Drug reference
Mild to moderate essential hypertension ▶BY MOUTH ▶Adult: 200 micrograms once daily for 3 weeks, dose to be taken in the morning, then increased if necessary to 400 micrograms daily in 1–2 divided doses (max. per dose 400 micrograms), maximum daily dose to be given in 2 divided doses; maximum 600 micrograms per day
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Bradycardia. second- or third- degree AV block. severe heart failure. sick sinus syndrome . sino-atrial block Asthma. cardiogenic shock. hypotension. marked bradycardia. metabolic acidosis. phaeochromocytoma (apart from specific use with alpha- blockers). Prinzmetal’s angina. second-degree AV block. severe peripheral arterial disease. sick sinus syndrome. third-degree AV block. uncontrolled heart failure CONTRA-INDICATIONS, FURTHER INFORMATION ▶Bronchospasm Beta-blockers, including those considered to be cardioselective, should usually be avoided in patients with a history of asthma, bronchospasm or a history of obstructive airways disease. However, when there is no alternative, a cardioselective beta-blocker can be given to these patients with caution and under specialist supervision. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken.
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First-degree AV block. moderate heart failure. severe coronary artery disease. unstable angina CAUTIONS, FURTHER INFORMATION ▶Elderly For centrally-acting antihypertensives, prescription potentially inappropriate (STOPP criteria), unless clear intolerance of, or lack of efficacy with, other classes of antihypertensives (generally less well tolerated by older people). See also Prescribing in the elderly p. 33. Diabetes. first-degree AV block. history of obstructive airways disease (introduce cautiously). myasthenia gravis. portal hypertension (risk of deterioration in liver function). psoriasis. symptoms of hypoglycaemia may be masked. symptoms of thyrotoxicosis may be masked CAUTIONS, FURTHER INFORMATION Cardiovascular system ▶Elderly Prescription potentially inappropriate (STOPP criteria): . in combination with verapamil or diltiazem (risk of heart block) . with bradycardia (heart rate less than 50 beats per minute), type II heart block or complete heart block (risk of complete heart block, asystole) . in diabetes mellitus patients with frequent hypoglycaemic episodes (risk of suppressing hypoglycaemic symptoms) . if prescribed a non-selective beta-blocker (including topical beta-blockers) in a history of asthma requiring treatment (risk of increased bronchospasm) See also Prescribing in the elderly p. 33.
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Caution is advised in patients with a history of hypersensitivity—may increase sensitivity to allergens and result in more serious hypersensitivity response. Furthermore beta-adrenoceptor blockers may reduce response to adrenaline (epinephrine).
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→Appendix 1: moxonidine
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▶Common or very common Asthenia. diarrhoea. dizziness. drowsiness. dry mouth. dyspepsia. headache. insomnia. nausea. pain. skin reactions. vertigo. vomiting ▶Uncommon Angioedema. bradycardia. nervousness. oedema. syncope. tinnitus ▶Common or very common Abdominal discomfort. bradycardia. confusion. depression. diarrhoea. dizziness. dry eye (reversible on discontinuation). dyspnoea. erectile dysfunction. fatigue. headache. heart failure. nausea. paraesthesia. peripheral coldness. peripheral vascular disease. rash (reversible on discontinuation). sleep disorders. syncope. visual impairment. vomiting ▶Uncommon Atrioventricular block. bronchospasm ▶Rare or very rare Hallucination SIDE-EFFECTS, FURTHER INFORMATION With administration by intravenous injection, excessive bradycardia can occur and may be countered with intravenous injection of atropine sulfate. Overdose Therapeutic overdosages with beta-blockers may cause lightheadedness, dizziness, and possibly syncope as a result of bradycardia and hypotension; heart failure may be precipitated or exacerbated. With administration by intravenous injection, excessive bradycardia can occur and may be countered with intravenous injection of atropine sulfate. For details on the management of poisoning, see Beta- blockers, under Emergency treatment of poisoning.
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Manufacturer advises avoid—no information available. Beta-blockers may cause intra-uterine growth restriction, neonatal hypoglycaemia, and bradycardia; the risk is greater in severe hypertension.
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Present in milk—manufacturer advises avoid. With systemic use in the mother, infants should be monitored as there is a risk of possible toxicity due to beta-blockade. However, the amount of most beta- blockers present in milk is too small to affect infants.
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Avoid if eGFR less than 30 mL/minute/1.73 m2. Dose adjustments Max. single dose 200 micrograms and max. daily dose 400 micrograms if eGFR 30–60 mL/minute/1.73 m2.
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Monitor lung function (in patients with a history of obstructive airway disease).
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 3 ▶Moxonidine (Non-proprietary) Moxonidine 200 microgram Moxonidine 200microgram tablets | 28 tablet P £5.80 DT = £1.23 Moxonidine 300 microgram Moxonidine 300microgram tablets | 28 tablet P £9.00 DT = £1.35 Moxonidine 400 microgram Moxonidine 400microgram tablets | 28 tablet P £10.50 DT = £1.33 ▶Physiotens (Mylan) Moxonidine 200 microgram Physiotens 200microgram tablets | 28 tablet P £9.72 DT = £1.23 Moxonidine 300 microgram Physiotens 300microgram tablets | 28 tablet P £11.49 DT = £1.35 Moxonidine 400 microgram Physiotens 400microgram tablets | 28 tablet P £13.26 DT = £1.33 BETA-ADRENOCEPTOR BLOCKERS Beta-adrenoceptor blocking drugs Cardiovascular system Overview Beta-adrenoceptor blocking drugs (beta-blockers) block the beta-adrenoceptors in the heart, peripheral vasculature, bronchi, pancreas, and liver. Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them, which may affect choice in treating particular diseases or individual patients. Intrinsic sympathomimetic activity (ISA, partial agonist activity) represents the capacity of beta-blockers to stimulate as well as to block adrenergic receptors. Celiprolol hydrochloride p. 165, pindolol p. 161, acebutolol p. 163, and oxprenolol hydrochloride have intrinsic sympathomimetic activity; they tend to cause less bradycardia than the other beta-blockers and may also cause less coldness of the extremities. Some beta-blockers are lipid soluble and some are water soluble. Water-soluble beta-blockers (such as atenolol p. 164, celiprolol hydrochloride, nadolol p. 161, and sotalol hydrochloride p. 115) are less likely to enter the brain, and may therefore cause less sleep disturbance and nightmares. Water-soluble beta-blockers are excreted by the kidneys and dosage reduction is often necessary in renal impairment. Beta-blockers with a relatively short duration of action have to be given two or three times daily. Many of these are, however, available in modified-release formulations so that administration once daily is adequate for hypertension. For angina twice-daily treatment may sometimes be needed even with a modified-release formulation. Some beta- blockers, such as atenolol, bisoprolol fumarate p. 165, celiprolol hydrochloride, and nadolol, have an intrinsically longer duration of action and need to be given only once daily. Beta-blockers slow the heart and can depress the myocardium; they are contra-indicated in patients with second- or third-degree heart block. Beta-blockers should also be avoided in patients with worsening unstable heart failure; care is required when initiating a beta-blocker in those with stable heart failure. Labetalol hydrochloride p. 160, celiprolol hydrochloride, carvedilol p. 160, and nebivolol p. 167 are beta-blockers that have, in addition, an arteriolar vasodilating action, by diverse mechanisms, and thus lower peripheral resistance. There is no evidence that these drugs have important advantages over other beta-blockers in the treatment of hypertension. Beta-blockers can precipitate bronchospasm and should therefore usually be avoided in patients with a history of asthma. When there is no suitable alternative, it may be necessary for a patient with well-controlled asthma, or chronic obstructive pulmonary disease (without significant reversible airways obstruction), to receive treatment with a beta-blocker for a co-existing condition (e.g. heart failure or following myocardial infarction). In this situation, a cardioselective beta-blocker should be selected and initiated at a low dose by a specialist; the patient should be closely monitored for adverse effects. Atenolol, bisoprolol fumarate, metoprolol tartrate p. 166, nebivolol, and (to a lesser extent) acebutolol, have less effect on the beta2(bronchial) receptors and are, therefore, relatively cardioselective, but they are not cardiospecific. They have a lesser effect on airways resistance but are not free of this side-effect. Beta-blockers are also associated with fatigue, coldness of the extremities (may be less common with those with ISA), and sleep disturbances with nightmares (may be less common with the water-soluble beta-blockers). Beta-blockers can affect carbohydrate metabolism, causing hypoglycaemia or hyperglycaemia in patients with or without diabetes; they can also interfere with metabolic and autonomic responses to hypoglycaemia, thereby masking symptoms such as tachycardia. However, beta-blockers are not contra-indicated in diabetes, although the cardioselective beta-blockers may be preferred. Beta- blockers should be avoided altogether in those with frequent episodes of hypoglycaemia. Beta-blockers, especially when combined with a thiazide diuretic, should be avoided for the routine treatment of uncomplicated hypertension in patients with diabetes or in those at high risk of developing diabetes. Hypertension The mode of action of beta-blockers in hypertension is not understood, but they reduce cardiac output, alter baroceptor reflex sensitivity, and block peripheral adrenoceptors. Some beta-blockers depress plasma renin secretion. It is possible that a central effect may also partly explain their mode of action. Beta-blockers are effective for reducing blood pressure but other antihypertensives are usually more effective for reducing the incidence of stroke, myocardial infarction, and cardiovascular mortality, especially in the elderly. Other antihypertensives are therefore preferred for routine initial treatment of uncomplicated hypertension. In general, the dose of a beta-blocker does not have to be high. Beta-blockers can be used to control the pulse rate in patients with phaeochromocytoma. However, they should never be used alone as beta-blockade without concurrent alpha-blockade may lead to a hypertensive crisis. For this reason phenoxybenzamine hydrochloride p. 193 should always be used together with the beta-blocker. Angina By reducing cardiac work beta-blockers improve exercise tolerance and relieve symptoms in patients with angina (see management of stable angina and acute coronary syndromes for further details). As with hypertension there is no good evidence of the superiority of any one drug, although occasionally a patient will respond better to one beta- blocker than to another. There is some evidence that sudden withdrawal may cause an exacerbation of angina and therefore gradual reduction of dose is preferable when beta- blockers are to be stopped. There is a risk of precipitating heart failure when beta-blockers and verapamil are used together in established ischaemic heart disease. Myocardial infarction For specific comments see management of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. Several studies have shown that some beta-blockers can reduce the recurrence rate of myocardial infarction. However, uncontrolled heart failure, hypotension, bradyarrhythmias, and obstructive airways disease render beta-blockers unsuitable in some patients following a myocardial infarction. Atenolol and metoprolol tartrate may reduce early mortality after intravenous and subsequent oral administration in the acute phase, while acebutolol, metoprolol tartrate, propranolol hydrochloride p. 162, and timolol maleate p. 163 have protective value when started in the early convalescent phase. The evidence relating to other beta-blockers is less convincing; some have not been tested in trials of secondary prevention. Arrhythmias Beta-blockers act as anti-arrhythmic drugs principally by attenuating the effects of the sympathetic system on automaticity and conductivity within the heart. They can be used in conjunction with digoxin to control the ventricular response in atrial fibrillation, especially in patients with thyrotoxicosis. Beta-blockers are also useful in the management of supraventricular tachycardias, and are used to control those following myocardial infarction. Esmolol hydrochloride p. 166 is a relatively cardioselective beta-blocker with a very short duration of action, used intravenously for the short-term treatment of supraventricular arrhythmias, sinus tachycardia, or hypertension, particularly in the peri-operative period. It may also be used in other situations, such as acute myocardial infarction, when sustained beta-blockade might be hazardous. Sotalol hydrochloride p. 115, a non-cardioselective beta- blocker with additional class III anti-arrhythmic activity, is used for prophylaxis in paroxysmal supraventricular arrhythmias. It also suppresses ventricular ectopic beats and non-sustained ventricular tachycardia. It has been shown to be more effective than lidocaine in the termination of spontaneous sustained ventricular tachycardia due to coronary disease or cardiomyopathy. However, it may induce torsade de pointes in susceptible patients. Heart failure Beta-blockers may produce benefit in heart failure by blocking sympathetic activity. Bisoprolol fumarate p. 165 and carvedilol p. 160 reduce mortality in any grade of stable heart failure; nebivolol p. 167 is licensed for stable mild to moderate heart failure in patients over 70 years. Ideally, treatment should be initiated by those experienced in the management of heart failure. Thyrotoxicosis Beta-blockers are used in pre-operative preparation for thyroidectomy. Administration of propranolol hydrochloride p. 162 can reverse clinical symptoms of thyrotoxicosis within 4 days. Routine tests of increased thyroid function remain unaltered. The thyroid gland is rendered less vascular thus making surgery easier. Other uses Beta-blockers have been used to alleviate some symptoms of anxiety; probably patients with palpitation, tremor, and tachycardia respond best. Beta-blockers are also used in the prophylaxis of migraine. Betaxolol p. 1243, levobunolol hydrochloride p. 1244, and timolol maleate p. 163 are used topically in glaucoma. Beta-adrenoceptor blockers f (systemic)
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Avoid abrupt withdrawal (if concomitant treatment with beta-blocker has to be stopped, discontinue beta-blocker first, then moxonidine after a few days). Avoid abrupt withdrawal especially in ischaemic heart disease. Sudden cessation of a beta-blocker can cause a rebound worsening of myocardial ischaemia and therefore gradual reduction of dose is preferable when beta-blockers are to be stopped. BETA-ADRENOCEPTOR BLOCKERS › ALPHA- AND BETA-ADRENOCEPTOR BLOCKERS eiiii F 159 Cardiovascular system
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200 micrograms once daily for 3 weeks, dose to
First-line fragment. Read the complete Indications and Dose section above.
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