pharmacokinetics part 2

Question 1

phase 1 metabolism

oxidation at carbon

Answer 1

adds oh or deacylation

Question 2

phase 1 metabolism

oxidation at Nitrogen

Answer 2

to secondary amine

to tertiary amine

Question 3

phase 1 metabolism

oxidation at sulphur atom

Answer 3

to thioeher

Question 4

phase 1 metabolism

drugs removed as soon as

Answer 4

it is converted into metabolite

Question 5

phase 1 metabolism

most cases metabolite is inactive and therefore the rate of metabolism determines phase 1 metabolism

Answer 5

the duration of therapeutic effect

Question 6

phase 1 metabolism

also metabolite can be active and therefore

Answer 6

activity remains until this is also removed from the body by further metabolism or excretion

Question 7

pro drug

Answer 7

drug in inactive precursor

Question 8

drug metabolism

enzymes are usually not saturated at theraputic doses therefore

Answer 8

half-life is not affected by does admin
or clearance and half life
and is not affected by other drugs which is metabolised by the same enzyme

Question 9

microsome contains

Answer 9

cytochrome p450
p450 reductase
b5 reductase
lipid environment

Question 10

there are —– p450 molecules per reductase

Answer 10

20

Question 11

cytochrome p450

what is it

Answer 11

membrane bound enzyme in most tissues especially liver
part of ER
contains Fe
and binds substrate O2 and CO

Question 12

what does cytochrome p450 do

Answer 12

catalyses oxidation of drug

generally determines deficiencies

Question 13

what is cyto p450 induced by

Answer 13

drug: phenobarbitan

environmental : smoking

Question 14

cyto p450 is inhibited by

Answer 14

cimetidine

grapefruit juices

Question 15

non p450 oxidation examples

Answer 15

monoamine oxidase

alcohol dehydrogenase

Question 16

reductions

Answer 16

p450 mediated in liver

gut flora

Question 17

hydrolysis of

Answer 17

esters

amide

Question 18

plasma pseudocholinesterase

Answer 18

breaks down mimics of Ach

Question 19

procaine is a local anaesthetic what happens to it

Answer 19

hydrolysis in plasma t1/2=10-20mins

of ester linkage

Question 20

conjugation reaction

glucurinidation what happens

Answer 20

glucuronic acid replaces the H in

• OH
• COOH to give water soluble inactive product

Question 21

glucurinidation activation equation

and enzyme

Answer 21

g-6-p—– g-1-p —(utp)— udp-glucose—-(nad)—- udp-glucuronic acid

UTP- glucurony transferase

Question 22

conjugation reaction

sulphation what happens

Answer 22

SO3- replaces H in -OH NH2 NHOH
very water soluble inactive
usually excretory products

Question 23

what is the sulphation activation equation

and enzyme

Answer 23

sulphate –(atp)– adenosine-5’-ps –(atp)– 3’p-adenosine -5’-ps PAPS
using enzyme sulpho-transferase

Question 24

3 main types of sulpho-tranferase

Answer 24

phenol
steroid
aryl amine

Question 25

where is sulpho-transferase found

Answer 25

cytosolic enzyme in liver gut most tissues

Question 26

sulphation | limited number of PAPS so what happens

Answer 26

low doses of phenol are conjugated with sulphate and high doses with glucurnic acid

Question 27

conjugation reaction | acetylation what happens

Answer 27

acetate replaces H in NH2 -SO2NH2 inactivates the functional group no real increase in water solubility

Question 28

acetylation requires activation

Answer 28

acetate to acetylcoa | via N-acetyl transferase transfers the acetate to drug

Question 29

consequences of metabolism

Answer 29

``` after metab parent drug is removed with effects metab is now a different compound so: no acitivity similar pharmacological activity different plasma activity toxicological action ```

Question 30

phase 1 metabolites what are they

Answer 30

usually inactive but show the consequences of metab | they may undergo phase 2 before excretion

Question 31

phase 2 metabolites what are they

Answer 31

nearly always inactive | usually much more water soluble and ready for excretion

Question 32

levels of p450 is determined genetically | so whats the difference with identical and non twins

Answer 32

identical : more or less same metabolism | non: different

Question 33

pharmacogenetics | mutation in plasma pseudocholinesterase what happens

Answer 33

causes no breakdown of suxamethonium | when given as a muscle relaxant it will not be removed

Question 34

isonizid can be acetylated (major) or hydrolysed | in population what happens

Answer 34

low plasma conc -fast acetylators (more effective enzyme) poor clinical response -low incidance rate for side effects vice versa for high plasma conc

Question 35

enzyme induction | what are the effects of phenobarbitone

Answer 35

long lasting effects induces enzyme breakdown of dicoumarol drugs interact with each other

Question 36

volatile route of elimination depends on

Answer 36

air borne partition coefficient tidal vol rate of ventilation extent of distribution to tissues

Question 37

renal excretion | 3 processes what are they

Answer 37

glomerular filtration ph dependent reabsorption renal tubular secretion

Question 38

biliary excretion | what happens

Answer 38

mixed in bile with bile salts large drugs or drug conjugates are eliminated in bile elimination depends on release in bile