Show the model answerAttempt it first — that is what makes it stick
Before any of the three
How a three-drug short note is marked
Three unrelated drugs sharing one allocation. A third of the time each, the same headings for all three, and for each one an answer to the question an anaesthetist is actually being asked: what does this change about my anaesthetic?
What earns the marks
| A third each | Three drugs, one allocation. Running out of time on the third is the commonest way to lose marks here |
|---|---|
| The same headings | Class, target, mechanism, kinetics, dose or monitoring, adverse effects |
| The anaesthetic consequence | Each of these three changes something you do: when you operate, which relaxant behaves oddly, and which antiemetic will not work |
| Numbers where they exist | A half-life, a toxic level, a stopping interval |
Read the question: Three drugs from three different systems, deliberately. There is no theme to find and no link to draw — trying to build one wastes the words that should be going into the third note.
| Drug | Class | Target or action | The perioperative consequence |
|---|---|---|---|
| Clopidogrel | Thienopyridine antiplatelet | P2Y12 receptor, irreversible | Determines when you can operate, and whether regional anaesthesia is available |
| Gentamicin | Aminoglycoside antimicrobial | Rapidly bactericidal against aerobic gram-negative bacteria | Potentiates non-depolarising neuromuscular blockade, and is nephro- and ototoxic |
| Ondansetron | 5-HT3 antagonist | 5-HT3 receptor, a ligand-gated cation channel | First-line antiemetic, and useless for anything vestibular |
Short note 1
Clopidogrel
A prodrug that irreversibly disables a receptor for the life of the platelet — which is why the note is really about time rather than about dose.
| Heading | Content |
|---|---|
| Class | Thienopyridine. The group also contains prasugrel and ticagrelor; ticlopidine is now rarely used. |
| Mechanism | Selective, irreversible binding to and inhibition of the P2Y12 receptor on the platelet, blocking adenosine diphosphate from binding to it. P2Y12 is a Gi-coupled receptor that inhibits adenylyl cyclase and amplifies the aggregation response, so blocking it inhibits ADP-mediated platelet activation and aggregation. |
| Prodrug | Requires in vivo metabolism to an active metabolite, by two separate metabolic steps. That is the origin of its variability. |
| Resistance | Defined as an inability to inhibit P2Y12-dependent platelet function adequately, and it occurs in 20 to 30% of patients — attributed to the metabolism. Prasugrel needs only one metabolic step, is more potent, and resistance is rare. |
| Duration | The binding is irreversible, so the effect lasts the life of the affected platelet. Recovery depends on new platelets, not on clearing the drug. |
| Perioperative | Discontinue a thienopyridine 5 to 7 days before elective surgery, and avoid regional anaesthesia until the effect has dissipated. Guidance for stopping aspirin- or clopidogrel-containing drugs favours 7 to 10 days before the procedure over stopping closer to it. |
| Adverse effects | Bleeding, which is the class problem. Prasugrel and ticagrelor are more effective at preventing thrombosis but increase major bleeding. |
Short note 2
Gentamicin
A water-soluble drug that is cleared entirely by the kidney and is toxic to the kidney and the ear — which is why the whole note turns on renal function.
| Heading | Content |
|---|---|
| Class and spectrum | Aminoglycoside. Rapidly bactericidal against aerobic gram-negative bacteria; gentamicin is active against Pseudomonas aeruginosa as well as the gram-negative bacilli. |
| Physicochemistry | Poorly lipid soluble. Less than 1% of an oral dose is absorbed, so it is given parenterally. Volume of distribution is similar to the extracellular fluid volume. |
| Elimination | Extensive renal excretion, almost exclusively by glomerular filtration. There is a linear relationship between plasma creatinine and the elimination half-time. |
| Half-life | 2 to 3 hours with normal renal function, prolonged 20- to 40-fold in renal failure. |
| Monitoring | Plasma concentration measurement is essential in renal dysfunction and is the best way to recognise potentially toxic levels, taken as above 9 µg/mL. Where concentrations cannot be measured, the dose is adjusted to the plasma creatinine. |
| Distribution | Penetrates pleural, ascitic and synovial fluid in the presence of inflammation. |
| Adverse effects | Four, and all of them track the plasma concentration: ototoxicity, nephrotoxicity, skeletal muscle weakness, and potentiation of non-depolarising neuromuscular blocking drugs. |
| Toxicity | Mechanism | How it presents |
|---|---|---|
| Ototoxicity | Accumulation in the perilymph with destruction of vestibular or cochlear sensory hairs; dose-dependent, mostly with chronic therapy and in the elderly, in whom renal dysfunction is likelier. Furosemide, mannitol and probably other diuretics accentuate it. | Vestibular: nystagmus, vertigo, nausea, acute onset of Ménière syndrome. Auditory: tinnitus, or a sensation of pressure or fullness in the ears. Deafness may develop suddenly. |
| Nephrotoxicity | Accumulation in the renal cortex producing acute tubular necrosis | An inability to concentrate urine, then proteinuria and red-cell casts. Usually reversible if the drug is stopped. Neomycin is the most nephrotoxic and is therefore not given parenterally. |
| Skeletal muscle weakness | Inhibition of the prejunctional release of acetylcholine, with reduced postsynaptic sensitivity to it | Occurs with large intrapleural or intraperitoneal doses. Intravenous calcium overcomes the effect at the neuromuscular junction. A single dose is unlikely to cause it in an otherwise healthy patient. |
| Neuromuscular blockade | The same prejunctional and postjunctional actions | Potentiation of non-depolarising neuromuscular blocking drugs. Patients with myasthenia gravis are uniquely susceptible. |
Short note 3
Ondansetron
One receptor, blocked at both ends of the same reflex, with a specificity that is the whole reason the class displaced the older antiemetics.
| Heading | Content |
|---|---|
| Class and structure | Carbazole, described as a carbazalone derivative, structurally related to serotonin. |
| Receptor | Specific antagonist at the 5-HT3 receptor — an excitatory, ligand-gated, non-selective cation channel, a pentamer of five subunits forming a central pore. No action at dopamine, histamine, adrenergic or cholinergic receptors. |
| Sites | Peripherally at the vagal afferents in the gut, and centrally at the area postrema, which has the highest density of 5-HT3 receptors in the brain. One drug therefore blocks both the peripheral trigger and the central relay. |
| Uses | Prophylaxis and treatment of chemotherapy- and radiotherapy-induced sickness, and equally of the postoperative kind. Licensed above 2 years of age. |
| Not effective for | Vestibular stimulation — motion sickness — and vomiting induced by dopamine agonists. Neither afferent runs through a 5-HT3 receptor. |
| Presentation and dose | Tablets and an orodispersible lyophilisate at 4 to 8 mg, a 16 mg suppository, and a 2 mg/mL solution for slow intravenous injection. 4 mg intravenously is the standard prophylactic dose. In preadolescent children, 0.15 mg/kg orally or 0.05 to 0.15 mg/kg intravenously. |
| Kinetics | Oral bioavailability about 60%, with therapeutic concentrations 30 to 60 minutes after a dose. About 75% protein bound. Hepatic hydroxylation then glucuronide conjugation to inactive metabolites; reduce the dose in hepatic impairment. Elimination half-time 3 to 4 hours. |
| Adverse effects | Headache, flushing, constipation, diarrhoea, and bradycardia after rapid intravenous administration. Slight QTc prolongation, an association shared across the class. Transient transaminase rises, seen only in patients receiving chemotherapy. |
Ondansetron and the rest of its class are taught in full in the antiemetics lesson.
If this came up in the viva
Viva points
The antiemetic third, asked the way it is usually asked.
Are 5-HT3 antagonists effective for motion sickness?
Answer
No. They are effective for chemotherapy- and radiotherapy-induced nausea and vomiting and for PONV, but not for nausea and vomiting caused by vestibular stimulation or by dopamine agonists — those causes need a drug acting on a different receptor.
Ondansetron and droperidol are both used for PONV prophylaxis at similar efficacy. Why is ondansetron free of the extrapyramidal effects droperidol can cause?
Answer
Ondansetron is specific for the 5-HT3 receptor, with no meaningful activity at dopamine, histamine, adrenergic or cholinergic receptors. Droperidol acts as a dopamine (D2) antagonist, and it is D2 blockade that produces extrapyramidal effects — a receptor ondansetron does not touch.