Pharmacology, Toxicology and Addiction MedicineTier 1Approach to a presentation

Associated with adverse drug interactions - hypotension

Red flags

Hypotension with bradycardia - beta-blocker/CCB/digoxin toxicity
Hypotension with wide QRS tachycardia - TCA/sodium channel blocker
Urticaria, angioedema, wheeze - anaphylaxis
Refractory to fluid bolus
Combined beta-blocker + CCB ingestion (more lethal than either alone)
Hypotension + reduced consciousness + hypoglycaemia - beta-blocker overlap

Differential by mechanism

Vasodilation

ACE-I/ARB (esp. first dose, volume-depleted), alpha-1 blockers, nitrates, PDE5 inhibitors
PDE5i + nitrate = profound refractory hypotension - ask about recreational nitrate ("poppers") use
Antipsychotics with alpha-1 blockade (clozapine, quetiapine, chlorpromazine)
Dihydropyridine CCBs

Negative inotropy/chronotropy

Beta-blockers, non-dihydropyridine CCBs (verapamil, diltiazem)
Digoxin toxicity

Volume/tone loss

Diuretics, SGLT2 inhibitors (osmotic diuresis)
Opioids (histamine release, esp. IV morphine)
Anaesthetic induction agents

Immune-mediated

Anaphylaxis - beta-lactams, NMBAs, contrast, biologics
Abrupt corticosteroid cessation -> adrenal crisis

Focused history

New drug or dose change, timing relative to last dose
Interacting combinations (PDE5i + nitrate, beta-blocker + CCB co-prescription)
Renal function/dialysis status (drug accumulation)
Allergy history, prior reactions to the same class
Overdose intent, quantity, co-ingestants

Focused examination

HR direction (brady vs tachycardic hypotension localises the cause)
Postural BP change
Warm (vasodilatory) vs cold peripheries (cardiogenic)
Skin - urticaria, angioedema, flushing
ECG - rate, PR, QRS, QTc

Investigation strategy

ECG immediately
Glucose (beta-blocker overdose can mask/cause hypoglycaemia)
UEC, calcium, magnesium
Lactate
Digoxin level if suspected; tryptase if anaphylaxis considered retrospectively

Management

1. Fluids first, but don't stop there

Crystalloid bolus - often insufficient alone in beta-blocker/CCB overdose

2. Beta-blocker overdose

Glucagon, high-dose insulin-euglycaemia therapy, IV calcium, atropine, transcutaneous/transvenous pacing

3. Calcium channel blocker overdose

High-dose insulin-euglycaemia therapy is mainstay, IV calcium (high-dose, repeated), lipid emulsion for severe/refractory lipophilic CCB toxicity, vasopressors

4. Anaphylaxis

IM adrenaline first-line - not antihistamines or fluids alone

5. Adrenal crisis

IV hydrocortisone empirically if suspected, do not wait for cortisol result

6. Digoxin toxicity with bradycardia/hypotension

DigiFab (digoxin-specific antibody fragments)

7. Refractory vasodilatory shock

Noradrenaline first-line vasopressor

Traps

Fluids alone frequently fail in beta-blocker/CCB overdose - escalate early to insulin-euglycaemia therapy
Combined beta-blocker + CCB ingestion is disproportionately lethal vs either alone
PDE5i + nitrate combination is easily missed on history unless asked directly
Don't delay adrenaline for anaphylaxis while trialling antihistamines

Talk track

1. Localise by heart rate

"Bradycardic hypotension points to a rate-limiting drug; tachycardic with a wide QRS points to sodium channel blockade."

2. Escalate past fluids early

"In CCB or beta-blocker overdose I don't wait for fluids to fail - high-dose insulin-euglycaemia goes in early."

3. Adrenaline is never second-line in anaphylaxis

"IM adrenaline first, everything else is adjunct."

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