Propranolol Information
Propranolol () Description
Propranolol () Hydrochloride, USP is a synthetic beta-adrenergic receptor blocking agent chemically described as (+)-1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride. Its structural formula is:
CHNO•HCl
Propranolol () Hydrochloride, USP is a stable, white, crystalline solid which is readily soluble in water and ethanol. Its molecular weight is 295.80.
Propranolol () Hydrochloride Injection, USP is available as a sterile injectable solution for intravenous administration. Each mL contains 1 mg of Propranolol () Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP.
Propranolol () Clinical Pharmacology
The effects of Propranolol () are due to selective blockade of beta-adrenergic receptors, leaving alpha-adrenergic responses intact. There are two well-characterized subtypes of beta receptors (beta and beta); Propranolol () interacts with both subtypes equally. Beta-adrenergic receptors are found primarily in the heart. Blockade of cardiac beta-adrenergic receptors leads to a decrease in the activity of both normal and ectopic pacemaker cells and a decrease in A-V nodal conduction velocity. All of these actions can contribute to antiarrhythmic activity and control of ventricular rate during arrhythmias. Blockade of cardiac beta‑adrenergic receptors also decreases the myocardial force of contraction and may provoke cardiac decompensation in patients with minimal cardiac reserve.
Beta-adrenergic receptors are found predominantly in smooth muscle–vascular, bronchial, gastrointestinal and genitourinary. Blockade of these receptors results in constriction. Clinically, Propranolol () may exacerbate respiratory symptoms in patients with obstructive pulmonary diseases such as asthma and emphysema (see and ).
Propranolol () ’s beta blocking effects are attributable to its S(-) enantiomer.
Propranolol () Clinical Studies
In a series of 225 patients with supraventricular (n = 145), ventricular (n = 69), or both (n = 11) arrythmias resistant to digitalis, intravenous Propranolol () hydrochloride was administered in single doses, averaging 1 to 5 mg. Approximately one-quarter of the patients with supraventricular arrhythmias (generally those with sinus or atrial tachycardia) reverted to normal sinus rhythm. About one-half had symptoms ameliorated either by a decrease in ventricular rate or an attenuation of frequency or severity of paroxysmal attacks.
Approximately one-half of patients with ventricular arrhythmias (generally those with frequent PVCs) reverted to normal sinus rhythm or responded with a reduction in ventricular rate.
Similar findings were seen in a series of 25 Bantu patients with atrial fibrillation (n = 16), sinus tachycardia (n = 5), and multifocal ventricular extrasystoles (n = 9).
In another series, 7 of 8 patients with digitalis-related tachyarrhythmia had ventricular rate decreases after intravenous Propranolol () . Similarly limited clinical experience has shown that intravenous Propranolol () will slow the ventricular rate in patients with Wolff-Parkinson-White syndrome or with tachycardia associated with thyrotoxicosis.
Onset of activity is usually within five minutes.
Propranolol () Contraindications
Propranolol () is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; and 4) in patients with known hypersensitivity to Propranolol () hydrochloride.
Propranolol () Warnings
Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia, especially in labile insulin-dependent diabetics. In these patients, it may be more difficult to adjust the dosage of insulin.
Propranolol () therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting, as in preparation for surgery. Hypoglycemia has been reported after prolonged physical exertion and in patients with renal insufficiency.
Propranolol () Precautions
Propranolol () should be used with caution in patients with impaired hepatic or renal function. Propranolol () is not indicated for the treatment of hypertensive emergencies.
Beta-adrenergic receptor blockade can cause reduction of intraocular pressure. Patients should be told that Propranolol () might interfere with the glaucoma screening test. Withdrawal may lead to a return of intraocular pressure.
Risk of anaphylactic reaction. While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Propranolol () Adverse Reactions
In a series of 225 patients, there were 6 deaths (see ). Cardiovascular events (hypotension, congestive heart failure, bradycardia, and heart block) were the most common. The only other event reported by more than one patient was nausea.
Other adverse events for intravenous Propranolol () , reported during post-marketing surveillance include cardiac arrest, dyspnea, and cutaneous ulcers.
The following adverse events have been reported with use of formulations of sustained- or immediate-release oral Propranolol () and may be expected with intravenous Propranolol () .
Propranolol () Overdosage
Propranolol () is not significantly dialyzable. In the event of overdose or exaggerated response, the following measures should be employed:
Hypotension and bradycardia have been reported following Propranolol () overdose and should be treated appropriately. Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a Propranolol () overdose. Glucagon should be administered as 50-150 mcg/kg intravenously followed by continuous drip of 1-5 mg/hour for positive chronotropic effect. Isoproterenol, dopamine, or phosphodiesterase inhibitors may also be useful. Epinephrine, however, may provoke uncontrolled hypertension. Bradycardia can be treated with atropine or isoproterenol. Serious bradycardia may require temporary cardiac pacing.
The electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance must be monitored. Isoproterenol and aminophylline may be useful for bronchospasm.
Propranolol () Dosage And Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
The usual dose is 1 to 3 mg administered under careful monitoring, such as electrocardiography and central venous pressure. The rate of administration should not exceed 1 mg (1 mL) per minute to diminish the possibility of lowering blood pressure and causing cardiac standstill. Sufficient time should be allowed for the drug to reach the site of action even when a slow circulation is present. If necessary, a second dose may be given after two minutes. Thereafter, additional drug should not be given in less than four hours. Additional Propranolol () hydrochloride should not be given when the desired alteration in rate or rhythm is achieved.
Transfer to oral therapy as soon as possible.
Propranolol () How Supplied
Each mL contains 1 mg of Propranolol () Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP. Supplied as: 1 mL vials in boxes of 10 (NDC 62778-057-22).
HIKMA FARMACÊUTICA (PORTUGAL), S.A.
Estrada do Rio da Mó, 8, 8A e 8B – Fervença –
2705-906 Terrugem SNT,
PORTUGAL
WEST-WARD PHARMACEUTICAL CORP.
Eatontown, NJ 07724 USA
Rev.: 04/2011
Propranolol () Principal Display Panel
