Hydrochlorothiazide

Hydrochlorothiazide is a prototype drug of thiazide diuretics. Hydrochlorothiazide is antihypertensive agent. It increases the urination and reduces the amount of water and sodium retained by the body. The drugs in this class are formally called benzothiadiazide, usually shortened to thiazides. The nature of the heterocyclic rings and the substitution on these ring may vary among the congeners but all of them retain a unsubstituted sulfonamide group. Development of thiazides and other modern diuretics began when a perceptive physician noticed that patients receiving sulfanilamide, an early antimicrobial agent, developed metabolic acidosis and a very alkaline urine. Careful study revealed that the drug was causing sodium bicarbonate diuresis. The realization that it could be useful diuretic led first to the development of acetazolamide and then to the thiazides.

Hydrochlorothiazide is primarily indicated in conditions like Diabetes insipidus, Edema, Hypercalciuria, Hypertension, Nephrolithiasis, Nephrotic syndrome, Edema, Proximal renal tubular acidosis, and can also be given in adjunctive therapy as an alternative drug of choice in Exercise induced hyperkalemia, Osteoporosis, Renal hypophosphatemic rickets.

Hydrochlorothiazide is contraindicated in conditions like Diabetes mellitus, Gout, Renal diseases, Anuria, Hyperlipidemia, Liver diseases, ECG abnormalities.

The severe or irreversible adverse effects of Hydrochlorothiazide, which give rise to further complications include Pancreatitis, Stevens Johnson syndrome, Systemic lupus erythematosus, Pneumonitis, Idiosyncratic hypersensitivity reactions. Hydrochlorothiazide produces potentially life-threatening effects which include Hyponatremia, Metabolic disturbances, Idiosyncratic hypersensitivity reactions. which are responsible for the discontinuation of Hydrochlorothiazide therapy. The signs and symptoms that are produced after the acute overdosage of Hydrochlorothiazide include Coma, Volume depletion, Hypokalemia, Hyperchloremic alkalosis, Hypersensitivity reactions, Electrolyte disturbances, Lethargy, Hemolytic anemia, Hyponatremia. The symptomatic adverse reactions produced by Hydrochlorothiazide are more or less tolerable and if they become severe, they can be treated symptomatically, these include Weakness, Thirst, Fatigue, Restlessness, Dry mouth, Lethargy, Allergic reactions, Cardiac arrhythmias, Hyperuricemia, Hypokalemia, Ectopic beats, Hypomagnesemia, Paralysis, UTI, Hyperlipidemia, Hyperglycemia, Dry mouth, paresthesia.

May potentiate effects of other hypotensive agents. Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage, hypotension could occur. (See Interactions.) Possible exacerbation or activation of systemic lupus erythematosus. Generally, do not use with lithium salts. (See Interactions.) May occur with or without history of allergy or bronchial asthma. Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.) Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia). Observe for signs of electrolyte imbalance (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pains, cramps, muscular fatigue, hypotension, tachycardia, nausea, vomiting). Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum concentrations if necessary. Serum and urinary electrolyte measurements are especially important with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of excessive diuresis. Weekly (or more frequent) electrolyte measurement recommended early in treatment; possible to extend interval between measurements to ≥3 months when electrolyte response has stabilized. May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute. May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability). Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia. Generally mild, usually does not require specific treatment except in renal or hepatic impairment. Chloride replacement may be required for metabolic acidosis. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate treatment usually is water restriction rather than salt administration except when hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is treatment of choice. Hyperuricemia or, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout unless patient is receiving uric acid lowering therapy. In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident. Antihypertensive effect may be enhanced after sympathectomy. May increase magnesium urinary excretion, resulting in hypomagnesemia. May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism. Discontinue prior to performing parathyroid tests. May increase cholesterol and triglyceride concentrations. Clinical importance of these changes is unknown. Diet low in saturated fat and cholesterol usually compensates. Orthostatic hypotension rarely occurs. When hydrochlorothiazide is used in fixed combination with other drugs (e.g., other antihypertensive agents), consider cautions, precautions, contraindications, and interactions associated with the concomitant agent(s). Category B. Diuretics are considered second-line agents for control of chronic hypertension in pregnant women; if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred. Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia. Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, do not use as routine therapy in pregnant women with mild edema who are otherwise healthy. Distributed into milk. Manufacturer states to discontinue nursing or the drug; however, considered to be compatible with breast-feeding. No controlled studies in children; use is supported by experience and published literature about hypertension treatment in children. Elderly may be at increased risk of dilutional hyponatremia, especially underweight females with poor oral fluid and electrolyte intake or excessive low-sodium nutritional supplement intake. (See Hyponatremia under Cautions.) Increased incidence of adverse effects and excessive reduction in BP in those >65 years of age. (See Geriatric Patients under Dosage and Administration.) Use with caution in hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma. Discontinue immediately if signs of impending hepatic coma appear. Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia. Effects may be cumulative in impaired renal function. Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or S cr ) occurs.

May potentiate effects of other hypotensive agents. Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage, hypotension could occur. (See Interactions.) Possible exacerbation or activation of systemic lupus erythematosus. Generally, do not use with lithium salts. (See Interactions.) May occur with or without history of allergy or bronchial asthma. Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.) Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia). Observe for signs of electrolyte imbalance (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pains, cramps, muscular fatigue, hypotension, tachycardia, nausea, vomiting). Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum concentrations if necessary. Serum and urinary electrolyte measurements are especially important with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of excessive diuresis. Weekly (or more frequent) electrolyte measurement recommended early in treatment; possible to extend interval between measurements to ≥3 months when electrolyte response has stabilized. May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute. May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability). Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia. Generally mild, usually does not require specific treatment except in renal or hepatic impairment. Chloride replacement may be required for metabolic acidosis. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate treatment usually is water restriction rather than salt administration except when hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is treatment of choice. Hyperuricemia or, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout unless patient is receiving uric acid lowering therapy. In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident. Antihypertensive effect may be enhanced after sympathectomy. May increase magnesium urinary excretion, resulting in hypomagnesemia. May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism. Discontinue prior to performing parathyroid tests. May increase cholesterol and triglyceride concentrations. Clinical importance of these changes is unknown. Diet low in saturated fat and cholesterol usually compensates. Orthostatic hypotension rarely occurs. When hydrochlorothiazide is used in fixed combination with other drugs (e.g., other antihypertensive agents), consider cautions, precautions, contraindications, and interactions associated with the concomitant agent(s). Category B. Diuretics are considered second-line agents for control of chronic hypertension in pregnant women; if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred. Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia. Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, do not use as routine therapy in pregnant women with mild edema who are otherwise healthy. Distributed into milk. Manufacturer states to discontinue nursing or the drug; however, considered to be compatible with breast-feeding. No controlled studies in children; use is supported by experience and published literature about hypertension treatment in children. Elderly may be at increased risk of dilutional hyponatremia, especially underweight females with poor oral fluid and electrolyte intake or excessive low-sodium nutritional supplement intake. (See Hyponatremia under Cautions.) Increased incidence of adverse effects and excessive reduction in BP in those >65 years of age. (See Geriatric Patients under Dosage and Administration.) Use with caution in hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma. Discontinue immediately if signs of impending hepatic coma appear. Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia. Effects may be cumulative in impaired renal function. Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or S cr ) occurs.

25 to 100 mg (62 (62.5)) 24 hourly PO — As Required

2.5 mg/kg (2.5 (2.5)) 12 hourly Oral —

1 mg/kg (1 (1)) 12 hourly Oral —

Hydrochlorothiazide is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAlbuterolShould not use concurrently without doctors prescription.AlcoholAllopurinolconcomitant administeration can lead to impaired renal functionAmantadine (HCl)Amphotericin BIncreased risk of hypokalemia when amphotericin given with Hydrochlorothiazide.AstemizoleAzilisartan MedoxomilConcomitant administeration of Azilisartan and diuretics (e.g. hydrochlorothiazide) can lead to volume depletionCalciferolCarbamazepineIncreased risk of hyponatremia when Carbamazepine given with diuretics. Carbenoxolone (Na)Celiprolol (HCl)CholestyramineIt will reduce absorption of Hydrochlorothiazide from GIColestipol (HCl)DiazoxideEnhanced hypotensive effect when Diazoxide given with Hydrochlorothiaide.DiflunisalFluconazoleFosinopril (Na)Halofantrine (HCl)Indacaterolconcomitant therapy may increase risk of hypokalemiamonitor closelyInsulin Lispro ProtamineLithiumVolume depletion by Hydrochlorothiazide increases lithium absorption and causes Lithium toxicityMetformin (HCl)Thiazide (hydrochlorothiazide) antagonize the effect of metformin.MoxonidineConcomitant administration of moxonidine and hydrochlorothiazide is not indicated, as hypotensive effect of both drugs may be enhanced.Nebivolol (HCl)Concurrent use may decrease the extent of absorption of Nebivolol (HCl).PimozideConcomitant administeration can lead to prolong QT intervalPinacidil MonohydratePiroxicam-beta-cyclodextrinPiroxicam causes sodium,potassium and fluid retention and may interfere with natriuretic action of diuretic agents (e.g hydrochlorothiazide) and thus precipitate the heart failurePropranolol (HCl)Riboflavin (Vitamin B2)Hydrochlorothiazide, may cause you to excrete more riboflavin in your urine.Rutin (Vitamin P)Rutin may have additive effects when used in combination with Hydrochlorothiazide.Sodium PhosphateShould not be use concurrently without doctors prescription.Sotalol (HCl)TenoxicamNSAIDs may cause sodium, potassium and fluid retention and may interfere with the natriuretic action of diuretic agents, which can increase the risk of nephrotoxicity of NSAIDs.TerfenadineConcomitant administeration can lead to prolong QT intervalTetracycline (HCl)TrimethoprimTubocurarine (Cl) Warfarin (Na) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Store in a well closed container, at room temperature. Protect from Moisture and Heat. Tab Store Below 40°C. Protect from Sunlight and Heat.