ANXIOLYTICS / SEDATIVE-HYPNOTICS / MINOR TRANQUILIZERS

frequenZy

Benzodiazepines: Increase the ‘blank’ of opening of Chloride channels

duration

Barbiturates: Increase the ‘blank’ of opening of Chloride channels

Bind to their respective active sites at (Ionotropic GABA-A receptors receptor →

Cl- channel)

↑ GABA binding at GABA-A receptor

opening of Cl- channels = hyperpolarization (inhibitory)

SHORT ACTING

Midazolam, Triazolam

INTERMEDIATE ACTING (ALTOE)

Alprazolam, Lorazepam, Temazepam, Oxazepam, Estazolam

LONG ACTING

The rest of BZDs represented by Diazepam (Valium®), Chlordiazepoxide, Chlorazepate

Prodrugs with active metabolites

✓ Diazepam to Nordiazepam

✓ N-desmethyldiazepam

No active metabolites: (COLA)

Short and intermediate acting BZPs

✓ Clonazepam ✓ Oxazepam ✓ Lorazepam ✓ Alprazolam

BENZODIAZEPINES

✓ Mgt of anxiety disorders

✓ Mgt of insomnia

✓ Mgt of seizures

✓ Pre-adjunct in anesthesia

BENZODIAZEPINES: side effects

CNS Depression

Anterograde Amnesia

Cross-tolerance

Physical / psychological dependence: o May lead to withdrawal symptoms o Remedy: Taper the dose slowly when terminating treatment

Paradoxical reaction – BZPs can induce anxiety attacks

CNS Depression

dose dependent Tranquilizer → sedative → hypnotic → respiratory depression → coma → death

Anterograde Amnesia

o Partial / temporary loss of memory

o Use in surgery is acceptable

o Flunitrazepam (Rohypnol®) – aka Roofies; date-r*pe drug

BARBITURATES

• More toxic than BZPs

• Steeper dose-response

Phenobarbital

o From Primidone

o Enzyme inducer (for hyperbilirubinemia)

Barbiturates: CI, Tox

CI: Disorders associated with porphyrin

Tox: Neutralization

BARBITURATES: ULTRA SHORT ACTING

Thiopental, Thiamylal, Methohexital

‣ Very lipid-soluble, lipophilic, with short duration of action

‣ Thiol-containing (-SH)

‣ Clinical Uses: ✓ Preferred for induction of anesthesia ✓ Tranquilizer

BARBITURATES: SHORT ACTING

567: Pentobarbital, Hexobarbital, Secobarbital

Clinical Use: Sedative

BARBITURATES: INTERMEDIATE ACTING

Amobarbital, Butabarbital

Clinical Use: Hypnotic

BARBITURATES: LONG ACTING

Phenobarbital, Barbital

Clinical Use: Anticonvulsant, mgt of neonatal hyperbilirubinemia

Ramelteon

• Novel drug

• MOA: Melatonin agonist

Buspirone

• MOA: 5-HT1A partial agonist

• Advantage over BZP and Barbs: ✓ No potential for abuse ✓ No euphoric effects ✓ No dependence ✓ No muscle relaxant effect

Zaleplon, Zolpidem, Eszopiclone

• Same MOA with BZPs

• Advantage: Less likely to affect sleeping patterns than BZPs