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Chemistry – Also called isoprenaline HCl , isoproterenol HCl is a synthetic beta adrenergic agent that occurs as a white to practically white, crystalline powder that is freely soluble in water and sparingly soluble in alcohol. The pH of the commercially available injection is 3.5 – 4.5.
Storage/Stability/Compatibility – Store isoproterenol preparations in tight, light-resistant containers. It is stable indefinitely at room temperature. Isoproterenol salts will darken with time, upon exposure to air, light, or heat. Sulfites or sulfur dioxide may be added to preparations as an antioxidant. Solutions may become pink or brownish-pink if exposed to air, alkalies or metals. Do not use solutions that are discolored or contain a precipitate. If isoproterenol is mixed with other drugs or fluids that results in a solution with a pH greater than 6, it is recommended that it be used immediately.
Isoproterenol for injection is reported to be compatible with all commonly used IV solutions (except 5% sodium bicarbonate), and the following drugs: calcium chloride/gluceptate, cephalothin sodium, cimetidine HCl, dobutamine HCl, heparin sodium, magnesium sulfate, multivitamin infusion, netilmicin sulfate, oxytetracycline HCl, potassium chloride, succinylcholine chloride, tetracycline HCl, verapamil HCl, and vitamin B complex w/C.
It is reported to be incompatible with: aminophylline or sodium bicarbonate. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.
Pharmacology – Isoproterenol is a synthetic beta1 and beta2 adrenergic agonist that has no appreciable alpha activity at therapeutic doses. It is thought that isoproterenol’s adrenergic activity is a result of stimulating cyclic-AMP production. Its primary actions are increased inotropism and chronotropism, relaxation of bronchial smooth muscle and peripheral vasodilitation. Isoproterenol may also increase perfusion to skeletal muscle (at the expense of vital organs in shock). Isoproterenol will also inhibit the antigen-mediated release of histamine and slow releasing substance of anaphylaxis (SRS-A).
Hemodynamic effects noted include decreased total peripheral resistance, increased cardiac output, increased venous return to the heart and increased rate of discharge by cardiac pacemakers.
Uses/Indications – Isoproterenol is primarily used in veterinary medicine in the treatment of acute bronchial constriction, cardiac arrhythmias (complete AV block) and occasionally as adjunctive therapy in shock or heart failure (limited use because of increases in heart rate and ventricular arrhythmogenicity).
Pharmacokinetics – Isoproterenol is rapidly inactivated by the GI tract and metabolized by the liver after oral administration. Sublingual administration is not reliably absorbed and effects may take up to 30 minutes to be seen. Intravenous administration result in immediate effects, but only persist for a few minutes after discontinuation.
It is unknown if isoproterenol is distributed into milk. The pharmacologic actions of isoproterenol are ended primarily through tissue uptake. Isoproterenol is metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) to a weakly active metabolite.
Contraindications/Precautions – Isoproterenol is contraindicated in patients that have tachycardias or AV block caused by cardiac glycoside intoxication. It is also contraindicated in ventricular arrhythmias that do not require increased inotropic activity.
Use isoproterenol with caution in patients with coronary insufficiency, hyperthyroidism, renal disease, hypertension or diabetes. Isoproterenol is not a substitute for adequate fluid replacement in shock.
Adverse Effects/Warnings – Isoproterenol can cause tachycardia, anxiety, tremors, excitability, headache, weakness and vomiting. Because of isoproterenol’s short duration of action, adverse effects are usually transient and do not require cessation of therapy, but may require lowering the dose or infusion rate. Isoproterenol is considered to be more arrhythmogenic than either dopamine or dobutamine, so it is rarely used in the treatment of heart failure.
Overdosage – In addition to the symptoms listed in the adverse effects section, high doses may cause an initial hypertension, followed by hypotension as well as tachycardias and other arrhythmias. Besides halting or reducing the drug, treatment is considered to be supportive. Should tachycardias persist, a beta blocker could be considered for treatment (if patient does not have a bronchospastic disease).
Drug Interactions – Do not use with other sympathomimetic amines (e.g., epinephrine) because of additive effects and toxicity. Propranolol (or other beta-blockers) may antagonize isoproterenol’s cardiac, bronchodilating, and vasodilating effects by blocking the beta effects of isoproterenol. Beta blockers may be administered to treat the tachycardia associated with isoproterenol use, but should not be given to patients with bronchospastic disease.
When isoproterenol is used with drugs that sensitize the myocardium (halothane, digoxin) monitor for signs of arrhythmias. Hypertension may result if isoproterenol is used with oxytocic agents. When isoproterenol is used with potassium depleting diuretics (e.g., furosemide) or other drugs that affect cardiac rhythm, there is an increased chance of arrhythmias occurring.
Although not unequivocally established, there is some evidence that isoproterenol used concomitantly with theophylline may induce increased cardiotoxic effects.
Doses – Note: Because of the cardiostimulatory properties of isoproterenol, its parenteral use in human medicine for the treatment of bronchospasm has been largely supplanted by other more beta2 specific drugs (e.g., terbutaline) and administration methods (nebulization). Use with care.
For short-term bronchodilitation:
a) Dilute 0.2 mg in 50 ml of saline and administer 0.4 micrograms/kg as an IV infusion, monitor heart rate continuously and discontinue when heart rate doubles. Effects may only last for an hour. (Derksen 1987)
Monitoring Parameters –
1) Cardiac rate/rhythm
2) Respiratory rate/auscultation during anaphylaxis
3) Urine flow if possible
4) Blood pressure, and blood gases if indicated and if possible
Client Information – Isoproterenol for injection should be used only by trained personnel in a setting where adequate monitoring can be performed.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Veterinary-Approved Products: None
Isoproterenol for Injection 1:5000 solution (0.2 mg/ml) in 1 & 5 ml amps; Isuprel® (Winthrop Pharm.); Generic; (Rx)
Isoproterenol sublingual or rectal Glossets 10 mg, 15 mg; Isuprel® Glossets (Winthrop); (Rx)
Isoproterenol is also available in aerosol or solution form for oral inhalation.