Allergy, a hypersensitivity to certain substances, is a reaction of the body’s immune system. Through a variety of mechanisms (see Malignant and immune disease), the immune system protects the body by eliminating unrecognized foreign substances, such as microorganisms (bacteria or viruses).
One way in which the immune system acts is through the production of antibodies. When the body encounters a particular foreign substance (or allergen) for the first time, one type of white blood cell, the lymphocyte, produces antibodies that attach themselves to another type of white blood cell, the mast cell. If the same substance is encountered again, the allergen binds to the antibodies on the mast cells, causing the release of chemicals known as mediators.
The most important mediator is histamine. Its release can produce a rash, swelling, narrowing of the airways, and a drop in blood pressure. Although these effects are important in protecting the body against infection, they may also be triggered inappropriately in an allergic reaction.
WHAT CAN GO WRONG
One of the most common allergic disorders, hay fever, is caused by an allergic reaction to inhaled pollen leading to allergic rhinitis – swelling and irritation of the nasal passages and watering of the nose and eyes. Other substances, such as house-dust mites, animal fur, and feathers, may cause a similar reaction in susceptible people.
Asthma, another allergic disorder, may result from the action of leukotrienes rather than histamine. Other allergic conditions include urticaria (hives) or other rashes (sometimes in response to a drug), some forms of eczema and dermatitis, and allergic alveolitis (farmer’s lung). Anaphylaxis is a serious systemic allergic reaction that occurs when an allergen reaches the bloodstream (see also Epinephrine).
WHY DRUGS ARE USED
Antihistamines and drugs that inhibit mast cell activity are used to prevent and treat allergic reactions. Other drugs minimize symptoms, and include decongestants to clear the nose in allergic rhinitis, bronchodilators to widen the airways of those with asthma, and corticosteroids applied to skin affected by eczema.
MAJOR DRUG GROUPS
· Leukotriene antagonists
· Drugs for asthma
Antihistamines are the most widely used drugs in the treatment of allergic reactions of all kinds. They can be subdivided according to their chemical structure, each subgroup having slightly different actions and characteristics (see table). Their main action is to counter the effects of histamine, one of the chemicals released in the body when there is an allergic reaction.
Histamine is also involved in other body functions, including blood vessel dilation and constriction, contraction of muscles in the respiratory and gastrointestinal tracts, and the release of digestive juices in the stomach. The antihistamine drugs described here are also known as H1 blockers because they block the action of histamine only on certain receptors, known as H1 receptors. Another group of antihistamines, known as H2 blockers, is used in the treatment of peptic ulcers (see Anti-ulcer drugs).
Some antihistamines have a significant anticholinergic action. This is used to advantage in a variety of conditions, but it also accounts for certain undesired side effects.
WHY THEY ARE USED
Antihistamines relieve allergy-related symptoms when it is not possible to prevent exposure to the substance that has provoked the reaction. They are most commonly used in the prevention of allergic rhinitis (hay fever), the inflammation of the nose and upper airways that results from an allergic reaction to a substance such as pollen, house dust, or animal fur. Antihistamines are more effective when taken before the start of an attack. If they are taken only after an attack has begun, beneficial effects may be delayed.
Antihistamines are not usually effective in asthma caused by similar allergens because the symptoms of this allergic disorder are not solely caused by the action of histamine, but are likely to be the result of more complex mechanisms. Antihistamines are usually the first drugs to be tried in the treatment of allergic disorders but alternatives can be prescribed (see Other allergy treatments).
Antihistamines are also prescribed for the itching, swelling, and redness of allergic reactions involving the skin such as urticaria (hives) and dermatitis. Irritation from chickenpox may be reduced by these drugs. Allergic reactions to insect stings may also be reduced by antihistamines. In such cases the drug may be taken by mouth or applied topically. Applied as drops, antihistamines can reduce inflammation and irritation of the eyes and eyelids in allergic conjunctivitis.
Antihistamines are often included as an ingredient in cough and cold preparations, when the anticholinergic effect of drying mucus secretions and their sedative effect on the coughing mechanism may be helpful.
Because most antihistamines have a depressant effect on the brain, they are sometimes used to promote sleep, especially when discomfort from itching is disturbing sleep (see also Sleeping drugs). The depressant effect of antihistamines on the brain also extends to the centres that control nausea and vomiting. Antihistamines are therefore often effective for preventing and controlling these symptoms (see Anti-emetics).
Occasionally, antihistamines are used to treat fever, rash, and breathing difficulties that may occur in adverse reactions to blood transfusions and allergic reactions to drugs. Promethazine and alimemazine are also used as premedication to provide sedation and to dry secretions during surgery, particularly in children.
HOW THEY WORK
Antihistamines block the action of histamine on H1 receptors. These are found in various body tissues, particularly the small blood vessels in the skin, nose, and eyes. This helps prevent the dilation of the vessels, thus reducing the redness, watering, and swelling. In addition, the anticholinergic action of these drugs contributes to this effect by reducing the secretions from tear glands and nasal passages. Antihistamine drugs pass from the blood into the brain. In the brain, the blocking action of the antihistamines on histamine activity may produce general sedation and depression of various brain functions, including the vomiting and coughing mechanisms.
HOW THEY AFFECT YOU
Antihistamines frequently cause a degree of drowsiness and may affect coordination, leading to clumsiness. Some newer drugs have little or no sedative effect (see table).
Anticholinergic side effects, including dry mouth, blurred vision, and difficulty passing urine, are common. Most side effects diminish with continued use and can often be helped by an adjustment in dosage or a change to a different drug.
RISKS AND SPECIAL PRECAUTIONS
It is advisable not to drive or operate machinery while taking antihistamines, particularly those more likely to cause drowsiness (see table). Antihistamines can also increase the sedative effects of alcohol, sleeping drugs, opioid analgesics, and anti-anxiety drugs.
In high doses, or in children, some antihistamines can cause excitement, agitation, and even, in extreme cases, hallucinations and seizures. Abnormal heart rhythms have occurred after high doses with some antihistamines or when drugs that interact with them, such as antifungals and antibiotics, have been taken at the same time. Heart rhythm problems may also affect people with liver disease, electrolyte disturbances, or abnormal heart activity. A person who has these conditions, or who has glaucoma or prostate trouble, should seek medical advice before taking antihistamines because their various drug actions may make such conditions worse.
Non-sedating Acrivastine, Cetirizine, Fexofenadine, Levocetirizine, Loratadine/desloratadine, Mizolastine
Sedating Alimemazine, Chlorphenamine, Cinnarizine, Clemastine, Diphenhydramine, Hydroxyzine, Promethazine
OTHER ALLERGY TREATMENTS
Sodium cromoglicate This drug prevents the release of histamine from mast cells in response to exposure to an allergen, thereby preventing the physical symptoms of allergies. Sodium cromoglicate is commonly given by inhaler for the prevention of allergy-induced rhinitis (hay fever) or asthma attacks and by drops for the treatment of allergic eye disorders.
Leukotriene antagonists Like histamine, leukotrienes are substances that occur naturally in the body and seem to play an important part in asthma. Drugs such as montelukast and zafirlukast (leukotriene antagonists) have been developed to prevent asthma attacks from occurring. They are not bronchodilators, however, and will not relieve an existing attack (see Drugs for asthma).
Corticosteroids These drugs for allergic rhinitis and asthma are usually given by inhaler, providing a high dose to the affected area. The dose of the drug to the rest of the body is very low, reducing the risk of long-term adverse effects.
Desensitization This may be tried in conditions such as allergic rhinitis due to pollen sensitivity and insect venom hypersensitivity, when avoidance, antihistamines, and other treatments have not been effective and tests have shown one or two specific allergens to be responsible. Desensitization often provides incomplete relief and can be time-consuming.
Treatment involves a series of injections containing increasing doses of an extract of the allergen. It is not understood how this prevents allergic reactions, but controlled exposure may trigger the immune system into producing increasing levels of antibodies so that the body no longer responds dramatically when the allergen is encountered naturally.
Desensitization must be carried out under medical supervision because it can provoke a severe allergic response. Therefore, it is important that you remain near emergency medical facilities for at least one hour after each injection.
COMPARISON OF ANTIHISTAMINES
The table here indicates the main uses of some common antihistamines and lists their relative strength of anticholinergic action, sedative effects, and duration of action.