Another name for ADH.
ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS.)... angiotensin
It is characterised by excessive thirst and the passing of large volumes of urine which have a low speci?c gravity and contain no abnormal constituents. It is either due to a lack of the antidiuretic hormone normally produced by the HYPOTHALAMUS and stored in the posterior PITUITARY GLAND, or to a defect in the renal tubules which prevents them from responding to the antidiuretic hormone VASOPRESSIN. When the disorder is due to vasopressin insu?ciency, a primary or secondary tumour in the area of the pituitary stalk is responsible for one-third of cases. In another one-third of cases there is no apparent cause, and such IDIOPATHIC cases are sometimes familial. A further one-third of cases result from a variety of lesions including trauma, basal MENINGITIS and granulomatous lesions in the pituitary-stalk area. When the renal tubules fail to respond to vasopressin this is usually because of a genetic defect transmitted as a sex-linked recessive characteristic, and the disease is called nephrogenic diabetes insipidus. Metabolic abnormalities such as HYPERCALCAEMIA and potassium depletion render the renal tubule less sensitive to vasopressin, and certain drugs such as lithium and tetracycline may have a similar e?ect.
If the disease is due to a de?ciency of vasopressin, treatment should be with the analogue of vasopressin called desmopressin which is more potent than the natural hormone and has less pressor activity. It also has the advantage in that it is absorbed from the nasal mucosa and so does not need to be injected.
Nephrogenic diabetes insipidus cannot be treated with desmopressin. The urine volume can, however, usually be reduced by half by a thiazide diuretic (see THIAZIDES).... diabetes insipidus
The pituitary gland is the most important ductless, or endocrine, gland in the body. (See
ENDOCRINE GLANDS.) It exerts overall control of the endocrine system through the media of a series of hormones which it produces. The adenohypophysis produces trophic hormones (that is, they work by stimulating or inhibiting other endocrine glands) and have therefore been given names ending with ‘trophic’ or ‘trophin’. The thyrotrophic hormone, or thyroid-stimulating hormone (TSH), exerts a powerful in?uence over the activity of the THYROID GLAND. The ADRENOCORTICOTROPHIC HORMONE (ACTH) stimulates the cortex of the adrenal glands. GROWTH HORMONE, also known as somatotrophin (SMH), controls the growth of the body. There are also two gonadotrophic hormones which play a vital part in the control of the gonads: these are the follicle-stimulating hormone (FSH), and the luteinising hormone (LH) which is also known as the interstitial-cell-stimulating hormone (ICSH) – see GONADOTROPHINS. The lactogenic hormone, also known as prolactin, mammotrophin and luteotrophin, induces lactation.
The neurohypophysis produces two hormones. One is oxytocin, which is widely used because of its stimulating e?ect on contraction of the UTERUS. The other is VASOPRESSIN, or the antidiuretic hormone (ADH), which acts on the renal tubules and the collecting tubules (see KIDNEYS) to increase the amount of water that they normally absorb.... pituitary gland
Adrenal glands These two glands, also known as suprarenal glands, lie immediately above the kidneys. The central or medullary portion of the glands forms the secretions known as ADRENALINE (or epinephrine) and NORADRENALINE. Adrenaline acts upon structures innervated by sympathetic nerves. Brie?y, the blood vessels of the skin and of the abdominal viscera (except the intestines) are constricted, and at the same time the arteries of the muscles and the coronary arteries are dilated; systolic blood pressure rises; blood sugar increases; the metabolic rate rises; muscle fatigue is diminished. The super?cial or cortical part of the glands produces steroid-based substances such as aldosterone, cortisone, hydrocortisone, and deoxycortone acetate, for the maintenance of life. It is the absence of these substances, due to atrophy or destruction of the suprarenal cortex, that is responsible for the condition known as ADDISON’S DISEASE. (See CORTICOSTEROIDS.)
Ovaries and testicles The ovary (see OVARIES) secretes at least two hormones – known, respectively, as oestradiol (follicular hormone) and progesterone (corpus luteum hormone). Oestradiol develops (under the stimulus of the anterior pituitary lobe – see PITUITARY GLAND below, and under separate entry) each time an ovum in the ovary becomes mature, and causes extensive proliferation of the ENDOMETRIUM lining the UTERUS, a stage ending with shedding of the ovum about 14 days before the onset of MENSTRUATION. The corpus luteum, which then forms, secretes both progesterone and oestradiol. Progesterone brings about great activity of the glands in the endometrium. The uterus is now ready to receive the ovum if it is fertilised. If fertilisation does not occur, the corpus luteum degenerates, the hormones cease acting, and menstruation takes place.
The hormone secreted by the testicles (see TESTICLE) is known as TESTOSTERONE. It is responsible for the growth of the male secondary sex characteristics.
Pancreas This gland is situated in the upper part of the abdomen and, in addition to the digestive enzymes, it produces INSULIN within specialised cells (islets of Langerhans). This controls carbohydrate metabolism; faulty or absent insulin production causes DIABETES MELLITUS.
Parathyroid glands These are four minute glands lying at the side of, or behind, the thyroid (see below). They have a certain e?ect in controlling the absorption of calcium salts by the bones and other tissues. When their secretion is defective, TETANY occurs.
Pituitary gland This gland is attached to the base of the brain and rests in a hollow on the base of the skull. It is the most important of all endocrine glands and consists of two embryologically and functionally distinct lobes.
The function of the anterior lobe depends on the secretion by the HYPOTHALAMUS of certain ‘neuro-hormones’ which control the secretion of the pituitary trophic hormones. The hypothalamic centres involved in the control of speci?c pituitary hormones appear to be anatomically separate. Through the pituitary trophic hormones the activity of the thyroid, adrenal cortex and the sex glands is controlled. The anterior pituitary and the target glands are linked through a feedback control cycle. The liberation of trophic hormones is inhibited by a rising concentration of the circulating hormone of the target gland, and stimulated by a fall in its concentration. Six trophic (polypeptide) hormones are formed by the anterior pituitary. Growth hormone (GH) and prolactin are simple proteins formed in the acidophil cells. Follicle-stimulating hormone (FSH), luteinising hormone (LH) and thyroid-stimulating hormone (TSH) are glycoproteins formed in the basophil cells. Adrenocorticotrophic hormone (ACTH), although a polypeptide, is derived from basophil cells.
The posterior pituitary lobe, or neurohypophysis, is closely connected with the hypothalamus by the hypothalamic-hypophyseal tracts. It is concerned with the production or storage of OXYTOCIN and vasopressin (the antidiuretic hormone).
PITUITARY HORMONES Growth hormone, gonadotrophic hormone, adrenocorticotrophic hormone and thyrotrophic hormones can be assayed in blood or urine by radio-immunoassay techniques. Growth hormone extracted from human pituitary glands obtained at autopsy was available for clinical use until 1985, when it was withdrawn as it is believed to carry the virus responsible for CREUTZFELDT-JAKOB DISEASE (COD). However, growth hormone produced by DNA recombinant techniques is now available as somatropin. Synthetic growth hormone is used to treat de?ciency of the natural hormone in children and adults, TURNER’S SYNDROME and chronic renal insu?ciency in children.
Human pituitary gonadotrophins are readily obtained from post-menopausal urine. Commercial extracts from this source are available and are e?ective for treatment of infertility due to gonadotrophin insu?ciency.
The adrenocorticotrophic hormone is extracted from animal pituitary glands and has been available therapeutically for many years. It is used as a test of adrenal function, and, under certain circumstances, in conditions for which corticosteroid therapy is indicated (see CORTICOSTEROIDS). The pharmacologically active polypeptide of ACTH has been synthesised and is called tetracosactrin. Thyrotrophic hormone is also available but it has no therapeutic application.
HYPOTHALAMIC RELEASING HORMONES which affect the release of each of the six anterior pituitary hormones have been identi?ed. Their blood levels are only one-thousandth of those of the pituitary trophic hormones. The release of thyrotrophin, adrenocorticotrophin, growth hormone, follicle-stimulating hormone and luteinising hormone is stimulated, while release of prolactin is inhibited. The structure of the releasing hormones for TSH, FSH-LH, GH and, most recently, ACTH is known and they have all been synthesised. Thyrotrophin-releasing hormone (TRH) is used as a diagnostic test of thyroid function but it has no therapeutic application. FSH-LH-releasing hormone provides a useful diagnostic test of gonadotrophin reserve in patients with pituitary disease, and is now used in the treatment of infertility and AMENORRHOEA in patients with functional hypothalamic disturbance. As this is the most common variety of secondary amenorrhoea, the potential use is great. Most cases of congenital de?ciency of GH, FSH, LH and ACTH are due to defects in the hypothalamic production of releasing hormone and are not a primary pituitary defect, so that the therapeutic implication of this synthesised group of releasing hormones is considerable.
GALACTORRHOEA is frequently due to a microadenoma (see ADENOMA) of the pituitary. DOPAMINE is the prolactin-release inhibiting hormone. Its duration of action is short so its therapeutic value is limited. However, BROMOCRIPTINE is a dopamine agonist with a more prolonged action and is e?ective treatment for galactorrhoea.
Thyroid gland The functions of the thyroid gland are controlled by the pituitary gland (see above) and the hypothalamus, situated in the brain. The thyroid, situated in the front of the neck below the LARYNX, helps to regulate the body’s METABOLISM. It comprises two lobes each side of the TRACHEA joined by an isthmus. Two types of secretory cells in the gland – follicular cells (the majority) and parafollicular cells – secrete, respectively, the iodine-containing hormones THYROXINE (T4) and TRI-IODOTHYRONINE (T3), and the hormone CALCITONIN. T3 and T4 help control metabolism and calcitonin, in conjunction with parathyroid hormone (see above), regulates the body’s calcium balance. De?ciencies in thyroid function produce HYPOTHYROIDISM and, in children, retarded development. Excess thyroid activity causes thyrotoxicosis. (See THYROID GLAND, DISEASES OF.)... endocrine glands
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
There are three main categories of licensed medicinal product. Drugs in small quantities can, if they are perceived to be safe, be licensed for general sale (GSL – general sales list), and may then be sold in any retail shop. P (pharmacy-only) medicines can be sold from a registered pharmacy by or under the supervision of a pharmacist (see PHARMACISTS); no prescription is needed. P and GSL medicines are together known as OTCs – that is, ‘over-thecounter medicines’. POM (prescription-only medicines) can only be obtained from a registered pharmacy on the prescription of a doctor or dentist. As more information is gathered on the safety of drugs, and more emphasis put on individual responsibility for health, there is a trend towards allowing drugs that were once POM to be more widely available as P medicines. Examples include HYDROCORTISONE 1 per cent cream for skin rashes, CIMETIDINE for indigestion, and ACICLOVIR for cold sores. Care is needed to avoid taking a P medicine that might alter the actions of another medicine taken with it, or that might be unsuitable for other reasons. Patients should read the patient-information lea?et, and seek the pharmacist’s advice if they have any doubt about the information. They should tell their pharmacist or doctor if the medicine results in any unexpected effects.
Potentially dangerous drugs are preparations referred to under the Misuse of Drugs Act 1971 and subsequent regulations approved in 1985. Described as CONTROLLED DRUGS, these include such preparations as COCAINE, MORPHINE, DIAMORPHINE, LSD (see LYSERGIC ACID
DIETHYLAMIDE (LSD)), PETHIDINE HYDROCHLORIDE, AMPHETAMINES, BARBITURATES and most BENZODIAZEPINES.
Naming of drugs A European Community Directive (92/27/EEC) requires the use of the Recommended International Non-proprietary Name (rINN) for medicinal substances. For most of these the British Approved Name (BAN) and rINN were identical; where the two were di?erent, the BAN has been modi?ed in line with the rINN. Doctors and other authorised subscribers are advised to write titles of drugs and preparations in full because uno?cial abbreviations may be misinterpreted. Where a drug or preparation has a non-proprietary (generic) title, this should be used in prescribing unless there is a genuine problem over the bioavailability properties of a proprietary drug and its generic equivalent.
Where proprietary – commercially registered
– names exist, they may in general be used only for products supplied by the trademark owners. Countries outside the European Union have their own regulations for the naming of medicines.
Methods of administration The ways in which drugs are given are increasingly ingenious. Most are still given by mouth; some oral preparations (‘slow release’ or ‘controlled release’ preparations) are designed to release their contents slowly into the gut, to maintain the action of the drug.
Buccal preparations are allowed to dissolve in the mouth, and sublingual ones are dissolved under the tongue. The other end of the gastrointestinal tract can also absorb drugs: suppositories inserted in the rectum can be used for their local actions – for example, as laxatives – or to allow absorption when taking the drug by mouth is di?cult or impossible – for example, during a convulsion, or when vomiting.
Small amounts of drug can be absorbed through the intact skin, and for very potent drugs like OESTROGENS (female sex hormones) or the anti-anginal drug GLYCERYL TRINITRATE, a drug-releasing ‘patch’ can be used. Drugs can be inhaled into the lungs as a ?ne powder to treat or prevent ASTHMA attacks. They can also be dispersed (‘nebulised’) as a ?ne mist which can be administered with compressed air or oxygen. Spraying a drug into the nostril, so that it can be absorbed through the lining of the nose into the bloodstream, can avoid destruction of the drug in the stomach. This route is used for a small number of drugs like antidiuretic hormone (see VASOPRESSIN).
Injection remains an important route of administering drugs both locally (for example, into joints or into the eyeball), and into the bloodstream. For this latter purpose, drugs can be given under the skin – that is, subcutaneously (s.c. – also called hypodermic injection); into muscle – intramuscularly (i.m.); or into a vein – intravenously (i.v.). Oily or crystalline preparations of drugs injected subcutaneously form a ‘depot’ from which they are absorbed only slowly into the blood. The action of drugs such as TESTOSTERONE and INSULIN can be prolonged by using such preparations, which also allow contraceptive ‘implants’ that work for some months (see CONTRACEPTION).... medicines
DIABETES INSIPIDUS, a condition characterised by the passing of a large volume of URINE every day, is due to lack of the antidiuretic hormone (see VASOPRESSIN). Enhanced production of the ADRENOCORTICOTROPHIC HORMONE (ACTH) leads to CUSHING’S SYNDROME. Excessive production of PROLACTIN by micro or macro adenomas (benign tumours) leads to hyperprolactinaemia and consequent AMENORRHOEA and GALACTORRHOEA. Some adenomas do not produce any hormone but cause effects by damaging the pituitary cells and inhibiting their hormone production.
The most sensitive cells to extrinsic pressure are the gonadotrophin-producing cells and the growth-hormone producing cells, so that if the tumour occurs in childhood, growth hormone will be suppressed and growth will slow. Gonadotrophin hormone suppression will prevent the development of puberty and, if the tumour occurs after puberty, will result in amenorrhoea in the female and lack of LIBIDO in both sexes. The thyroid-stimulating hormone cells are the next to suffer and the pressure effects on these cells will result in hypothyroidism (see under THYROID GLAND, DISEASES OF).
Fortunately the ACTH-producing cells are the most resistant to extrinsic pressure and this is teleologically sound as ACTH is the one pituitary hormone that is essential to life. However, these cells can suffer damage from intracellular tumours, and adrenocortical insu?ciency is not uncommon.
Information about these disorders may be obtained from the Pituitary Foundation.... pituitary-linked disorders
Varices develop as a consequence of portal hypertension.
Blood in the portal vein, passing from the intestines to the liver, meets resistance due to liver disease.
The increased blood pressure causes blood to be diverted into small veins in the walls of the oesophagus and stomach.
These veins may become distended and rupture, causing vomiting of blood and black faeces.
There are usually other symptoms of chronic liver disease.
To control acute bleeding, a balloon catheter may be passed into the oesophagus to press on the bleeding varices.
The varices may be treated with an intravenous injection of vasopressin and/or by injection, via an endoscope, of a sclerosant that seals off the affected veins.... oesophageal varices
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