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بسم الله الرحمن الرحيم. Anesthetic Drugs. Dr: Samah Gaafar Al-shaygi. Used as adjunct to surgery to render the patient un-aware & unresponsive to pain. Exert their action on the CNS. A useful anesthetic is easily controlled (rapid induction & recovery). Mechanism of action theories:
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بسم الله الرحمن الرحيم Anesthetic Drugs Dr: Samah Gaafar Al-shaygi
Used as adjunct to surgery to render the patient un-aware & unresponsive to pain. • Exert their action on the CNS. • A useful anesthetic is easily controlled (rapid induction & recovery). Mechanism of action theories: • Interaction with the lipid bilayer & recently with ligand-gated membrane channels. • The potency is related to lipid solubility not to chemical structures. • Most anesthetics enhance GABAA & inhibit the excitatory ones in the synapse.
Stages of anesthesia: • Loss of consciousness. • Analgesia. • Muscle relaxation. • Usually in surgery a group of drugs is used not a single one.
Inhalation Anesthetics • E.g: ether, halothane, isoflurane, desflurane. • All small, lipid soluble molecules. • Enter & leave through the lungs.
Factors determine the speed of induction & recovery: • Drug properties: solubility in the blood & in the fats. • Physiological factors: alveolar ventilation & cardiac output. • Nitrous oxide has low solubility in blood & ether a high sol. • Metabolic degradation determines their toxicity not duration of action. • Chloroform (free radicals) hepatotoxicity. • Halothane (bromide) hepatotoxicity.
Operating theatre staff incidence of liver diseases, leukemia, abortion & congenital malformations. Halothane: • Relatively fast induction & recovery. • Potent. CVS & RES. Failure easily. • Not analgesic. A.E: • CVS problems. Ventricular extra-systoles. • Hepatotoxicity.2-3 weeks • Malignant hyperthermia (excessive Ca+2 excessive metabolic heat production in muscles leading to muscle contraction & acidosis. Dantrolene blocks the Ca receptors. Susceptibility is due to mutation in the gene coding for ryanodine receptors. • Limited use in obse. Due to muscle relaxation.
Nitrous oxide: • Rapid action. • Low potency, not alone as a surgical anesthetic (70% N2O in O2) as adjunct to others. • Effective analgesics. A.E: • Bone marrow suppression (prolonged, repeated). • Transient hypoxemia.
Enflurane: • Moderate speed of induction & fast recovery. • Little FL production so no renal toxicity. • Seizures & malignant hyperthermia. Isoflorane: • Most used one. • Little A.E. (hypotension, myocardial ischemia in patient with coronary dx). • no seizures.
Ether: • Obsolete. • Slow onset & recovery. • Easy to administer & control. • Analgesic & muscle relaxant. A.E: • Highly explosive, nausea & vomiting, respiratory irritation.
Intravenous Anesthetic agents • Used for induction (20-30 sec). • Not for maintenance due to slow elimination. • Except propofol & ketamine. Thiopental: • Very lipid soluble. • In a form of Na salt. • Is unstable. • Act in 20 sec. & lasts for 5-10 min.
It binds to plasma protein. • No analgesic effect. A.E: • Narrow therapeutic window. • CVS & respiratory depression. • Local pain & tissue necrosis (procaine). • Porpheria.
Etomidate: • Similar to thiopental but has larger window & metabolized faster. A.E: • Involuntary movement during induction. • P.o nausea & vomiting. • Adrenal cortex suppression.
propofol: • Very rapidly metabolized. • Used as continuous infusion with no need for inhalation agent. • No side effects as etomidate.
ketamin: • Slow onset 2-5 min. • Dissociative anesthesia (marked analgesia, amnesia & paralysis without actual loss of consciousness. A.E: • Increased B.P. • Hallucinations, delirium & irrational behavior. • Increases the ICP.
midazolam: • A benzodiazepine. • Slow on & off set. • Usually as a preoperative sedation especially when a full anesthesia is not needed as endoscopy.
Local Anesthetics • They are weak bases working by blocking Na channels. • The block is more pronounced in small than in large nerves. • A.E. mainly are CVS & CNS ones. • Restlessness, tremor, convulsions. Mostly with procaine and less with lidocaine & prilocaine. • Hypotension. The exception is cocaine. • Hypersensitivity reactions.