Basic Principles V

Question 1

purposes of biotransformation

Answer 1

drug detoxification, prepare drug for excretion

Question 2

sites of biotransformation

Answer 2

liver in the cytoplasm, mitochondria, and cellular structural components. Also can happen anywhere else in the body

Question 3

hepatic microsomal drug metabolizing system

Answer 3

liver: smooth endoplasmic reticulum, can do both phase 1 and 2.

Question 4

induction

Answer 4

increase metabolism of the primary drug or other drugs

Question 5

inhibition

Answer 5

use a drug to block the metabolism of another drug or endogenous compound

Question 6

non-microsomal systems

Answer 6

other organs, plasma, red blood cells. Usually phase I. Inhibition: intentional or accidental

Question 7

drug oxidation

Answer 7

phase 1 rxn. Adds oxygen or changes the proportion of oxygen in the molecule. Very important, the most common metabolic transformation

Question 8

components of hepatic mixed function oxidase system

Answer 8

1. NADPH 2. cytochrome p450 reductase 3. cytochrome p450 4. Mg++ 5. phospholipid 6. O2

Question 9

P450 characteristics

Answer 9

12 P450 groups in humans, some for toxins, others for endogenous compounds. Low specificity, very large genetic variations, and catalyze primarily oxidations but also some reductions

Question 10

CYP2D6

Answer 10

largest degree of genetic variations. 70 nucleotide variations exist. Results in inactive enzymes or reduced catalytic activity. 4 phenotypes of patients for metabolic activity: poor, intermediate, extensive, ultrarapid. Poor cant metabolize at all, ultra rapid have a huge first pass metabolism. varies by race.

Question 11

what happens when you take more than 1 drug that is metabolized by the same type of P450 enzyme?

Answer 11

competition with inhibition, leading to potential toxicities. Induction might happen, decreasing effectiveness for a given dose

Question 12

drug reductions

Answer 12

add hydrogen or change the proportion of hydrogen in the molecule

Question 13

drug hydrolysis

Answer 13

cleave a molecule by the addition of a water molecule

Question 14

phase II reactions

Answer 14

conjugation: synth a new molecule by combining drugs or metabolic productts of phase 1 with a molecule provided by the cell. Metabolic energy is used and a covalent bond is formed

Question 15

types of conjugation

Answer 15

glucoronide formation, glycine conjugation, glutamine conjugation, acetylation, acylation, sulfate conjugation, methylation, riboside and riboside phosphate formation, mercapturic acid formation