Alkylating agents are important because they interfere with the growth and reproduction of cells, disrupting their replication. This CYTOTOXIC property is used to retard the division and growth of cancer cells, and alkylating drugs are widely used in the chemotherapy of malignant tumours – often in conjunction with surgery and sometimes with radiotherapy. Unfortunately, troublesome side-effects occur, such as: damage to veins when the drug is given intravenously, with resultant leakage into adjacent tissues; impaired kidney function due to the formation of URIC ACID crystals; nausea and vomiting; ALOPECIA (hair loss); suppression of BONE MARROW activity (production of blood cells); and adverse effects on reproductive function, including TERATOGENESIS. Indeed, cytotoxic drugs must not be given in pregnancy, especially during the ?rst three months. Prolonged use of alkylating drugs, especially when accompanying radiotherapy, is also associated with a sign?cant rise in the incidence of acute non-lymphocytic LEUKAEMIA. Among the dozen or so alkylating drugs in use are CYCLOPHOSPHAMIDE, CHLORAMBUCIL, MELPHALAN, BUSULFAN and THIOTEPA. (See also CHEMOTHERAPY.)... alkylating agents
Sulphonylureas The main group of hypoglycaemic agents, these act on the beta cells to stimulate insulin release; consequently they are e?ective only when there is some residual pancreatic beta-cell activity (see INSULIN). They also act on peripheral tissues to increase sensitivity, although this is less important. All sulphonylureas may lead to HYPOGLYCAEMIA four hours or more after food, but this is relatively uncommon, and usually an indication of overdose.
There are several di?erent sulphonylureas; apart from some di?erences in their duration or action (and hence in their suitability for individual patients) there is little di?erence in their e?ectiveness. Only chlorpropamide has appreciably more side-effects – mainly because of its prolonged duration of action and consequent risk of hypoglycaemia. There is also the common and unpleasant chlorpropamide/ alcohol-?ush phenomenon when the patient takes alcohol. Selection of an individual sulphonylurea depends on the patient’s age and renal function, and often just on personal preference. Elderly patients are particularly prone to the risks of hypoglycaemia when long-acting drugs are used. In these patients chlorpropamide, and preferably glibenclamide, should be avoided and replaced by others such as gliclazide or tolbutamide.
These drugs may cause weight gain and are indicated only if poor control persists despite adequate attempts at dieting. They should not be used during breast feeding, and caution is necessary in the elderly and in those with renal or hepatic insu?ciency. They should also be avoided in porphyria (see PORPHYRIAS). During surgery and intercurrent illness (such as myocardial infarction, COMA, infection and trauma), insulin therapy should be temporarily substituted. Insulin is generally used during pregnancy and should be used in the presence of ketoacidosis.
Side-effects Chie?y gastrointestinal disturbances and headache; these are generally mild and infrequent. After drinking alcohol, chlorpropamide may cause facial ?ushing. It also may enhance the action of antidiuretic hormone (see VASOPRESSIN), very rarely causing HYPONATRAEMIA.
Sensitivity reactions are very rare, usually occurring in the ?rst six to eight weeks of therapy. They include transient rashes which rarely progress to erythema multiforme (see under ERYTHEMA) and exfoliate DERMATITIS, fever and jaundice; chlorpropamide may also occasionally result in photosensitivity. Rare blood disorders include THROMBOCYTOPENIA, AGRANULOCYTOSIS and aplastic ANAEMIA.
Biguanides Metformin, the only available member of this group, acts by reducing GLUCONEOGENESIS and by increasing peripheral utilisation of glucose. It can act only if there is some residual insulin activity, hence it is only of value in the treatment of non-insulin dependent (type 2) diabetics. It may be used alone or with a sulphonylurea, and is indicated when strict dieting and sulphonylurea treatment have failed to control the diabetes. It is particularly valuable in overweight patients, in whom it may be used ?rst. Metformin has several advantages: hypoglycaemia is not usually a problem; weight gain is uncommon; and plasma insulin levels are lowered. Gastrointestinal side-effects are initially common and persistent in some patients, especially when high doses are being taken. Lactic acidosis is a rarely seen hazard occurring in patients with renal impairment, in whom metformin should not be used.
Other antidiabetics Acarbose is an inhibitor of intestinal alpha glucosidases (enzymes that process GLUCOSIDES), delaying the digestion of starch and sucrose, and hence the increase in blood glucose concentrations after a meal containing carbohydrate. It has been introduced for the treatment of type 2 patients inadequately controlled by diet or diet with oral hypoglycaemics.
Guar gum, if taken in adequate doses, acts by delaying carbohydrate absorption, and therefore reducing the postprandial blood glucose levels. It is also used to relieve symptoms of the DUMPING SYNDROME.... hypoglycaemic agents
This substance may be contaminated in manufacture with the highly toxic , commonly known as dioxin (see defoliant poisoning).... agent orange
Health Encyclopedia