Anxiolytic, Sedative and Hypnotic Drugs-part 2

Question 1

How is GABA metabolised?

Answer 1

GABA –> succinic semialdehyde (SSA) by GABA transaminase SSA –> succinic acid by SSA dehydrogenase Mitochondrial enzymes

Question 2

What receptor is involved in GABAergic central neurotransmission?

Answer 2

GABA A receptor complex

Question 3

What are the principal clinical uses of benzodiazepines?

Answer 3

• Long-acting = anxiolytics, e.g. diazepam - Short-acting = sedatives/hypnotics, e.g. temazepam

Question 4

What are the adverse effects of barbiturates?

Answer 4

• Enzyme inducers - Alter natural sleep (reduce REM) –> hangover, irritability - Depress respiration (tf low safety margins) - O.d. is lethal - Dependence - withdrawal syndrome - Tolerance - Potentiate effects of other CNS depressants (alcohol)w

Question 5

What are the adverse effects of benzodiazepines?

Answer 5

• Dependence - withdrawal syndrome (less intense than barbs) - Tolerance (less than barbs) - Potentiate other CNS depressants (alcohol, barbs) - Sedation, confusion, amnesia, ataxia

Question 6

What are the advantages of benzodiazepines over barbiturates?

Answer 6

• Mild effect on REM sleep - Don’t induce liver enzymes - Wide safety margin - overdose –> prolonged rousable sleep –> flumazenil

Question 7

Summarise the pharmacokinetics of benzodiazpepines

Answer 7

• Duration of action - varies - short or long-acting - Admin - peak [plasma] in 1h, well-absorbed orally, i.v. for status epilepticus - Distribution - binds PPs strongly, highly lipid soluble –> wide distribution - Extensive hepatic metabolism

Question 8

What do sedatives do?

Answer 8

Reduce mental and physical activity without producing loss of consciousness

Question 9

How does BDZ binding affect the GABA A receptor complex?

Answer 9

• Facilitates action of GABA on Cl- channel - Enhances GABA binding - increases affinity

Question 10

How does Barb binding affect the GABA A receptor complex?

Answer 10

• Enhances GABA binding - Direct agonist of Cl- channel - Enhances GABA action on Cl- channel

Question 11

How is GABA synthesised?

Answer 11

Glutamate –> GABA by glutamate decarboxylase

Question 12

What are the clinical uses of benzodiazepines and barbiturates?

Answer 12

• Sedatives/hypnotics - Anxiolytics - Anaesthetics - barbs - Anti-convulsants - Anti-spastics

Question 13

What can long-acting benzodiazepines be metabolised into?

Answer 13

Short-acting benzodiazepines