Diuretic 

Thiazides and related diuretics include- Bendroflumethiazide, Benzthiazide, Chlorthiazide, Hydrochlorthiazide, Hydroflumethazide, Indapamide, Methyclothizide, Metolazone, Polythiazide, Quinethazone, Trichlormethiazide Refer Hydrochlorthiazide- Thiazide and related diuretics 

Cardiovascular- Hydrochlorthiazide- allergicmyocarditis Indapamide- premature ventricular contractions, irregular heart beats, Mertazolone- raspidly acting -chest pain, (percodial pain) cold extrtemities, edema, slow acting- venous trombosis, cheat pain, excessive volume depletin, hemoconcentration

CNS- Indapamide- loss of energy, numbness of extremities, tension, irritability, agitatin, tingling of extremities Metazolane- slow acting- syncope, neutropathy, rapidly acting- weird feeling, neuropathy

GI- cholecytitis (possible increased risk in patients with gallstones) Metazolone- rapidly acting- bitter taste

GU- Bendroflumethizide- alergic glomerulonephritis Chlorthiazide IV- hematuria Indapamide- frequent urination, polyuria

Dermatoligic- Bendroflumethiazide- ecchymosis Indapamide- hives Metozolone- rapidly acting- dry skin Trichometiazide- lichenoid dermatits-

Musculoskeletal- Metolazone- joint pain, back pain, (rapidly acting) swelling, (slow acting) Respiratory- Indapamide- rhinorhea Metolazone- rapidly acting- cough, epistaxis, sinus congestion, sore throat Trichormethazone- dyspnea

Miscellaneous- - neutropenia Bendroflumethiazide- metabolic acidosis in diabetes Indapmide- flushing, weight loss Methyclothiazide- inappropiate ADH secretion Metolazone- slow acting- chills, acute gouty attack rapoid acting- eye itching, tinnitus

Lab test abnormalities- hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypochloremic alkalosis, hypophosatemia, increase in BUN, elevation of creatinine, decreased serum PBL levels.

Clinical hypokalemia- occurred in patients given indapamide

Fluid/electrolyte imbalance- potassium replacement is the most important therapy along with removal of the offending drug

Anuria,pregnancy,sulphonamide allergy.

Special precautions:

Renal/hepatic impairment, diabetes, gout, hyperlipedemia. Fluid/electrolyte balance-perrform initial and periodic detreminations of electrolyte and BUN, uric acid, and glucose.

Observe patients for cliniacl signs of fluid or electrolyte imbalance( hypocholremic alkalosis , hypokalemia, hypomagnesemia, changes in serum and urinary calcium)

Hypokalemia- may develop (with consequent weakness, cramps, cardiac dysrhthmias) during concomittant, corticosteroids, ACTh, andespicially with brisk diuresis, with severe liver diseases or cirrhosis, vomiting, or diarrhea, after prolonged theapy. Inadequate oral electrolyte intake also contributes to hypokalemia

. Hyponatremia/hypochloremia- Thiazide-induced hyponatremia has been associated with death and neurologic damage in elderly patients.

CNS manifestation include seizures, coma, and extensor-planar response. When symptoms consistent with electrolye electrolye imbalance occur rapidly, discontinue the drug and initiate supportive measures immediately. Parentral electrolye may be required.

Hypomagnesemia- thiazide diuretics have been shown to increase urinary excretion of magnesium, resulting in hypomagnesemia

Hypercalcemia- cal cium excretion may be decreased by thiazidde diuretics.Thiazides may cause a slight intermittent elevation of serum calcium in the absence of calcium metabolism disorders.

Hypereuricemia- may occur or acute gout may be precipitated in certain patients receiving thiazides, even in those patients without a history of gouty attacks.

Glucose tolerance- hyperglycemia may occur with thiazide diuretics. Insulin or oral hypoglycemic agent dosage requirements may be altered. Latent diabetes mellitus may become manifest during thiazide diuretic administration, diabetic complications may occur.

Post-sympathectomy- antihypertensive effects may be enhanced in postsympathetomy patients.

Lipids- use thiazide with caution innpatients with moderate or high cholesterol concentrations in patients with elevated triglyceride levels.

Photosensitivity- photosensitization may occur,therfore caution patients to take protective measures (sunscreens,protective clothing)

Drug/Lab interactions- thiazides may decrease serum PBI levels without signs of thyroid disturbance. Thiazide may also cause diagnostic interference of serum electrolye levels, blood and urine glucose levels( usually only in patients with a prediposition to glucose intolerance ) serum bilirubin levels by displacement from albumin binding) and serum uric acid levels

. Warnings-

Parentral use- use IV cholrthiazide only when patients are unable to take oral mediaction or in an emergency. In infants and children Ivuse is not recommended. Avoid simultaneius administration of chorthiazide with whole blood or its derivatives.

Lupus erythematous -exacerbation or activation has occured.

Hypersensitivity- reactions may occur in patients with or without a history of allergy or bronchial asdthma, cross sensitivity with sufonamides may also occur. Have epinephrine 1:1000 immediately available.

Renal function impairment- use with caution in severe renal disease since these agents may precipitate azotemia Cummulative effects of the drugmay develop in patients with impaired renal function. Monitor renal function periodically

Hepatic function impairment- use with caution since minor alterations in fliud and electrolyte balance may precipitate hepatic coma.

Pregnancy- routine use during normal pregnancy is inappropiate. Lactation- discontinue nursing or the drug taking into account the importance of the drug to the mother. Children- safety and efficacy have not been established.

Indications:

Diuretic Dosage:

Initial- 25 to 200mg daily for several days.. Infants-(below 6 mths)- upto 3.3mg/kg/day daily in 2 dose. Infants-(6 mths to 2 years)- 12.5 to 37.5mg daily in 2 doses.

Children -(2 to 12 years)- 37.5 to 100mg daily in 2 doses.

Overdosage-

Symptoms Changes due to plasma voume depletion (eg ortostatic hypotension, dizziness, syncope, electrolyte abnormalites, hemoconcentration, hemodynamic changes) signs of potassium deficiency (eg confusion, dizziness, muscular weakness, and GI disturbances) nausea and vomiting. In severe cases hypotension, and depressed respiration may occur.

Lethargy of varying degrees may progress to coma within a few hours, with minimal depression of respiration and cardiovascular function without significant electrolyte changes or dehydration.

GI irritation and hypermotility temporary BUN elevation, CNS effects, cardiac abnormalites and seizures have also been reported especially in patients with compromised renal function.

Treatment

1.Perform gastric lavage or induce emesis, give activated charcoal.

2. Prevent aspiration

3. Avoid cathartics since electrolyte and fluid loss may be enhanced.

4. GI effects are usually of short duration, but may require symptomatic treatment

5. Monitor serum electrolyte levels and renal function

6. Maintain hydration electrolyte balance, respiration, and cardio-vascular-renal function

7.Asymptomatic hyperurecemia usually responds to fluids but if clinical gout is suspected indomethicin may be started

8. Support respiratin and cardiac circulation if hypotension and depressed respiration occur.

9. Dialysis is unlikely to be effective.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Alteration in Color vision

Drugs causing adverse reactions- ( 388 )

1. Troxidone

2. Sulfonamides

3. Streptomycin

4. Mathaqualone

5. Barbiturates

6. Digitalis

7. Thiazides 

Classification: Diuretics Patent position: Major brands: ESIDREX HIND-CIBA-GEIGY MARKET LEADER BIDURET BIDDLE SAWYER Domestic production 93/94 6.08T Demand projection 94/95 5T

Raw materials:

1.Chloro disulfonamido aniline

2.Paraformaldehyde

3.Chloro disulformylaniline

4.Chloroaniline di sulphonamide ** ** Concessional duty

Manufacturers:

1.Unichem Laboratories Ltd.

Thiazide diuretics

1. May cause GI upset, may be taken with food

2. Drug will initially increase urination which should subside after a few weeks, take early during the day or as directed

3. Notify physician, if muscle pain,weakneess or cramps, nausea, vomiting, restlessness, excess thirsr, tiredness, drowsiness, increased heart rate or pulse, diarrhea, or dizziness occurs

4. May cause photosensitivity (sensitivity to sunlight). Avoid prologed exposure to the sun and othe ultraviolet light. Use sunscreens and wear protective clothing until tolerance is determined

5. May increase blood sugar levels in diabetes

6. Do not drink alcohol or take other medications without physicians approval, this includes nonprescription medicines for appetite control, asthma, colds, cough,hay fever or sinus

7. Do not interrupt , discontinue or adjust the dose, even if feeling well. Follow physicians instruction regarding missed dose.

8. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to sulfonamides, bumetamide, furosemide, acetazolamide, dichlorphernamide, methazolamide or other thiazide diuretics or other related medicines. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.

9. Pregnancy- should not be taken during pregnancy unless recommended by your doctor.

10. Breast feeding- avoid the use of thiazide diuretics during the first month of breast feeding.

11. Children- extra caution is necessary because these medicines can make the condition worse

12. Elderly- dizziness, lightheadedness or signs of too much potassium loss more likely to ocur in elderly. who are more sensitive than younger adults to theefects of thiazide diuretics

13. Other medicines- tell your doctor if you are taking any of the following- Cholestyramine or Colestipol - usewith thiazide diuretics may prevent the diuretic from working properly , take the diuretic at least 1 hour before or 4 hours after cholestyramine or colestipol Digitalis glycosides - use with thiazide diuretics may cause high blood levels of digoxin which may increase the chance of side effects. Lithium- use with thiazide diuretics may cause high blood levels which may increase the chance of side effects

14.Other medical problems- tell your doctor if you have any other medical problems- Diabetes mellitus or - loop diurtetics may increase the amount of sugar in the blood. Gout or Lupus erythematous or Pancreatitis - thiazide diuretics may make these conditons worse Heart or blood vessel disease- thiazide diuretics may cause high cholesterol levels or high triglyceride levels Kidney disease or Liver disease - higher blood levels of thiazide diuretic may occur which may prevent the thiazide diuretic from working properly

15. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for you for next dose go back to your regular dosing schedule. Do not double doses.

 Thiazides and related diuretics include- Bendroflumethiazide, Benzthiazide, Chlorthiazide, Hydrochlorthiazide, Hydroflumethazide, Indapamide, Methyclothizide, Metolazone, Polythiazide, Quinethazone, Trichlormethiazide Refer Hydrochlorthiazide- Thiazide and related diuretics 

Pharmacology-

Thiazides diuretics increase the urinary excretion of sodium and chloride in approximately equivalent amounts. They inhibit reabsorption of sodium and chloride in the cortical thick ascendiing loop of the Henle and early distal tubules.

Pharmacokinetics-

The antihypertensive action requires seceral days to produce efects. Administartion for up to 2 to 4 weeks is usually required for optimal therapeutic efect. Despite the extensive use of diuretics pharmacokinetic data are limited. It is important to emphasise the lack ofrelationship between plasma levels and diuretic effect.

Pregnancy-

Routine use during normal pregnancy is inappropiate.

Lactation-

Discontinue nursing or the drug taking into account the importance of the drug to the mother.

Children-

Safety and efficacy have not been established.