Anxiolytic, Sedative and Hypnotic Drugs-part 2

Question 1

What do hypnotics do?

Answer 1

Induce sleep

Question 2

What would an ideal benzodiazepine or barbiturate do?

Answer 2

• Produce natural sleep , Not depress respiration , Have a wide margin of safety ,Not produce hangovers or dependence , Not interact with other drugs

Question 3

What receptor is involved in GABAergic central neurotransmission?

Answer 3

GABA A receptor complex

Question 4

What are benzodiazepines mainly used for,Give an example s

Answer 4

Question 5

What are the adverse effects of barbiturates?

Answer 5

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

Question 6

What drugs can increase free [plasma] of benzodiazepines?

Answer 6

Aspirin Heparin

Question 7

What are the advantages of benzodiazepines over barbiturates?

Answer 7

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

Question 8

How does GABA binding affect the GABA A receptor complex?

Answer 8

• Linkage of GABA receptor protein and BDZ receptor protein mediated by GABA modulin - Enhances BDZ binding - Momentary opening of Cl- channel

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 is GABA synthesised?

Answer 10

Glutamate –> GABA by glutamate decarboxylase

Question 11

What are the clinical uses of benzodiazepines and barbiturates?

Answer 11

• Sedatives/hypnotics , Anti-spastics,
• ANAESTHETICS (BARBs ONLY : THIOPENTONE)
• ANTICONVULSANTS (DIAZEPAM; CLONAZEPAM; PHENOBARBITAL)
• ANTI-SPASTICS (DIAZEPAM)

Question 12

Recall inhibitors of GABA metabolism and the consequences of their actions

Answer 12

•

• INHIBITORS OF GABA METABOLISM causes LARGE increase in ­ BRAIN GABA
• SODIUM VALPROATE (EPILIM)
• VIGABATRIN (SABRIL)

Question 13

For OTHER named SEDATIVE/HYPNOTICS, comment on :

t½ ,RECEPTORS it acts on, efficacy ,HANGOVER EFFECTS and DEPENDENCY

Answer 13

ZOPICLONE

• SHORT ACTING (t½ » 5h)
• ACTS AT BZ RECEPTORS (CYCLOPYRROLONE)
• SIMILAR EFFICACY TO BZs
• MINIMAL HANGOVER EFFECTS BUT

DEPENDENCY STILL A PROBLEM

Question 14

Give informatoin on OTHER named ANXIOLYTICS

Answer 14

SOME ANTIDEPRESSANT DRUGS

•SSRIs(LESS SEDATION & DEPENDENCE / DELAYED

RESPONSE / LONG-TERM TREATMENT)

_SOME ANTIEPILEPTC DRUGS(_e.g. VALPROATE, TIAGABINE)

_SOME ANTIPSYCHOTIC DRUGS(_e.g. OLANZAPINE, QUETIAPINE)

PROPRANOLOL

•IMPROVES PHYSICAL SYMPTOMS

ØTACHYCARDIA (b1)

ØTREMOR (b2)

BUSPIRONE

5HT1A AGONIST

FEWER SIDE-EFFECTS (< SEDATION)

SLOW ONSET OF ACTION (DAYS / WEEKS)