Drug metabolism

Question 1

what are the 4 stages of a drugs journey through the body

Answer 1

absorption
distribution
metabolism
excretion

Question 2

absorption

Answer 2

drugs are absorbed from administration site to the body’s circulation

Question 3

give 5 examples to administer drugs

Answer 3

oral
intramuscular
subcutaneous
intravenous
transdermal

Question 4

what is oral administration of drugs

Answer 4

swallowing

Question 5

what is intramuscular administration of drugs

Answer 5

flu jab in arm muscle

Question 6

what is subcutaneous administration of drugs

Answer 6

injecting insulin just under the skin

Question 7

what is intravenous administration of drugs

Answer 7

chemotherapy through vein

Question 8

what is transdermal administration of drugs

Answer 8

wearing skin patch

Question 9

distribution

Answer 9

main vehicle - bloodstream

undesired effects = side effects, toxicity

Question 10

what is the purpose of metabolism

Answer 10

deactivate the medicine (sometimes activate the drug)

Question 11

metabolism

Answer 11

process to break down medicine via enzymatic process

Question 12

what is the main site of metabolism

Answer 12

liver

Question 13

what are the products of metabolism called

Answer 13

metabolites

Question 14

excretion

Answer 14

removal of compounds via urine or faeces

Question 15

name 4 things monitoring metabolism will provide

Answer 15

what drug has been used

how effective the person processes the drug

how long the drug stays in the body

what happens to the drug

Question 16

what is drug metabolism also known as

Answer 16

biotransformation

Question 17

what two phases is drug metabolism divided into

Answer 17

phase 1 = functionalisation phase

phase 2= conjugation phase

Question 18

which metabolism phase is studied the most

Answer 18

phase 1

Question 19

phase 1 common drug metabolism routes

Answer 19

oxidation, reduction, hydrolysis

Question 20

phase 2 common drug metabolism routes

Answer 20

conjugation and condensation

Question 21

purpose of phase 1

IMPORTANT

Answer 21

to expose or add polar function group to the original molecule

Question 22

purpose of phase 2

IMPORTANT

Answer 22

to add a very polar molecule to the metabolite or the original molecule to make the molecule water soluble and read for excretion

Question 23

oxidation

Answer 23

adding OH group - replacing H in the molecule

adding O such as alcohol - aldehyde

losing hydrogen - carbon carbon single bond to double bond

Question 24

reduction

Answer 24

losing or reducing some form of O

carboxylic acid to alcohol

Question 25

hydrolysis

Answer 25

Breaking up a molecule by water Ester to alcohol and carboxylic acid

Question 26

what are two oxidation reactions involving cytochrome P450

Answer 26

aromatic hydroxylation de-alyklation

Question 27

what is aromatic hydroxylation

Answer 27

using OH group to replace aromatic ring hydrogens oxidation reaction

Question 28

what is de-alkylation reaction

Answer 28

removes alkyl groups such as methyl and ethyl depending on type of atom the alkyl group is attached to is often referred to as N- or O- dealkylations

Question 29

what are 3 oxidation reactions not catalyses by cytochrome P450

Answer 29

alcohol dehydrogenase aldehydge dehydrogenase hydrolysis

Question 30

summary of phase 1 metabolism

Answer 30

Virtually every possible chemical reaction a compound can undergo in the lab can also be catalysed by enzyme systems The products normally end up containing chemically reactive functional groups such as, OH, NH2, COOH Many drugs can undergo more than one of the phase 1 reactions

Question 31

phase 2 metabolism

Answer 31

the phase 2 (conjugation) generally leads to a water-soluble product can be excreted in faeces or urine the most commonly used sugar for this purpose is glucuronic acid which can conjugate with alcohol, phenol, amine and COOH phase 2 metabolites are more water-soluble preparing the drug or the metabolite for excretion by one pathway or another

Question 32

genetic factors affecting drug metabolism

Answer 32

body weight race sex

Question 33

physiologic factors affecting drug metabolism

Answer 33

``` age diet diseases/conditions kidney function liver function ```

Question 34

morphine as an opioid analgesic

Answer 34

μ-Opioid receptor (MOR) in the central nervous system Morphine is an agonist of this receptor μ-Opioid receptor activation causes analgesia and sedation Opioid addiction also related to μ-opioid receptor Class A

Question 35

codeine

Answer 35

Codeine does crossed BBB but can’t bind effectively to the opioid receptor Only 15% of codeine is O-demethylated to morphine The principal pathways for metabolism of codeine occur in the liver Less strong biological effect Class B

Question 36

heroin

Answer 36

Heroin is totally metabolised into morphine when taken orally If injected it will rapid crossing BBB into the brain (a lipophilic molecule) Then rapidly metabolised into morphine So you have a high concentration of morphine in the brain to bind to the opioid receptor Class A