ALPHA-ADRENERGIC CRISIS

    DEFINITION

    Stimulation of alpha-adrenergic receptors due to exposure to partial
    or pure alpha agonists, resulting in a syndrome characterised
    predominantly by vasoconstriction and hypertension.

    TOXIC CAUSES

    Phenylpropanolamine 
    Phenylephrine 
    Ephedrine 
    Mephentermine
    Metaraminol
    Methoxamine
    Pseudoephedrine.

    CLINICAL FEATURES

    Hypertension, bradycardia (reflex) and mydriasis.  Hypertension is
    typically accompanied by headache and, exceptionally, may result in
    intracranial haemorrhage.  Life-threatening ventricular  arrhythmias
    (including AV block and ventricular tachycardia) may also occur. 
    Convulsions, myocardial infarction and acute renal failure have been
    reported.

    DIFFERENTIAL DIAGNOSIS

    Acute hypertension of non-toxic origin.
    Monoamine oxidase inhibitors (in overdose or in combination with
    certain drugs or tyramine-containing).
    Substances with sympathomimetic or anticholinergic effects.

    RELEVANT INVESTIGATIONS

    Routine clinical chemistry, including serum creatinine.
    Creatine phosphokinase activity, including measurement of isoenzymes
    if indicated.
    Electrocardiogram.
    CT Scan of head if indicated (focal neurological signs or persistent
    headache).

    TREATMENT

    In mild asymptomatic cases, simple observation with close monitoring
    of vital signs is sufficient.

    Where the diastolic blood pressure remains above 120 mmHg or there is
    evidence of end-organ damage, specific therapy with one of the
    following short-acting parenteral hypotensive agents should be
    instituted.  Aim to carefully lower the diastolic blood pressure to
    100 mmHg.

          Sodium Nitroprusside
         Direct generalised vasodilator.
         Dose:     Commence continuous IV infusion at 0.5 µg/kg/min.
                   Titrate to blood pressure to a maximum dose of 10
                   µg/kg/min.
         Must be administered under close observation, ideally with
         continuous blood pressure monitoring.
         Solution and tubing must be covered to prevent photodegradation.

          Phentolamine
         Competitive alpha-adrenoreceptor blocker.
         Dose:     2.5 - 5 mg (0.05 - 0.1 mg/kg) IV every 5 minutes until
                   desired effect achieved.
         Thereafter, continuous infusion of 25 to 100 mg/12 hours with
         close monitoring of blood pressure.

    Caution: Atropine and beta blockers are contraindicated.

    Treat ventricular arrhythmias and convulsions.

    CLINICAL COURSE MONITORING 

    The course is usually self-limiting and a full recovery is to be
    expected.  Until clinical features resolve, monitoring should include
    vital signs (pulse, blood pressure, temperature), cardiac rhythm and
    fluid and electrolyte balance.

    LONG-TERM COMPLICATIONS

    Unusual unless there are complications of a severe hypertensive
    crisis.  These potentially include intracranial haemorrhage,
    myocardial infarction and retinal haemorrhage.

    AUTHOR(S)/PEER REVIEW

    Author:        Albert J. Nantel, Directeur, Centre de Toxicologie du
                   Quebec, Quebec, Canada.

    Peer Review:   Cardiff September 1996: J-F. Deng, L. Fruchtengarten,
                   L. Lubomirov, T. Meredith, H. Persson.