Thiazide diuretics dosage

Pharmacology Thiazide diuretics increase the urinary excretion of sodium and chloride in approximately equivalent amounts. They inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henie and the early distal tubules. Other common actions include Increased potassium and bicarbonate excretion, decreased calcium excretion and uric acid retention. At maximal therapeutic dosages all thiazides are approximately equal in diuretic efficacy. 

Some pharmacokinetic characteristics and the initial and usual maintenance dosages of hydrochlorothiazide are listed in Table 11-2. Although thiazide diuretics are more natriuretic at higher doses (up to 100-200 mg of hydrochlorothiazide), when used as a single agent, lower doses (25-50 mg) exert as much antihypertensive effect as do higher doses. In contrast to thiazides, the blood pressure response to loop diuretics continues to increase at doses many times greater than the usual therapeutic dose. 

Lithium is often used in the treatment of mania in the aged. Because it is cleared by the kidneys, dosages must be adjusted appropriately and blood levels monitored. Concurrent use of thiazide diuretics reduces the clearance of lithium and should be accompanied by further reduction in dosage and more frequent measurement of lithium blood levels. 

Furosemide and thiazide diuretics (Fig. 8.4) have been approved for use in dairy cattle for treatment of postparturient edema of the mammary gland and associated structures (56). Furosemide and hydrochlorothiazide are administered intramuscularly or intravenously at a dosage of 500 and 125-250 mg/animal, respectively. Chlorothiazide and trichlormetliiazide are administered orally at dosage of 2000 and 200 mg/animal, respectively. 

Dosage Dose should be individualized by titration 180 mg/d to 240 mg/d Dose should be individualized by titration 30 mg/d or 60 mg/d Dose should be individualized 2.5 mg BID alone or in combination with a thiazide diuretic... 

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... 

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. 

Thiazide diuretics are useful in early cardiac failure as they are relatively mild diuretics which can mobilize the oedema. Increasing the dosage of a thiazide above the recommended dose would elicit more side effects without markedly improving therapeutic effects. Changing to a more powerful agent from a different diuretic class is preferable if the patient s condition deteriorates. 

Furosemide is the classic member of the group of so-called high-ceiling or loop diuretics, which can achieve a much greater peak diuresis than the thiazides. It is widely and frequently used both orally and parenterally over a wider dosage range than the thiazide diuretics, because its concentration-effect curve is steeper and because it is effective in patients with moderate renal insufficiency (creatinine clearance 5-25 ml/minute), in... 

Ingestion is the most common route of both accidental and intentional exposures to the thiazide diuretics. Thiazides and related diuretics are available in oral dosage forms. Chlorothiazide is also available in a parenteral dosage form. 

Thiazides reduce the blood pressure (Chapter 11). Initially, the reduction reflects the reduction of blood volume, but with continued use these agents appear to reduce vascular resistance as well. The antihj rtensive effect is modest but significant and is maximal at doses lower than the maximal diuretic dosage. Compared with older thiazides and thiazide-like agents, indapamide may have a greater ratio of vasodilating effect relative to its sodium diuretic effect. 

Uses of indapamide inciude the treatment of essentiai hypertension and edema resulting from congestive heart failure. Like metolazone. indapamide is an effective diuretic drug when GFR faiis beiow 40 mL/min. The duration of action is approximately 24 hours, with the normal oral adult dosage starting at 2.5 mg given each morning. The dose may be increased to 5.0 mg/day, but doses beyond this ievei do not appear to provide additional results. Effects on urine content and side effects are similar to effects induced by thiazide diuretics. 

Clonidine hydrochloride is used in the treatment of grades of hypertension. The usual initial dose of clonidine hydrochloride is 50 to 100 pg orally thrice daily increased every second or third day according to the response of the patient. The usual maintenance dose is 0.3 to 1.2 mg daily but doses of up to 1.8 mg or more daily may be required. To reduce side effects a similar dose of clonidine may be given in conjunction with a thiazide diuretic but combination with a 13-blocking agent should be avoided where possible clonidine may also be given in a sustained-release formulation which enables twice-daily dosage, or by a transdermal delivery system which is applied once a week and delivers 100-300 pg daily at a constant rate (4). 

The manufacturers say that amlodipine has been safely given with thiazide diuretics and no dosage adjustment of amlodipine is required. Additive antihypertensive effects are expected when diuretics such as hydrochlorothiazide are used in combination with calcium-channel blockers, and such combinations are used clinically. 

Clinical reports [215—222] agree that debrisoquine is an effective antihypertensive agent with a duration of action of 8-12 hours, permitting flexibility of dosage. Like other similar drugs it is potentiated by thiazide-type diuretics and other antihypertensives. In all these respects it appears to be interchangeable... 

Tolerance Tolerance may occur, usually between the second and third month of therapy. Adding a diuretic or increasing the dosage of methyidopa frequently restores blood pressure control. A thiazide is recommended if therapy was not started with a thiazide or if effective control of blood pressure cannot be maintained on 2 g methyidopa daily. 

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