Heart and Circulation

Efficiency of the circulation may be impaired by a weakening of the heart's pumping action (heart failure) or irregularity of heartbeat (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 to the heart muscle (coronary heart disease), causing angina. These last disorders can be complicated by the formation of clots which may block a blood vessel. In the arteries supplying the heart muscle, this is known as coronary thrombosis, and inside the brain it is the most frequent cause of stroke.

One common circulatory disorder is abnormally high blood pressure (hypertension), in which the pressure of the circulating blood on the vessel walls is increased for reasons not yet fully understood. One factor may be loss of elasticity of the blood vessel walls (arteriosclerosis).

A number of other conditions are caused by temporary alterations to blood vessel size. These include migraine and Raynaud's disease.

Digitalis medicaments

Digitalis is the collective term for a number of naturally occurring substances (also called cardiac glycosides) found in the leaves of herbs of the foxglove family and used for certain heart disorders. The principal medicaments in this group are digoxin and digitoxin. Digoxin is more commonly used because it is shorter-acting and dosage is easier to adjust.

The normal heartbeat results from electrical impulses generated in nerve tissue within the heart. These cause the heart muscle to contract and pump blood. By reducing the passage 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 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 heartbeat increases the flow of blood to the kidneys. This increases urine production and helps to remove the excess fluid that often accumulates as a result of heart failure.

Digitalis relieves 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 is also increased initially.

Digitalis medicaments can be toxic and, if blood levels rise too high, may produce symptoms of digitalis poisoning. These include excessive tiredness, confusion, loss of appetite, nausea, vomiting, and diarrhea. If such symptoms occur, it is important to report them to your physician promptly.

Digoxin is normally removed from the body by the kidneys; if kidney function is impaired, the medicament 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 doses, especially if liver function is reduced.

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

Beta blockers

Epinephrine (from the adrenal gland) and similar substances act in part through beta receptors in the body. Beta blockers (also called beta adrenergic blocking agents) prevent the actions of epinephrine-like substances on beta receptors. Used mainly in heart disorders, they are occasionally prescribed for other conditions.

By occupying the beta receptors, beta blockers nullify the stimulating action of norepinephrine. Thus they reduce the force and speed of the heartbeat, prevent the dilation of the airways to the lungs, and prevent the dilation of the blood vessels surrounding the brain and leading to the extremities.

Taken to treat angina, beta blockers reduce the frequency and severity of attacks. As part of the treatment for hypertension, they 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, marked by either irregular or rapid heartbeat.

Because beta blockers affect many parts of the body, they commonly produce minor side effects. By reducing heart rate and air flow to the lungs, they may reduce 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 medicaments, due to the reduction in blood supply to the limbs. Reduced circulation can also lead to temporary impotence during beta blocker treatment.

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. Cardio-selective beta blockers, which act principally on the heart, are thought to be less likely than non-cardio-selective ones to cause such problems. But all beta blockers are prescribed with caution for people with asthma, bronchitis, or other forms of respiratory disease.

Beta blockers are not usually prescribed for people who have poor circulation in the limbs, because they reduce the flow of blood and may aggravate such conditions. They are not normally given to people who are subject to heart failure because they may further reduce the force of the heartbeat. Diabetics 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, symptoms such as palpitations and tremor may be 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. Blood pressure may also rise markedly. When the treatment needs to be stopped, it should be withdrawn gradually under medical supervision.

Vasodilators

Vasodilators -medicaments that dilate blood vessels -are commonly prescribed for disorders in which narrowing of the blood vessels leads to reduced blood flow and a consequent lower oxygen supply to parts of the body. Disorders of this type include angina, when a narrowing of the coronary arteries reduces the supply of blood, thereby causing painful spasm. They also include peripheral vascular disease, when blood vessels in the arms and legs cannot supply sufficient blood to the extremities. Vasodilators are also widely used in the treatment of high blood pressure (hypertension) and heart failure.

Several classes of vasodilator medicaments are prescribed, including nitrates, sympatholytics, calcium channel blockers, and ACE (angiotensin-converting enzyme) inhibitors.

Vasodilators widen the blood vessels by relaxing the muscles that surround them. They achieve this either by affecting the action of the muscles directly (nitrates and calcium channel blockers) or by interfering with the nerve signals that govern contraction of the blood vessels (sympatholytics). ACE inhibitors act by blocking enzyme activity in the blood.

In addition to relieving the symptoms of the disorders for which they are taken, vasodilators can have a number of minor adverse effects related to their action on the blood circulation. Flushing and headaches are common at the start of treatment. Dizziness and fainting may also occur as a result of lowered blood pressure. Dilation of the blood vessels can also cause a fluid buildup, leading to swelling, particularly of the ankles.

The major risk is that blood pressure may sometimes fall too low. For this reason these medicaments are prescribed with caution for those with unstable blood pressure. It may also be advisable to take the first dose of vasodilator medicaments at a time when you are able to sit or lie down afterward.

Diuretics

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

The normal filtration process of the kidneys 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 certain amounts are expelled from the body together with the waste products in the urine. Diuretics interfere with this normal kidney action by reducing the amounts of sodium and water taken back into the bloodstream, thus increasing the volume of urine produced. In this way the water content of the blood is reduced and excess water is drawn out of the tissues for elimination in the urine.

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 edema may notice that swelling -particularly of the ankles -is reduced, and those with heart failure may find that breathlessness is relieved.

Diuretics can cause chemical imbalances in the blood. Most common of these is a fall in potassium levels in the blood (hypokalemia), which can cause weakness, particularly in the elderly. Low potassium can also trigger abnormal heart rhythms, especially in those taking digitalis medicaments. The imbalance can usually be corrected by potassium supplements or by a potassium-sparing diuretic. A diet that is rich in potassium (containing plenty of fresh fruits and vegetables) may be helpful.

Some diuretics may increase levels of uric acid in the blood and thus the risk of gout in susceptible people. They may also raise blood sugar levels, which can cause problems for diabetics.

Anti-arrhythmic medicaments

The heart contains two upper and two lower chambers. The pumping actions of these two sets of chambers are normally coordinated by electrical impulses so that the heart beats with a regular rhythm. If this coordination breaks down, the heart may beat abnormally, either irregularly or faster or slower than usual. The general term for abnormal heart rhythm is arrhythmia. There are several types of arrhythmia, depending on the part of the heart that is affected.

The heart's rhythm can be disrupted in any disorder that affects the heart's mechanism for controlling its beat. Other conditions, including over activity of the thyroid gland, and certain medicaments -for example, anticholinergic medicaments and caffeine -can also disturb heart rhythm.

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

The heart's pumping action is governed by electrical impulses under the control of the sympathetic nervous system. These signals pass through the heart muscle and cause each of the two pairs of heart chambers -the atria and the ventricles to contract in turn.

All anti-arrhythmic medicaments alter the conduction of electrical signals in the heart, but each medicament or medicament group affects this sequence of events in a different way. Some block the transmission of signals to the heart (beta blockers); some affect the way signals are conducted within the heart (digitalis medicaments); others affect the response of the heart muscle to the signals received (calcium channel blockers, disopyramide, procainamide, and quinidine).

These medicaments 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 medicaments tend to depress normal heart function, and may produce dizziness on standing up (postural hypotension), or increased breathlessness on exertion. Mild nausea and visual disturbances are also fairly frequent. Verapamil can cause constipation, especially in high doses. Disopyramide may interfere with the parasympathetic nervous system, resulting in a number of anticholinergic effects.

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

Quinidine can be toxic in overdose, resulting in a syndrome called cinchonism, which includes disturbed hearing, giddiness, and impaired vision (even blindness). Because some people are particularly sensitive to this medicament, a test dose is usually given before regular treatment is started.

Anti-angina medicaments

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 typically occurs during exertion or emotional stress. In variant angina, pain may also occur at rest. In classic angina, narrowing of the coronary arteries results from deposits of fat -called atheroma - on the walls of the arteries, whereas in variant angina it is caused by contraction (spasm) of the muscle fibers in the artery walls.

Atheroma deposits build up in the arteries, especially in smokers and in people who eat a high-fat diet. This is why, as a basic part of angina treatment, physicians recommend that you stop smoking and change your diet. Overweight people are also advised to lose weight in order to reduce the demands placed on their hearts. While such changes in lifestyle often produce an improvement in symptoms, medicament treatment to relieve angina is also frequently necessary.

Three types of medicaments are used to treat angina: beta blockers, nitrates, and calcium channel blockers.

Nitrates and calcium channel blockers dilate blood vessels by relaxing the muscle layer in the blood vessel wall. This reduces strain on the heart by making it easier to pump blood.

Beta blockers interrupt the transmission of signals in the heart and so reduce stimulation of the heart muscle during exercise or stress. This also reduces the oxygen requirement of the heart muscle and makes angina attacks less likely to occur.

Treatment with one or more of these medicaments is usually effective in controlling angina. Medicaments 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 medicaments do not usually cause serious adverse effects, but they can produce a variety of minor symptoms. By dilating blood vessels throughout the body, nitrates and calcium channel blockers can cause dizziness and sometimes fainting (especially when standing). Other possible side effects are headaches at the start of treatment, flushing of the skin -especially of the face -and swelling of the ankles. Tolerance to nitrates can develop. A daily nitrate-free period of 10 to 12 hours is recommended with chronic use of these medicaments. Beta blockers often cause cold hands and feet, and can produce tiredness and a feeling of heaviness in the legs.

Antihypertensive medicaments

Blood pressure is a measurement of the force exerted by the blood circulating in the arteries. Two readings are taken: one indicates force while the heart's ventricles are contracting (systolic pressure). It is a higher figure than the other reading, which measures the blood-flow push 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 physician may diagnose hypertension.

Blood pressure may be raised as a result of an underlying disorder, which a physician will try to identify. Usually, however, it is not possible to find a cause. This condition is essential hypertension.

Although hypertension is usually without symptoms, severely raised 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 include diabetics, smokers, people with preexisting heart damage, and those whose blood contains a high level of fat. High blood pressure is more common among black people than among whites.

A small reduction in blood pressure may be brought about by reducing weight, exercising regularly, and keeping to a low-salt diet. But for more severely raised blood pressure, one or more antihypertensive medicaments may be prescribed. Several different classes of medicaments have antihypertensive properties, including centrally acting antihypertensives, diuretics, beta blockers, calcium channel blockers, ACE (angiotensin converting enzyme) inhibitors, and sympatholytics.

Blood pressure depends not only on the force with which the heart pumps blood, but also on the diameter of blood vessels and the volume of blood in circulation: blood pressure is increased if the vessels are narrow or the volume of blood is high.

Antihypertensive medicaments lower blood pressure either by dilating the blood vessels or by reducing blood volume. Antihypertensive medicaments work in different ways and some have more than one action.

Since most people with hypertension have few, if any, symptoms, medicament side effects may be more noticeable than any immediate beneficial effect. Some antihypertensive medicaments may cause dizziness and fainting at the start of treatment because they can sometimes produce an excessive fall in blood pressure. It may take a while for the physician to determine a dosage that avoids such effects.

Since your physician needs to know exactly how treatment with a particular medicament affects your hypertension -the benefits as well as side effects -it is important to keep using antihypertensive medication as prescribed, even though you may feel the problem is under control. Sudden withdrawal of some of these medicaments may cause a dangerous rebound in blood pressure: when treatment is stopped the dose needs to be reduced gradually under medical supervision.

Lipid-lowering medicaments

The blood contains several types of fats (also known as lipids). Some of these are beneficial but others -particularly saturated fats such as cholesterol found in meat and dairy products -can be damaging if present in excess. The main risk is atherosclerosis, in which fatty deposits, called atheroma, build up in the arteries, restricting and disrupting the flow of blood. This can lead to a greater likelihood of the formation of abnormal blood clots leading to potentially fatal disorders such as stroke and heart attack.

For most people, cutting down the amount of fat in the diet is sufficient to reduce the risk of atherosclerosis. However, for others, often those with an inherited tendency to high levels of fat in the blood (hyperlipidemia), treatment with lipid-lowering medicaments may also be recommended.

Bile salts, which contain large amounts of cholesterol, are normally released into the bowel to aid digestion and are then reabsorbed into the bloodstream. By blocking the reabsorption of cholesterol-carrying bile salts, some medicaments, notably cholestyramine, colestipol, and neomycin, increase the loss of cholesterol from the body and thus help to lower the level of fat in the bloodstream. Other medicaments - clofibrate, gemfibrozil, niacin, and probucol -prevent conversion of fatty acids to lipids in the liver. Statin medicaments inhibit an enzyme which produces cholesterol in the liver, so reducing cholesterol levels.

Lipid-lowering medicaments do not correct the underlying cause of raised levels of fat in the blood, therefore it is usually necessary to continue medicament treatment indefinitely. Withdrawal of treatment almost always leads to a return of high blood lipid levels.

Because hyperlipidemia and atherosclerosis are without symptoms, you are unlikely to notice any short-term benefits from these medicaments. By increasing the amount of bile in the digestive tract, several of these medicaments can cause nausea and constipation (colestipol and cholestyramine) or diarrhea (clofibrate, niacin, and probucol).

Cholestyramine, colestipol, and neomycin are not absorbed from the bowel into the bloodstream and therefore have few adverse effects. They may, however, limit absorption of certain fat-soluble vitamins; supplements may be recommended. They may also interfere with the absorption of other medicaments. Other lipid-lowering medicaments that act in the liver, in particular clofibrate, can increase susceptibility to gallstones. They can occasionally upset the balance of different types of lipids in the bloodstream. Regular monitoring of blood samples is often advised. They are used with caution in those with reduced liver function. Medicaments that block cholesterol formation, such as the statin medicaments, should be given with the evening meal to achieve maximum benefit.

Medicaments that affect blood clotting

When bleeding occurs from 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. There is a danger that a lack of blood clotting will result in excessive blood loss; inappropriate development of clots can lead to blockage of the blood to a vital organ.

Medicaments 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 hemophilia exists -the symptoms almost always appearing 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 injury.
Regular medicament treatment for hemophilia is not normally required. But 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 so halt bleeding. Injections may need to be repeated for several days after injury.
It is sometimes useful to promote blood clotting in non-hemophiliacs when bleeding is difficult to stop (for example, after surgery). In such cases, blood clots are sometimes stabilized by reducing the action of plasmin with an antifibrinolytic (or hemostatic) medicament such as aminocaproic acid; this is also occasionally given to hemophiliacs prior to minor surgery such as tooth extraction.
A tendency to bleed may also occur as a consequence of vitamin K deficiency.

Medicaments used to prevent abnormal blood clotting
Blood clots normally form only in 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 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 carried away in the bloodstream. The likelihood of this occurring is increased by long periods of little or no activity. When an abnormal clot forms, there is a risk that it may lodge in a blood vessel, thus blocking the blood supply to a vital organ such as the brain or heart.
Three main types of medicaments are used to prevent and disperse clots: antiplatelet medicaments, anticoagulant medicaments, and thrombolytic medicaments.

Antiplatelet medicaments
Taken regularly by people with a tendency to form clots in the fast-flowing blood of the heart and arteries, these 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 medicament is ASA. ASA has an antiplatelet action when given in much lower doses than would be necessary to reduce pain. In these low doses adverse effects that may occur when the medicament is given in pain-relieving doses are unlikely. Other less common antiplatelet medicaments include dipyridamole and sulfinpyrazone.

Anticoagulants
Anticoagulant medicaments help to maintain normal blood flow in people who are 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 anti-coagulant medicaments reduce the activity of certain blood-clotting factors, although the precise mode of action of each medicament differs. They do not, however, dissolve clots that have already formed: these are treated with thrombolytics.
Anticoagulants fall into two groups: those such as heparin and enoxaparin that are given by injection and act immediately, and those that are given by mouth and take effect after a few days, such as warfarin.

Injected anticoagulants
Heparin is used mainly in the hospital during or after surgery. In addition, it is also given during kidney dialysis to prevent clots from forming in the dialysis equipment. Heparin cannot be given by mouth; it is given intravenously or subcutaneously. (Enoxaparin can only be given subcutaneously.)
Heparin is sometimes given prior to starting regular treatment with an oral anticoagulant.

Oral anticoagulants
These medicaments are mainly used to prevent the formation of clots in veins -they are less likely to prevent the formation of blood clots 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 as a preventive treatment to people who are at risk from strokes.
A common problem with these medicaments is that over dosage may lead to bleeding from the nose, gums, or in the urinary tract, or easy bruising. For this reason the dosage needs to be carefully calculated; regular blood tests are performed to ensure that the clotting mechanism is correctly adjusted. Warfarin is the most widely used medicament of this type.
The action of oral anticoagulant medicaments may be affected by many other medicaments and foods high in vitamin K such as green, leafy vegetables. It may therefore be necessary to alter the dosage of anticoagulant when other medicaments also are needed. People who have been prescribed anticoagulants should avoid certain foods and carry a warning list of medicaments which should not be administered. ASA, in particular, should not be taken together with anticoagulants except on the direction of a physician.

Thrombolytics
Also known as fibrinolytics, these medicaments are used to dissolve clots that have already formed. They are usually administered in the hospital by intravenous injection to clear a blocked blood vessel -for example, in coronary thrombosis. As well as being given intravenously, thrombolytic medicaments may also be administered directly into a blocked blood vessel.
The main thrombolytic medicaments are streptokinase and tissue plasminogen activator (tPA), both of which act by increasing the blood level of plasmin, the naturally occurring enzyme that normally breaks down fibrin.
The most common problems with the use of these medicaments are increased susceptibility to bleeding and bruising. Streptokinase can cause allergic reactions which may take the form of hives (urticaria), swelling, and breathing difficulty.

Vitamin K is required for the production of several blood clotting factors. It is absorbed from the intestine in fats, but in some diseases of the small intestine or pancreas in which fat is poorly absorbed, the level of vitamin K in the circulation is low, resulting in impaired blood clotting. A similar problem sometimes occurs in newborn babies due to an absence of the vitamin. Injections of a vitamin K preparation called phytonadione are used to restore normal levels.

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