CNS Depressant Drugs 322 PHL Lab # 4 King Saud University College Of Pharmacy Department of Pharmacology CNS Depressant Drugs 322 PHL Lab # 4

Classification of CNS Depressant Drugs According to Their Pharmacological action 1- Sedative – hypnotics 2- Tranquillizers 3- Anesthetics

General signs for CNS depressants 1- ↓ vitality 2- ↓ excitability 3- ↓ HR & RR

I. Sedative – hypnotics Sedatives: Drugs which calm the patient & cause sedation and in large doses they induce sleeping. Hypnotics: Drugs which induce sleep that resembles to the natural sleep e.g. Barbiturates

Natural Sleep Sleep: Physiological depression of consciousness. Sleep cycle: Starts with latency period → NREM → REM → cycles of NREM alternate with REM (about 4 cycles)

Natural Sleep REM NREM Rapid eye movement. Consist of one stage (dreaming stage). Lasts for 20 min. Dreaming . Non rapid eye movement. Consist of 4 stages. Lasts for 90 min. Thinking.

II- Tranquillizers Definition: Tranquillizers are drugs which relief mental anxiety & stress without affecting the consciousness. e.g. Chlorpromazine (CPZ) MOA: It is D2 , 5-HT , H1, α1 antagonist

III- Anesthetics Definition: Drugs which cause unconsciousness & generalized loss of pain sensation, thus allow surgical procedures to be carried out . e.g. thiopental (IV) , halothane (inhalation) MOA: Interfering with propagation of nerve impulses by interfering with electrolytes conductance through the cell membrane.

Sedative – hypnotics: Classification Barbiturates 1-Long acting (12-24 hr) e.g. Phenobarbital 2-Intermediate acting (8-12hr) e.g. Amobarbital 3-Short acting (4-8 hr) e.g. Pentobarbital 4-Ultrashort acting (0.5-1 hr) e.g. Thiopental Non-barbiturates Benzodiazepines Non- benzodiazepine

1- Barbiturates MOA: They have GABA like action (They facilitating the GABA action → mediate opening of chloride channels →increase CL influx → hyperpolarization Classification according to their duration of action: 1-Long-acting . 2-Intermediate-acting . 3-Short acting . 4-Ultrashort acting .

2- Benzodiazepines Benzodiazepines enhance the response to GABAa by facilitating the opening of GABA-activated chloride channels

2- Benzodiazepines They bind specifically to a regulatory site of the receptor, distinct from the GABA-binding site, and act allosterically to increase the affinity of GABA for the receptor e.g. Diazepam (sedative) (Triazolam (hypnotic

3- Non-barbiturate Non-BZD (5-HTA1) agonist e.g. buspirone. Chloral hydrate (prodrug) converted to trichloroethanol. Antihistamine e.g. diphenhydramine. Paraldehyde . Promethazine .

Specific signs of sedative-hypnotic Drugs: Thiopental, Phenobarbital & chloral hydrate . Signs: 1- Staggering gait . 2- Sleeping posture . 3- Loss of righting reflex (onset time) . 4- ↓ Touch & pain reflexes ( lost with thiopental ) .

Specific signs for CBZ Signs: 1- No loss of righting reflex . 2- Creeping gait. 3- Abdomen touches the ground. 4- State of catalepsy (loss of muscles control)→(onset time) 5- ↓ Touch & pain reflexes.

Lab work ROA Dose Conc. Drug IP 100 mg/kg 2.5 % 200 mg/kg 2% 300 mg/kg Thiopental 200 mg/kg 2% phenobarbital 300 mg/kg 3 % Chloralhydrate 15 mg/kg 0.1% C.P.Z