Clenbuterol toxicity

Reviewed and revised 24 May 2014

OVERVIEW

• Clenbuterol is a long acting beta-2-adrenergic agonist used in veterinary medicine and as a banned doping agent in athletes
• veterinary uses: equine bronchodilator and bovine tocolytic agent
• previously used for anabolic effects in livestock, but banned due to risk of toxicity from contaminated meat
• toxicity may also occur from contamination of illicit drugs, such as heroin
• more recently it has been used by the general public for body building and as a slimming agent (increases BMR and fat catabolism)

MECHANISM OF ACTION

•  synthetic sympathomimetic amine
• long acting beta-2-adrenergic agonist

TOXICOKINETICS

• Absorption: well absorbed orally with high bioavailability, peak serum concentrations at 2-3 hours post-ingestion
• Distribution: as an amphetamine-like lipid soluble weak base it has a large volume of distribution
• Metabolism and elimination: long t1/2 25 – 40 hours

RISK ASSESSMENT

• Estimated doses that produced typical beta-2-agonist features range from 30 to 300mcg
• there have been multiple outbreaks from eating contaminated meat, with effects lasting 3-5 days
• Doses used by bodybuilders usually range from 20 to 200mcg, up to three times daily

CLINICAL FEATURES

Effects include:

• Sympathomimetic effects due to beta agonism: restlessness/ anxiety, headache, diaphoresis, tachycardia, tachypnoea, tachyarrhythmias, hypertension
• Gastrointestinal disturbance: N&V, diarrhoea
• Rhabdomyolysis
• Metabolic effects: hypokalaemia, hyperglycaemia, less commonly hypoglycaemia, hypomagnesaemia, hypophosphataemia
• Myocardial ischaemia in otherwise healthy people
• Hypotension may also be seen due to beta 2 agonism
• Respiratory distress after nasal insufflation

Complications

• Intracranial hemorrhage (intracerebral hemorrhage, SAH)
• Acute cardiogenic pulmonary edema
• Hypertensive encephalopathy
• Aortic or carotid artery dissection
• Arrhythmia
• Acute coronary syndromes

INVESTIGATIONS

(Guided by clinical assessment)

Laboratory tests

• ECG (ACS, dysrhythmia)
• Paracetamol level if deliberate self harm
• FBC, UEC, glucose, LFTs, CK, troponin, CMP

MANAGEMENT

Resuscitation

• attend to ABCs
• treat agitation, seizures and hypertension and other sympathomimetic effects with benzodiazepines initially
• for refractory hypertension consider metoprolol or esmolol infusion – may be a risk of unopposed alpha agonism worsening hypertension, in which case labetolol may be preferred

Supportive care and monitoring

• FAST HUGS IN BED Please
• Serial ECGs

Decontamination

• consider 50g activated charcoal <1h after ingestion (uncertain benefit)

Disposition

• Observe for a minimum of 4 hours after ingestion or 8 hours if slow release
• most cases should be discussed with a toxicologist

References and Links

Journal articles

• Brett J, Dawson AH, Brown JA. Clenbuterol toxicity: a NSW poisons information centre experience. Med J Aust. 2014 Mar 3;200(4):219-21. PubMed PMID: 24580525. [Free Full Text]