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Drugs Related to General Anaesthesia (GA)

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1. INDUCTION AGENTS

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Propofol (2,6-diisopropylphenol)

• Mechanism: Potentiates GABA-A receptor (increases Cl⁻ influx) - produces dose-dependent CNS depression
• Dose: 1.5-2.5 mg/kg IV (reduced in elderly, premedicated, or ASA III-IV patients)
• Onset: ~30-40 seconds; Duration: 5-10 min (due to rapid redistribution)
• Advantages: Fastest recovery, antiemetic properties, smooth emergence, can be used for TIVA (total IV anaesthesia)
• Disadvantages: Pain on injection, hypotension (vasodilation + negative inotropy), no analgesia, apnoea at induction doses
• Formulation: 1% emulsion in soybean oil/egg lecithin - avoid in egg/soy allergy (though the allergy risk is debated)
• Currently the most popular induction agent worldwide - Morgan & Mikhail, p. 26

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Thiopental (Thiopentone)

• Class: Oxybarbiturate
• Mechanism: Barbiturate - binds GABA-A receptor (increases duration of Cl⁻ channel opening)
• Dose: 3-5 mg/kg IV
• Onset: One arm-brain circulation (~30 sec); Duration: 5-10 min (redistribution)
• Advantages: Rapid, reliable, decreases ICP and CMRO₂, anticonvulsant
• Disadvantages: Cardiovascular depression, bronchospasm, no analgesia, contraindicated in porphyria, long context-sensitive half-life (so NOT suitable for infusion)
• Note: Largely replaced by propofol in most countries but still used where propofol unavailable

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Methohexital

• Class: Methylated oxybarbiturate
• Dose: 1-1.5 mg/kg IV
• Notably popular for ECT (electroconvulsive therapy) due to its ability to lower the seizure threshold
• Faster recovery than thiopental

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Etomidate

• Class: Imidazole derivative (carboxylated imidazole)
• Mechanism: GABA-A potentiation (like barbiturates/propofol)
• Dose: 0.3 mg/kg IV
• Onset: ~30 sec; Duration: 5-15 min
• Key advantage: Minimal hemodynamic effects - agent of choice for hemodynamically unstable patients, elevated ICP (lowers ICP/CBF/CMRO₂ without dropping MAP), septic shock
• Disadvantages:
  • Adrenal suppression - irreversibly inhibits 11β-hydroxylase; even a single dose transiently suppresses cortisol synthesis
  • Myoclonus on induction (no clinical significance during RSI)
  • Pain on injection
  • No analgesia
• Used in up to 90% of ED intubations - Rosen's EM, p. 35

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Ketamine

• Class: Phencyclidine derivative (dissociative anaesthetic)
• Mechanism: NMDA receptor antagonist; also has opioid, muscarinic, and sigma receptor activity
• Dose: 1-2 mg/kg IV (or 4-6 mg/kg IM)
• Onset: IV ~30 sec, IM ~3-4 min; Duration: 10-15 min
• Produces "dissociative" state: eyes may remain open, protective airway reflexes usually preserved, ventilatory drive maintained
• Hemodynamic effects: Sympathomimetic - increases HR, BP, CO (due to catecholamine release) - good for hypovolemic/trauma patients
• Bronchodilatory: Agent of choice for RSI in status asthmaticus
• Disadvantages: Emergence phenomena/hallucinations (minimized by co-administering midazolam), increases ICP and IOP, increases secretions (pretreat with atropine/glycopyrrolate), can cause laryngospasm
• Caution in severely depleted catecholamine states - direct myocardial depressant may be unmasked

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Benzodiazepines as Induction Agents

• Midazolam: 0.1-0.2 mg/kg IV - water-soluble at acid pH; short-acting (30-90 min); used for premedication, co-induction with propofol/ketamine, sedation
• Diazepam / Lorazepam: Longer acting; more for premedication and sedation than primary induction

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2. MUSCLE RELAXANTS (Neuromuscular Blocking Agents - NMBAs)

A. Depolarizing NMBAs

Succinylcholine (Suxamethonium)

• Mechanism: Structural analogue of two ACh molecules - binds NMJ nicotinic receptors causing sustained depolarization (Phase I block) → fasciculations followed by flaccid paralysis; resistant to AChE
• Metabolism: Rapidly hydrolyzed by plasma pseudocholinesterase to succinylmonocholine → succinic acid + choline
• Dose: 1.5 mg/kg IV (based on total body weight regardless of obesity)
• Onset: ~45 seconds; Duration: 6-10 min (spontaneous respiration), full recovery ~15 min
• Drug of choice for RSI due to rapid onset + short duration
• Side effects:
  • Bradycardia (especially with repeat dosing in children) - due to muscarinic stimulation
  • Hyperkalemia (K⁺ rises ~0.5 mEq/L normally; can be LETHAL in burns, denervation injuries, crush injuries, prolonged immobility - avoid after 24 hours post-burn/denervation)
  • Raised ICP, IOP, intragastric pressure
  • Malignant hyperthermia (MH) trigger - ABSOLUTE CONTRAINDICATION in MH-susceptible patients
  • Prolonged block with pseudocholinesterase deficiency (genetic or acquired)
  • Muscle pain/myalgia post-op (from fasciculations)
• Contraindicated in: MH, hyperkalaemia risk states, myopathies, neuromuscular disorders, pseudocholinesterase deficiency

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B. Non-Depolarizing NMBAs

Short-Acting

• Mivacurium: Hydrolyzed by pseudocholinesterase; duration ~15-20 min; only short-acting non-depolarizer

Intermediate-Acting

• Rocuronium: Dose 0.6 mg/kg (standard), 1.2 mg/kg (RSI dose - gives intubating conditions in ~60 sec, rivaling succinylcholine); reversed by sugammadex; safe in MH-susceptible patients; increasing use replacing succinylcholine
• Vecuronium: Dose 0.1 mg/kg; minimal cardiovascular effects; hepatic elimination
• Atracurium: Undergoes Hofmann elimination + ester hydrolysis (independent of liver/kidney) → safe in organ failure; metabolite laudanosine (CNS excitation in high doses); causes histamine release
• Cisatracurium: More potent isomer of atracurium; Hofmann elimination; minimal histamine release; preferred in organ failure

Long-Acting

• Pancuronium: Dose 0.1 mg/kg; vagolytic → tachycardia and hypertension; cheap; used for prolonged intubation in ICU

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3. ANALGESICS IN GA

Opioids (Intraoperative Analgesia)

NSAIDs / Adjunct Analgesics

• Ketorolac, Diclofenac, Parecoxib (COX-2): IV/IM peri-operative pain, opioid-sparing
• Paracetamol (IV): Regular schedule, safe, opioid-sparing
• Dexmedetomidine: Alpha-2 agonist; analgesic + sedative + anxiolytic; loading dose 1 mcg/kg over 10 min; minimal respiratory depression; causes bradycardia and hypotension; used for awake fiberoptic intubation and procedural sedation
• Ketamine (sub-anesthetic): 0.1-0.5 mg/kg IV bolus or infusion for opioid-sparing analgesia, especially for opioid-tolerant patients

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4. SEDATIVES / PREMEDICANTS

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5. VOLATILE (INHALATION) MAINTENANCE AGENTS

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6. REVERSAL AGENTS

A. Reversal of Non-Depolarizing NMBAs

Acetylcholinesterase Inhibitors (traditional)

Sugammadex (Bridion)

• Class: Modified gamma-cyclodextrin - forms tight 1:1 encapsulation complex with rocuronium/vecuronium (NOT succinylcholine or benzylisoquinolines)
• Mechanism: Encapsulates the steroid NMBA molecule directly, removing it from circulation - reversal is NOT dependent on AChE inhibition
• Doses:
  • Routine reversal (TOF count ≥2): 2 mg/kg
  • Deep block (post-tetanic count 1-2): 4 mg/kg
  • Immediate reversal (e.g., can't intubate, can't oxygenate after rocuronium): 16 mg/kg
• Advantages: Reverses deep block rapidly; no need for anticholinergic co-administration; safer, faster, more complete than neostigmine
• Can reverse succinylcholine? No - it is selective for aminosteroid compounds only

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B. Reversal of Opioids

Naloxone

• Mechanism: Competitive antagonist at all opioid receptors (μ, κ, δ)
• Dose: 0.04-0.4 mg IV (titrate in 0.04 mg increments to avoid acute withdrawal/pain/pulmonary edema)
• Duration: 30-45 min (shorter than most opioids - may need repeat dosing or infusion)
• Reverses: Respiratory depression, sedation, analgesia (caution - reversal of analgesia causes acute pain)

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C. Reversal of Benzodiazepines

Flumazenil

• Mechanism: Competitive antagonist at GABA-A benzodiazepine receptor
• Dose: 0.2 mg IV q1min to max 1 mg
• Duration: 45-90 min (shorter than most benzodiazepines - resedation possible)
• Caution: Can precipitate seizures in chronic benzodiazepine users; lowers seizure threshold

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Summary Table

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• Propofol is the most widely used induction agent but causes hypotension - use etomidate in hemodynamic instability
• Rocuronium at 1.2 mg/kg provides near-equivalent RSI conditions to succinylcholine and is reversible with sugammadex 16 mg/kg
• Succinylcholine remains gold standard for RSI but is contraindicated in MH, burns >24h, denervation injuries
• Sugammadex has largely replaced neostigmine in modern practice for aminosteroid NMBA reversal
• Ketamine is unique: it provides analgesia + amnesia + bronchodilation + hemodynamic stability - ideal for trauma/asthma RSI

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GA Drugs — With Mnemonics, Tricks & Medical Dictionary

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📖 MEDICAL DICTIONARY (Hard Terms Explained Simply)

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🧠 MNEMONICS & MEMORY TRICKS

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INDUCTION AGENTS — "PEKMT" or "KEEP"

"KEEP the Patient Educated and Medicated Thoroughly"

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PROPOFOL — "The Milk of Amnesia"

• White emulsion = looks like milk ✓
• Causes amnesia ✓
• "Goes in white, comes out clean" - fast metabolism, no hangover
• PROPOFOL side effects: "PAIN DROPS BP"
  • Pain on injection
  • Apnoea
  • Injection site reactions
  • Nausea (actually antiemetic - opposite! Remember: propofol is the ANTI-nausea agent)
  • Drop in BP (hypotension)
  • Rapid redistribution (short acting)
  • Oil-based (avoid in egg/soy allergy)
  • Pleasant recovery
  • Seizure-like movements (rare)
  • BP drops

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KETAMINE — "DREAM"

"K for Kick — kicks everything UP" (except bronchospasm, which it kicks DOWN)

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ETOMIDATE — "ETOMIDATE = Excellent To use, Only Minor Issues, DO Adrenals Tend to Err"

"Eto-mi-DATE keeps you stable on a DATE" - Hemodynamically stable = best for sick patients

• Myoclonus
• Adrenal suppression (11β-hydroxylase inhibition)
• Cortisol suppression
• Emesis (nausea/vomiting)

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THIOPENTAL — "THIO HATES PORPHYRIA"

• Thio = sulfur-containing barbiturate
• Contraindications: "THIO BAD IN"
  • Porphyria (absolute contraindication)
  • Asthma (bronchospasm)
  • Do not infuse (huge context-sensitive half-life)

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MUSCLE RELAXANTS — DEPOLARIZING vs NON-DEPOLARIZING

"DEP = Does Excite Partly" (Depolarizing = fasciculations first) "NON-DEP = No Excitation, Direct block"

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SUCCINYLCHOLINE — "SUCKS for these patients"

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NON-DEPOLARIZING NMBAs — Duration Memory Trick

"Short Mivacurium, IntermediateAVAR, Long Pancuronium"

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ROCURONIUM vs SUCCINYLCHOLINE for RSI

"ROCO at HIGH dose (1.2 mg/kg) = SUCC equivalent — but ROCO is reversible with SUGAR (Sugammadex)"

• Succ = 1.5 mg/kg | Roco RSI = 1.2 mg/kg
• "Sugar fixes Rock" = Sugammadex reverses Rocuronium

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ATRACURIUM memory trick — "ATRA-HOFMANN"

"ATRAcurium is broken by HOFMANN — no liver, no kidney needed"

• Safe in hepatic AND renal failure
• Metabolite: Laudanosine (remember: "Lauda = Loud = Excites the brain")

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OPIOIDS — Potency Ladder (weakest to strongest)

"Codeine → Morphine → Fentanyl → Sufentanil → Remifentanil (ultra-short)"

• Codeine = 0.1x
• Morphine = 1x (reference)
• Fentanyl = 100x → "F for Fierce"
• Sufentanil = 500-1000x → "S for Superior"
• Remifentanil = ~200x but ultra-short (ester hydrolysis)

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REMIFENTANIL — "REMI = Rapidly Eliminated by Multiple Esterases Instantly"

• Metabolized by non-specific plasma AND tissue esterases (NOT pseudocholinesterase, NOT liver)
• Duration: ~5 min regardless of infusion length (zero context-sensitive half-life)
• Risk: POST-OP HYPERALGESIA after prolonged infusion = "Remi leaves pain behind"

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REVERSAL AGENTS — "NSF"

"Need Sugar For Narcotics" = Neostigmine / Sugammadex / Flumazenil / Naloxone

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SUGAMMADEX — "SUGAR CAGES ROCK"

• Sugar-based molecule (cyclodextrin = cyclic sugar)
• Cages rocuronium/vecuronium in a tight complex
• Rock = Rocuronium (its primary target)
• Dose trick: "2-4-16"
  • 2 mg/kg = routine (TOF ≥2)
  • 4 mg/kg = deep block (PTC 1-2)
  • 16 mg/kg = IMMEDIATE emergency reversal

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NEOSTIGMINE — "NEO NEEDS A FRIEND"

• Neostigmine increases ACh everywhere (including heart - bradycardia, gut - secretions, bronchi - spasm)
• So it ALWAYS needs a friend: Glycopyrrolate (or atropine)
• "NEO always brings GLYCO to the party"
• Dose ratio: 0.2 mg glycopyrrolate per 1 mg neostigmine

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NALOXONE — "NAL reverses ALL opioids" but be CAREFUL:

"Naloxone reverses pain WITH the respiratory depression"

• Titrate slowly (0.04 mg increments) or you'll cause: acute pain + hypertension + pulmonary edema
• Duration 30-45 min = SHORTER than most opioids → "Watch for re-narcotization"

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FLUMAZENIL — "FLU-mazenil FLUshed out benzos"

• Short duration (45-90 min) → "Re-sedation possible"
• Risk: Seizures in chronic benzo users → "Don't FLU someone who relies on their benzo"

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🎯 QUICK CLINICAL DECISION TRICKS

"Which induction agent for which patient?"

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"Which NMBA for which situation?"

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The "Balanced Anaesthesia Triangle"

         HYPNOSIS
        (Propofol/
         Volatile)
            /\
           /  \
          /    \
ANALGESIA ------PARALYSIS
(Fentanyl)   (Rocuronium/
              Vecuronium)

"3 legs of the stool — remove one leg and the stool falls" If you only give one component, you need massive doses with massive side effects. Balanced = lower doses of each + better safety profile.

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📌 RAPID FIRE ASSOCIATIONS

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⚡ ONE-LINE SUMMARIES FOR EXAM

1. Propofol - white emulsion, fast, antiemetic, hypotension, most popular worldwide
2. Ketamine - dissociative, bronchodilator, raises BP, preserves reflexes, increases ICP
3. Etomidate - hemodynamically stable, adrenal suppression, myoclonus
4. Thiopental - fast barbiturate, contraindicated in porphyria, not for infusion
5. Succinylcholine - fastest RSI drug, contraindicated in burns/denervation/MH/hyperK
6. Rocuronium - intermediate, RSI at 1.2 mg/kg, reversed by sugammadex
7. Atracurium/Cisatracurium - Hofmann elimination, safe in organ failure
8. Pancuronium - long-acting, vagolytic tachycardia
9. Fentanyl - 100x morphine, standard intraop opioid
10. Remifentanil - ultra-short, ester hydrolysis, TIVA, post-op hyperalgesia
11. Sugammadex - encapsulates aminosteroid NMBAs, 2/4/16 mg/kg dosing
12. Neostigmine - AChE inhibitor, always give with glycopyrrolate
13. Naloxone - reverses opioids, short-acting, titrate slowly
14. Flumazenil - reverses benzos, re-sedation risk, seizure risk in dependent patients