Thiazide diuretics adverse effects

Thiazide diuretics and /3-blockers without ISA may affect serum lipids adversely, but these effects generally are transient and of no clinical consequence. 

Furosemide, torsemide, and bumetanide are sulfonamide derivatives, hence chemically related to the thiazides. They share the thiazides adverse effects of serum uric acid elevation and diabetogenic potential. Ethacrynic acid (Edecrin) is chemically unrelated to other diuretics and does not appear to have diabetogenic potential. 

Hyponatremia is an important adverse effect of thiazide diuretics. It is due to a combination of hypovolemia-induced elevation of ADH, reduction in the diluting capacity of the kidney, and increased thirst. It can be prevented by reducing the dose of the drug or limiting water intake. 

The special risk is observed in patients with hepatic or renal impairment. It is not advised to use allopurinol in acute attacks of gout, but it is useful in chronic gout. Excretion of allopurinol and its active metabolite oxypurinol is primarily via the kidneys and therefore the dosage should be reduced if renal function is impaired. The adverse effects have been reported in patients receiving allopurinol with thiazide diuretics, particularly in patients with impaired renal function. The metabolism of azathioprine and mercaptopurine is inhibited by allopurinol and their doses should be reduced to one-quarter to one-third of the usual dose when either of them is given with allopurinol to avoid potentially life-threatening toxicity.27-29... 

The thiazide diuretics are primarily used for most patients with mild or moderate hypertension. Used alone they can lower blood pressure by 10-15 mmHg. In more severe hypertension diuretics are used in combination with other agents. Adverse effects include hypokalemia (lowered serum potassium), impotence, impaired glucose tolerance, hyperlipidemia, and hyperuricemia (elevated uric acid in the blood). 

Adverse effects Thiazide diuretics induce hypokalemia and hyperuricemia in 70% of patients, and hyperglycemia in 10% of patients. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular hypertrophy, ischemic heart disease, or chronic congestive heart failure) and who are concurrently being treated with both thiazide diuretics and digitalis glycosides (see p. 160). Diuretics should be avoided in the treatment of hypertensive diabetics or patients with hyperlipidemia. 

Summary of adverse effects commonly observed with thiazide diuretics. 

Q8 In addition to the intended therapeutic effects, thiazide diuretics can have adverse effects of hypokalaemia, hyperglycaemia and hyperuricaemia. These are not often observed when the usual low dose of thiazide is used. If the dosage is increased, the therapeutic effect is not greatly enhanced, but the likelihood of adverse effects increases considerably. It is therefore better to change to a more powerful agent, such as a loop diuretic, than to increase the dose of the thiazide. 

More recently, it has been shown that hypokalemia and other dose-related adverse metabolic effects of thiazide diuretics increase the risk of sudden death and negate the cardiovascular benefit of blood pressure lowering when high doses these drugs are prescribed (21). Hence, another explanation for the apparent inability of antihypertensive therapy to lower mortality in patients with coronary heart disease is that high thiazide doses were used in many of the trials that were analyzed. As pointed out by Temple (2), this explanation is supported by the results of a trial of antihypertensive therapy in elderly patients with isolated systolic hypertension (22). In this study, only low doses of a thiazide diuretic were prescribed and a 4-mm Hg average decrease in diastolic blood pressure was associated with a 36% reduction in the... 

Diuretics related to the thiazides. Several compounds, although strictly not thiazides, share structural similarities with them and probably act at the same site on the nephron they therefore exhibit moderate therapeutic efficacy. Overall, these substances have a longer duration of action, are used for oedema and hypertension and their profile of adverse effects is similar to that of the thiazides. They are listed below. 

Adverse effects are most commonly manifest as acute pancreatitis. The strongest association is with alcohol abuse. High plasma calcium, including that caused by hypervitaminosis D, and parenteral nutrition also increase the risk. Corticosteroids, didanosine, azathoipurine, diuretics (including thiazides and frusemide), sodium valproate, mesalazine and paracetamol (in overdose) have also been causally related. 

Chlortalidone (chlorthalidone) is chemically unrelated to the thiazide diuretics but shares many of their actions and adverse effects. 

When problems do arise they usually reflect either interactions, which with caution could have been avoided, or relative overdosage. In the course of time the recommended antihypertensive doses of diuretics have been reduced, and some adverse effects that were noted in the early years are now of less significance these include hypotension, dehydration, reduction of the glomerular filtration rate, and severe hypokalemia. Continued use of thiazides in excessive doses may reflect ignorance of their very flat dose-response curve (1). At currently recommended low doses, diuretics improve overall quality of life, even in asymptomatic patients with mild hypertension (2). The large HANE study (3) provided no evidence of superior efficacy or tolerability of new classes of antihypertensive drugs. 

The adverse effects of thiazide and thiazide-like diuretics on male sexual function include reduced libido, erectile dysfunction, and difficulty in ejaculating. The exact incidence of sexual dysfunction in patients taking diuretics is poorly documented, perhaps because of the personal nature of the problem and the reluctance of patients and/or physicians to discuss it. However, these abnormalities have been reported with incidence rates of 3-32%. The true incidence of sexual dysfunction probably lies closer to the lower end of this range (119). In a meta-analysis of 13 randomized, placebo-controlled trials conducted over a mean of 4 years the NNH (number needed to harm) for erectile impotence with thiazide diuretics in hypertension was 20 and the relative risk was 5.0 (120). 

Andersson OK, Gudbrandsson T, Jamerson K. Metabolic adverse effects of thiazide diuretics the importance of normokalaemia. J Intern Med Suppl 1991 735 89-96. 

The risks and benefits of distal tubular diuretics have been assessed in preterm infants under 3 weeks of age with or developing chronic lung disease (36). Acute and chronic administration of distal diuretics improved pulmonary mechanics adverse effects were not reported. However, additional studies are needed to assess whether thiazide administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay, and long-term outcome in patients exposed to corticosteroids and bronchodilators, and whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect. 

Four of the adverse effects asscxiiated with the thiazide on thiazide-like diuretics are highly predictable because of Ibtir chemical makeup or their site of action along the nephiM... 

Women receive the same benefits from antihypertensive therapy as men. However, ACE inhibitors and ARBs are contraindicated in women who intend to become pregnant because they are teratogenic. Thiazide diuretics may be especially beneficial in postmenopausal women with osteoporosis because they cause retention of calcium and have been shown to positively affect bone mineral density. Women tend to have higher rates of drug-related adverse effects than men. 

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