4 - Elementary Drug Metabolism

Question 1

drugs need to be made more ___ for exctretion

Answer 1

polar - some drugs are already highly charged but others need to be metabolised by the liver first

Question 2

what are the main routes of excretion?

Answer 2

kidneys

Question 3

what is another route of excretion?

Answer 3

through bile- excretion in faeces

minor contributions via sweat or milk

Question 4

examples of a drug that is converted from prodrug to active compound by metabolism

Answer 4

enalapril to enalaprilat

Question 5

example of a drug having unchanged activity on metabolism

Answer 5

diazepam to nordiazepam

Question 6

phase 1 metabolism in liver involves which three processes?

Answer 6

oxidation, reduction, hydrolysis

Question 7

phase 2 metabolism in liver involves what process?

Answer 7

conjugation

Question 8

phase 1 makes a drug ___ ___

Answer 8

more polar

Question 9

phase 2 ___ an ____ compound

Answer 9

adds an endogenous compound

Question 10

what compounds can be added in phase 2? 6

Answer 10

glucoronyl, sulphate, methyl, acetyl, glycyl or glutathione

Question 11

CYP 450 - ___ proteins located in the ___ ___ of the liver _____ (and elsewhere) mediating ____ reactions (phase__) of many lipid soluble drugs

Answer 11

haem,

endoplasmic reticulum

hepatocytes

oxidation

phase 1

Question 12

CYP 3A4

what does the 3 denote?

Answer 12

gene family

Question 13

CYP 3A4

what does the A denote?

Answer 13

gene subfamily

Question 14

CYP 3A4

what does the 4 denote?

Answer 14

individual gene

Question 15

what are the main cytochrome p450 monoxygenase gene families in the liver?

Answer 15

CYP1, CYP2, CYP3

Question 16

the monoxygenase CYP cyles:
what you need to know

1. drug enters as a drug ____
2. molecular ___ provides __ atoms
3. one atom is added to the drug to yield ___ ____ , which ___ the cycle
4. The second atom combines with ____ to form ___

Answer 16

1. drug enters as a drug substrate
2. molecular oxygen provides 2 atoms
3. one atom is added to the drug to yield the hydroxyl product , which leaves the cycle
4. The second atom combines with protons to form water

Question 17

phase 2 involves the conjugation of ___ ___ groups (e.g. ____, ___ (SH) or ___ (__) )with ______, ____, ___ or ___ groups

Answer 17

chemically reactive groups (e.g. hydroxyl, thiol (SH) or amino (NH2) with glucoronyl, methyl, sulphate or acetyl groups

Question 18

____ is a common phase 2 reatcion

Answer 18

glucuronidation

Question 19

what is the molecule that transfers a glucuronyl group in glucuronidation?

Answer 19

UDP - alpha - glucuronide

Question 20

what enzyme causes the glucuronyl transfer?

Answer 20

UDP- glucuronyl trasferase

Question 21

give two examples of endogenous sustances that are suject to glucuronidation

Answer 21

bilirubin, adrenal corticosteroids

Question 22

what are the three basic processes of renal excretion

Answer 22

1. glumerular filtration (glomerulous)
2. active tubular secretion (proximal convoluted tubule)
3. passive reabsorption by diffusion across the tubular epithelium

Question 23

ultrafiltration occurs only with ___ drugs

Answer 23

free/ unbound

Question 24

clearance by filtration = ___ x ___

Answer 24

glomerular filtration rate x fraction of drug unbound in plasma

Question 25

up to ___ % of renal plasma flow is filtered through the glomerulus . the rest is delivered to the peritubular capillaries of the proximal tubule

Answer 25

20%

Question 26

epithelial cells of the proximal tubule contain __ , independent transporter systems that ____ secrete drugs into the lumen of the nephron

Answer 26

2, actively

Question 27

what are the two transporter systems actively secreting drugs in the proximal tubule

Answer 27

organic anion transporter (OAT) and organic cation transporter (OCT)

Question 28

OATs handle ___ drugs and OCTs handle ___ drugs

Answer 28

acidis, basic

Question 29

active tubular secretion is a ___ process , each carrier ha a transport maximum

Answer 29

saturable

Question 30

what factors promote tubular reabsorption ?

Answer 30

lipid solbility, low polarity, low blow rate, (pH will depend on the direction of movement)

Question 31

having an alkaline urinary pH promotes the excretion of ___ and the reverse is tru for acids

Answer 31

acids,

Question 32

uriniary ____ can be used to accelerate the excretion of aspirin (weak acid) in overdose

Answer 32

alkalisation