Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

PROPRANOLOL HCL

Chemistry - A non-specific beta-adrenergic blocking agent, propranolol HCl occurs as a bitter-tasting, odorless, white to almost white powder with a pKa of 9.45 and a melting point of about161°C. One gram of propranolol is soluble in about 20 ml of water or alcohol. At a pH from 4-5, solutions of propranolol will fluoresce. The commercially available injectable solutions are adjustedwith citric acid to a pH 2.8 - 3.5.

Storage, Stability, Compatibility

All propranolol preparations should be stored at room temperature (15-30°C) and protected from light. Propranolol solutions will decompose rapidly at alkaline pH. Propranolol injection is reported to be compatible with D5W, 0.9% sodium chloride, orlactated Ringer's injection. It is also physically compatible with dobutamine HCl, verapamil HCland benzquinamide HCl.

Pharmacology - PROPRANOLOL HCL

Propranolol blocks both beta1 and beta2 adrenergic receptors in the myocardium, bronchi, and vascular smooth muscle. Propranolol does not have any intrinsic sympathomimeticactivity (ISA). Additional y, propranolol possesses membrane-stabilizing effects (quinidine-like)affecting the cardiac action potential and direct myocardial depressant effects. Cardiovasculareffects secondary to propranolol include: decreased sinus heart rate, depressed AV conduction, diminished cardiac output at rest and during exercise, decreased myocardial oxygen demand, decrease hepatic and renal blood flow, reduced blood pressure, and inhibition of isoproterenol-induced tachycardia. Electrophysiologic effects on the heart include decreased automaticity, increased or no effect on effective refractory period, and no effect on conduction velocity.
Additional pharmacologic effects of propranolol, include increased airway resistance (especially inpatients with bronchoconstrictive disease), prevention of migraine headaches, increased uterineactivity (more so in the non-pregnant uterus), decreased platelet aggregability, inhibitedglycogenolysis in cardiac and skeletal muscle and increased numbers of circulating eosinophils.

Uses, Indications

While propranolol is used for hypertension, migraine headache prophylaxisand angina in human patients, it is used primarily in veterinary medicine for its antiarrhythmiceffects. Dysrhythmias treated with propranolol include, atrial premature complexes, ventricularpremature complexes, supraventricular premature complexes and tachyarrhythmias, ventricular oratrial tachyarrhythmias secondary to digitalis, atrial tachycardia secondary to WPW with normal
QRS complexes, and atrial fibrillation (generally in combination with digoxin). Propranololreportedly improves cardiac performance in animals with hypertrophic cardiomyopathy. It has beenused to treat systemic hypertension and symptoms associated with thyrotoxicosis andpheochromocytoma.

Pharmacokinetics - PROPRANOLOL HCL

Propranolol is well absorbed after oral administration, but a rapid first-passeffect through the liver reduces systemic bioavailability to approximately 2-27% in dogs, therebyexplaining the significant difference between oral and intravenous dosages. These values reportedlyincrease with chronic dosing.
Propranolol is highly lipid soluble and readily crosses the blood-brain barrier. The apparentvolume of distribution has been reported to 3.3 - 11 L/kg in the dog. Propranolol will cross theplacenta and enters milk (at very low levels). In humans, propranolol is approximately 90% boundto plasma proteins.
Propranolol is principally metabolized by the liver. An active metabolite, 4-hydroxypropranolol, has been identified after oral administration in humans. Less than 1% of a dose is excretedunchanged into the urine. The half-life in dogs has been reported to range from 0.77 - 2 hours, andin horses, less than 2 hours.
Contraindications/Precautions - Propranolol is contraindicated in patients with overt heart failure, hypersensitivity to this class of agents, greater than 1st degree heart block, or sinus bradycardia.
Non-specific beta-blockers are generally contraindicated in patients with CHF unless secondary toa tachyarrhythmia responsive to beta-blocker therapy. They are also relatively contraindicated inpatients with bronchospastic lung disease.
Propranolol should be used cautiously in patients with significant renal or hepatic insufficiency. Itshould also be used cautiously in patients with sinus node dysfunction.
Propranolol can mask the symptoms associated with hypoglycemia. It can also cause hypoglycemia or hyperglycemia and, therefore, should be used cautiously in labile diabetic patients.
Propranolol can mask the symptoms associated with thyrotoxicosis, but it has been used clinical yto treat the symptoms associated with this condition.
Use propranolol cautiously with digitalis or in digitalis intoxicated patients; severe bradycardiasmay result.

Adverse Effects, Warnings

It is reported that adverse effects most commonly occur in geriatricanimals or those that have acute decompensating heart disease. Adverse effects considered to beclinically relevant include: bradycardia, lethargy and depression, impaired AV conduction, CHF orworsening of heart failure, hypotension, hypoglycemia, and bronchoconstriction. Syncope anddiarrhea have also been reported in canine patients.
Exacerbation of symptoms have been reported following abrupt cessation of beta-blockers inhumans. It is recommended to withdraw therapy gradually in patients who have been receiving thedrug chronically.
Overdosage - The most predominant symptoms expected would be hypotension and bradycardia.
Other possible effects could include: CNS (depressed consciousness to seizures), bronchospasm, hypoglycemia, hyperkalemia, respiratory depression, pulmonary edema, other arrhythmias(especially AV block), or asystole.
If overdose is secondary to a recent oral ingestion, emptying the gut and charcoal administrationmay be considered. Monitor ECG, blood glucose, potassium, and, if possible, blood pressure.
Treatment of the cardiovascular and CNS effects are symptomatic. Use fluids, and pressor agents totreat hypotension. Bradycardia may be treated with atropine. If atropine fails, isoproterenol givencautiously has been recommended. Use of a transvenous pacemaker may be necessary. Cardiacfailure can be treated with a digitalis glycosides, diuretics, oxygen and, if necessary, IVaminophylline. Glucagon (5-10 mg IV - Human dose) may increase heart rate and blood pressureand reduce the cardiodepressant effects of propranolol. Seizures generally will respond to IV diazepam.

Drug Interactions

Sympathomimetics (metaproterenol, terbutaline, beta effects of epinephrine, phenylpropanolamine, etc.) may have their actions blocked by propranolol. Additive myocardialdepression may occur with the concurrent use of propranolol and myocardial depressantanesthetic agents. Phenothiazines given with propranolol may exhibit enhanced hypotensiveeffects. Thyroid hormones may decrease the effect of beta blocking agents. Propranolol dosesmay need to be decreased when initiating methimazole or propylthiouracil therapy.
Cimetidine may decrease the metabolism of propranolol and increase blood levels. Furosemideand hydralazine may increase the effects of propranolol. Effects of tubocurarine and succinylcholine may be enhanced with propranolol therapy. Hepatic enzyme induction by phenobarbital, rifampin or phenytoin may increase the metabolism of propranolol. Unopposed alphaeffects of epinephrine may lead to rapid increases in blood pressure and decrease in heart ratewhen given with propranolol. Propranolol may prolong the hypoglycemic effects of insulin therapy. Lidocaine clearance may be impaired by propranolol. Effects of theophylline(bronchodilitation) may be blocked by propranolol. Concurrent use of beta blockers with calciumchannel blockers (or other negative inotropes should be done with caution; particularly in patientswith preexisting cardiomyopathy or CHF.

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