual drugs
- 1 + 1 = 2
- e.g. Sedative + ethanol
Additive
Drug Interaction
- Its response is elicited by combined drugs is greater than the combined responses of each individual
- 1 + 1 = 3
- e.g. Penicillin G removes the cell wall, Gentamicin inhibits production of protein
Synergistic
Drug Interaction
- Drug which has no effect enhances the effect of the second drug
- 0 + 1 = 2
- e.g. Cimetidine + anticoagulant
(enhances the anticoagulation)
Potentiation
- Drug inhibits the effect of another drug
- 1 + 1 = 0
- e.g. Heparin + protamine
Antagonism
