Fellowship of the Royal College of Anaesthetists (FRCA) Pharmacology Flashcards

24 sample cards from the Pharmacology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. State the leading molecular hypothesis for the mechanism of general anaesthesia.

   Most IV and volatile agents enhance inhibitory neurotransmission by potentiating $GABA_A$ receptor chloride currents (and glycine receptors), while some (ketamine, nitrous oxide, xenon) antagonise excitatory NMDA receptors. Two-pore $K^+$ channels are also implicated.

2. What is target-controlled infusion (TCI) and name two propofol models.

   TCI is a computer-controlled infusion that uses a pharmacokinetic model to achieve and maintain a user-set target plasma or effect-site concentration. Common propofol models: Marsh (weight-based) and Schnider (incorporates age, height, lean body mass).

3. Distinguish plasma-site versus effect-site targeting in TCI.

   Plasma (Cp) targeting aims for a set plasma concentration and reaches the effect site more slowly. Effect-site (Ce) targeting overshoots plasma concentration to drive the effect-site to target faster, giving more rapid onset of clinical effect but a larger initial bolus.

4. Compare midazolam and diazepam pharmacokinetics.

   Midazolam is water-soluble in its formulation but lipophilic at physiological pH (ring closure), with short half-life (~2–4 h) and active metabolite 1-hydroxymidazolam. Diazepam is long-acting (half-life 20–100 h) with active metabolites desmethyldiazepam, oxazepam and temazepam, causing prolonged sedation.

5. How do benzodiazepines act at the $GABA_A$ receptor and what is the antidote?

   Benzodiazepines bind a specific site on the $GABA_A$ receptor and increase the frequency of chloride channel opening (potentiating GABA). The specific competitive antagonist is flumazenil, given in $0.2\ \text{mg}$ increments.

6. Classify opioid receptors and the main effects of the $\mu$ receptor.

   Opioid receptors: $\mu$ (MOP), $\kappa$ (KOP), $\delta$ (DOP) and the nociceptin/orphanin (NOP) receptor — all G-protein coupled. $\mu$ activation gives analgesia, respiratory depression, euphoria, miosis, bradycardia, reduced gut motility and physical dependence.

7. Why must morphine be used cautiously in renal failure?

   Morphine is metabolised by glucuronidation to morphine-3-glucuronide (inactive/neuroexcitatory) and morphine-6-glucuronide (M6G), an active analgesic and respiratory depressant cleared renally. In renal impairment M6G accumulates, causing prolonged sedation and respiratory depression.

8. Describe the mechanism of action of NSAIDs.

   NSAIDs inhibit cyclo-oxygenase (COX-1 and COX-2), reducing conversion of arachidonic acid to prostaglandins, prostacyclin and thromboxane. This gives analgesia, anti-inflammatory and antipyretic effects. COX-1 inhibition underlies gastric and renal/platelet side effects.

9. List the main contraindications/cautions for perioperative NSAIDs.

   Renal impairment/hypovolaemia, active peptic ulceration or GI bleeding, aspirin-sensitive asthma, bleeding diatheses/anticoagulation, heart failure and uncontrolled hypertension, and caution in the elderly. They impair platelet function and renal perfusion via prostaglandin inhibition.

10. Summarise current understanding of paracetamol's mechanism of action.

    Paracetamol is a centrally-acting analgesic and antipyretic with weak peripheral COX activity. Proposed mechanisms include central COX inhibition, the active metabolite AM404 acting on cannabinoid/TRPV1 and descending serotonergic pathways. It is not significantly anti-inflammatory.

11. Describe paracetamol toxicity mechanism and its antidote.

    In overdose, glucuronidation/sulphation saturate and excess paracetamol forms NAPQI via CYP2E1. NAPQI depletes glutathione and causes hepatocellular necrosis. N-acetylcysteine replenishes glutathione and is the antidote, most effective within 8 hours.

12. Name three classes of adjuvant analgesics and an example of each.

    Anticonvulsants (gabapentin, pregabalin — neuropathic pain), tricyclic antidepressants (amitriptyline) and SNRIs (duloxetine), and $\alpha_2$-agonists (clonidine, dexmedetomidine). Ketamine (NMDA antagonist) is also used as an analgesic adjuvant.

13. What determines the speed of onset and duration of local anaesthetics?

    Onset depends on $pK_a$ (proportion unionised at tissue pH that crosses membranes — closer $pK_a$ to 7.4 means faster onset). Duration depends on protein binding and lipid solubility; potency correlates with lipid solubility.

14. State the maximum safe doses of lidocaine with and without adrenaline.

    Plain lidocaine: approximately $3\ \text{mg·kg}^{-1}$. Lidocaine with adrenaline: approximately $7\ \text{mg·kg}^{-1}$ (adrenaline causes vasoconstriction, slowing systemic absorption). Bupivacaine maximum is approximately $2\ \text{mg·kg}^{-1}$.

15. Outline the management of local anaesthetic systemic toxicity (LAST).

    Stop injection, call for help, manage airway/breathing/circulation with 100% oxygen, control seizures (benzodiazepine), and give IV lipid emulsion 20%: initial bolus $1.5\ \text{mL·kg}^{-1}$ over 1 min followed by an infusion of $15\ \text{mL·kg}^{-1}\text{·h}^{-1}$. Prolonged CPR may be needed.

16. Describe the mechanism and characteristics of a phase I suxamethonium block.

    Suxamethonium is a depolarising neuromuscular blocker that binds nicotinic ACh receptors, causing sustained depolarisation. Phase I block shows fasciculations then flaccid paralysis, no fade on train-of-four, no post-tetanic potentiation, and is not antagonised (potentiated) by anticholinesterases.

17. List key adverse effects and contraindications of suxamethonium.

    Hyperkalaemia (dangerous in burns, spinal cord injury, prolonged immobility — avoid after ~24–72 h), malignant hyperthermia trigger, bradycardia, raised intraocular/intragastric/intracranial pressure, myalgia, anaphylaxis, and prolonged block with atypical cholinesterase.

18. Compare aminosteroid and benzylisoquinolinium non-depolarising blockers with examples.

    Aminosteroids (rocuronium, vecuronium, pancuronium) are metabolised hepatically/renally and reversible by sugammadex. Benzylisoquinoliniums (atracurium, cisatracurium, mivacurium) — atracurium/cisatracurium undergo organ-independent Hofmann elimination and may cause histamine release.

19. Why is cisatracurium favoured in organ failure?

    Cisatracurium undergoes Hofmann elimination — spontaneous non-enzymatic degradation dependent on temperature and pH, independent of hepatic or renal function. Unlike atracurium it causes negligible histamine release and produces little laudanosine.

20. Explain how neostigmine reverses non-depolarising blockade and why glycopyrronium is co-administered.

    Neostigmine inhibits acetylcholinesterase, increasing ACh at the neuromuscular junction to outcompete the blocker. The resulting muscarinic effects (bradycardia, salivation, bronchospasm) are countered by an antimuscarinic such as glycopyrronium or atropine.

21. Describe sugammadex and its dosing principle.

    Sugammadex is a modified $\gamma$-cyclodextrin that encapsulates aminosteroid relaxants (rocuronium > vecuronium) in plasma, terminating their effect. Dose: $2\ \text{mg·kg}^{-1}$ for moderate block, $4\ \text{mg·kg}^{-1}$ for deep block, $16\ \text{mg·kg}^{-1}$ for immediate reversal after rocuronium.

22. Compare the receptor actions of adrenaline, noradrenaline and dobutamine.

    Adrenaline: $\alpha_1$, $\beta_1$, $\beta_2$ (dose-dependent). Noradrenaline: predominantly $\alpha_1$ with some $\beta_1$ (vasopressor). Dobutamine: predominantly $\beta_1$ (inotrope) with mild $\beta_2$ — increases contractility and may reduce afterload.

23. Distinguish the actions of atropine and glycopyrronium.

    Both are antimuscarinic anticholinergics. Atropine is a tertiary amine that crosses the blood-brain barrier (central effects, more tachycardia) and placenta. Glycopyrronium is a quaternary amine that does not cross the BBB or placenta, giving fewer central effects and good antisialagogue action.

24. Outline the mechanism and reversal of warfarin and heparin.

    Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of factors II, VII, IX, X (and proteins C/S); monitored by INR, reversed by vitamin K and prothrombin complex concentrate. Unfractionated heparin potentiates antithrombin III (monitored by APTT) and is reversed by protamine.

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