Basic Principles of Pharm V

Question 1

Purpose of biotransformation

Answer 1

1. Drug detoxification (change structure –> change activity)
2. Prepare drug for excretion (reduce characteristics of drug that made it easy to absorb, ie make it larger, add charge, make it more water soluble)

Question 2

Sites of biotransformation

Answer 2

1. liver (primary site) – on cellular structural components, SER, lipid environment, cytoplasm, mitochondria
2. everywhere else in body

Question 3

Hepatic microsomal drug metabolizing systems

Answer 3

utilizes SER in liver

1. Induction – increase metabolism of primary drug or other drugs – might be observed as in increase in first pass metabolism
2. inhibition – use a drug to block the metabolism of another drug or endogenous compound

Question 4

Non-microsomal drug metabolizing systems

Answer 4

Other organs, plasma, red cells. Usually phase I.

Inhibition – intentional or accidental

Question 5

P450 characteristics

Answer 5

Low specificity, very large genetic variations, catalyze primarily oxidations but also some reductions

Question 6

What happens when various drugs are metabolized by the same type of cytochrome P450 enzyme?

Answer 6

Slow metabolism

• competition with inhibition –> potential toxicities
• induction –> decrease in effectiveness for a given dose

Question 7

drug reduction

Answer 7

add hydrogen or change the proportion of hydrogen in the molecule

Question 8

drug hydrolysis

Answer 8

cleave a molecule by the addition of a water molecule

Question 9

Phase 1 reactions

Answer 9

basically drug modification. may have variable effects on activity, both in target tissue and secondary receptors in other tissues

Question 10

Phase II reactions

Answer 10

Conjugation – synthesize a new molecule by combining the drug or metabolic product of phase 1 with a molecule provided by the cell
Types: glucuronide formation, glycine conjugation, glutamine conjugation, acetylation/acylation, sulfate conjugation, methylation, riboside or riboside phosphate formation, mercapturic acid formation