General Anesthetics Drugs used to induce a state of unconsciousness with the overall aim of ensuring hypnosis, amnesia, analgesia, immobility, skeletal muscle relaxation, and loss of control of reflexes of the autonomic nervous system.

Features of ideal anesthetic 1. Rapid and smooth induction and recovery. 2. Wide safety margin. Minimal side effects. Balanced anesthesia Use of more than one agent to obtain ideal anesthesia.

Adjuncts to general anesthetics I. Muscle relaxants II. Pre-anesthetic medications. Muscle relaxants Facilitate intubation. Suppress muscle tone. Atracurium, Vecuronium, Succinylcholine.

Pre-anesthetic medication Anticholinergics: prevent secretion of fluids into the respiratory tract . Benzodiazepines: relieve anxiety. Thiopental-Propofol: rapid induction of anesthesia . Antiemetic : post surgical N&V. Antihistaminics: allergic reactions. H2-receptor blockers: reduce gastric acidity Opiates: induce analgesia.

Depth of anesthesia ( Four stages). Stage I - Analgesia. - Loss of pain sensation. - The patient is conscious and conversational. Stage II - Excitement. - Increased, irregular blood pressure. - Increased respiratory rate. Patient may experience delirium & violent behavior. Dilated & reactive eye.

Stage III - Surgical anesthesia. - Regular respiration & relaxation of sk. muscles. - Eye reflexes decrease until the pupil is fixed. Stage IV - Medullary paralysis. - Severe depression of vasomotor and respiratory centers. - Death may occur.

Classification 1. Inhalation Anesthetics Gases: nitrous oxide Volatile Liquids: Ether Halogenated compounds 2. Intravenous Anesthetics

Mechanism of action Interaction with membrane ion channels. Enhancing the action of inhibitory neurotransmitters, GABA and glycine thus decrease neuronal excitability. Inhibition of excitatory neurotransmitters e.g. ketamine is NMDA receptor antagonist

Inhalation Anesthetics Methoxyflurane Halothane Enflurane Isoflurane Desflurane Sevoflurane Nitrous oxide .

Pharmacokinetics of general anesthetics Induction of anesthesia Maintenance of anesthesia Depth of anesthesia. Recovery of anesthesia MAC value

Induction, Maintenance and Recovery Time elapsed between onset of administration of anesthetic and development of effective surgical anesthesia. Maintenance Time during which the patient is surgically anesthetized. Recovery The time from discontinuation of anesthetic drug until consciousness is regained.

Factors controlling induction & recovery The anesthetic concentration in the inspired air (Direct). Blood solubility: Blood: gas partition coefficient (Inverse relation). Pulmonary blood flow (Inverse). Rate and depth of ventilation (Direct).

Desflurane 0.42 poor & Rapid Nitrous Oxide 0.47 Rapid DRUGS Solubility Induction & Recovery (Blood : gas partition coefficient ) Methoxyflurane 12 Slow Halothane 2.3 Slow Enflurane 1.8 Medium Isoflurane 1.4 Medium Sevoflurane 0.69 Rapid Desflurane 0.42 poor & Rapid Nitrous Oxide 0.47 Rapid

Minimum Alveolar Concentration (MAC) It is the concentration of inhalation anesthetic that produce immobility in 50 % patients in response to surgical incision. Depends on potency of anesthetic agents. The lower the MAC value the more potent the drug. MAC is increased by CNS stimulants. MAC is decreased by CNS depressants & in old people.

POTENCY MAC Methoxyflurane 0.16 Halothane 0.75 Isoflurane 1.4 Enflurane 1.7 Sevoflurane 2 Desflurane 6-7 Nitrous oxide >100

Pharmacological Actions CNS -  metabolic rate. -  ICP (due to cerebral vasodilatation) # in head injuries. - Dose - dependent EEG changes (Enflurane).

CVS Hypotension Bradycardia except ( Isoflurane, Desflurane) Myocardial depression (Halothane , Enflurane) - Sensitize heart to catecholamines (Halothane)

Respiratory system - All respiratory depressants. Bronchodilators (Halothane – Sevoflurane).  mucociliary movement. Airway irritation (Desflurane- Enflurane). Liver - Decrease hepatic flow. - Hepatotoxicity (Only halothane ).

Uterus Uterine relaxation Nitrous oxide: has minimal relaxant effect (labor). Skeletal muscles - All are skeletal muscle relaxants to varying degree.

Methoxyflurane The most potent (high lipid solubility). 50 % is metabolized to fluoride (nephrotoxic). Slow induction (20 minutes). For veterinary use only.

Halothane (Fluothane) Non irritant (pleasant odor) Potent anesthetic. Weak analgesic. Weak skeletal muscle relaxant. Slow induction and recovery (blood solubility). Metabolized to hepatotoxic metabolite, trifluroethanol.

CVS depression Hypotension Bradycardia (vagomimetic action)  Myocardial contractility.  Cardiac output Respiratory depression. Uterine relaxant. The agent of choice in children (Pleasant).

Adverse Effects Hepatotoxicity (repeated use). Malignant hyperthermia. Decrease the cardiac output. Sensitizes heart to action of catecholamines  cardiac arrhythmias.

Enflurane (Ethrane) More rapid induction and recovery than halothane. Less potent than halothane. Better muscle relaxation. Better analgesic properties. is metabolized to fluoride (8%). Excreted in the kidney

CVS depression - Hypotension -  Cardiac output - No sensitization of the heart to catecholamines Disadvantages Pungent (less induction -not for pediatrics). CNS stimulation (Epilepsy-like seizure- abnormal EEG).

Contraindications patients with seizure disorders. renal failures.

Isoflurane (Forane) Less potent than halothane Better analgesic action. More rapid induction & recovery than halothane Stable compound (2%). Low biotransformation (less fluoride). No hepatotoxicity. No sensitization of the heart. No cardiac arrhythmias.

- Potent coronary vasodilator. -  H R Disadvantages CVS depression Hypotension ( VR) - Potent coronary vasodilator. -  H R Disadvantages Pungent (not for pediatrics).

Desflurane (Suprane) Pungent odor (irritation - cough) Rapid induction & fast recovery (low blood solubility). Less potent than halothane. Less metabolized (0.05 %). CVS - Hypotension -  VR -  H R

Sevoflurane Less potent than halothane Rapid induction and recovery. Less metabolized (3- 5% fluoride) Better smell No airway irritation (children) CVS - Hypotension -  VR - Little effect on HR

Nitrous Oxide (N2O) The most potent analgesic. Weak anesthetic (low potency, combined). The most rapid induction & recovery due to low blood solubility. No muscle relaxation. No respiratory depression. Not hepatotoxic. Minimal CVS adverse effects.

Adverse Effects Diffusion hypoxia: (respiratory diseases). Nausea and vomiting. Inactivation of B 12  megaloblastic anemia. Chronic use: Bone marrow depression- leukopenia Abortion - Congenital anomalies

Therapeutic Uses Outpatient anesthesia (dental procedures). As a component of balanced anesthesia. Neuroleptanalgesia. Delivery Contraindications 1. Pregnancy. 2. Pernicious anemia. 3. Immunosuppression.

Intravenous Anesthetics 1. Ultra short acting barbiturates. 2. Benzodiazepines. 3. Opioids. 4. Ketamine. 5. Propofol 6. Etomidate. 7. Neuroleptics

Intravenous Anesthetics Rapid induction & recovery except BZs Should be injected slowly. Recovery is due to redistribution from CNS. Can be used alone in short operation. Outpatients anesthesia. NO need for special equipments. Analgesic activity (Opioids & ketamine ). Amnesic action (BZs & ketamine).

Ultra Short acting Barbiturates Thiopental (Pentothal) Methohexital (Brevital) Thiamylal (Surital)

Thiopentone Rapid onset of action 1 min (high lipid solubility) Ultra short duration of action 15 - 20 min Metabolized slowly by the liver.

No skeletal muscle relaxation. CNS:  ICP (Used in head injuries). Pharmacodynamics Potent anesthetic. No analgesic activity No skeletal muscle relaxation. CNS:  ICP (Used in head injuries). CVS: Hypotension & Dysrhythmia. Respiratory depression (dose-dependent).

Uses As anesthetic alone in minor surgery. Induction of anesthesia in major surgery. Adverse Effects Respiratory depression CVS collapse. Extravasations. Precipitation of porphyria attack. Hypersensitivity reaction.

Contraindication 1. Chronic obstructive lung disease. 2. Porphyria. 3. Hypersensitive patients. 4. Severe hypotension (hypovolemic & shock patient).

Benzodiazepines Midazolam (Versed) Diazepam (Valium) Lorazepam (Ativan) The best one is Midazolam Amnesic action. Reduce anxiety. No analgesic activity

Uses 1. Induction of general anesthesia. 2. Alone in minor procedure (endoscopy). 3. Balanced anesthesia (midazolam). 4. Pre-anesthetic medication (diazepam) Side Effects Slow induction & recovery. Respiratory depression.

- Ultra-short acting hypnotic (non barbiturates). Etomidate (Amidate) - Ultra-short acting hypnotic (non barbiturates). - No analgesic activity. Rapid onset of action Short duration of action. - Decreases  ICP. Minimal CVS and respiratory depressant effects. Uses Induction of Anesthesia

Side Effects Involuntary movements during induction (diazepam). Postoperative nausea -vomiting. Adrenal suppression (inhibition of steroidogenesis) Pain at sit of injection. Teratogenic.

Propofol - No analgesia. - Hypnotic (non barbiturates). - No analgesia. Rapid onset – Faster recovery than thiopental. Short duration of action. - Decreases  ICP. Antiemetic action. Uses Induction of anesthesia Maintenance of anesthesia (balanced anesthesia).

Side Effects 1. Hypotension (PVR). 2. Excitation (involuntary movements). 3. Pain at site of injection. 4. Expensive. 5. Clinical infections due to bacterial contamination.

Dissociative anesthesia Analgesia. Amnesia. Immobility. Ketamine Non barbiturate Dissociative anesthesia Analgesia. Amnesia. Immobility. Complete separation from the surrounding environment. Pharmacokinetics - Rapid onset of action (slower than thiopental)

- Short duration of action. - Metabolized in the liver to active metabolite (Norketamine). Pharmacodynamics 1. BP & cardiac output (central sympathetic activity) 2.  Increases plasma catecholamine levels. 3.  ICP 4. Potent bronchodilator (asthmatics).

Advantages Can be given IV, IM (Children). No bronchospasm. Hypovolemic or shock patients. Side Effects Post operative hallucination, vivid dreams & disorientation & illusions (Diazepam). Risk of hypertension & cerebral hemorrhage.  ICP

Contraindications CVS diseases (hypertension-stroke). Head injuries. Uses Minor operations (children, elderly, shock patients . Short duration diagnostic procedures

Opiate Drugs Fentanyl (Sublimaze) Alfentanil (Alfenta) Sufentanil (Sufenta) Fentanyl -Rapid onset - Short duration of action. - Potent analgesia. - No muscle relaxation

Uses Cardiac surgery ( + nitrous oxide). Neuroleptanalgesia (fentanyl + droperidol ). Neuroleptanesthesia (Fentanyl + droperidol+ nitrous oxide). Side Effects Respiratory depression, bronchospasm (wooden rigidity). Hypotension. Nausea & vomiting.

Increase in ICP. Prolongation of labor & fetal distress. Urinary retention. Contraindication 1. Head injuries. 2. Pregnancy. 3. Bronchial asthma. 4. Chronic obstructive lung diseases. 5. Hypovolemic shock (Large dose only).

Neuroleptanalgesia A state of analgesia, sedation, muscle relaxation BUT no loss of consciousness. Innovar (Fentanyl + Droperidol ). Contraindicated in parkinsonism. Diagnostic procedures that require co-operation of the patient. Neuroleptanesthesia : a combination of (Fentanyl + Droperidol + nitrous oxide).

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