drug metabolism Flashcards Preview

MD3002 post MSA > drug metabolism > Flashcards

Flashcards in drug metabolism Deck (31):
1

where does metabolism happen (biotransformation)

gut lumen and wall
plasma
lungs
kidneys
nerves
liver

2

what is phase one metabolism

usually oxidation, reduction or hydrolysis

introduce/reveal a chemical group
'functionalisation'
products are usually more reactive

prepares for phase 2

e.g. adds OH, NH2, -SH, -COOH

3

what is phase 2 metabolism

synthetic or conjugative
usually hydrophilic or inactive compounds

adding something on!

e.g. sulfation
acetylation
amino acid conjugation
fatty acid conjugation
condensation

requires something to conjugate with

can then be excreted in bile or urine

4

what are the possible results of metabolism

deactivation/ activation
type of pharmacological response
drug uptake/ distribution
hydrophilicity

5

what enzymes are responsible for oxidation

mixed functional oxidases- cytochrome P450
alcohol dehydrogenase
xanthine oxidase

6

name some reduction reactions

ketone reduction
anaerobic cytochrome P450 metabolism

7

name some hydrolysis reaction

ester hydrolysis
amide hydrolysis

8

what does cytochrome p450 require

oxygen
NADPH

9

what are the problems with drug metabolism

overlapping substrate specificities
drugs for same enzyme
different enzymes for same substrate
enzyme can be saturated
conjugate can be depleted
variation between people

10

what are the sources of excretion

breath
urine
saliva
perspiration
faeces
milk
bile
hair

remember that drug or metabolite could be excreted

11

how are substances transfered from plasma to bile

organic cation transporters
organic anion transporters
p glycoproteins

12

describe entero hepatic recirculation

hydrophilic conjugates e.g. glucuronides are delivered to intestine

hydrolysis can occur in intestine by gut microbiota (depends on person) - will affect half life and efficacy - think of antibiotics and oral synthetic oestrogens

13

what drugs can be filtered

below 20 kDa
not if bound to plasma albumin

14

describe tubular secretion of drugs

OATs and OCTs
OATs transport against a chemical gradient
cleared even if bound to albumin

15

how do you change urine pH in order to favour excretion of weak acids

make urine more alkaline

16

what is zero order kinetics

straight line
constant rate of drug removal

eg alcohol - 1 unit per hour approx

few drugs
does not vary with amount of drug present
enzyme saturation

17

what is first order kinetics

curvey graph

able to calculate a half life

most drugs
constant fraction metabolised per unit time
increases proportionately to drug
more drug, faster metabolism

eg aspirin

18

how do you calculate the apparent volume of distribution of a drug

total amount of drug in the body /
blood plasma concentration of the drug

19

what is the sum of all routes of elimination equal to (l/h)

clearance

20

what is the half life dependent on

ln2 x Vd/
Cl

21

what factors affect drug metabolism

age
genetic variation
race
disease
other medications

22

where are microsomal CYP450s found

in endoplasmic reticulum, mostlly in kidney but also lung, liver and intestine

23

describe the metabolism of aspirin

first undergoes hydrolysis to produce salicylic acid

some salicylic acid is excreted in urine

the rest is conjugated to from glucoronide

24

what is ion trapping

more ionised drug
is less able to be reabsorbed from the nephron so is eliminated

25

if urine is acidic what substances are more likely to be excreted

weak bases

26

what is optimum pH for salicylic acid elimination in the urine

8 (slightly basic)

27

what does a low Vd suggest

there is a high amount of drug in the plasma
probs water soluble
the drug is able to get to where its needed

28

what does a high Vd suggest

probs fat soluble
there is a low amount of drug in the plasma
drug is not able to go where it is needed and stays in fatty tissue

29

you start an infusion of 30 mg of hydrocodone
the plasma concentration is 1.07

the clearance is 0.5

what is the half life

38.8

Vd= total amount / plasma concentration

half life = Ln2 x Vd/ Cl


type in as Ln2 = x

x times vd = y

y / CL

ln2 = 0.69

30

describe elimination for a drug which has an easily saturable enzyme at or near the therapeutic concentration

zero order kinetics.
clearance is not variable with plasma concentration

31

describe clearance for a drug which does not have an easily saturable enzyme

first order kinetics
clearance varies with plasma concentration