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CNS Depressants Lab # 2 Objectives • To demonstrate the effect of different types of CNS depressants as : - General anaesthetics - Hypnotics المنومات - Sedatives المسكنات - tranquilizers المهدئات To learn how to distinguish between their signs if they are given as unknown drugs. Introduction • CNS depressants are drugs that can be used to slow down brain activity or function . • There are numerous CNS depressants; most act on the brain by affecting the neurotransmitter gamma-aminobutyric acid (GABA). • GABA works by decreasing brain activity. • CNS depressants have ability to increase GABA activity that they produce a drowsy or calming effect that is beneficial to those suffering from anxiety or sleep disorders. General Anaesthetics • They are drugs which produce reversible loss of consciousness الوعى. • Mechanism of action : - They alter chloride channel opening cause hyperpolarization so they decrease firing. - They facilitate the inhibitory effects of GABA . Stages Of Anesthesia I. Stage of analgesia: decrease feeling of pain but the patient is still conscious. II. Stage of excitement: delirium , respiration is irregular and the consciousness is lost but the feeling of severe pain is present. III. Stage of surgical anesthesia: regular respiration, relaxation of the skeletal muscles and the feeling of surgery is lost. The Target Stage Stages Of Anesthesia IV. Stage of medullary depression: severe depression in vasomotor center in the medulla and respiratory center. Without full circulatory and respiratory support the result is death. Classification of General Anesthetics • There are two types of General Anesthetics agents: 1) Inhaled Anesthetics 2) Intravenous Anesthetics A- Inhaled agents: 1) Volatile liquid: e.g. Halothane, Isoflurane, Enflurane, Desflurane, Sevoflurane and Methoxyflurane. 2) Gas: e.g. Nitrous oxide . B- IV agents: Ultra short acting Barbiturates ( e.g. Thiopental), Ketamine, Propofol, Midazolam (Benzodiazepines) and Fentanyl ( Opioid). Hypnotics • They are drugs that induce sleep in case of insomnia. e.g. Barbiturates and Benzodiazepines. • Barbiturates & Benzodiazepines act by enhance the actions of GABA. Classification of Barbiturates • Based on the duration of action 1. Ultrashort acting: ( 15 minutes) e.g. Thiopental. 2. Short acting: ( 2-4 hours) e.g. Pentobarbital . 3. Intermediate acting: (4-6 hours) e.g. Amobarbital. 4. Long acting: ( 6-8 hours): e.g. Phenobarbital. Sedatives • Drug that cause sedation and to calm the patient down without inducing sleep. • When the dose increased they will induce sleep. • E.g. Chloral Hydrate • Trichloroethanol is the active metabolite of chloral hydrate . • Trichloroacetic acid is the toxic metabolite . Tranquilizers • They are drugs which used to relieve mental anxiety and stress. • E.g. chlorpromazine (CPZ). • Work by blocking dopamine (D 2 )receptor. Righting reflex • Test the ability of the mice to assume optimal position . • When it lost: (-ve) • With Phenobarbital righting reflex –ve • With Chloral hydrate: at sedative dose the righting reflex is +ve , when the dose repeated it will induce sleep and the righting reflex will be –ve. • With chlorpromazine: righting reflex is +ve and still +ve even the dose is repeated . Chlorpromazine (CPZ) • After injection of CPZ we can observe signs as: • Ataxic gait: loss of muscle coordination . • Catalepsy : rigid body • Grasping test (CPZ): When you trying to put the mice on the cord, the mice will fall down Calculate the dose Type Example Conc (g%) Dose (mg/kg) Hypnotic Phenobarbital 2% 200 Sedative Chloral Hydrate 3% 150 Tranquilizer Chlorpromazine 0.2% 40 Injection volume = Dose (mg/Kg) x Body weight in Grams Conc g% x 10000 = xxxxx ml