Pharm_Sedatives & Hypnotics Flashcards
CNS depressants:
Sedative vs Hypnotic vs Anxiolytic
What is the relation or co-relation of the terms?
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
Pharmacological treatment for Anxiety Disorders
Benzodiazepines
and
Non-benzodiazepines
Benzodiazepines
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.
Non-benzodiazepines
Non-benzodiazepines:
* Barbiturates: eg, phenobarbital.
* Buspirone.
* Zolpidem.
* Propranolol.
Chlorine channel (5 peptide schematic diagram)
–> GABA site
–> Barbiturate site
–> Benzodiazepine site
Mechanism of Action for Benzodiazepines
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)
Short acting BZD
Midazolam
1. Anxiety
2. Induction of G.A.
3. Procedural sedation
Short Acting BZD for Insomnia
Midazolam/ Triazolam ?
Triazolam
Indicated for Insomnia, not for the following:
(anxiety, introduction of GA, procedural sedation)
Intermediate Acting BZD and its indication
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)
Long acting BZD
and its indication
Diazepam
(Brand name: Valium etc.)
Chronic conditions such as Alcohol withdrawal syndrome, refractory seizures, status epilepticus etc.
Side effects of BZD
Drowsiness, confusion, amnesia
Impaired muscle co-ordination (impairs manual skills)
Other unwanted effects of BZD
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
Antidote for BZD toxicity/ overdose
Flumazenil
Non-benzodiazepines
- Zolpidem
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.
Non-benzodiazepines
- Buspirone
- 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.
Non-benzodiazepines
- Barbiturates
Recall the 3 diff duration of action for Non-BZD.
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?
Duration of action,
Drugs and indication.
for Barbiturates
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.
Which of the following is more likely to induce dose-dependent CNS depression?
BZD/ non-BZD?
non-BZD
- Barbiturates
(Refer to graph)
Non-benzodiazepines
- Propanolol
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.
