PharmacologyTier 1Medical Sciences concept

Adrenaline in anaphylaxis - mechanism and timing

Core concept

Adrenaline is the only drug that treats anaphylaxis. Everything else treats symptoms.

Receptor	Effect	Why it matters
alpha-1	Vasoconstriction	Reverses vasodilation and capillary leak - the cause of shock; reduces mucosal oedema (airway, laryngeal)
beta-1	inc inotropy, inc chronotropy	Restores cardiac output
beta-2	Bronchodilation	Reverses bronchospasm
beta-2 on mast cells/basophils	inc cAMP -> dec degranulation	Stops further mediator release - the disease-modifying action

Delay in giving IM adrenaline is the intervention most strongly associated with death
- Early adrenaline -> improved survival, fewer biphasic reactions
- Antihistamines and corticosteroids have never been shown to affect mortality - they do not touch the airway or the circulation
There is no absolute contraindication to adrenaline in anaphylaxis

Dose and route

IM into the mid anterolateral thigh (vastus lateralis): 0.01 mg/kg of 1:1000 (1 mg/mL), max 0.5 mg
- Adult 0.5 mg = 0.5 mL of 1:1000
- Repeat every 5 minutes as needed
IM thigh > IM deltoid > SC - faster peak, higher levels. Subcutaneous and inhaled routes are inadequate.
IV adrenaline infusion only with monitoring and experience, for refractory anaphylaxis (bolus IV adrenaline is a common cause of iatrogenic harm - hypertensive crisis, arrhythmia, ischaemia)
Autoinjectors: 150 microg (7.5-20 kg), 300 microg (>20 kg), 500 microg devices

Adjuncts, in order

Lie flat, legs elevated - sitting or standing a hypotensive patient up has caused deaths ("empty ventricle")
High-flow oxygen; large-volume IV crystalloid (20 mL/kg boluses) - vasodilation and leak mean these patients are profoundly volume-depleted
Nebulised adrenaline for stridor; salbutamol for persisting wheeze
Refractory anaphylaxis: adrenaline infusion, then vasopressin/noradrenaline/metaraminol; glucagon 1-2 mg IV if on a beta-blocker (bypasses the blocked receptor via direct adenylate cyclase activation)

Pharmacokinetics

IM onset 3-5 min, peak ~10 min, t1/2 ~2-3 min (COMT and MAO) -> the short half-life is why it must be repeated or infused

Diagnose clinically and treat immediately - acute onset with airway/breathing/circulation involvement, or any acute skin/mucosal change plus respiratory or cardiovascular compromise
Tryptase (at presentation, 1-2 hr and >24 hr baseline) confirms retrospectively; a normal tryptase does not exclude anaphylaxis, especially food-triggered
Observe after the reaction
- At least 4 hours after the last dose of adrenaline, longer if repeated doses, severe/protracted reaction, asthma, or a remote location
- Biphasic reactions in ~3-5%, typically within 4-12 hr
Before discharge, every patient
- Two adrenaline autoinjectors + demonstrated technique
- ASCIA Action Plan
- Allergen avoidance advice and allergy/immunology referral
- Medical alert identification
Beta-blockers and ACE inhibitors worsen severity and reduce adrenaline responsiveness - review them
Risk factors for fatal anaphylaxis: adolescence/young adulthood, asthma (especially poorly controlled), nut and insect venom triggers, upright posture, delayed adrenaline

Vasopressor mechanisms of action
Beta-blocker comparative pharmacology (glucagon rescue)
Mast cell disorders - mastocytosis, hereditary alpha-tryptasaemia (raised baseline tryptase)
Asthma pharmacotherapy; anti-IgE biologics
Drug hypersensitivity and HLA associations
Perioperative anaphylaxis - neuromuscular blockers, antibiotics, chlorhexidine
Hereditary angioedema (does NOT respond to adrenaline - needs C1-inhibitor concentrate or icatibant)

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