general anaesthesia in pharmacology dental, Summaries of Pharmacology

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General anaesthetics (GAs) are drugs which

produce reversible loss of all sensation and

consciousness.

The cardinal features of general anaesthesia are:

• Loss of all sensation, especially pain

• Sleep (unconsciousness) and amnesia

• Immobility and muscle relaxation

• Abolition of somatic and autonomic reflexes

MECHANISM OF ACTION OF GAs

1. Potentiation of inhibitory GABA action to open Cl

channel (Barbiturates, BZD, Propofol)

2. Potentiation of inhibitory glycine action to open Cl

channel in spinal cord and medulla (Barbiturates, Propofol)

3. Direct activation of Cl

   channel (Barbiturates) 

4. Inhibition of neuronal cation channel gated by N N receptor which mediate analgesia, amnesia
5. Inhibition of excitatory NMDA type glutamate receptor (gates Ca 2+ ion) (ketamine, N 2 O)

PROPERTIES OF AN IDEAL ANAESTHETIC

A. For the patient: It should be pleasant, nonirritating,

should not cause nausea or vomiting. Induction and

recovery should be fast with no after effects.

B. For the surgeon: It should provide adequate

analgesia, immobility and muscle relaxation. It

should be non-inflammable and non-explosive so

that cautery may be used.

C. For the anaesthetist: Its administration should be

easy, controllable and versatile.

Intravenous Fast acting drugs Slower acting drugs Thiopentone sod. Benzodiazepines Methohexitone sod. Diazepam Propofol Lorazepam Etomidate Midazolam Dissociative anaesthesia Ketamine Opioid analgesia Fentanyl

NITROUS OXIDE (N 2 O)

• Colourless, odourless, heavier than air
• Unconsciousness cannot be produced without concommitant hypoxia as MAC is 105 %
• Patient may recall the events during anaesthesia
• Good analgesic- 20 % is equivalent to morphine
• Used as carrier with other anesthetics – concentration of other anesthetic reduced to 1 / 3. Second gas effect. Advantages:
• Non-inflammable, non-irritating
• Rapid induction and rapid recovery
• Analgesia in sub anesthetic concentration

USES:

• N

2

O ( 50 %) + O

2 ( 50 %) used for tooth extraction, obstetric analgesia, painful dressing in burns patient

• Measurement of coronary / cerebral blood flow by Fick’s principle

DIETHYL ETHER

• Colourless, volatile liquid with a pungent odour
• Produces irritating vapours – inflammable, explosive
• Mixture of ether with air / nitrous oxide / O 2 may explode
• On skin – Vasodilatation, warmth, pain – Rubefacient Advantages:
• Wide margin of safety
• Can be used without pre-anesthetic medication
• Excellent analgesic + Potent anesthetic
• Good muscle relaxant – curarimimetic
• Reflex resp. stimulation, bronchodilation due to irritation
• No/little arrhythmias, hepatotoxicity, nephrotoxicity

HALOTHANE

• Fluorinated volatile anesthetic liquid-heavy, colourless
• Non-irritating, Non-inflammatory, Sweet-fruity odour
• Structurally similar to chloroform Advantages:
• Non-irritating, Non-inflammatory to respiratory tract
• Potent GA - Pleasant and speedy induction and recovery
• Inhibits pharyngeal and laryngeal reflex – tracheal intubation becomes easy
• No bronchospasm/laryngospasm, cause bronchodilation
• Inhibits intestinal & uterine contraction – useful in assisting external or internal version

Disadvantages:

• Poor analgesic
• Inadequate muscle relaxation for abdominal surgery
• Directly depress myocardial contractiliy by Ca 2 + conc
• Cardiac output decreases, BP falls, HR falls by vagal +
• Increased intracranial tension due to vasodilatation
• Respiration is depressed
• Urine formation decreased – due to GFR by fall in BP
• Malignant hyperthermia – abnormal RYR

Disadvantages:

• Poor analgesic
• Poor muscle relaxant
• Difficult to assess depth of anesthesia
• Pharyngeal, laryngeal reflexes persist – cough, apnoea, laryngospasm, bronchospasm occur
• Severe depression of respiratory centres
• Depresses myocardium, VMC – CV collapse
• Relaxes gastrointestinal sphincter – silent regurgitation

KETAMINE (DISSOCIATIVE ANESTHESIA)

• Profound analgesia, a feeling of dissociation from surrounding, immobility, amnesia with light sleep
• Primary site of action: Cortex & subcortical areas
• MOA: Non-competitive blocker of neuronal post synaptic NMDA receptor Advantages:
• Rapid, induction and recovery
• Only IV GA with potent analgesia and CVS stimulation – increases BP, HR, CO
• Potent bronchodilatation
• No cardiovascular or respiratory depression

PRE-ANESTHETIC MEDICATION:

Drugs used before anesthesia to make it more pleasant and safe

1. Relief of anxiety and apprehension – antianxiety drugs
2. Amnesia of pre- and post-op events – sedative hypnotic
3. Supplement analgesic action of anesthetics – opioids
4. Decrease secretion, vagal stimulation – anticholinergics
5. Reduce postoperative vomiting – antiemetics
6. Decrease acidity & gastric juice to decrease aspiration - H 2 blockers or PPIs
7. Antibiotic prophylaxis
8. Neuromuscular blockers to attain muscle relaxation (^19)