Brands, Medical Use, Clinical Data
Drug Category
- Sympatholytics
- Antihypertensive Agents
- Adrenergic beta-Antagonists
- EENT Drugs
Dosage Forms
- Liquid
- Solution
- Suspension
Brands / Synonyms
Betaxolol HCL; Betaxololum [INN-Latin]; Betaxon; Betoptic; Betoptic Pilo; Betoptic S; Kerlone; Kerlone
Indications
For the management of hypertension.
Pharmacology
Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.
Mechanism of Action
Betaxolol selectively blocks catecholamine stimulation of beta(1)-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Betaxolol can also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles, causing bronchospasm.
Absorption
Absorption of an oral dose is complete. There is a small and consistent first-pass effect resulting in an absolute bioavailability of 89% ± 5% that is unaffected by the concomitant ingestion of food or alcohol.
Toxicity
Oral LD50s are 350 to 400 mg betaxolol/kg in mice and 860 to 980 mg/kg in rats. Predicted symptoms of overdose include bradycardia, congestive heart failure, hypotension, bronchospasm, and hypoglycemia.
Biotrnasformation / Drug Metabolism
Primarily hepatic. Approximately 15% of the dose administered is excreted as unchanged drug, the remainder being metabolites whose contribution to the clinical effect is negligible.
Contraindications
Contraindications include hypersensitivity to betaxolol or any component of the formulation; sinus bradycardia;
heart block greater than first-degree (except in patients with a functioning artificial pacemaker); cardiogenic
shock; uncompensated cardiac failure; pulmonary edema; pregnancy (2nd or 3rd trimester).
Drug Interactions
The following drugs have been coadministered with Kerlone and have not altered its pharmacokinetics: cimetidine,
nifedipine, chlorthalidone, and hydrochlorothiazide. Concomitant administration of Kerlone with the oral
anticoagulant warfarin has been shown not to potentiate the anticoagulant effect of warfarin.
Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents.
Patients treated with a beta-adrenergic receptor blocking agent plus a catecholamine depletor should therefore be
closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural
hypotension.
Should it be decided to discontinue therapy in patients receiving beta-blockers and clonidine concurrently, the
beta-blocker should be discontinued slowly over several days before the gradual withdrawal of clonidine.
Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking
agents when heart function is normal, but should be avoided in patients with impaired cardiac function. Hypotension,
AV conduction disturbances, and left ventricular failure have been reported in some patients receiving
beta-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen. Hypotension was
more likely to occur if the calcium antagonist were a dihydropyridine derivative, e.g., nifedipine, while left
ventricular failure and AV conduction disturbances, including complete heart block, were more likely to occur with
either verapamil or diltiazem.
Risk of Anaphylactic Reaction: Although it is known that patients on beta-blockers may be refractory
to epinephrine in the treatment of anaphylactic shock, beta-blockers can, in addition, interfere with the modulation
of allergic reaction and lead to an increased severity and/or frequency of attacks. Severe allergic reactions
including anaphylaxis have been reported in patients exposed to a variety of allergens either by repeated challenge,
or accidental contact, and with diagnostic or therapeutic agents while receiving beta-blockers. Such patients may be
unresponsive to the usual doses of epinephrine used to treat allergic reaction.
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