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Collections of knowledge containing reference notes.

  • Methohexitone

     

    A barbiturate derivative (Brevital™, Brietal™) intravenous anaesthetic agent, no longer available in Australia although still used in other parts of the world.

    Preferred for use in electroconvulsive therapy for its pro-seizure effects and comparatively short duration.

    Compared to thiopentone

    • Oxybarbiturate
    • Made up in 50 mL to 1% solution
    • 3x more potent
    • 3x clearance (12 mL/kg/min)
    • tß½ 3 h (STP 8h)
    • Greater ionised proportion
    • Less protein binding (65%)
    • More rapid recovery: 2-3 min (smaller fat compartment, no active metabolites, ⇡ clearance)
    • Higher incidence of pain on injection
    • Pro-convulsant/epileptiform EEG (excitatory in 30%)
    • PONV (30%)
    • Less dec MAP, more inc HR than STP
    • More pronounced resp depression
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  • Etomidate

     

    Etomidate (Amidate™) is short-acting intravenous anesthetic agent first developed in 1964. It is available and used in the United Kingdom, Europe, New Zealand, United States, but not Australia.

    Advocates highlight etomidate's hemodynamic stability when used for induction. Critics point to the well-established adrenocortical suppression, and wide-range of suitable alternatives (propofol, ketamine, thiopentone) in trained hands.

    A. Physiochemistry

    • Carboxylated imidazole
    • 2 isomers - only R(+) hypnotic
    • Haemodynamic stability, minimal respiratory depression, cerebral protection, wide margin of safety.
    • Originally formulated in propylene glycol (painful), now in soybean lipid.

    B. Pharmacokinetics

    1. Dose - 0.3 mg/kg (0.1-0.4 mg/kg)
    2. Absorption - IV
    3. Distribution - 4 L/kg
    4. Protein binding - 75% (like thiopentone)
    5. Onset 30-60s ; Offset
    6. Metabolism - alpha1 ½ 2.5m, alpha2 ½ 30m, tß½ 3.5h; hepatic ester hydrolysis of ester side chain.
    7. Clearance - 20 mL/kg/min

    C. Pharmacodynamics

    1. Mech - probably by GABAa receptors.
    2. CNS - hypnosis; no analgesic action; ⇣ CBF and CMRO2
    3. CVS - stable; may have slight dec MAP 15% due to ⇣ SVR.
    4. Resp - minimal; sometimes brief hypoventilation or apnoea post-induction.
    5. Endo - adrenocortical suppression - inhibits 11ß-hydroxylase (11-deoxycortisol → cortisol). Temporary & reversed by vit C.
      • ⇡ ICU mortality when used for sedation.
    6. SEs - excitatory phenom, involuntary muscle movement (50%), PONV (30%), thrombophlebitis (20%), pain on injection.
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  • Pethidine/Meperidine

     

    Pethidine (Meperidine) is a phenylpiperidine synthetic opioid first synthesized in 1938. Although widely used in the 20th century, it has fallen out of favour over the past decade due to abuse potential, limited advantages over other opioids and the existence of toxic metabolites.

    A. Physiochemistry

    • pKa - 8.5 (9% nonionised @ 7.4)
    • Octanol water coefficient - 39 (so 40x lipid solubility of morphine)
    • phenylpiperidine opioid

    B. Pharmacokinetics

    1. Dose - 25-100 mg (10% morphine potency). Limit 1000 mg 1st day, then 600 mg/day there after.
    2. Absorption - IV, IM, epidural, po (55% biov)
    3. Distribution - Vdss 4.5 L/kg. Crosses placenta - foetal 80% of maternal.
    4. Protein binding - 60%
    5. Onset 10 min ; Offset 2-3 h
    6. Metabolism - ß½ 3 h; N-demethylation to norpethidine and then hydrolysis to norpethidinic acid; also direct hydrolysis to pethidinic acid. Renal elimination.
      • Norpethidine - ß½ 15 h; 50% analgesic properties, 2x convulsant effects.
    7. Clearance - 20 mL/kg/min (same as morph & fentanyl)

    C. Pharmacodynamics

    1. Mech - mu and kappa agonist, causing potent spinal and supraspinal analgesia.
    2. CNS - more euphoria, less N/V than morphine. No miosis, but may cause mydriasis (pupil dilation -atropine-like kappa action). No EEG changes like morphine. ⇡ latency & amplitude of SSEPs.
      • NB: has LA action, so can be used as sole agent for neuroaxial block.
      • anti-shivering effect (kappa)
    3. CVS - ⇣ MAP (> than morphine) due to histamine release & alpha adrenergic blockade (vasodilation). Inc HR (atropine like effect). Large doses depress myocardial contractility. May cause hypertensive crisis in those on MAOIs.
      • vasodilation
      • tachycardia
      • depress myocardial contractility
    4. Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.
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  • Suxamethonium

     

    Suxamethonium chloride (suxamethonium, succinylcholine or sux) is a depolarising muscle relaxant that produces rapid-onset, short-duration, deep muscle relaxation. First identified in 1906 and used medically in 1951, it is one of the oldest anaesthesia drugs still widely used. Due to its unique properties and low cost, it remains on the World Health Organisation's List of Essential Medicines

    A. Physiochemistry

    • (CH3)3-N-CH2CH2-OCO-CH2CH2-OCO-CH2CH2-N-(CH3)3
    • pH 3.5
    • Shelf life 3 years at 4°C, though only 'months' at 20°C.

    B. Pharmacokinetics

    1. Dose - ED95 0.5 mg/kg, IV 1.5 mg/kg, IM 2.5-4 mg/kg.
    2. Absorption - IM, IV.
    3. Distribution - >0.2 L/kg; crosses placenta slightly but little effect on foetus.
    4. Protein binding ?
    5. Onset 30s IV, 2-3 min IM; Offset 3-5 min.
    6. Metabolism - PChE to succinylmonocholine (5% activity) & choline -> succinic acid & choline.
      • tß½ 5 minutes

    C. Pharmacodynamics

    1. Mechanism - binds to alpha subunit of nicotinic ACh receptor, producing persistent depolarisation (phase 1 & phase 2 blocks).
    2. CNS - ⇡ intra-ocular pressure (4-8 mmHg rise), ⇡ intra-celebral pressure (to 30 mmHg at 2-4 min).
    3. CVS - arrhythmias (both bradycardia & tachycardia possible), ⇡ systolic blood pressure, (both negative inotropic and chronotropic effects).
    4. Resp - 'sux apnoea' pharmacogenetic diversity (94% normal, 3.8% heterozyg (10 min duration of effect), <1% homozog (1-2h duration))
    5. Renal - hyperkalaemia due to K+ release from muscle; beware in neuromuscular conditions, denervation, and extensive burns.
    6. GIT - ⇡ intragastric pressure, ⇡ secretions, salivation.
    7. SEs - anaphylaxis, malignant hyperthermia, sux apnoea, muscle pains, masseter spasm.
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  • Attention deficit and hyperactivity disorder

    Collection
     

    Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterised by inattention, hyperactivity, and impulsivity. It is most commonly diagnosed in childhood, with a male predominance (approximately 2-3:1), though symptoms often persist into adulthood. Global prevalence is estimated at ~5-7% in children and ~2-3% in adults. Meta-analyses show ADHD is primarily genetic with 70–80% heritability.

    Anesthesia issues

    1. Medication considerations
      • Stimulants (methylphenidate, amphetamines)
        • May increase sympathetic tone (tachycardia, hypertension, arrhythmias)
        • Possible attenuation of response to indirect-acting vasopressors (e.g. ephedrine, metaraminol); prefer direct-acting agents (phenylephrine, epinephrine)
        • Withdrawal or omission perioperatively may cause fatigue, irritability, behavioural instability.
        • Possible altered anaesthetic requirements; stimulants may increase MAC slightly, though evidence is inconsistent.
      • Non-stimulants (atomoxetine, guanfacine, clonidine) - α2-agonists (guanfacine, clonidine) can potentiate sedation and hypotension.
    2. Behavioural and perioperative management
      • Difficulty with preoperative cooperation and anxiolysis (may need structured preparation, early anxiolytic use, or parental presence in paediatrics); Increased anxiety or agitation in unfamiliar environments.
      • Impulsivity may increase risk of perioperative non-adherence (e.g. fasting rules, device removal).
      • Higher risk of emergence agitation or delirium, especially in children.
      • May display increased postoperative anxiety, irritability, or oppositional behaviour
      • Pain perception and reporting may be inconsistent, complicating assessment and analgesia planning.
    3. Comorbidities
      • High association with anxiety, depression, and substance use disorders (impact on anaesthetic planning and perioperative risk)
      • Sleep disturbances common, may complicate recovery and pain management
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