Cardiovascular system

2 Cardiovascular system

2.1 Positive inotropic drugs

71 2.7.3 Cardiopulmonary resuscitation 123

2.1.1 Cardiac glycosides

71 2.8 Anticoagulants and protamine 123

2.1.2 Phosphodiesterase inhibitors

73 2.8.1 Parenteral anticoagulants 123

2.2 Diuretics

73 2.8.2 Oral anticoagulants 128

2.2.1 Thiazides and related diuretics

74 2.8.3 Protamine sulphate 131

2.2.2 Loop diuretics

75 2.9 Antiplatelet drugs

2.2.3 Potassium-sparing diuretics and aldosterone antagonists

2.10 Myocardial infarction and fibri-

77 nolysis

2.2.4 Potassium-sparing diuretics with

2.10.1 Management of myocardial other diuretics

78 infarction

2.2.5 Osmotic diuretics

79 2.10.2 Fibrinolytic drugs 136

2.2.6 Mercurial diuretics

79 2.11 Antifibrinolytic drugs and haemostatics

2.2.7 Carbonic anhydrase inhibitors

2.2.8 Diuretics with potassium

79 2.12 Lipid-regulating drugs

2.3 Anti-arrhythmic drugs

2.13 Local sclerosants

2.3.1 Management of arrhythmias

79 C ardiov

2.3.2 Drugs for arrhythmias

81 This chapter also includes advice on the drug man-

2.4 agement of the following: Beta-adrenoceptor blocking

ascular drugs

angina, p. 109

85 arrhythmias, p. 79

2.5 Hypertension and heart failure

92 cardiovascular disease risk, p. 92 and p. 140 heart failure, p. 100

syst

2.5.1 Vasodilator antihypertensive hypertension, p. 92 drugs

93 myocardial infarction, p. 135

em

2.5.2 Centrally acting antihypertensive phaeochromocytoma, p. 99 drugs

2.5.3 Adrenergic neurone blocking drugs

2.5.4 Alpha-adrenoceptor blocking drugs

98 2.1 Positive inotropic drugs

2.5.5 Drugs affecting the renin-angio- tensin system

2.1.1 Cardiac glycosides

2.5.5.1 Angiotensin-converting enzyme

2.1.2 Phosphodiesterase inhibitors

inhibitors

2.5.5.2 Angiotensin-II receptor antago- Positive inotropic drugs increase the force of contrac- nists

tion of the myocardium; for sympathomimetics with

2.5.5.3 inotropic activity see section 2.7.1.

Renin inhibitors

2.6 Nitrates, calcium-channel block- ers, and other antianginal drugs 108

2.1.1 Cardiac glycosides

2.6.1 Nitrates

2.6.2 Cardiac glycosides increase the force of myocardial

Calcium-channel blockers

contraction and reduce conductivity within the atrio-

2.6.3 Other antianginal drugs

ventricular (AV) node. Digoxin is the most commonly

2.6.4 Peripheral vasodilators and used cardiac glycoside. related drugs

Cardiac glycosides are most useful in the treatment of

2.7 supraventricular tachycardias, especially for controlling

Sympathomimetics

121 ventricular response in persistent atrial fibrillation (sec-

2.7.1 Inotropic sympathomimetics

tion 2.3.1). For reference to the role of digoxin in heart Vasoconstrictor sympatho-

2.7.2 failure, see section 2.5.5.

mimetics

For management of atrial fibrillation the maintenance dose of the cardiac glycoside can usually be determined For management of atrial fibrillation the maintenance dose of the cardiac glycoside can usually be determined

Digoxin is now rarely used for rapid control of heart rate (see section 2.3 for the management of supraventricular arrhythmias). Even with intravenous administration, response may take many hours; persistence of tachy- cardia is therefore not an indication for exceeding the recommended dose. The intramuscular route is not recommended.

In patients with heart failure who are in sinus rhythm a loading dose is not required, and a satisfactory plasma- digoxin concentration can be achieved over a period of about a week.

Digoxin has a long half-life and maintenance doses need to be given only once daily (although higher doses may

be divided to avoid nausea). Digitoxin also has a long half-life and maintenance doses need to be given only once daily or on alternate days. Renal function is the most important determinant of digoxin dosage, whereas elimination of digitoxin depends on metabolism by the liver.

Unwanted effects depend both on the concentration of the cardiac glycoside in the plasma and on the sensitiv- ity of the conducting system or of the myocardium, which is often increased in heart disease. It can some- times be difficult to distinguish between toxic effects and clinical deterioration because symptoms of both are similar. Also, the plasma concentration alone cannot indicate toxicity reliably but the likelihood of toxicity increases progressively through the range 1.5 to 3 micr- ograms/litre for digoxin. Cardiac glycosides should be used with special care in the elderly who may be particularly susceptible to digitalis toxicity.

Regular monitoring of plasma-digoxin concentration during maintenance treatment is not necessary unless problems are suspected. Hypokalaemia predisposes the patient to digitalis toxicity; it is managed by giving a potassium sparing diuretic or, if necessary, potassium supplementation.

Toxicity can often be managed by discontinuing digoxin; serious manifestations require urgent specialist manage- ment. Digoxin-specific antibody fragments are avail- able for reversal of life-threatening overdosage (see below).