Q1 LONG ANSWER 10M ★ High-yield

Classify general anaesthetics. Describe MAC and the factors governing induction, the stages of anaesthesia and the individual agents.

Pharmacology · 2nd Professional — Para-Clinical

Definition and Classification

General anaesthetics produce reversible loss of consciousness, sensation, reflex activity and muscle tone, allowing surgery to be performed.

Group	Drugs	Notes
Inhalational — volatile liquids	Halothane, isoflurane, sevoflurane, desflurane, enflurane	Sevoflurane is non-irritant and pleasant, so it is used for inhalational induction in children
Inhalational — gases	Nitrous oxide, xenon	Nitrous oxide is a good analgesic but a weak anaesthetic
Intravenous — inducing agents	Propofol, thiopentone, etomidate	Rapid and pleasant induction; action terminated by redistribution
Intravenous — dissociative	Ketamine	NMDA receptor antagonist; profound analgesia with preserved airway reflexes
Intravenous — slower acting	Benzodiazepines (midazolam), opioids (fentanyl), dexmedetomidine	Adjuncts and for sedation

Pharmacokinetics of Inhalational Agents

Property	Meaning	Consequence
MAC (minimum alveolar concentration)	The alveolar concentration at which 50% of subjects do not move to a surgical stimulus — the measure of potency	A low MAC means a potent agent. Halothane 0.75%, isoflurane 1.2%, sevoflurane 2%, nitrous oxide 105% — which is why nitrous oxide alone cannot produce anaesthesia at atmospheric pressure
Blood:gas partition coefficient	Solubility in blood — determines speed of induction and recovery	A low coefficient means faster induction, because the blood is saturated quickly and partial pressure in the brain rises rapidly. Nitrous oxide 0.47 and desflurane 0.42 are fastest; halothane 2.3 is slow
Oil:gas partition coefficient	Lipid solubility	Correlates inversely with MAC — the MEYER–overton relationship: the more lipid-soluble, the more potent
MAC is reduced by	—	Old age, hypothermia, pregnancy, opioids, benzodiazepines, alpha2 agonists, hypotension
MAC is increased by	—	Youth, hyperthermia, chronic alcohol use, sympathomimetics

CLINICAL PEARL

Potency and speed are two separate properties, and confusing them is the commonest error here.
MAC tells you how much drug is needed — potency.
Blood solubility tells you how fast it acts. Nitrous oxide is the weakest agent (MAC 105%) and among the fastest (blood:gas 0.47)
halothane is potent and slow. Neither figure predicts the other.

Stages of Anaesthesia (guedel)

Stage	Name	Features
I	Analgesia	From induction to loss of consciousness; analgesia and amnesia are present; reflexes intact
II	Excitement (delirium)	Loss of consciousness to onset of regular breathing; struggling, irregular breathing, dilated pupils, retching and vomiting; the dangerous stage, which is passed through as quickly as possible — hence rapid intravenous induction
III	Surgical anaesthesia	Regular breathing to cessation of spontaneous respiration; divided into four planes of increasing depth, with progressive loss of reflexes, pupillary dilatation and intercostal paralysis; plane 2–3 is used for surgery
IV	Medullary paralysis	Respiratory arrest to circulatory collapse and death; must never be reached

These classical stages are seen only with slow inhalational induction using ether, and are rarely observable in modern practice where intravenous induction passes through stages I and II within seconds — but they remain the framework for understanding depth

Individual Agents

Agent	Advantages	Disadvantages
Propofol	Smooth rapid induction and clear-headed recovery; antiemetic; suitable for day-care surgery and for infusion (total intravenous anaesthesia)	Pain ON injection; marked hypotension and apnoea; no analgesia; propofol infusion syndrome with prolonged high-dose use
Thiopentone	Very rapid onset; anticonvulsant; reduces intracranial pressure	Action terminated by redistribution, so repeated doses cumulate; no analgesia; laryngospasm; tissue necrosis if extravasated; contraindicated in porphyria
Ketamine	Profound analgesia; preserves airway reflexes and respiration; bronchodilates; raises blood pressure, so useful in shock, asthma and in field conditions	Emergence delirium with vivid hallucinations (reduced by a benzodiazepine); raises intracranial and intraocular pressure; increased secretions
Etomidate	Cardiovascular stability — the agent of choice in the haemodynamically unstable	Adrenal suppression even after a single dose; myoclonus; pain on injection
Halothane	Potent, non-irritant, cheap; bronchodilator	Halothane hepatitis (rare but often fatal, more likely on repeated exposure); sensitises the myocardium to catecholamines, causing arrhythmia; malignant hyperthermia; no analgesia
Isoflurane, sevoflurane	Less arrhythmogenic and less hepatotoxic; sevoflurane is non-irritant and is used for inhalational induction in children	Isoflurane is pungent; sevoflurane forms compound A with soda lime; both trigger malignant hyperthermia
Nitrous oxide	Excellent analgesia; rapid onset and offset; no cardiovascular depression	Weak anaesthetic; diffusion hypoxia on discontinuation; expands air-filled cavities (pneumothorax, bowel obstruction, middle ear); with prolonged exposure inactivates methionine synthase causing megaloblastic anaemia and neuropathy

Preanaesthetic Medication and Adjuncts

Purposes — relieve anxiety, provide amnesia and analgesia, reduce secretions, prevent vagal reflexes, reduce gastric acid and volume, and reduce the dose of anaesthetic needed
Anxiolytic and amnesic — midazolam, lorazepam
Antisialagogue and vagolytic — glycopyrrolate (preferred, as it does not cross into the CNS) or atropine
Analgesic — fentanyl, morphine
Antiemetic — ondansetron, dexamethasone, metoclopramide
Aspiration prophylaxis — ranitidine or a proton pump inhibitor, and sodium citrate; important in obstetric and emergency anaesthesia
Muscle relaxants — succinylcholine for intubation; a non-depolarising agent for maintenance

Balanced Anaesthesia

No single agent provides everything safely — a dose of one drug large enough to give unconsciousness, analgesia and relaxation together would be dangerously close to medullary depression
Balanced anaesthesia uses separate drugs for separate components — an induction agent for unconsciousness, an opioid for analgesia, a muscle relaxant for relaxation, and a volatile agent or infusion for maintenance
Each drug is then used at a low dose, so its own adverse effects are minimised while the desired effects add up — the same principle as combination antihypertensive therapy
Total intravenous anaesthesia (TIVA) uses a propofol infusion with an opioid, avoiding volatile agents altogether; it reduces nausea and is used where malignant hyperthermia is a risk
Monitoring is what makes it safe — pulse oximetry, capnography, ECG, blood pressure and temperature as a minimum; capnography confirms tracheal placement and is the single most valuable monitor

Applied Aspects

Malignant hyperthermia — triggered by volatile agents and succinylcholine in genetically susceptible people (ryanodine receptor); masseter spasm, rigidity, a rapidly rising temperature, acidosis and rhabdomyolysis. Treated with dantrolene, cooling and supportive care; dantrolene must be stocked wherever these agents are used
Avoid nitrous oxide where a closed air space exists — pneumothorax, bowel obstruction, middle ear surgery, air embolism — since it diffuses in faster than nitrogen diffuses out and expands the space
Give 100% oxygen for several minutes after stopping nitrous oxide to prevent diffusion hypoxia, as the gas floods out of the blood and dilutes alveolar oxygen
Ketamine is invaluable where monitoring and oxygen are limited — in disaster and field settings, and in India in peripheral hospitals — because it maintains blood pressure and respiration
Etomidate for a single induction in the shocked patient, accepting the adrenal suppression; it should not be used as an infusion
Awareness under anaesthesia is a devastating complication when a muscle relaxant is given without adequate anaesthesia; depth monitoring and careful technique prevent it
Thiopentone must never be given intra-arterially — intense vasospasm and gangrene follow; the pain of injection is the warning sign
Propofol supports bacterial growth, so ampoules are used immediately and never shared between patients; outbreaks of infection have been traced to reuse
Avoid halothane in repeated exposures within 3 months, and in anyone with unexplained jaundice after a previous anaesthetic
Ketamine raises intracranial pressure and is avoided in head injury and in uncontrolled hypertension, though this is now considered less absolute than formerly
Preoxygenation before induction gives several minutes of safe apnoea time, and is the single most valuable manoeuvre in a difficult airway

All questions in Central Nervous System Drugs

Every Pharmacology chapter →