GENERAL ANESTHETICS

GENERAL ANESTHESIA : a state characterized by unconsciousness, analgesia, amnesia, skeletal muscle relaxation, and loss of reflexes. GENERAL ANESTHETICS : drugs that cause a general anesthesia. These drugs depress all excitable tissues including central neurons, cardiac muscle, and smooth and striatal muscle. However, these tissues have different sensitivities to anesthetics and the areas of the brain responsible for consciousness are among the most sensitive.

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STAGE OF ANESTHESIA A. Analgesia The patient has decrease awarenes of pain, sometimes with amnesia B. Disinhibition The patient appears to be delirious and excited. Amnesia occurs, reflexes are enhanced, and respiration is typically irregular. C. Surgical Anesthesia The patient is unconscious and has no pain reflexes; respiration is very regular, and blood pressure is maintained. A. Medullary Depression The patient develops severe respiratory and cardiovascular depression that requires mechanical and pharmacological support.

GENERAL ANESTHETICS
General anesthesia ussualy involves the administration of drugs for premedication, induction of anesthesia, and maintenance of anesthesia. Premedication : - relief from anxiety (by benzodiazepines such as diazepam or lorazepam) - reduction in secretions and vagal reflexes (by muscarinic antagonists usually atropine or hyoscine to prevent salivation and bronchial secretion and to prevent bradycardia) - reduction of pain (by opioid analgesics)

GENERAL ANESTHETICS Induction of anesthesia is most commonly achieved by the iv administration of barbiturates (thiopentone) or nonbarbiturates (propofol). Unconsciousness occurs within seconds and is maintained by the administration of inhalation anesthetics (nitrous oxide, halothane, isoflurane, etc).

GENERAL ANESTHETICS
CLASSIFICATION OF GENERAL ANESTHETICS Inhalational Anesthetics - Gas : Nitrous oxide - Volatile liquids : Halotan, enfluran, isofluran, metoksifluran, Intravenous Anesthetics - Barbiturates (thiopental, methohexital) - Benzodiazepines (diazepam, lorazepam, midazolam) - Opioid analgesics (morphine, fentanyl) - Miscellaneous drugs (mitomidat, ketamine, propofol)

GENERAL ANESTHETICS
INHALATIONAL ANESTHETICS - An ideal inhalational anesthetic would be characterized by : 1) Rapid and pleasant induction of and recovery from anesthesia; 2) Rapid changes in the depth of anesthesia; 3) Adequate relaxation of skeletal muscles; 4) A wide margin of safety; and 5) The absence of toxic effects or other adverse properties in normal doses.

GENERAL ANESTHETICS
- The speed of induction of anesthesia depends mainly on its solubility in blood and the inspired concentration of gas. The more rapidly a drug equilibrates with the blood, the more quickly the drug passes into the brain to produce anesthetic effects. A drug of low solubility (eg, nitrous oxide) equilibrates more rapidly than those of higher blood solubility (eg, halothane).

GENERAL ANESTHETICS
INHALATIONAL ANESTHETICS Nitrous Oxide (N2O)
- relatively low soluble in blood (blood:gas partition coefficient 0.47). - is not potent enough to use as a sole anesthetic agent, but it is commonly used together with other general anesthetics. The conc. of 80% or more can be used as a sole anesthetic, but it can cause hypoxia. - is a good analgesic and a 50% mixture in oxygen is used when analgesia is required (eg, in childbirth, road traffic accidents). - has little effect on the cardiovascular and respiratory systems. - doesnt give effect on skeletal muscle relaxation.

GENERAL ANESTHETICS

Halothane
- a potent agent and non-iritant; - induction is smooth and pleasant; - causes a concentration-dependent hypotension, largerly by myocardial depression, and often causes arrhythmias; - depresses the respiratory centre, with a resulting decrease in the minute volume and an increase in artrerial Pco2;

GENERAL ANESTHETICS
- the most important toxic effect of halothane is massive hepatic necrosis which occurs in about 1 in 35 000 cases, although lesser degreese of liver damage probably occur much more often; - more than 20% of the administered halothane is biotransformed by the liver to metabolites, some of which may either directly damage the liver or bind to cellular macromolecules and generate antigens that are recognized as foreign by the body.

GENERAL ANESTHETICS
Enflurane - is similar in action to halothane; - also depresses myocardial contractility and causes a dose-dependent hypotension; - is a much lower incidence of arrhythmias than with halothane and much less sensization of the myocardium to catecolamines; - undergoes much less metabolism (2%) than halothane and is unlikely to causes hepatitis.

GENERAL ANESTHETICS
INTRAVENOUS ANESTHETICS Barbiturates
- most commonly used barbiturates for anesthesia : thiopental & methohexital; - have high lipid solubility, which promotes rapid entry into the brain; - are used for induction of anesthesia; - produces a dose-dependent depression of respiration; - decreases the arterial blood pressure only transiently then returns essenstially to normal; - decreases blood flow to skin and brain, but not to the other organs.

GENERAL ANESTHETICS
Benzodiazepines
- most widely used benzodiazepines for preanesthesia : diazepam, lorazepam, and midazolam; - the onset of CNS effects is slower than that of thiopental, and it has a longer duration of action; - the conc of diazepam in plasma declines rapidly owing to redistribution, with an initial half-life of 10 to 15 min; however, drowsiness often returns after 6 to 8 hours. This is probably due to absorption from the gastrointestinal tract after excretion in the bile. - the onset of drowsiness is slightly less rapid after administration of lorazepam and is slightly more rapid with midazolam; - Cause only moderate depression of circulation and respiration.

GENERAL ANESTHETICS
Etomidate - is a potent hypnotic agent without analgesic properties; - an iv injection of 0.3 mg/kg to an adult patient will induce sleep that lasts for approx 5 mins; - cardivascular & respiratory depression do not usually occur; - the induction of anesthesia with etomidate is usually followed by the administration of analgesic and muscle relaxant drugs and/or potent inhalational anesthetics;

GENERAL ANESTHETICS
Opioid Analgesics - frequently used as supplements during general anesthesia with inhalational or iv agents : morphine (1-2 mg), meperidine (10-25 mg), fentanyl (0.05-0.1 mg), sufentanil (0.005-0.01 mg), alfentanil (0.15-0.3 mg); - cause respiratory depression, mild decreases in blood pressure, delay in awakening, and postoperative nausea or vomiting.