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The state of general anesthesia is drug induced absence of perception of all sensations PRINCIPLES OF THE ADMINISTRATION OF GENERAL ANAESTHETICS Uptake and Distribution of inhalational general anesthetics Depth of Anesthesia - Tension of anaesthetic agent in brain - controls - rates of induction and recovery Tension and partial pressure are interchangeable terms Tension in the arterial blood and brain are same and are determined by: Concentration of the anaesthetic in the inspired air depends on rate of ventilation Transfer of the gas from the alveoli to the blood Decreased in disease (ex. emphysema) Rate of transfer is determined by: Solubility(Blood gas partition coefficient.) Rate of blood flow(directly proportional to the C.O. Partial pressures of the agent in arterial and mixed venous blood. Loss of the agent from the arterial blood to all the tissue of the body ANAESTHESIA MACHINES Are devices by which the anesthesiologist is able to deliver Measured quantities of anaesthetic gases and oxygen through accurate flowmeters and with the use of special vaporizers it is possible to add the vapor of volatile anesthetic liquid to the gas stream. The mixture of oxygen and anaesthetic agent is then delivered to a breathing circuit for administration by Inhalation. • General Anesthetics are the most dangerous drugs • Therapeutic index ranges between 2-4 • 2-3 times dose causes circulatory failure Oral dose delivers the total dose • • • • • • When gas or vapor is inhaled only a small amount is absorbed Whereas the rest is exhaled out in next 1-2 seconds The drug reaches the brain by leaving the blood Anaesthetic blood levels of these cannot be measures accurately Concentrations in the lungs can be easily frequently and accurately be measured The partials pressures of the anaesthetic in the lung and the brain are almost equal at equilibrium Minimum Alveolar Concentration • • MAC is the measure of potency of general anesthetics It is the minimum alveolar concentration (MAC) at one atmospheric pressure that produces immobility in 50% patients or animals exposed to noxious stimuli ELIMINATION OF GENERAL ANAESTHETICS Free gases and vapors wash out of the lungs: The arterial blood tension declines first. Followed by that in the tissues where the anaesthetic agent persists for a longer time. Tissue having low blood flow (muscle) relieve the agent much slowly. OTHER ROUTES: These agents are also eliminated in smaller quantities from skin, mucous membrane and the kidneys DEPTH OF GENERAL ANAESTHESIA OCCURS IN STAGES STAGE - 1 STAGE - 2 STAGE - 3 STAGE - 4 ANALGESIA DELERIUM SURGICAL ANESTHESIA MEDULLARY PARALYSES APPROACHES FOR TESTING DEPTH OF ANAESTHESIA - Blinking of eyelids on striking the eyelashes. - Swallowing - Regularity and depth of respiration. - Increase in respiratory rate and B.P.on incision - Tightness of jaw muscles. Above responses fade on deepening of the anesthesia. Deep anesthesia Leeds to: • Respiratory depression • Apnea • Lowering of B.P. • Asystole PREANAESTHETIC MEDICATION Decrease anxiety with out drowsiness Amnesia Relieve preoperative pain Decrease requirement for an inhalational agent. Minimising undesirable effects of anesthetics. (salivation, decrease in heart rate, coughing, vomiting) Decrease volume and acidity of the gastric contents. Decrease stress response in preoperative period PREANAESTHETIC MEDICATION 2-3 drugs are used concomitantly: Sedatives Hypnotics Antianxiety drugs Opoids Antiemetics H-2 antagonists Gastrokinetic agents Anticholinergics DRUGS USED IN PREANAESTHETIC MEDICATIONS Benzodiazepines: Diazepam, Lorazepam, Midazolam. Barbibiturates: Pentobarbitone, secobarbitone. Antihistamines: Hydroxyzine, Diphenhydramine. Phenothiazines: Promethazine. Butyrophenones: Droperidol. Opoids: Morphine, fentanyl, meperidine. Anticholinergics: atropine, scopolamine, glycopyrrolate. Antiemetics: Ondansetron Drugs decreasing gastric acidity: H-2 antagonists. Antacids. Gastrokinetic agents. MECHANISM OF ACTIONS OF GENERAL ANAESTHETICS All drugs belong to diverse groups Inert gases as xenon Inorganic/Organic compds as Nitrous oxide and Chloroform. Complex Organic Molecules Halogenated Alkanes and ethers The Mode of action is without any satisfactory explanation. POSTULATIONS: -Influence synaptic transmission. -Axonal conduction is unaffected. -Potentiate release of inhibitory neurotransmitters. -Inhibit excitatory synapses. MECHANISM OF ACTIONS OF GENERAL ANAESTHETICS Action of these agents is on Lipid bilayer and/or protein lipid interface OR ION CHANNELS (Na/K/Ca) OR Ligand gated Channels l-Glutamate. NMDA NAChR GABA-A MECHANISM OF ACTIONS OF GENERAL ANAESTHETICS At the molecular level, anesthetics probably exert their effects by direct interactions with proteins rather than by disturbing the matrix of the lipid bilayer as earlier postulated. Anesthetics May bind to hydrophobic pockets or clefts, producing small changes in protein Conformation alerting receptor of channel function. It is also possible that specialized areas Of the membrane such as the boundary lipids surrounding membrane Proteins are important sites of anaesthetic binding and action. MECHANISM OF ACTION: The exact mechanism by which inhalational anesthetics function is not known. There appears to be a correlation between anesthetic potency and lipid solubility (Meyer-Overton theory), suggesting that these anesthetics likely affect the lipid matrix of nerve cell membranes in the brain. Furthermore, NMR and electron spin resonance studies indicate that anesthetics cause a local disordering of the lipid membrane matrix, possibly decreasing the number of molecules that alternate simultaneously between the gel and crystalline states, and thereby altering membrane function. NEUROLEPT ANALGESIA - State of quiescence - Reduced motor activity - Reduced anxiety - Indifference to the surroundings without loss of consciousness The patient responds to commands. Drugs: a neurolept compd (Droperidol) plus an opoid analgesic (fentanyl) Neurolept analgesia may be converted into neurolept anaesthesia by concominant administration of 65% nitrous oxide DISSOCIATIVE ANAESTHESIA a state of sedation, immobility, amnesia and marked analgesia (feeling of dissociation) a single drug such as ketamine can result in this state. GENERAL ANAESTHETICS CLASSIFICATION Inhalation agents: NEWER AGENTS Halothane Enflurane Volatile liquids: Isoflurane Desflurane Sevoflurane Gases: Nitrous oxide Intravenous agents: Thiopentone Benzodiazepines Etomidate Ketamine Propofol OLDER DRUGS Chloroform Ether Ethylchloride Trichlorethylene Cyclopropane Ethylene CHARACTERSITICS OF AN IDEAL ANAESTHETIC 1. Rapid and pleasant induction 2. Rapid changes in the depth of anesthesia 3. Adequate Muscle Relaxation 4. Wide margin of safety 5. Absence of toxic/adverse effects