Acebutolol is a cardioselective beta blocker with ISA (Intrinsic Sympathomimetic Activity, see article on Pindolol). It is therefore more suitable than non cardioselective beta blockers, if a patient with Asthma bronchiale or chronic obstructive lung disease (COLD) needs treatment with a beta blocker. In doses lower than 800mg daily its constricting effects on the bronchial system and smooth muscle vessels are only 10% to 30% of those observed under Propranolol treatment. But there is experimental evidence that the cardioselective properties diminish at doses of 800mg/day or more. The drug has lipophilic properties, this means that it crosses the Blood Brain Barrier. Acebutolol has no negative impact on serum lipids (cholesterol and triglycerides), in particular no HDL decrease has been observed. In this regard it is unlike to many other beta blockers which have this unfavourable property. The drug works in hypertensive patients with high or normal and low renin plasma concentrations, although acebutolol may be more efficient in patients with high or normal renin plasma concentrations. It seems that in clinical relevant concentrations a membrane stabilizing effect does not play an important role.

Pharmacokinetics

Acebutolol is well absorbed from the GI tract, but undergoes substantial first-pass-metabolization, leading to a bioavailability of only 35% to 50%. Peak plasma levels of acebutolol are reached within 2 to 2,5 hours after oral dosing, those of the active main metabolite diacetolol after 4 hours. Acebutolol has a halflife of 3 to 4 hours, diacetolol one of 8 to 13 hours. Acebutolol undergoes extensive hepatic metabolization resulting in the desbutyl amine acetolol which is readily converted into diacetolol. Diacetolol is as aktive as acebutolol (equipotency) and appears to have the same pharmakologic profile. Geriatric patients tend to have higher peak plasma levels of both acebutolol and diacetolol and a slightly prolonged excretion. Excretion is substantially prolonged in patients with renal impairment; a dose reduction may be needed. Liver cirrhosis does not seem to alter the pharmakokinetic profile of parent drug and metabolite.

Uses

hypertension
angina pectoris, including instable angina
ventricular and atrial cardiac arrhythmias
acute myocardial infarction in high risk patients

Contraindications and Precautions

See article on Propranolol. Acebutolol may be suitable in patients with Asthma bronchiale or COLD.

Side Effects

See article on Propranolol. The development of ANA (Anti-Nuclear-Antibodies) has been found in 10 to 30% of patients under treatment with acebutolol. A systemic disease with arthralgic pain and myalgias has been developed in 1%. A lupus erythematosus like syndrome with skin rash and multiforme organ involvement is even less frequent. The incidence of both ANA and symptomatic disease under acebutolol is higher than under Propranolol. Female patients develop these symptoms more likely than male patients. Also, a few cases of hepatotoxicity with increased liver enzymes (ALT, AST) have been seen. Altogether, 5 to 6% of all patients treated have to discontinue acebutolol due to intolerable side effects. The treatment should be, if possible, discontinued gradually in order to avoid a withdrawal syndrome with increased frequency of angina and even precipitation of myocardial infarction.

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Comparison of Drugs Used to Treat Chronic Hypertension - Statistical Data Included
From American Family Physician, 7/1/99

Physicians today have a variety of drugs from which to choose when treating a patient with hypertension. These medications must be carefully chosen to fit the patient's needs, and even then, responses will vary. The Medical Letter recently outlined the most common drugs prescribed for hypertension in the United States. All categories of drugs were reviewed, except for those used in hypertensive emergencies.

Angiotensin-converting enzyme (ACE) inhibitors are considered generally effective and well tolerated but appear to be less effective in black patients. ACE inhibitors prolong survival in patients with heart failure or left ventricular dysfunction after acute myocardial infarction. They may also preserve renal function in patients with diabetes or nondiabetic nephropathies. However, patients who are volume depleted, have bilateral renovascular disease or congestive heart failure, or are taking diuretics should not take ACE inhibitors. In addition, pregnant women should not use ACE inhibitors because of the risk of fetal injury and death, but exposure at the time of conception or early in pregnancy does not appear to produce adverse outcomes.

Beta blockers are also considered to be generally effective and, like ACE inhibitors, they appear to be less effective in black patients. Beta blockers alone appear to be less effective than diuretics alone in treating hypertension in the elderly. The cardioselective beta blockers, including metoprolol, acebutolol and betaxolol, have a greater effect on cardiac adrenergic receptors than on receptors in the bronchi and blood vessels. However, they become less selective with increased dosages, and even low dosages of cardioselective beta blockers can cause bronchospasm in patients with asthma.

Calcium-channel blockers cause vasodilatation, which decreases peripheral resistance. The heart's response to this action varies, depending on the specific medication given. Some classes of calcium- channel blockers actually slow the heart rate, affecting atrioventricular conduction, and should be used with caution in patients taking beta blockers concurrently. Calcium-channel blockers should also be used with caution in patients with heart failure. Short- acting calcium-channel blockers, particularly nefedipine, should not be used for treatment of hypertension.

Diuretics decrease mortality in patients with hypertension. Many thiazide diuretics used in the treatment of isolated systolic hypertension have also been shown to reduce the incidence of stroke and cardiovascular events in elderly patients. One advantage to using diuretics is that small dosages are very effective. Dosages as low as 6.25 mg daily can enhance the effectiveness of other drugs and minimize adverse effects such as hypokalemia.

Central alpha-adrenergic agonists do not inhibit reflex responses as completely as sympatholytic drugs that act peripherally. However, they can produce adverse effects such as sedation, dry mouth and depression.

Alpha-adrenergic blocking agents cause less tachycardia than vasodilators but often cause postural hypotension, particularly after the first dose. Unlike beta blockers and diuretics, these drugs do not adversely affect serum lipid levels; rather, they may increase the ratio of high-density lipoprotein (HDL) to total cholesterol. While they may relieve the symptoms of prostatism in men, they may cause stress incontinence in women.

Direct vasodilators often cause reflex tachycardia but rarely cause orthostatic hypotension as do alpha blockers. Vasodilators are typically given in combination with a beta blocker or a centrally acting drug to minimize the reflex increase in heart rate and cardiac output. A loop diuretic should also be given in conjunction with vasodilators to avoid sodium and water retention. Patients with coronary artery disease should not be given vasodilators.

The authors conclude that diuretics, beta blockers, ACE inhibitors, angiotensin receptor antagonists and calcium-channel blockers are the agents best tolerated in the treatment of hypertension. Some, but not all, of the consultants believe that use of calcium-channel blockers should be reserved for patients who do not respond to or cannot tolerate diuretics, beta blockers or ACE inhibitors.

Barbara Apgar, M.D., M.S.

Medical Letter consultants. Drugs for hypertension. Med Lett Drugs Ther March 12, 1999;41(1048):23-8.

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