Cardiac Drugs

Many drugs for the treatment of heart disease are now available, and the number is constantly increasing. Drugs are strictly regulated: new drugs can be placed on the market only after approval, following a series of tests, by the Food and Drug Administration. Three features of every drug are evaluated: (1) efficacy, (2) side effects, and (3) toxicity.

To demonstrate the effectiveness of a cardiac drug, controlled studies have to be performed. Typically its action is compared with that of a placebo, tablets similar in appearance to the drug but containing an inert substance, such as sugar. Inasmuch as responses to drugs vary from person to person, and some patients may even show improvement when taking the placebo (owing to psychological influences), large numbers of observations are often needed to demonstrate that a drug has the predicted effect on heart disease.

Side effects consist of undesirable consequences of taking a drug that may develop while the drug is administered in the recommended dose and exerting the desired effect on disease. Among common side effects of cardiac drugs are nausea, diarrhea, sleepiness, and reduced sexual drive.

Drug toxicity refers to serious, even fatal consequences of administering a drug. There are two mechanisms of drug toxicity: (1) toxic effect caused by a dosage that is too high for a given patient; and (2) toxic effect caused in certain patients who have or develop hypersensitivity to a certain drug even though it is being administered in the recommended dosage. Hypersensitivity to a drug often involves

allergic reactions that may become progressively more severe as treatment with the drug continues or when treatment is repeated. Some of these reactions may be life-threatening.

Frequently treatment of a cardiac condition requires the administration of more than one drug. In that case it is necessary to take into consideration the relationship of drugs to each other, or drug interaction . In many instances two drugs have no such relationship: each drug exerts its effect independently of the other. However, drug interaction is common and may take place in a variety of ways:

Two drugs may facilitate each other's action, so that smaller doses of each may attain the desired effect with better tolerance and lower potential for toxicity (synergistic action).

Two drugs may reduce each other's potency, making higher doses necessary to produce the desired effect (antagonistic action).

The addition of a second drug may alter the action of the first drug, which may previously have been effective and well tolerated: the new drug may make the first drug toxic in some instances or simply ineffective in others.

Drug interactions are of considerable importance in patients requiring treatment by multiple drugs, and caution is required in selecting compatible drugs and regulating dosages.

Drugs are foreign substances the body tries to destroy or excrete. Different drugs are handled in different ways: some are eliminated with the urine or feces, some are destroyed by one of the organs (usually the liver), and some are changed into inert substances. The length of time it takes to eliminate an active drug plays a role in the way the drug is administered. Most drugs are absorbed from the gastrointestinal tract into the bloodstream, where their level can be measured. Blood level of a drug decreases at a fixed rate for each drug. The time required to halve drug content in the blood from its initial level is called the half-life of a drug, and it helps in determining how often a given drug has to be taken by the patient. Most cardiac drugs have half-lives of a few hours and hence must be administered at least three times a day. Those with a long half-life need to be taken only once daily.

The standard method for administering cardiac drugs is in the form of tablets or capsules. Liquid medicines are rarely used. However,

for a variety of reasons drugs may have to enter the body by other than the oral route, or parenterally . Parenteral drug administration involves injecting the drug underneath the skin (subcutaneous), into a muscle (intramuscular), or into a vein (intravenous). A drug may be administered parenterally either because it acts faster thus administered than when given orally or because it would be destroyed by digestive juices.

In acutely ill patients parenteral administration of drugs is preferred. In such cases the most common means is continuous intravenous drip. The drug is dissolved in a solution of salt or glucose, and a measured amount enters the body, maintaining a steady level of the drug. By regulating the speed of the drip, the effect of the drug can be increased or decreased as the need arises. Other parenteral modes of administering drugs include sublingual (some drugs, such as nitroglycerin, take effect rapidly when dissolved under the tongue) and transdermal (some drugs can be absorbed through the intact skin as an ointment or on specially designed patches).

Drugs used specifically in the treatment of heart disease are categorized according to their pharmacological effects. Some drugs have multiple actions and are used for different purposes, such as for treatment of high blood pressure and of heart failure. In most categories there are several drugs with almost identical effects. Commonly used cardiac drugs can be grouped in two ways. The first is according to physiological action:

Drugs enhancing the force of cardiac contraction . The classic drug, digitalis, is derived from the foxglove plant and has been in continuous use for more than two hundred years. A few newer drugs are now available, predominantly for short-term treatment.

Diuretics . This widely administered group of drugs is used to counter fluid retention caused by heart failure and to treat hypertension.

Beta-adrenergic blocking agents . These drugs are capable of blocking one of the functions of the autonomic nervous system. The prototype of a drug in this category is propranolol, first developed in the 1960s. There are multiple uses of these drugs in heart disease—to reduce high blood pressure, to reduce or eliminate attacks of angina pectoris, to reduce or prevent certain arrhythmias, and to slow the heart rate.

Calcium channel blocking agents . These drugs relieve or prevent spasm of blood vessels (particularly the coronary arteries), reducing high blood pressure, and reducing or eliminating attacks of angina pectoris. In addition, several of these drugs have antiarrhythmic properties.

The second grouping is according to therapeutic effect:

Antiarrhythmic drugs . Drugs aimed at the prevention or elimination of arrhythmias include some drugs in the categories mentioned above. Quinidine and procainamide are the prototypes and other powerful antiarrhythmic drugs have been introduced, some of them highly toxic but uniquely effective in life-threatening arrhythmias.

Anti-heart failure drugs . Besides diuretics and drugs enhancing the force of cardiac contraction, these include vasodilator drugs that reduce the heart's workload and mitral regurgitation.

Antihypertensive drugs . Several categories of drugs have the property of reducing blood pressure, by various mechanisms. Treatment of hypertension thus often involves the use of more than one drug, which together may act synergistically.

Antithrombotic drugs . The problem of clot formation within the heart or the blood vessels is addressed by three types of drugs. (1) Thrombolytic drugs, capable of dissolving existing clots. (2) Drugs inhibiting aggregation of platelets in the blood, such as aspirin, are used prophylactically. (3) Anticoagulant drugs are a more effective means of clot prevention. However, they carry a risk of bleeding and require periodic tests of their effectiveness.

Antianginal drugs . Nitrates (nitroglycerin and long-acting derivatives of it) dilate the coronary arteries. Other drugs include beta-adrenergic and calcium channel blocking agents, both of which act by reducing the requirements of the heart for oxygen.

Lipid-lowering drugs . These help reduce atherosclerosis by lowering the blood levels of cholesterol and triglyceride.

Drugs administered for remedial purposes need monitoring. In some cases the effects are obvious to the physician or patient. For instance, diuretics cause the patient to pass large quantities of

urine, and their effects can be measured by recording daily body weight. Antihypertensive drugs require frequent measurement of the blood pressure, which often can be done by the patient. The effectiveness of antianginal drugs is determined by the patient's observation regarding the number and severity of attacks of angina. In such cases the dosage of a drug and suitability of a particular therapy can be directly determined. Measurement of the blood content of some drugs may provide guidance in regulating dosages.

The effectiveness of drugs administered prophylactically cannot be evaluated directly. In some cases tests are available to help establish the dosage of a drug (for example, the prothrombin time test for anticoagulants) or to determine effectiveness (such as serum cholesterol level in the evaluation of cholesterol-reducing diets or drugs). If no tests are available to determine the safety of a prophylactic drug, a standard dosage is prescribed and maintained, provided no side effects develop.

Drug toxicity often presents serious problems. Immediate reactions in patients to a new drug can usually be controlled by reducing dosage or substituting a similarly acting drug. However, some cardiac drugs produce toxic reactions only after weeks or months of apparently successful treatment; furthermore, the toxic effect may not be apparent. Among such slowly appearing toxic effects are drug-induced reduction in white blood cells or platelets in the patient's blood, liver damage, development of cataracts, changes in personality, and depression. Some drugs have been suspected of being carcinogenic.

As stated, the potential toxicity of many cardiac drugs requires thoughtful consideration of the risks and benefits, especially in cases where a drug must be administered for long periods or permanently. Careful clinical observation and the performance of periodic blood and liver function tests may sometimes aid in detecting drug toxicity. Nevertheless, in certain life-threatening conditions, such as ventricular arrhythmias, the risk of serious toxic reaction is acceptable as a lesser evil.