ATENOLOL

Chemistry - A beta1 adrenergic blocking agent, atenolol occurs as a white, crystalline powder. At 37°C, 26.5 mg are soluble in 1 ml of water. The pH of the commercially available injection is adjusted to 5.5-6.5.

Storage, Stability, Compatibility

Tablets should be stored at room temperature and protectedfrom heat, light and moisture. The injection solution should be stored at room temperature and protected from light.
Atenolol injection is reported to be physically compatible with morphine sulfate injection andmeperidine HCl for at least 4 hours. Dextrose injections, sodium chloride injections and combinations of the two are recommended to be used as diluents when given parenterally.

Pharmacology - ATENOLOL

Atenolol is a relatively specific beta 1 blocker. At higher dosages this specificitymay be lost and beta 2 blockade can occur. Atenolol does not possess any intrinsic sympathomimetic activity like pindolol nor does it possess membrane stabilizing activity like pindolol orpropranolol. Cardiovascular effects secondary to atenolol's negative inotropic and chronotropicactions include: decreased sinus heart rate, slowed AV conduction, diminished cardiac output at restand during exercise, decreased myocardial oxygen demand, reduced blood pressure, and inhibitionof isoproterenol-induced tachycardia.

Uses, Indications

Because atenolol is relatively safe to use in animals with bronchospastic disease, it is often chosen over propranolol. It may be effective in supraventricular tachyarrhythmias, premature ventricular contractions (PVC's, VPC's), systemic hypertension and in treating cats with hypertrophic cardiomyopathy.

Pharmacokinetics - ATENOLOL

Only about 50-60% of an oral dose is absorbed in humans, but it is rapidlyabsorbed. The drug has very low protein binding characteristics (5-15%) and is distributed well intomost tissues. Atenolol has low lipid solubility and unlike propranolol, only small amounts ofatenolol are distributed into the CNS. Atenolol crosses the placenta and levels in milk are higherthan those found in plasma. Atenolol is minimally biotransformed in the liver; 40-50% is excretedunchanged in the urine and the bulk of the remainder is excreted in the feces unchanged(unabsorbed drug). Reported half life in dogs is 3.2 hours; 6-7 hours in humans.

Contraindications, Precautions, Reproductive Safety

Atenolol is contraindicated in patientswith overt heart failure, hypersensitivity to this class of agents, greater than first degree heart block, or sinus bradycardia. Non-specific beta-blockers are generally contraindicated in patients with CHFunless secondary to a tachyarrhythmia responsive to beta-blocker therapy. They are also relativelycontraindicated in patients with bronchospastic lung disease.
Atenolol should be used cautiously in patients with significant renal insufficiency. It should alsobe used cautiously in patients with sinus node dysfunction.
Atenolol (at high dosages) can mask the symptoms associated with hypoglycemia. It can alsocause hypoglycemia or hyperglycemia and, therefore, should be used cautiously in labile diabeticpatients.
Atenolol can mask the symptoms associated with thyrotoxicosis, but it may be used clinically totreat the symptoms associated with this condition.

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 (less so with beta 1 specific drugs like atenolol). Syncope and diarrhea have also been reported in canine patients withbeta blockers.
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 the drug chronically.
Overdosage - There is limited information available on atenolol overdosage. Humans have apparently survived dosages of up to 5 grams. The most predominant symptoms expected would beextensions of the drug's pharmacologic effects: hypotension, bradycardia, bronchospasm, cardiacfailure and hypoglycemia.
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 effects are symptomatic. Use fluids and pressor agents to treathypotension. 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 and oxygen. Glucagon (5-10 mg IV -
Human dose) may increase heart rate and blood pressure and reduce the cardiodepressant effects ofatenolol.

Drug Interactions

Sympathomimetics (metaproterenol, terbutaline, beta effects of epinephrine, phenylpropanolamine, etc.) may have their actions blocked by atenolol and they may, in turn, reducethe efficacy of atenolol. Additive myocardial depression may occur with the concurrent use ofatenolol and myocardial depressant anesthetic agents. Phenothiazines given with atenolol mayexhibit enhanced hypotensive effects. Furosemide and hydralazine or other hypotensiveproducing drugs may increase the hypotensive effects of atenolol. Atenolol may prolong thehypoglycemic effects of insulin therapy. Concurrent use of beta blockers with calcium channelblockers (or other negative inotropics) should be done with caution, particularly in patients withpreexisting cardiomyopathy or CHF.