FunMed: PBL 5 (Groggy Grandmother - Benzodiazepines)

Question 1

Define ‘allosteric’

Answer 1

Binding of molecule to enzyme at site other than active site –> modulation of enzyme by causing change in shape

Question 2

Define ‘first order elimination’

Answer 2

Decrease in drug levels which is dependent on plasma concentrations (substrate is rate limiting factor) - exponential graph

Question 3

Define ‘zero order elimination’

Answer 3

Decrease in drug levels independent of plasma concentration (straight line)

Question 4

What are benzodiazepines?

Answer 4

Psychoactive drug which enhances effect of GABA (inhibitory neurotransmitter) at the GABAa receptor to cause sedative, anticonvulsant and muscle relaxant properties

Question 5

Define ‘anxiolytic’

Answer 5

Reducing anxiety effect

Question 6

What are the 3 main subclasses of benzodiazepines?

Answer 6

Hypnotics, anxiolytics and general

Question 7

What is GABA?

Answer 7

Chief inhibitory neurotransmitter in CNS; works to reduce neuronal excitability

Question 8

Describe the mode of action of benzodiazepines

Answer 8

Binding of drug to GABAa receptor on post-synaptic membrane has positive allosteric effect (promotes binding of GABA to receptor) to increase chloride ion influx –> hyperpolarisation

Question 9

Describe the GABAa ion channel

Answer 9

Present on post-synaptic neuronal membranes, and consists of 5 subunits (2 alpha, 2 beta, 1 gamma) and is achloride ion channel with 2 binding sites for GABA and 1 for benzodiazepines

Question 10

Where are GABAa receptors located?

Answer 10

Cerebellum, limbin system and cerebral corx

Question 11

What are side effects of benzodiazepines?

Answer 11

Poor memory, sedation, hypotension, dizziness, seizure, agitation –> falls, shoplifting

Question 12

What are the main differences between different benzodiazepines?

Answer 12

Half-lives and potency

Question 13

What is the effect of benzodiazepines with greater half-lives?

Answer 13

Longer half-life will promote greater sedation through the night, so is better for sleeping, but has greater risk of residual effects next day

Question 14

Describe the metabolism of benzodiazepines

Answer 14

Diazepam can be hydroxylated to temazepam (active metabolite) in liver or demethylated to form desmethyldiazepam. Desmethyldiazepam can then be hydroxylated to oxazepam. Both oxazepam and temazepam then undergo glucuronide conjugation –> excretion

Question 15

What is the difference between diazepam and temazepam?

Answer 15

Temazepam can be directly conjugated (no need for metabolism) whereas diazepam requires metabolsim

Question 16

What is the significance of desmethyldiazepam?

Answer 16

Active metabolite of diazepam (and many other benzodiazepines) which has a half-life over 40 hours, so has long duration of action

Question 17

What does phase I metabolism involve?

Answer 17

Biotransformation: oxidation, reduction and hydrolysis (and adding polar molecules)

Question 18

What does phase II metabolism involve?

Answer 18

Conjugation (to increase water solubility) with glucuronide, sulfate, methyl or acetyl groups

Question 19

Define ‘bioavailability’

Answer 19

Proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect

Question 20

What factors affect the rate of drug absorption?

Answer 20

Gastrointestinal motility (peristaltic action), intestinal absorption, size of drug (smaller = easier to diffuse), whether food has been consumed

Question 21

What is ‘first pass effect’?

Answer 21

All drugs absorbed by GI tract –> portal blood –> liver –> metabolism –> systemic blood

Question 22

Which enzymes (broadly) metabolise benzodiazepines and which enzyme is most commonly used (phase I reactions)

Answer 22

CYP450 enzymes (cytochrome) and specifically, CYP3A4

Question 23

Why are the elderly more prone to adverse effects of benzodiazepines?

Answer 23

They have reduced metabolic capability, renal excretion and increased sensitivity to effects

Question 24

Why may there be issues with drug compliance?

Answer 24

Patient feels better, no faith in doctor, office visiting time restrictions, medication cost, ineffective communication of side-effects, motivation to recover

Question 25

What is one issue with benzodiazepines?

Answer 25

Great potential to interact with other drugs

Question 26

Give an example of primary (non-fulfilment) compliance

Answer 26

Prescription not used

Question 27

Give an example of secondary (non-persistence) compliance

Answer 27

Stop taking medication early

Question 28

Give an example of tertiary (non-comforming) compliance

Answer 28

Not taking medication as prescribed