GUT- Drugs and Liver Disease

Question 1

what effect does metabolism have on drugs

Answer 1

decreases efficiency

Question 2

what are the different pathways drug can go down when entering the body

Answer 2

spontaneous change into another substance
excreted unchanged by the body
metabolised by enzymes into different compounds to facilitate excretion
converted into more water soluble compound

Question 3

where is the principle site of metabolism

Answer 3

SER of the hepatocytes

Question 4

what is the main family of enzymes involved in drug metabolism

Answer 4

CYP450

Question 5

how does age affect drug metabolism

Answer 5

some enzymes are not efficient yet e.g., in infants

Question 6

how does gender affect drug metabolism

Answer 6

females are more affected with toxicity - this may be hormonal / due to fat distribution

Question 7

how does pregnancy affect drug metabolism

Answer 7

water levels are increased, fat is increased and therefore distribution of the drug changes

Question 8

how does liver disease affect drug metabolism

Answer 8

altered hepatic flow
altered expression of drug metabolising enzymes
altered availability of co-substrates
altered binding of drugs to plasma proteins

Question 9

what is the effect of CYP2D6 polymorphism

Answer 9

some people with a deficiency are poor metabolisers

some people have two copies and are termed ultra-metabolisers

Question 10

what is phase 1 of metabolism of drugs

Answer 10

occurs in SER
catalysed by CYP450 enzymes
make substrate into polar compounds
oxidation, reduction, hydration, dehalogenation

Question 11

what is phase 2 of metabolism of drugs

Answer 11

conjugation to make it more water soluble

sulfation, glucuronidation, glutathione conjugation, acetylation, AA conjugation, methylation

Question 12

what are prodrugs

Answer 12

drugs which are administered in an inactive form and must undergo metabolic conversion for activation

Question 13

what action can drug metabolites have

Answer 13

substrates, inducers, and inhibitors

Question 14

what is the mechanism of action of a drug metabolite acting as a substrate

Answer 14

reacting molecules that bind to enzymes

Question 15

what is the mechanism of action of a drug metabolite acting as an inducer

Answer 15

increase activity of microsomal oxidases and conjugating systems

Question 16

what is the mechanism of action of a drug metabolite acting as an inhibitor

Answer 16

differ selectively towards isoforms are a classified by the mechanism of action (e.g., some competes for the active site)

Question 17

enzyme induction may result in

Answer 17

increased CYP enzyme synthesis
faster drug metabolism
subtherapeutic drug concentrations
the risk of ineffective drug therapy

Question 18

drug interactions are often classified as either

Answer 18

pharmacodynamic (additive / antagonists effects)

pharmacokinetic (Induction / inhibition, alterations in absorption etc..)

Question 19

what effect can co-administration of drugs have

Answer 19

affect the metabolism of eachother

Question 20

contrast drug metabolites acting as inhibitors vs inducers

Answer 20

inhibitors - work on enzyme levels to block / compete for active site

inducers- work by increasing gene transcription that results in higher enzyme content