Thiazides Health Dictionary

Diabetes insipidus is a relatively rare condition and must be di?erentiated from DIABETES MELLITUS which is an entirely di?erent disease.

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 ENZYME that converts angiotensin I to angiotensin II (see ANGIOTENSIN) is called angiotensin-converting enzyme. Angiotensin II controls the blood pressure and is the most potent endogenous pressor substance produced in the body; angiotensin I has no such pressor activity. Inhibition of the enzyme that converts angiotensin I to angiotensin II will thus have marked effects on lowering the blood pressure, and ACE inhibitors have a valuable role in treating heart failure when thiazides and beta blockers cannot be used or fail to work, especially after myocardial infarction (see HEART, DISEASES OF). Captopril was the ?rst ACE inhibitor to be synthesised: it reduces peripheral resistance by causing arteriolar dilatation and thus lowers blood pressure. Other drugs such as enalapril, lisinopril, cilazapril, quinapril and ramipril have since been developed. Some kidney disorders increase the production of angiotensin II and so cause HYPERTENSION.... angiotensin-convertingenzyme (ace) inhibitors

See THIAZIDES.... benzothiadiazines

Bumetanide is a strong loop diuretic which is active when taken by mouth. It acts quickly – within a half-hour – and its action is over in a few hours. (See THIAZIDES; DIURETICS.)... bumetanide

Calcium-channel blockers inhibit the inward ?ow of calcium through the specialised slow channels of cardiac and arterial smooth-muscle cells. By thus relaxing the smooth muscle, they have important applications in the treatment of HYPERTENSION and ANGINA PECTORIS. Various types of calcium-channel blockers are available in the United Kingdom; these di?er in their sites of action, leading to notable di?erences in their therapeutic effects. All the drugs are rapidly and completely absorbed, but extensive ?rst-pass metabolism in the liver reduces bioavailability to around one-?fth. Their hypotensive e?ect is additive with that of beta blockers (see BETA-ADRENOCEPTOR-BLOCKING DRUGS); the two should, therefore, be used together with great caution – if at all. Calcium-channel blockers are particularly useful when beta blockers are contraindicated, for example in asthmatics. However, they should be prescribed for hypertension only when THIAZIDES and beta blockers have failed, are contraindicated or not tolerated.

Verapamil, the longest-available, is used to treat angina and hypertension. It is the only calcium-channel blocker e?ective against cardiac ARRHYTHMIA and it is the drug of choice in terminating supraventricular tachycardia. It may precipitate heart failure, and cause HYPOTENSION at high doses. Nifedipine and diltiazem act more on the vessels and less on the myocardium than verapamil; they have no antiarrhythmic activity. They are used in the prophylaxis and treatment of angina, and in hypertension. Nicardipine and similar drugs act mainly on the vessels, but are valuable in the treatment of hypertension and angina. Important di?erences exist between di?erent calcium-channel blockers so their use must be carefully assessed. They should not be stopped suddenty, as this may precipitate angina. (See also HEART, DISEASES OF.)... calcium-channel blockers

A potent diuretic, with a rapid onset, and a short duration (4–6 hours), of action. (See THIAZIDES; DIURETICS.)... ethacrynic acid

A potent loop diuretic with a rapid onset (30 minutes), and short duration, of action. (See THIAZIDES, DIURETICS.)... frusemide

See THIAZIDES.... hydrochlorothiazide

A thiazide-type diuretic (see THIAZIDES; DIURETICS) which is particularly e?ective when combined with a loop diuretic (see LOOP DIURETICS), when it produces profound diuresis. The drug is also useful for treating kidney stones (see under KIDNEYS, DISEASES OF).... metolazone

Substances which increase urine and solute production by the KIDNEYS. They are used in the treatment of heart failure, HYPERTENSION, and sometimes for ASCITES secondary to liver failure. They may work by extra-renal or renal mechanisms.

The potential side-effects of diuretics are HYPOKALAEMIA, DEHYDRATION, and GOUT (in susceptible individuals).

Extra-renal mechanisms (a) Inhibiting release of antidiuretic hormone (e.g. water, alcohol); (b) increased renal blood ?ow (e.g. dopamine in renal doses).

Renal mechanisms (a) Osmotic diuretics act by ‘holding’ water in the renal tubules and preventing its reabsorption (e.g. mannitol); (b) loop diuretics prevent sodium, and therefore water, reabsorption (e.g. FRUSEMIDE); (c) drugs acting on the cortical segment of the Loop of Henle prevent sodium reabsorption, but are ‘weaker’ than loop diuretics (e.g. THIAZIDES); (d) drugs acting on the distal tubule prevent sodium reabsorption by retaining potassium

(e.g. spironalactone).... diuretics

Unnecessary drugs during pregnancy should be avoided because of the adverse e?ect of some drugs on the fetus which have no harmful e?ect on the mother. Drugs may pass through the PLACENTA and damage the fetus because their pharmacological effects are enhanced as the enzyme systems responsible for their degradation are undeveloped in the fetus. Thus, if the drug can pass through the placenta, the pharmacological e?ect on the fetus may be great whilst that on the mother is minimal. WARFARIN may thus induce fetal and placental haemorrhage and the administration of THIAZIDES may produce THROMBOCYTOPENIA in the newborn. Many progestogens have androgenic side-effects and their administration to a mother for the purpose of preventing recurrent abortion may produce VIRILISATION of the female fetus. Tetracycline administered during the last trimester commonly stains the deciduous teeth of the child yellow.

The other dangers of administering drugs in pregnancy are the teratogenic effects (see TERATOGENESIS). It is understandable that a drug may interfere with a mechanism essential for growth and result in arrested or distorted development of the fetus and yet cause no disturbance in the adult, in whom these di?erentiation and organisation processes have ceased to be relevant. Thus the e?ect of a drug upon a fetus may di?er qualitatively as well as quantitatively from its e?ect on the mother. The susceptibility of the embryo will depend on the stage of development it has reached when the drug is given. The stage of early di?erentiation – that is, from the beginning of the third week to the end of the tenth week of pregnancy – is the time of greatest susceptibility. After this time the risk of congenital malformation from drug treatment is less, although the death of the fetus can occur at any time.... drugs in pregnancy

Presence of abnormally low levels of potassium in the blood. May occur, with dehydration, in the elderly or in diabetics. A common cause is the prolonged use of the thiazides and loop diuretic drugs that leech potassium from the body. In severe degree may cause muscle weakness or paralysis. May also be caused by excessive fluid loss due to chronic diarrhoea.

Symptoms: Always tired. Lethargy. Irregular heart-beats from heart-muscle irritability. Possible cardiac arrest. Breathlessness.

Alternatives. Teas. Plantain, Chamomile, Mullein, Coltsfoot. Mistletoe. Nettles, Gotu Kola, or Yarrow. Decoction. Irish Moss, Agar-Agar, Kelp, Dandelion root.

Powders. Formula. Dandelion, Hawthorn, Liquorice. Equal parts. Dose: 500mg (two 00 capsules or one- third teaspoon) thrice daily.

Tinctures. Formula. Equal parts: Hawthorn, Dandelion, Liquorice. Dose: 1-2 teaspoons, thrice daily. Diet. Bananas: (fruit with highest potassium). Dates, Raisins. Oily fish. Figs. Prunes, Carrot leaves, Cider vinegar (impressive record), Black Molasses. ... hypokalaemia

n. a drug that increases the volume of urine produced by promoting the excretion of salts and water from the kidney. The main classes of diuretics act by inhibiting the reabsorption of salts and water from the kidney tubules into the bloodstream. Thiazide diuretics (e.g. *bendroflumethiazide, *chlortalidone) act at the distal convoluted tubules (see nephron), preventing the reabsorption of sodium and potassium. Potassium-sparing diuretics (e.g. *amiloride, *spironolactone, *triamterene) prevent excessive loss of potassium at the distal convoluted tubules, and loop diuretics (e.g. *furosemide) prevent reabsorption of sodium and potassium in *Henle’s loop. Diuretics are used to reduce the oedema due to salt and water retention in disorders of the heart, kidneys, liver, or lungs. Thiazides and potassium-sparing diuretics are also used – in conjunction with other drugs – in the treatment of high blood pressure. Treatment with thiazide and loop diuretics often results in potassium deficiency; this is corrected by simultaneous administration of potassium salts or a potassium-sparing diuretic.... diuretic

Means high BLOOD PRESSURE (raised pressure of the circulating blood), but since there is a wide range of ‘normal’ blood pressure in the population, a precise level of pressure above which an individual is deemed hypertensive is arbitrary. (A healthy young adult would be expected to have a systolic pressure of around 120 mm Hg and a diastolic of 80 mm Hg, recorded as 120/80.) Hypertension is not a disease as such but a quantitative deviation from the norm. A person with a pressure higher than the average for his or her age group is usually symptomless – although sometimes such people may develop headaches. The identi?cation of people with hypertension is important because it is a signal that they will be more likely to have a STROKE or myocardial infarct (coronary thrombosis or heart attack) than someone whose pressure is in the ‘normal’ range. Preventive steps can then be taken to lessen the likelihood of their developing these potentially life-threatening conditions.

Blood pressure is measured using two values. The systolic pressure – the greater of the two – represents the pressure when blood is pumped from the left VENTRICLE of the heart into the AORTA. The diastolic pressure is the measurement when both ventricles relax between beats. The pressures are measured in millimetres (mm) of mercury (Hg). Despite the grey area between normal and raised blood pressure, the World Health Organisation (WHO) has de?ned hypertension as a blood pressure consistently greater than 160 mm Hg (systolic) and 95 mm Hg (diastolic). Young children have readings well below these, but blood pressure rises with age and a healthy person may well live symptom free with a systolic pressure above the WHO ?gure. A useful working de?nition of hypertension is the ?gure at which the bene?ts of treating the condition outweigh the risks and costs of the treatment.

Between 10 and 20 per cent of the adult population in the UK has hypertension, with more men than women affected. Incidence is highest in the middle-aged and elderly. Because most people with hypertension are symptomless, the condition is often ?rst identi?ed during a routine medical examination, otherwise a diagnosis is usually made when complications occur. Many people’s blood pressure rises when they are anxious or after exercise, so if someone’s pressure is above normal at the ?rst testing, it should be taken again after, say, 10 minutes’ rest, by which time the reading should have settled to the person’s regular level. BP measurements should then be taken on two subsequent occasions. If the pressure is still high, the cause needs to be determined: this is done using a combination of personal and family histories (hypertension can run in families), a physical examination and investigations, including an ECG and blood tests for renal disease.

Over 90 per cent of hypertensive people have no immediately identi?able cause for their condition. They are described as having essential hypertension. In those patients with an identi?able cause, the hypertension is described as secondary. Among the causes of secondary hypertension are:

Lifestyle factors such as smoking, alcohol, stress, excessive dietary salt and obesity.

Diseases of the KIDNEYS.

Pregnancy (ECLAMPSIA).

Various ENDOCRINE disorders – for example, PHAEOCHROMOCYTOMA, CUSHING’S DISEASE, ACROMEGALY, thyrotoxicosis (see under THYROID GLAND, DISEASES OF).

COARCTATION OF THE AORTA.

Drugs – for example, oestrogen-containing oral contraceptives (see under CONTRACEPTION), ANABOLIC STEROIDS, CORTICOSTEROIDS, NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS).

Treatment People with severe hypertension may need prompt admission to hospital for urgent investigation and treatment. Those with a mild to moderate rise in blood pressure for which no cause is identi?able should be advised to change their lifestyle: smokers should stop the habit, and those with high alcohol consumption should greatly reduce or stop their drinking. Obese people should reduce their food consumption, especially of animal fats, and take more exercise. Everyone with hypertension should follow a low-salt diet and take regular exercise. Patients should also be taught how to relax, which helps to reduce blood pressure and, if they have a stressful life, working patterns should be modi?ed if possible. If these lifestyle changes do not reduce a person’s blood pressure su?ciently, drugs to achieve this will be needed. A wide range of anti-hypertensive drugs are available on prescription.

A ?rst-line treatment is one of the THIAZIDES, e?ective at a low dosage and especially useful in the elderly. Beta blockers (see BETAADRENOCEPTOR-BLOCKING DRUGS), such as oxprenolol, acebutol or atenolol, are also ?rst-line treatments. ACE inhibitors (see ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS) and CALCIUM-CHANNEL BLOCKERS can be used if the ?rst-line choices are not e?ective. The drug treatment of hypertension is complex, and sometimes various drugs or combinations of drugs have to be tried to ?nd what regimen is e?ective and suits the patient. Mild to moderate hypertension can usually be treated in general practice, but patients who do not respond or have complications will normally require specialist advice. Patients on anti-hypertensive treatments require regular monitoring, and, as treatment may be necessary for several years, particular attention should be paid to identifying sideeffects. Nevertheless, e?ective treatment of hypertension does enable affected individuals to live longer and more comfortable lives than would otherwise be the case. Older people with moderately raised blood pressure are often able to live with the condition, and treatment with anti-hypertensive drugs may produce symptoms of HYPOTENSION.

In summary, hypertension is a complex disorder, with di?erent patients responding di?erently to treatment. So the condition sometimes requires careful assessment before the most e?ective therapy for a particular individual is identi?ed, and continued monitoring of patients with the disorder is advisable.

Complications Untreated hypertension may eventually result in serious complications. People with high blood pressure have blood vessels with thickened, less ?exible walls, a narrowed LUMEN and convoluted shape. Sometimes arteries become rigid. ANEURYSM may develop and widespread ATHEROMA (fat deposits) is apparent in the arterial linings. Such changes adversely affect the blood supply to body tissues and organs and so damage their functioning. Patients suffer STROKE (haemorrhage from or thrombosis in the arteries of the BRAIN) and heart attacks (coronary thrombosis

– see HEART, DISEASES OF). Those with hypertension may suffer damage to the retina of the EYE and to the OPTIC DISC. Indeed, the diagnosis of hypertension is sometimes made during a routine eye test, when the doctor or optician notices changes in the retinal arteries or optic disc. Kidney function is often affected, with patients excreting protein and excessive salt in their urine. Occasionally someone with persistent hypertension may suffer an acceleration of damage to the blood vessels – a condition described as ‘malignant’ hypertension, and one requiring urgent hospital treatment.

Hypertension is a potentially dangerous disease because it develops into a cycle of self-perpetuating damage. Faulty blood vessels lead to high blood pressure which in turn aggravates the damage in the vessels and thus in the tissues and organs they supply with blood; this further raises the affected individual’s blood pressure and the pathological cycle continues.... hypertension