Pharm_Sedatives & Hypnotics

Question 1

CNS depressants:
Sedative vs Hypnotic vs Anxiolytic
What is the relation or co-relation of the terms?

Answer 1

CNS depressant:
Sedative: causes sedation, relaxation.
Hypnotic: induces drowsiness and sleep, may have amnestic effects.
Anxiolytic: Reduces anxiety.

*NB: These actions are closely-related. The same drug can have more than one action depending on dose. Eg:

Low dose –> anxiolytic and sedative effects
Higher doses –> hypnotic
Even higher doses –> can cause anesthesia, used for surgery

Question 2

Pharmacological treatment for Anxiety Disorders

Answer 2

Benzodiazepines
and
Non-benzodiazepines

Question 3

Benzodiazepines

Answer 3

Sedative-hypnotics, anxiolytics

Benzodiazepines:
* Used as anxiolytics / sedatives: eg, diazepam, lorazepam.
* Used as hypnotics: eg, diazepam, triazolam, temazepam.
* Used as pre-anaesthetics: eg, diazepam, midazolam.
* May also have anti-convulsant effects: eg, diazepam.

Question 4

Non-benzodiazepines

Answer 4

Non-benzodiazepines:
* Barbiturates: eg, phenobarbital.
* Buspirone.
* Zolpidem.
* Propranolol.

Question 5

Chlorine channel (5 peptide schematic diagram)
–> GABA site
–> Barbiturate site
–> Benzodiazepine site

Answer 5

Question 6

Mechanism of Action for Benzodiazepines

Answer 6

GABA inhibitory transmitter in brain regions; act via GABA A receptors Cl- channels.

1) When there’s no agonist, Cl- channels are closed
2) When Receptor binding GABA is present,
- binding of GABA causes Cl- to open, leading to hyper polarization of the cell
3) Binding of GABA is enhanced by BZD, resulting in greater entry of Cl- ion. (Neurons not firing)

Question 7

Short acting BZD

Answer 7

Midazolam
1. Anxiety
2. Induction of G.A.
3. Procedural sedation

Question 8

Short Acting BZD for Insomnia
Midazolam/ Triazolam ?

Answer 8

Triazolam
Indicated for Insomnia, not for the following:
(anxiety, introduction of GA, procedural sedation)

Question 9

Intermediate Acting BZD and its indication

Answer 9

All other names that ends of with ~olam~or ~zepam
except Diazepam
(Common brand names; Xanax, Ativan)

Indication for Panic Disorder, anxiety
(Insomnia, status epilepticus, alcohol withdrawl syndrome, insomnia)

Question 10

Long acting BZD
and its indication

Answer 10

Diazepam
(Brand name: Valium etc.)

Chronic conditions such as Alcohol withdrawal syndrome, refractory seizures, status epilepticus etc.

Question 11

Side effects of BZD

Answer 11

Drowsiness, confusion, amnesia
Impaired muscle co-ordination (impairs manual skills)

Question 12

Other unwanted effects of BZD

Answer 12

1) Acute toxicity/ overdose
- RD, especially with alcohol
- Antidote: BZD antagonist: Flumazenil

2) Tolerance & dependence
(Tolerance develops faster for epilepsy than for use to induce sleep)

3) Withdrawal effects
- Disturbed sleep, rebound anxiety, tremor and convulsions

Question 13

Antidote for BZD toxicity/ overdose

Answer 13

Flumazenil

Question 14

Non-benzodiazepines
- Zolpidem

Answer 14

Also potentiates GABA-A mediated Cl- currents at the same site as BZD.

Has good hypnotic effect:
–> primarily used to treat insomnia.

Not effective as anxiolytics.

Question 15

Non-benzodiazepines
- Buspirone

Answer 15

• A serotonin 5-HT1A receptor partial agonist. Also binds dopamine receptors.
• Indicated for GAD but anxiolytic effects takes 1-2 weeks.
• Lacks anticonvulsant and muscle relaxant properties.

Question 16

Non-benzodiazepines
- Barbiturates

Recall the 3 diff duration of action for Non-BZD.

Answer 16

Also potentiate GABAA mediated Cl- currents, but at a site distinct from benzodiazepines.

Use as a sedative-hypnotic has largely been replaced by benzodiazepines due to barbiturates’ tendency to develop tolerance and dependence.

Severe withdrawal symptoms.

Flumazenil not effective for treating barbiturate overdose.

At anesthetic doses, barbiturates such as phenobarbital can directly open Cl- channels as well as block Na+ channels.

How is the the duration of action for non-BZD different from BZD?

Question 17

Duration of action,
Drugs and indication.
for Barbiturates

Answer 17

Ultrashort (20 min)
I.V induction of anesthesia:
- Eg, Thiopental

Short (3-8hrs)
Sedative & Hypnotic:
- Eg, pentobarbital and amobarbital.

Long acting (1-2 days)
Anticonvulsant:
- Eg, phenobarbital.

Question 18

Which of the following is more likely to induce dose-dependent CNS depression?

BZD/ non-BZD?

Answer 18

non-BZD
- Barbiturates
(Refer to graph)

Question 19

Non-benzodiazepines
- Propanolol

Answer 19

A beta-adrenergic receptor antagonist.

Used for treating performance anxiety and social phobias.

Reduces physical symptoms associated with adrenergic activation.

Contraindicated in patients with asthma and heart conditions.