General anesthetics notes
- 1. GENERAL ANESTHETICS MRS.REKHA AMIT BHALERAO Department of Pharmaceutical Chemistry PES MODERN COLLEGE OF PHARMACY, FOR LADIES
- 2. INTRODUCTION General anesthetics are the drugs, which produce controlled, reversible depression of the functional activities of the central nervous system producing loss of sensation and consciousness. Stages of General Anesthesia. When an inhalation anesthetic is administered to a patient some of the following well defined stages are produced by increasing the blood concentration of the agent. They are ; ● Stage I (Stage of analgesia): This is the period from the beginning of anesthetic ad- ministration to the loss of consciousness. The patient progressively loses pain. This stage is also called stage of analgesia. ● Stage II (Stage of delirium): This period extends from the loss of consciousness through a stage of irregular and specific breathing to the reestablishment of regular breath- ing. Respiration is normal and regular. The patient may laugh, vomit or struggle and for this reason it is called the stage of excitement. ● Stage III (Stage of surgical anesthesia): In this stage excitement is lost and skeletal muscle relaxation is produced. Most types of surgeries are done in this stage. ● Stage IV (Stage of medullary depression): Overdose of the anesthetic may bring the patient to this stage. Respiratory and circulatory failure occur in this stage. GENERAL ANESTHETICS 52
- 3. CHARACTERISTIC FEATURES OF IDEAL GENERAL ANESTHETIC An ideal general anesthetic should possess the following characteristic features: ● It should be inert ● It should be potent and non-inflammable ● It should be non-irritating to mucous membrane ● It should produce rapid and smooth anesthesia ● It should produce analgesia and muscle relaxation in addition to anesthesia ● It should not produce severe hypotension ● It should not produce nausea and vomiting ● It should be compatible with adjuvant drugs used in anesthesia ● It should be economical ● It should be stable to heat, light and alkalies
- 4. MECHANISM OF ACTION OF GENERAL ANESTHETICS The general anesthetics inhibit CNS neuronal activity. But their precise mechanism of neuronal inhibition is not clear. Several mechanisms were proposed to explain general anesthesia. They are: (i) Lipid Theory. According to this theory the more lipid soluble general anesthetics concentrate in hydrophobic regions of neuronal cell membrane and causes swelling of these membranes. Due to this swelling of structure of membrane alters, thereby blocks the Na+ channels. Thus the generation of action potential is inhibited and produces anesthesia. In 1901, Meyer and Overton correlated the potency of general anesthetics with their lipid solubility. The higher the value of partition coefficient of the compound, more will be its general anesthetic potency. (ii)Protein Theory. According to this theory the anesthetic bind to the hydrophobic sites of protein molecules of neuronal cell membrane, thus the membrane function is altered and produces anesthesia.
- 5. CLASSIFICATION OF GENERAL ANESTHETICS The general anesthetics are classified according to their nature (volatile or non-volatile) at room temperature. A. Volatile Inhalation general anesthetics: They are administered by inhalation and are further subdivided as Gases: Ex: Cyclopropane: Ethyl chloride, Nitrous oxide Liquids: Halothane, Enflurane, Diethyl ether, Trichloroethylene, Chloroform B. Non-Volatile or Intravenous anesthetics. They are non-volatile at room temperature and are administered by intravenous route. Barbiturates : Thiopental sodium, Methohexital sodium. Non-Barbiturates/dissociative aneshthetics: Ketamine Hydrochloride, Propofol, etc.
- 6. Inhalation general anesthetics : Enflurane: Chemically enflurane is 2-chloro-1,1,2- trifluoroethyldifluoromethylether. Enflurane is available as a clear, colourless non-inflammable liquid with sweet odor. Enflurane Halothane: Chemically halothane is 2-bromo, 2-chloro, 1,1,1-trifluoroethane. Halothane is a colourless, non-inflammable liquid having chloroform like odour It is non-irritant to the skin and mucous membrane. Uses Halothane is one of the most widely used potent anesthetic agents (2-2.5%). It is usually administered through N2O-air mixture. It has more rapid induction and recovery compared to ether . Disadvantages of halothane are; It reduces cardiac output It causes peripheral vasodilation leading to hypotension or low blood pressure It is a dose-dependent respiratory depressant Halothane
- 7. Barbiturates induce general anesthesia rapidly and pleasantly (painlessly). They have maximum effect in about 1 minute and duration about 5-8 minutes. Induction doses produce the highest blood concentration, the greatest effects on body systems and the most side effects. Usual, recommended induction doses of thiopental: Adults : 2.5-4.5 mg/kg Children : 5-6 mg/kg Infants : 7-8 mg/kg Intravenous anesthetics : Barbiturates
- 8. Methohexital: It is a derivative of barbituric acid. It is prepared by condensation of ethylcyanoacetate with 2-chloro-3-pentyne in presence of sodium ethylate. Thiopentone or Thiopental Sodium is an intravenous anesthetic. It is a barbituric acid derivative and is synthesized by condensing thiourea with ethyl (ethyl 1-methyl butyl) malonate. Intravenous anesthetics : Barbiturates Methohexital Thiopental Sodium
- 9. Non- Barbiturates: Ketamine Hydrochloride: Ketamine is a cyclohexanol derivative. Chemically ketamine is (+) 2 (o-chlorophenyl)- 2-methylaminocyclohexanone. Ketamine is considered a dissociative anesthetic, this means that the drug distorts the users perception of sight and sound and produces feelings of detachment from the environment and ones self. The drug also has anesthetic properties that have been used in both human and veterinary medicine, and is currently a Schedule III controlled substance. For humans it has been used in radiation and burn therapy, treatment of battlefield injuries, and for children who have adverse reactions to other anesthetics
- 10. SPECIFIC GENERAL ANESTHETICS: CYCLOPROPANE CH2—CH2—CH2 Br Br 1,3-Dibromopropane Zn / C H OH ⎯⎯⎯⎯2 ⎯5 ⎯→ CH2 H2C CH2 Cyclopropane Properties ● Cyclopropane is a colourless flammable gas with characteristic odour and pungent taste. It is supplied in compressed form in metal cylinders ● Cyclopropane forms explosive mixture with air ● The cylinders of cyclopropane are painted red Uses. Cyclopropane is used as general anesthetic. It produces rapid and smooth induction, good muscle relaxation and has wide margin of safety. It is administered by inhalation. Chemistry. Cyclopropane is a cyclic aliphatic hydrocarbon. It is prepared from 1, 3- dibromopropane with zinc and alcohol in absence of water.
- 11. ETHYL CHLORIDE: Chemistry. Ethyl chloride is a chloro derivative of ethane. It is gas at normal conditions and is available in compressed form. Ethyl chloride is prepared from ethyl alcohol by passing dry hydrogen chloride into it. Properties ● Ethyl chloride is a volatile liquid having a pleasant ethereal odour and burning taste ● It is lightly soluble in water and also miscible with alcohol and ether Uses. Ethyl chloride is used as a general anesthetic administered by inhalation. NITROUS OXIDE Chemistry. Nitrous oxide was the first anesthetic. Joseph Priestly first reported ni- trous oxide preparation in 1772. It is prepared by heating ammonium nitrate to 2000C. NH4NO3 ⎯⎯→ N2O + H2O. Properties ● Nitrous oxide is available as a colourless, tasteless and odourless gas ● It is supplied in blue coloured metal cylinders ● It is soluble in water, alcohol and ether