A large number of drugs have a high affinity for albumin and other plasma proteins. Binding to plasma protein inhibits distribution outside the blood since only unbound drug will be further distributed. Plasma protein binding therefore reduces active drug concentration and ultimate response to the drug. Drugs can compete for the same protein binding sites and this is a form of drug interaction. A well-known and important example is that of warfarin and aspirin.
Warfarin is an anticoagulant, which binds extensively to plasma proteins, and this is taken into account when dosages are worked out. Aspirin taken with warfarin competes for the same protein binding sites, which means that they each displace the other and the amount of free drug in the plasma is increased for both drugs.
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Blood flows through the heart and circulation because it is under pressure. This is commonly known as blood pressure and can be measured in mmHg. A normal blood pressure measurement would be is the blood pressure when the ventricles are contracting and the lower figure is the blood pressure when the ventricles are relaxed. Blood pressure is highest in the aorta and reduces in blood vessels further away from the heart until it reaches As the heart and circulation is a closed system, the blood pressure is maintained with each contraction of the ventricles.
Blood pressure depends on the total volume of blood in the system and on the resistance provided by all the blood vessels. Peripheral vascular resistance depends on the diameter of blood vessels, the viscosity of blood and the total blood vessel length. Under normal circumstances, blood viscosity and total blood vessel length remain the same and do not affect blood pressure. Blood vessel diameter, however, can and does change from moment to moment by vasoconstriction.
The underlying pathology is thrombus formation or extension in the coronary arteries. A variant of unstable angina at rest is due to unpredictable spasm of the coronary arteries. Drugs that either improve the blood supply to the myocardium, or reduce its metabolic demand for oxygen or both can be used to treat angina. These drugs include nitrates, potassium channel activators, β-blockers and calcium channel blockers.
Myocardial infarction occurs when there is a prolonged reduction in oxygen supply to a region of myocardium, due to narrowing of the arteries combined with sudden formation of a thrombus and blockage of a coronary artery. Death of a part of the myocardium occurs due a disruption in its blood supply.
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The endocrine system includes the endocrine glands and the hormones that they produce. It is a varied and complex system involving many glands and many hormones that work in balance via interconnected feedback control systems. Hormones are chemicals that are released into the blood stream where they travel to distant tissues and their sites of action.
As with any body system, there is the possibility of disease and malfunction: glands can secrete too much of their hormones; cells in tissues can have altered sensitivity to hormones; feedback control systems can break down. In these cases, hormones or their synthetic analogues are used as drugs.
They are most frequently used as aerosol inhalers and in nebulizers. An example of an antimuscarinic bronchodilator is ipratropium. Side effects are rare, but patients may get a dry mouth, urinary retention and constipation, all of which are typical effects of parasympathetic inhibition. High doses of antimuscarinic bronchodilators should not be used if the patient has glaucoma or an enlarged prostate gland, because they would make the glaucoma and urinary retention worse.
Xanthines are a group of drugs that directly cause relaxation of bronchial smooth muscle and some central respiratory stimulation. They also have a slight diuretic effect.
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They provide an alternative for those who cannot tolerate ACE inhibitors because of a persistent dry cough, but should not be used in pregnancy either. Neither ACE inhibitors nor angiotensin II receptor inhibitors seem to benefit patients of African origin. Nitrates are used primarily to treat ischaemic heart disease. These drugs are potent coronary vasodilators and can increase blood flow to the myocardium.
However, in many cases of angina, the coronary arteries are partially occluded and blood flow through them does not increase significantly.
Aspirin should not be used because it competes with uric acid for tubular secretion in the kidney. Long-term treatment with drugs that control uric acid levels prevents future episodes of gout and helps resolve tophi. However, these drugs do not relieve the pain and inflammation of an acute attack and may take many months to have an effect. Concurrent treatment with colchicine or a NSAID is necessary for the first three to six months. Allopurinol reduces the amount of uric acid in blood and urine by slowing the rate at which the liver produces uric acid.
Side effects of calcitonin are nausea, vomiting and diarrhoea together with flushing, paraesthesia and a peculiar taste in the mouth. The mechanism of action of bisphosphonates is not completely understood. They are deposited in place of normal bone and may slow bone turnover because they are resistant to degradation by enzymes produced by osteoclasts or they may inhibit the activity of osteoclasts.
Bisphosphonates are given orally and about in bone. They should not be taken at the same time as milk because it impairs their absorption. An example is sodium etidronate.