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
T.b. gambiense infection, enlarged glands in the neck (Winterbottom’s sign) may be striking. Onset of disease is accompanied by fever, progressive ANAEMIA, and enlarged glands; these signs and symptoms are followed by increasing lethargy, slowing of mentality, and physical weakness, and give way to headache and an increasing tendency to sleep. These symptoms are caused by proliferation of parasites in the patient’s cerebral blood vessels; this is accompanied by in?ammatory changes and disorganisation of nervous tissue. Patients become emaciated and develop bed sores. Death ?nally takes place either as a result of gross emaciation or of an intercurrent infection.
Diagnosis is by detection of trypanosomes in a blood specimen or, alternatively, a sample of cerebrospinal ?uid. Serological tests are of great value in diagnosis.
Treatment is with suramine or pentamidine; when cerebral involvement has ensued, melarsoprol – which penetrates the blood-brain barrier – is of value. In T.b. gambiense infection, e?ornithine has recently given encouraging results; however, this form of CHEMOTHERAPY is not e?ective in a T.b. rhodesiense infection. From the point of view of prevention, control of the tsetse-?y population is crucial; even so, only a very small percentage of these vectors is infected with Trypanosoma spp.... sleeping sickness
Causes Tropical sprue is thought to be due to an inborn error of metabolism, characterised primarily by an inability to absorb fats from the intestines. Its epidemiological pattern suggests that an infection such as DYSENTERY may be the precipitating factor. Subsequently there is interference with the absorption of carbohydrates, vitamins, and minerals, leading to anaemia and HYPOCALCAEMIA.
Symptoms Of gradual or rapid onset, there is initial weakness, soreness of the tongue, dif?culty swallowing, indigestion, diarrhoea and poor appetite. Anaemia is typically macrocytic, and mild HYPOGLYCAEMIA may occur. Untreated, the patient steadily loses weight and, unless appropriate treatment is started early, death may be expected because of exhaustion and some intercurrent infection.
Treatment This consists of bed rest, a high-protein diet (initially skimmed milk), and treatment of the anaemia and any other de?ciencies present. Minimum fat should be given to sufferers, who should also take folic acid and cyanocobalamin for the anaemia; large vitamin-B-complex supplements (such as Marmite®) are helpful. Vitamins A and D, together with calcium supplements, help to raise the concentration of calcium in the blood. A long convalescence is often required, which may lead to marked depression, and patients should be sent home to a temperate climate.
Non-tropical sprue is the result of GLUTEN hypersensitivty and is treated with a gluten-free diet.... sprue