BMA Concise Guide to Medicine & Drugs

HEART AND CIRCULATION

The blood transports oxygen, nutrients, and heat, contains chemical messages in the form of drugs and hormones, and carries away waste products for excretion by the kidneys. Blood is pumped by the heart to and from the lungs, and then in a separate circuit to the rest of the body, including the brain, digestive organs, muscles, kidneys, and skin.

The heart is a pump with four chambers – two atria and two ventricles. The atrium and ventricle on the left side pump oxygenated blood to the body, while those on the right pump deoxygenated blood to the lungs. Backflow of blood is stopped by one-way valves at the chamber exits. Arteries carry blood away from the heart. Their muscle walls are elastic, contracting and dilating in response to nerve signals. Veins carry blood back to the heart. Their walls are thinner and less elastic than those of arteries.

WHAT CAN GO WRONG

The efficiency of the circulation may be impaired by weakening of the pumping action of the heart (heart failure) or by irregularity of the heart rate (arrhythmia). In addition, the blood vessels may be narrowed and clogged by fatty deposits (atherosclerosis). This may reduce blood supply to the brain, the extremities (peripheral vascular disease), or the heart muscle (coronary heart disease), causing angina. These last disorders can be complicated by the formation of clots that may block a blood vessel. A clot in the arteries supplying the heart muscle is known as coronary thrombosis; a clot in an artery inside the brain is the most frequent cause of stroke.

One common circulatory disorder is abnormally high blood pressure (hypertension), in which the pressure of circulating blood on the vessel walls is increased for reasons not yet fully understood. One factor may be loss of elasticity of the vessel walls (arteriosclerosis). Several other conditions, such as migraine and Raynaud’s disease, are caused by temporary alterations to blood vessel size.

WHY DRUGS ARE USED

Because people suffering from heart disease often have more than one problem, several drugs may be prescribed at once. Many act directly on the heart to alter the rate and rhythm of the heart beat. These are known as anti-arrhythmics and include beta blockers, calcium channel blockers, and digoxin.

Other drugs affect the diameter of the blood vessels, either by dilating them (vasodilators) to improve blood flow and reduce blood pressure, or by constricting them (vasoconstrictors).

Drugs may also reduce blood volume and fat levels, and alter clotting ability. Diuretics (used in the treatment of hypertension and heart failure) increase the body’s excretion of salt and water. Lipid-lowering drugs reduce blood cholesterol levels, thereby minimizing the risk of atherosclerosis. Drugs to reduce blood clotting are administered if there is a risk of abnormal blood clots forming in the heart, veins, or arteries. Drugs that increase clotting are given when the body’s natural clotting mechanism is defective.

MAJOR DRUG GROUPS

· Digitalis drugs

· Beta blockers

· Vasodilators

· Diuretics

· Anti-arrhythmics

· Anti-angina drugs

· Antihypertensive drugs

· Lipid-lowering drugs

· Drugs that affect blood clotting

Digitalis drugs

Digitalis is the collective term for the naturally occurring substances (also called cardiac glycosides) that are found in the leaves of plants of the foxglove family and used to treat certain heart disorders. The principal drugs in this group are digoxin and digitoxin. Digoxin is more commonly used because it is shorter acting and dosage is easier to adjust (see also Risks and special precautions).

WHY THEY ARE USED

Digitalis drugs do not cure heart disease but improve the heart’s pumping action and thereby relieve many of the symptoms that result from poor heart function. They are useful for treating conditions in which the heart beats irregularly or too rapidly (notably in atrial fibrillation, see Anti-arrhythmics), when it pumps too weakly (in congestive heart failure), or when the heart muscle is damaged and weakened following a heart attack.

Digitalis drugs can be used for a short period when the heart is working poorly, but in many cases they have to be taken indefinitely. Their effect does not diminish with time. In heart failure, digitalis drugs are often given together with a diuretic drug.

HOW THEY WORK

The normal heart beat results from electrical impulses generated in nerve tissue within the heart. These cause the heart muscle to contract and pump blood. By reducing the flow of electrical impulses in the heart, digitalis makes the heart beat more slowly.

The force with which the heart muscle contracts depends on chemical changes in the heart muscle. By promoting these chemical changes, digitalis increases the force of muscle contraction each time the heart is stimulated. This compensates for the loss of power that occurs when some of the muscle is damaged following a heart attack. The stronger heart beat increases blood flow to the kidneys. This increases urine production and helps to remove the excess fluid that often accumulates as a result of heart failure.

HOW THEY AFFECT YOU

Digitalis relieves the symptoms of heart failure – fatigue, breathlessness, and swelling of the legs – and increases your capacity for exercise. The frequency with which you need to pass urine may also be increased initially.

RISKS AND SPECIAL PRECAUTIONS

Digitalis drugs can be toxic; if blood levels rise too high, symptoms of digitalis poisoning (including nausea, appetite loss, vomiting, diarrhoea, confusion, and visual disturbance) may occur. It is important to report such symptoms to your doctor promptly.

Digoxin is normally removed from the body by the kidneys; if kidney function is impaired, the drug is more likely to accumulate in the body and cause toxic effects. Digitoxin, which is broken down in the liver, is sometimes preferred in such cases. Digitoxin can accumulate after repeated dosage if liver function is severely impaired.

Both digoxin and digitoxin are more toxic when blood potassium levels are low. Potassium deficiency is commonly due to diuretics, so that people taking these with digitalis drugs need to have the effects of both drugs and blood potassium levels carefully monitored. Potassium supplements may be required.

COMMON DRUGS

Digitoxin, Digoxin

Beta blockers

Beta blockers are drugs that interrupt the transmission of stimuli through beta receptors of the body. Since the actions that they block originate in the adrenal glands (and elsewhere) they are also sometimes called beta adrenergic blocking agents. There are two types of beta receptor in the body: beta 1 and beta 2. Beta 1 receptors are located mainly in the heart muscle; beta 2 receptors in the airways and blood vessels. Cardioselective drugs act mainly on beta 1 receptors: non-cardioselective drugs on both types. Used mainly in heart disorders, these drugs are occasionally prescribed for other conditions.

WHY THEY ARE USED

Beta blockers are used for treating angina and irregular heart rhythms. They may also be used for treating hypertension but are not usually used to initiate treatment. They are often given after a heart attack to reduce the likelihood of abnormal heart rhythms or further damage to the heart muscle. They are also prescribed to improve heart function in heart muscle disorders, known as cardiomyopathies.

Beta blockers may also be given to prevent migraine headaches, or to reduce the physical symptoms of anxiety. These drugs may be given to control symptoms of an overactive thyroid gland. A beta blocker is sometimes given in the form of eye drops in glaucoma to lower the fluid pressure inside the eye.

HOW THEY WORK

By occupying the beta receptors, in different parts of the body, beta blockers nullify the stimulating action of norepinephrine (noradrenaline), the main “fight or flight” hormone. As a result, they reduce the force and speed of the heart beat and prevent the dilation of the blood vessels surrounding the brain and leading to the extremities.

Heart Slowing of the heart rate and reduction of the force of the heart beat reduces the workload of the heart, helping to prevent angina and abnormal heart rhythms. This action may worsen heart failure, however.

Lungs Constriction of the airways may provoke breathlessness in asthmatic people or those with chronic bronchitis.

Brain Dilation of the blood vessels that surround the brain is inhibited, thereby preventing migraine.

Blood vessels Constriction of the blood vessels may cause coldness of the hands and feet.

Blood pressure The pressure is lowered due to reduction in the rate and force at which the heart pumps blood around the body.

Eye Beta blocker eye drops reduce fluid production, lowering pressure inside the eye.

Muscles Muscle tremor caused by anxiety or overactivity of the thyroid gland is reduced.

HOW THEY AFFECT YOU

Beta blockers are taken to treat angina. They reduce the frequency and severity of attacks. As part of the treatment for hypertension, beta blockers help to lower blood pressure and thus reduce the risks that are associated with this condition. Beta blockers help to prevent severe attacks of arrhythmia, in which the heart beat is wild and uncontrolled.

Because beta blockers affect many parts of the body, they often produce minor side effects. By reducing the heart rate and air flow to the lungs, they may reduce the capacity for strenuous exercise, although this is unlikely to be noticed by somebody whose physical activity was previously limited by heart problems. Many people experience cold hands and feet while taking these drugs as a result of the reduction in the blood supply to the limbs. Reduced circulation can also lead to temporary erectile dysfunction during treatment.

RISKS AND SPECIAL PRECAUTIONS

The main risk of beta blockers is that of provoking breathing difficulties as a result of their blocking effect on beta receptors in the lungs. Cardioselective beta blockers, which act principally on the heart, are thought less likely than non-cardioselective ones to cause such problems. But all beta blockers are prescribed with caution for people who have asthma, bronchitis, or other forms of respiratory disease.

Beta blockers are not commonly prescribed to people who have poor circulation in the limbs because they reduce blood flow and may aggravate such conditions. They may be of some benefit in heart failure, but treatment is usually initiated by specialists. People with diabetes who need to take beta blockers should be aware that they may notice a change in the warning signs of low blood sugar; in particular, they may find that symptoms such as palpitations and tremor are suppressed.

Beta blockers should not be stopped suddenly after prolonged use; this may provoke a sudden and severe recurrence of symptoms of the original disorder, even a heart attack. The blood pressure may also rise markedly. When treatment with beta blockers needs to be stopped, it should be withdrawn gradually under medical supervision.

COMMON DRUGS

Cardioselective Acebutolol, Atenolol, Betaxolol, Bisoprolol, Celiprolol, Esmolol, Metoprolol, Nebivolol

Non-cardioselective Carvedilol, Labetalol, Nadolol, Oxprenolol, Pindolol, Propranolol, Sotalol, Timolol

Vasodilators

Vasodilators are drugs that widen blood vessels. Their most obvious use is to reverse narrowing of the blood vessels when this leads to reduced blood flow and, consequently, a lower oxygen supply to parts of the body. This problem occurs in angina, when narrowing of the coronary arteries reduces blood supply to the heart muscle. Vasodilators are often used to treat high blood pressure (hypertension).

WHY THEY ARE USED

Vasodilators improve blood flow and thus the oxygen supply to areas of the body where they are most needed. In angina, dilation of blood vessels throughout the body reduces the force with which the heart needs to pump and thereby eases its workload (see also Anti-angina drugs). This may also be helpful in treating congestive heart failure when other treatments are not effective.

Because blood pressure is partly dependent on the diameter of blood vessels, vasodilators are often helpful for hypertension.

In peripheral vascular disease, narrowed blood vessels in the legs cannot supply sufficient blood to the extremities, often leading to pain in the legs during exercise. Unfortunately, because the vessels are narrowed by atherosclerosis, vasodilators have little effect.

HOW THEY WORK

Vasodilators widen the blood vessels by relaxing the muscles surrounding them, either by affecting the action of the muscles directly (nitrates, hydralazine, and calcium channel blockers), or by interfering with the nerve signals that govern contraction of the blood vessels (alpha blockers). ACE (angiotensin-converting enzyme) inhibitors block the activity of an enzyme in the blood that is responsible for producing angiotensin II, a powerful vasoconstrictor. Angiotensin II blockers prevent angiotensin II from constricting the blood vessels by blocking its receptors within the vessels.

HOW THEY AFFECT YOU

As well as relieving the symptoms of the disorders for which they are taken, vasodilators can have many minor side effects related to their action on the circulation. Flushing and headaches are common at the start of treatment. Dizziness and fainting may also occur as a result of lowered blood pressure, which is often worse on standing. Dilation of the blood vessels can also cause fluid build-up, leading to swelling, particularly of the ankles.

RISKS AND SPECIAL PRECAUTIONS

The major risk is of blood pressure falling too low; vasodilators are used with caution in people with unstable blood pressure. It is also advisable to sit or lie down after taking the first dose of a vasodilator.

COMMON DRUGS

ACE inhibitors Captopril, Cilazapril, Enalapril, Fosinopril, Lisinopril, Perindopril, Quinapril, Ramipril, Trandolapril

Angiotensin II blockers Candesartan, Irbesartan, Losartan, Telmisartan, Valsartan

Alpha blockers Doxazosin, Indoramin, Prazosin, Terazosin

Potassium channel activators Nicorandil

Nitrates Glyceryl trinitrate, Isosorbide dinitrate/mononitrate

Calcium channel blockers Amlodipine, Diltiazem, Felodipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Verapamil

Peripheral vasodilators Cilastazol, Naftidrofuryl, Pentoxifylline

Other drugs Hydralazine, Minoxidil

Diuretics

Diuretic drugs help to turn excess body water into urine. As the urine is expelled, two disorders are relieved: the tissues become less water-swollen (oedema) and the heart action improves because it has to pump a smaller volume of blood. There are several classes of diuretic, each of which has different uses, modes of action, and effects (see Types of diuretic). But all diuretics act on the kidneys, the organs that govern the water content of the body.

WHY THEY ARE USED

Diuretics are most commonly used in the treatment of high blood pressure (hypertension). By removing a larger amount of water than usual from the bloodstream, the kidneys reduce the total volume of blood circulating. This drop in volume causes a reduction of the pressure within the blood vessels (see Antihypertensive drugs).

Diuretics are also widely used to treat heart failure in which the heart’s pumping mechanism has become weak. In the treatment of this disorder, they remove fluid that has accumulated in the tissues and lungs. The resulting drop in blood volume reduces the work of the heart.

Other conditions for which diuretics are often prescribed include nephrotic syndrome (a kidney disorder that causes oedema), liver cirrhosis (in which fluid may accumulate in the abdominal cavity), and premenstrual syndrome (when hormonal activity can lead to fluid retention and bloating).

Less commonly, diuretics are used to treat glaucoma and Ménière’s disease (see Anti-emetics).

TYPES OF DIURETIC

Thiazides The most commonly prescribed diuretics, thiazides are often given with potassium supplements, or in conjunction with a potassium-sparing diuretic, because they may lead to potassium deficiency.

Loop diuretics These fast-acting, powerful drugs increase urine output for a few hours and are therefore sometimes used in emergencies. They can cause excessive potassium loss, which may need to be prevented as for thiazides. Large doses given into a vein may disturb hearing.

Potassium-sparing diuretics These mild diuretics are usually used in conjunction with a thiazide or a loop diuretic to prevent excessive loss of potassium.

Osmotic diuretics Prescribed only rarely, osmotics are used to maintain the urine flow through the kidneys after surgery or injury, and to reduce pressure rapidly within fluid-filled body cavities.

Acetazolamide This mild diuretic is used mainly to treat acute glaucoma.

HOW THEY WORK

The kidneys’ normal filtration process takes water, salts (mainly potassium and sodium), and waste products out of the bloodstream. Most of the salts and water are returned to the bloodstream, but some are expelled from the body together with the waste products in the urine. Diuretics interfere with this filtration process by reducing the amounts of sodium and water taken back into the bloodstream, thus increasing the volume of urine produced. Modifying the filtration process in this way means that the water content of the blood is reduced; less water in the blood causes excess water present in the tissues to be drawn out and eliminated in urine.

HOW THEY AFFECT YOU

All diuretics increase the frequency with which you need to pass urine. This is most noticeable at the start of treatment. People who have suffered from oedema may notice that swelling – particularly of the ankles – is reduced, and those with heart failure may find that breathlessness is relieved.

RISKS AND SPECIAL PRECAUTIONS

Diuretics can cause blood chemical imbalances, of which a fall in potassium levels (hypokalaemia) is the most common. Hypokalaemia can cause confusion, weakness, and trigger abnormal heart rhythms (especially in people taking digitalis drugs). Potassium supplements or a potassium-sparing diuretic usually corrects the imbalance. A diet that is rich in potassium (containing plenty of fresh fruits and vegetables) may be helpful.

Some diuretics may raise blood levels of uric acid, increasing the risk of gout. They may also raise blood sugar levels, causing problems for diabetics.

COMMON DRUGS

Loop diuretics Bumetanide, Furosemide/frusemide, Torasemide

Potassium-sparing diuretics Amiloride, Eplerenone, Spironolactone, Triamterene

Thiazides Bendroflumethiazide, Chlortalidone, Cyclopenthiazide, Hydrochlorothiazide, Hydroflumethiazide, Indapamide, Metolazone, Xipamide

Anti-arrhythmics

The heart contains two upper and two lower chambers, which are known as the atria and ventricles. The pumping actions of these two sets of chambers are normally coordinated by electrical impulses that originate in the heart’s pacemaker and then travel along conducting pathways so that the heart beats with a regular rhythm. If this coordination breaks down, the heart will beat abnormally, either irregularly or faster or slower than usual. The general term for abnormal heart rhythm is arrhythmia.

Arrhythmias may occur as a result of a birth defect, coronary heart disease, or other less common heart disorders. A variety of more general conditions, including overactivity of the thyroid gland, and certain drugs, such as caffeine and anticholinergic drugs, can also disturb heart rhythm.

Arrhythmias can be divided into two groups: tachycardias (such as atrial fibrillation), in which the heart rate is faster than normal; and bradycardias (such as heart block), in which the rate is slower.

Atrial fibrillation In this common type of arrhythmia, the atria contract irregularly at such a high rate that the ventricles cannot keep pace. The condition is treated with digoxin, verapamil, amiodarone, or a beta blocker.

Ventricular tachycardia This condition arises from abnormal electrical activity in the ventricles that causes the ventricles to contract rapidly. Treatment with disopyramide, procainamide, or amiodarone may be effective, although implanted defibrillators are replacing drug treatment for this condition.

Supraventricular tachycardia This condition occurs when extra electrical impulses arise in the pacemaker or atria, stimulating the ventricles into contracting rapidly. Attacks may disappear on their own without treatment, but drugs such as adenosine, digoxin, verapamil, or propranolol may be given.

Heart block When impulses are not conducted from the atria to the ventricles, the ventricles start to beat at a slower rate. Some cases of heart block do not require treatment. For more severe heart block accompanied by dizziness and fainting, the fitting of an artificial pacemaker is usually necessary.

A wide range of drugs is used to regulate heart rhythm, including beta blockers, digitalis drugs, and calcium channel blockers. Other drugs used are disopyramide, lidocaine, and procainamide.

WHY THEY ARE USED

Minor disturbances of heart rhythm are common and do not usually require drug treatment. However, if the heart’s pumping action is seriously affected, the circulation of blood throughout the body may become inefficient, and drug treatment may be necessary.

Drugs may be taken to treat individual attacks of arrhythmia, or they may be taken on a regular basis to prevent or control abnormal heart rhythms. The particular drug prescribed depends on the type of arrhythmia to be treated, but because people differ in their response, it may be necessary to try several in order to find the most effective one. When the arrhythmia is sudden and severe, it may be necessary to inject a drug immediately to restore normal heart function.

HOW THEY WORK

The heart’s pumping action is governed by electrical impulses under the control of the sympathetic nervous system (see Autonomic nervous system). These signals pass through the heart muscle, causing the two pairs of chambers – the atria and ventricles – to contract in turn.

All anti-arrhythmic drugs alter the conduction of electrical signals in the heart. However, each drug or drug group has a different effect on the sequence of events controlling the pumping action. Some block the transmission of signals to the heart (beta blockers); some affect the way in which signals are conducted within the heart (digitalis drugs); others affect the response of the heart muscle to the signals received (calcium channel blockers, disopyramide, and procainamide).

HOW THEY AFFECT YOU

These drugs usually prevent symptoms of arrhythmia and may restore a regular heart rhythm. Although they do not prevent all arrhythmias, they usually reduce the frequency and severity of any symptoms.

Unfortunately, as well as suppressing arrhythmias, many of these drugs tend to depress normal heart function, and may produce dizziness on standing up, or increased breathlessness on exertion. Mild nausea and visual disturbances are also fairly frequent. Verapamil can cause constipation, especially when it is prescribed in high doses. Disopyramide may interfere with the parasympathetic nervous system (see Autonomic nervous system), resulting in a number of anticholinergic effects.

RISKS AND SPECIAL PRECAUTIONS

These drugs, under certain circumstances, may further disrupt heart rhythm, and therefore they are used only when the likely benefit outweighs the risks.

Amiodarone may accumulate in the tissues over time, and may lead to light-sensitive rashes, changes in thyroid function, and lung problems.

COMMON DRUGS

Beta blockers, Sotalol

Calcium channel blockers Felodipine, Verapamil

Digitalis drugs, Digitoxin, Digoxin

Other drugs Adenosine, Amiodarone, Disopyramide, Flecainide, Lidocaine, Mexiletine, Moracizine, Procainamide, Propafenone

Anti-angina drugs

Angina is chest pain produced when insufficient oxygen reaches the heart muscle. This is usually caused by a narrowing of the blood vessels (coronary arteries) that carry blood and oxygen to the heart muscle. In the most common type of angina (classic angina), pain usually occurs during physical exertion or emotional stress. In variant angina, pain may also occur at rest. In classic angina, the narrowing of the coronary arteries results from deposits of fat, known as atheroma, on the walls of the arteries. In the variant type, however, angina is caused by contraction (spasm) of the muscle fibres in the artery walls.

Atheroma deposits build up more rapidly in the arteries of smokers and people who eat a high-fat diet. This is why, as a basic component of angina treatment, doctors recommend that smoking should be given up and the diet changed. Overweight people are also advised to lose weight in order to reduce the demands placed on the heart. While such changes in lifestyle often produce an improvement in symptoms, drug treatment to relieve angina is also frequently necessary.

The drugs used to treat angina include beta blockers, nitrates, calcium channel blockers, and potassium channel openers.

WHY THEY ARE USED

Frequent episodes of angina can be disabling and, if left untreated, can lead to an increased risk of a heart attack. Drugs can both relieve angina attacks and reduce their frequency. People who suffer only occasional episodes are usually prescribed a rapid-acting drug to take at the first signs of an attack, or before an activity that is known to bring on an attack. Glyceryl trinitrate, a rapid-acting nitrate drug, is usually prescribed for this purpose.

If attacks become more frequent or more severe, regular preventative treatment may be advised. Beta blockers, long-acting nitrates, and calcium channel blockers are used as regular medication to prevent attacks. The introduction of adhesive patches to administer nitrates through the patient’s skin has extended the duration of action of glyceryl trinitrate, making treatment easier.

Drugs can often control angina for many years, but they cannot cure the disorder. When severe angina cannot be controlled by drugs, then surgery to increase the blood flow to the heart may be recommended.

HOW THEY WORK

Nitrates and calcium channel blockers dilate blood vessels by relaxing the muscle layer in the blood vessel walls (see also Vasodilators). Blood is more easily pumped through the dilated vessels, reducing the strain on the heart.

Beta blockers reduce heart muscle stimulation during exercise or stress by interrupting signal transmission in the heart. Decreased heart muscle stimulation means that less oxygen is required, reducing the risk of angina attacks. For further information about these drugs, see beta blockers.

HOW THEY AFFECT YOU

Treatment with one or more of these medicines usually effectively controls angina. Drugs to prevent attacks allow sufferers to undertake more strenuous activities without provoking pain, and if an attack does occur, nitrates usually provide effective relief.

These drugs do not usually cause serious adverse effects but can produce a variety of minor symptoms. By dilating blood vessels throughout the body, nitrates and calcium channel blockers can cause dizziness (especially on standing) and may cause fainting. Other possible side effects are headaches at the start of treatment, flushing of the skin (especially of the face), and ankle swelling. Beta blockers often cause cold hands and feet, and sometimes they may produce tiredness and a feeling of heaviness in the legs.

COMMON DRUGS

Calcium channel blockers Amlodipine, Diltiazem, Felodipine, Nicardipine, Nifedipine, Verapamil

Beta blockers

Nitrates Glyceryl trinitrate, Isosorbide dinitrate/mononitrate

Potassium channel opener Nicorandil

Heparin/low molecular weight heparins Dalteparin, Enoxaparin

Other drugs Aspirin, Ivabradine, Simvastatin

Antihypertensive drugs

Blood pressure is the force exerted by the blood against the artery walls. Two measurements are taken: one indicates force while the heart’s ventricles are contracting (systolic pressure). This reading is a higher figure than the other one, which measures the blood pressure during ventricle relaxation (diastolic pressure). Blood pressure varies among individuals and normally increases with age. If a person’s blood pressure is higher than normal on at least three separate occasions, a doctor may diagnose the condition as hypertension.

Blood pressure may be elevated as a result of an underlying disorder, which the doctor will try to identify. Usually, however, it is not possible to determine a cause. This condition is referred to as essential hypertension.

Although hypertension does not usually cause any symptoms, severely raised blood pressure may produce headaches, palpitations, and general feelings of ill-health. It is important to reduce high blood pressure because it can have serious consequences, including stroke, heart attack, heart failure, and kidney damage. Certain groups are particularly at risk from high blood pressure. These risk groups include diabetics, smokers, people with pre-existing heart damage, and those whose blood contains a high level of fat. High blood pressure is more common among black people than among whites, and in countries, such as Japan, where the diet is high in salt.

A small reduction in blood pressure may be brought about by reducing weight, exercising regularly, and avoiding an excessive amount of salt in the diet. However, for more severely raised blood pressure, one or more antihypertensive drugs may be prescribed. Several classes of drug have antihypertensive properties, including the centrally acting antihypertensives, diuretics, beta blockers, calcium channel blockers, ACE (angiotensin-converting enzyme) inhibitors (see Vasodilators), and alpha blockers.

WHY THEY ARE USED

Antihypertensive drugs are prescribed when diet, exercise, and other simple remedies have not brought about an adequate reduction in blood pressure, and your doctor sees a risk of serious consequences if the condition is not treated. These drugs do not cure hypertension and may have to be taken indefinitely.

HOW THEY WORK

Blood pressure depends not only on the force with which the heart pumps blood, but also on the diameter of blood vessels and volume of blood in circulation: blood pressure is increased either if the vessels are narrow or the volume of blood is high. Antihypertensives lower blood pressure either by dilating the blood vessels or by reducing blood volume. Each type of antihypertensive acts in a different way to lower blood pressure.

Centrally acting drugs act on the mechanism in the brain that controls the diameter of the blood vessels.

Beta blockers reduce the force of the heart beat.

Diuretics act on the kidneys to reduce blood volume.

ACE inhibitors act on enzymes in the blood to dilate blood vessels.

Vasodilators and calcium channel blockers act on the arterial wall muscles to prevent constriction.

Alpha blockers block nerve signals that trigger constriction of blood vessels.

CHOICE OF DRUG

Drug treatment depends on the severity of the hypertension. At the beginning of treatment for mild or moderately high blood pressure, a single drug is used. A thiazide diuretic is often chosen for initial treatment, but it is also increasingly common to use a calcium channel blocker or an ACE inhibitor. For those over 50 or of Afro-Caribbean descent, a calcium channel blocker is usually the first-line treatment. If a single drug does not reduce the blood pressure sufficiently, a combination of these drugs may be used. Some people who have moderate hypertension require an additional drug, in which case an alpha blocker or beta blocker may also be prescribed.

Severe hypertension is usually controlled with a combination of several drugs, which may need to be given in high doses. Your doctor may need to try a number of drugs before finding a combination that controls blood pressure without unacceptable side effects.

HOW THEY AFFECT YOU

Treatment with antihypertensive drugs relieves symptoms such as headache and palpitations. However, since most people with hypertension have few, if any, symptoms, side effects may be more noticeable than any immediate beneficial effect. Some antihypertensive drugs may cause dizziness and fainting at the start of treatment because they can sometimes cause an excessive fall in blood pressure. It may take a while for your doctor to determine a dosage that avoids such effects. For detailed information on the adverse effects of drugs that are used to treat hypertension, consult the individual drug profiles in Part 2.

RISKS AND SPECIAL PRECAUTIONS

Because your doctor needs to know exactly how treatment with a particular drug affects your hypertension – the benefits as well as the side effects – it is important for you to keep using the antihypertensive medication as prescribed, even though you may feel that the problem is under control. Sudden withdrawal of some of these drugs may cause a potentially dangerous rebound increase in blood pressure. The dose needs to be reduced gradually under medical supervision.

COMMON DRUGS

ACE inhibitors

Angiotensin II blockers Candesartan, Irbesartan, Losartan, Olmesartan

Beta blockers

Calcium channel blockers Amlodipine, Diltiazem, Felodipine, Isradipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Verapamil

Centrally acting antihypertensives Clonidine, Methyldopa, Moxonidine

Diuretics

Alpha blockers Doxazosin, Indoramin, Prazosin, Terazosin

Vasodilators

Lipid-lowering drugs

The blood contains several types of fats, or lipids. They are necessary for normal body function but can be damaging in excess, particularly saturated fats such as cholesterol. The main risk is atherosclerosis, in which fatty deposits (atheroma) build up in the arteries, restricting and disrupting blood flow. This can increase the likelihood of abnormal blood clots forming, leading to potentially fatal disorders such as stroke and heart attack.

For most people, reducing their fat intake reduces the risk of atherosclerosis; but for those with an inherited tendency to high blood levels of fat (hyperlipidaemia), lipid-lowering drugs may also be recommended.

WHY THEY ARE USED

Lipid-lowering drugs are generally used only when dietary measures have failed to control hyperlipidaemia. They may be prescribed at an earlier stage to people at increased risk of atherosclerosis – such as diabetics and those already suffering from circulatory disorders. The drugs may help the body to remove existing atheroma in the blood vessels and prevent accumulation of new deposits. Low-dose simvastatin is available over the counter to help lower cholesterol levels in certain people.

For maximum benefit, lipid-lowering drugs are used in conjunction with a low-fat diet and a reduction in other risk factors such as obesity and smoking. The choice of drug depends on the type of lipid causing problems, so a full medical history, examination, and laboratory analysis of blood samples are needed before drug treatment is prescribed.

HOW THEY WORK

Cholesterol and triglycerides are two of the major fats in the blood. One or both may be raised, influencing the choice of lipid-lowering drug. Bile salts contain a large amount of cholesterol and are normally released into the bowel to aid digestion before being reabsorbed into the blood. Drugs that bind to bile salts reduce cholesterol levels by blocking their reabsorption, allowing them to be lost from the body.

Other drugs act on the liver. Fibrates and nicotinic acid and its derivatives can reduce the level of both cholesterol and triglycerides in the blood. Fish oil preparations reduce blood triglycerides. Statins lower blood cholesterol. It is now believed that low-grade inflammation is one of the causes of atheroma, and statins have an anti-inflammatory action, which may partly explain their effectiveness.

Lipid-lowering drugs do not correct the underlying cause of raised levels of fat in the blood, so it is usually necessary to continue with diet and drug treatment indefinitely. Stopping treatment usually leads to a return of high blood lipid levels.

HOW THEY AFFECT YOU

Because hyperlipidaemia and atherosclerosis are usually without symptoms, you are unlikely to notice any short-term benefits from these drugs. Rather, the aim of treatment is to reduce long-term complications. There may be minor side effects from some of these drugs.

The statin drugs appear to be well tolerated and are widely used to lower cholesterol levels when diet alone is not effective.

RISKS AND SPECIAL PRECAUTIONS

Drugs that bind to bile salts can limit absorption of some fat-soluble vitamins, and vitamin supplements may therefore be needed. The fibrates can increase susceptibility to gallstones and occasionally upset the balance of fats in the blood. Statins are used with caution in people with reduced kidney or liver function, and monitoring of blood samples is often advised. You should consult your doctor or pharmacist before taking simvastatin.

COMMON DRUGS

Statins Atorvastatin, Fluvastatin, Pravastatin, Rosuvastatin, Simvastatin

Drugs that bind to bile salts Colestipol, Colestyramine, Ezetimibe, Ispaghula

Fibrates Bezafibrate, Ciprofibrate, Fenofibrate, Gemfibrozil

Other drugs acting on the liver Omega-3 acid ethyl esters, Omega-3 marine triglycerides

Nicotinic acid and derivatives Acipimox, Nicotinic acid

Drugs that affect blood clotting

When bleeding occurs as a result of injury or surgery, the body normally acts swiftly to stem the flow by sealing the breaks in the blood vessels. This occurs in two stages – first when cells called platelets accumulate as a plug at the opening in the blood vessel wall, and then when these platelets produce chemicals that activate clotting factors in the blood to form a protein called fibrin. Vitamin K plays an important role in this process. An enzyme in the blood called plasmin ensures that clots are broken down when the injury has been repaired.

Some disorders interfere with this process, either preventing clot formation or creating clots uncontrollably. If the blood does not clot, there is a danger of excessive blood loss. Inappropriate development of clots may block the supply of blood to a vital organ.

DRUGS USED TO PROMOTE BLOOD CLOTTING

Fibrin formation depends on the presence in the blood of several clotting-factor proteins. When Factor VIII is absent or at low levels, an inherited disease called haemophilia exists; the symptoms almost always appear only in males. Factor IX deficiency causes another bleeding condition called Christmas disease, named after the person in whom it was first identified. Lack of these clotting factors can lead to uncontrolled bleeding or excessive bruising following even minor injuries.

Regular drug treatment for haemophilia is not normally required. However, if severe bleeding or bruising occurs, a concentrated form of the missing factor, extracted from normal blood, may be injected in order to promote clotting and thereby halt bleeding. Injections may need to be repeated for several days after injury.

It is sometimes useful to promote blood clotting in non-haemophiliacs when bleeding is difficult to stop (for example, following surgery). In such cases, blood clots are sometimes stabilized by reducing the action of plasmin with an antifibrinolytic (or haemostatic) drug like tranexamic acid; this is also occasionally given to haemophiliacs before minor surgery such as tooth extraction.

A tendency to bleed may also occur with deficiency of vitamin K, which is required for the production of several blood clotting factors. Vitamin K is absorbed from the intestine in fats, but some diseases of the small intestine or pancreas cause fat to be poorly absorbed. As a result, the level of vitamin K in the circulation is low, causing impaired blood clotting. A similar problem sometimes occurs in newborn babies due to absence of vitamin K. Injections of phytomenadione, a vitamin K preparation, are used to restore levels to normal.

DRUGS USED TO PREVENT ABNORMAL BLOOD CLOTTING

Blood clots normally form only as a response to injury. In some people, however, there is a tendency for clots to form in the blood vessels without apparent cause. Disturbed blood flow occurring as a result of the presence of fatty deposits – atheroma – inside the blood vessels increases the risk of the formation of this type of abnormal clot (or thrombus). In addition, a portion of a blood clot (known as an embolus) formed in response to injury or surgery may sometimes break off and be removed in the bloodstream. The likelihood of this happening is increased by long periods of little or no activity. When an abnormal clot forms, there is a risk that it may become lodged in a blood vessel, thereby blocking the blood supply to a vital organ such as the brain or heart.

Three main types of drugs are used to prevent and disperse clots: antiplatelet drugs, anticoagulants, and thrombolytics.

ANTIPLATELET DRUGS

Taken regularly by people with a tendency to form clots in the fast-flowing blood of the heart and arteries, these drugs are also given to prevent clots from forming after heart surgery. They reduce the tendency of platelets to stick together when blood flow is disrupted.

The most widely used antiplatelet drug is aspirin (see also Analgesics), which has an antiplatelet action even when given in much lower doses than would be necessary to reduce pain. In these low doses adverse effects that may occur when aspirin is given in pain-relieving doses are unlikely. Other antiplatelet drugs are clopidogrel and dipyridamole.

ANTICOAGULANTS

Anticoagulants help to maintain normal blood flow in people at risk from clot formation. They can either prevent the formation of blood clots in the veins or stabilize an existing clot so that it does not break away and become a circulation-stopping embolism. All anticoagulants reduce the activity of certain blood clotting factors, but each drug’s mode of action differs. These medicines do not dissolve clots that have already formed, however: these are treated with thrombolytic drugs.

Anticoagulants fall into two groups: those that are given by intravenous injection and act immediately, and those that are given by mouth and take effect after a few days.

INJECTED ANTICOAGULANTS

Heparin is the most widely used drug of this type and it is used mainly in hospital during or after surgery. It is also given during kidney dialysis to prevent clots from forming in the dialysis equipment. Because heparin cannot be taken by mouth, it is less suitable for long-term treatment in the home.

A number of synthetic injected anticoagulants have recently been developed. Some act for a longer time than heparin, and others are alternatives for people who react adversely to heparin.

ORAL ANTICOAGULANTS

Warfarin is the most widely used of the oral anticoagulants. These drugs are mainly prescribed to prevent the formation of clots in veins and in the chambers of the heart (they are less likely to prevent clot formation in arteries). Oral anticoagulants may be given following injury or surgery (in particular, heart valve replacement) when there is a high risk of embolism. They are also given long-term as preventative treatment to people at risk of strokes. A common problem with these drugs is that overdosage may lead to bleeding from the nose or gums, or in the urinary tract. For this reason, the dosage needs to be carefully calculated; regular blood tests are performed to ensure that the clotting mechanism is correctly adjusted, although this is not necessary with new oral anticoagulants such as dabigatran and rivaroxaban.

The action of oral anticoagulants may be affected by many other drugs, and it may therefore be necessary to alter the dosage of anticoagulant when other drugs also need to be given. In particular, no anticoagulant should be taken together with aspirin except on the direction of a doctor.

THROMBOLYTICS

Also known as fibrinolytics, these drugs are used to dissolve clots that have already formed. They are usually given in hospital intravenously to clear a blocked blood vessel (in coronary thrombosis, for example). The sooner they are given after the start of symptoms, the more likely they are to reduce the size and severity of a heart attack. Thrombolytic drugs may be given either intravenously or directly into the blocked blood vessel. The main thrombolytics are streptokinase and alteplase, which act by increasing the blood level of plasmin, the enzyme that breaks down fibrin. When given promptly, alteplase appears to be tolerated better than streptokinase.

The most common problems with these drugs are increased susceptibility to bleeding and bruising, and allergic reactions to streptokinase, such as rashes or breathing difficulty. Once streptokinase has been given, patients are given a card indicating this, because further treatment with the same drug may be less effective and an alternative (such as alteplase) used instead.

COMMON DRUGS

Blood clotting factors Factor VIIa, Factor VIII, Factor IX, Fresh frozen plasma

Antifibrinolytic or haemostatic drugs Etamsylate, Tranexamic acid

Vitamin K Phytomenadione

Antiplatelet drugs Abciximab, Aspirin, Clopidogrel, Dipyridamole, Eptifibatide, Prasugrel, Tirofiban

Injected anticoagulants Danaparoid, Epoprostenol, Fondaparinux, Heparin, Lepirudin

Thrombolytic drugs Alteplase, Reteplase, Streptokinase, Tenecteplase

Oral anticoagulants Acenocoumarol/nicoumalone, Dabigatran, Rivaroxaban, Warfarin

Heparin/low molecular weight heparins Dalteparin, Enoxaparin, Tinzaparin