Hydrochlorothiazide

In this presentation, mainly I concentrated on Hydrochlorothiazide, which is a thiazide diuretic; and talking about it's pharmacokinetics, drug indication, contraindication, adverse drug reactions and taking the drug during pregnancy and lactation, finally I hope you enjoy it as much as I DID, SALAAM.

1. Hydrochlorothiazide Muhammad Jabar Rashid 1

2. Content Hydrochlorothiazide Dosage Forms & Trade Names Pharmacokinetics & Mechanism of action Action Therapeutic uses Adverse effects Contraindication & Drug Interaction Pregnancy & Lactation Overdose   2

3. Hydrochlorothiazide HCTZ , HCT , or HZT The thiazides are the most widely used diuretics. They are sulfonamide derivatives. Sometimes called “ low ceiling diuretics ” because increasing the dose above normal therapeutic doses doesn't promote further diuretic response. Because the site of action of the thiazide derivatives is on the luminal membrane , these drugs must be excreted into the tubular lumen to be effective . Therefore , with decreased renal function, thiazide diuretics lose efficacy . 3

4. Dosage Forms & Trade Names Trade Names: Microzide , HydroDiuril , Hydro, Esidrix Dosage Forms: Tablet, Capsule, Solution. Tablet/Capsule: 12.5 mg, 25 mg, 50 mg 4 Co-Diovan: Valsartan – Hydrochlorothiazide ( ARB+Thiazide )

5. Pharmacokinetics   The drugs are effective orally . Most thiazides take 1 to 3 weeks to produce a stable reduction in blood pressure . They exhibit a prolonged half-life . All thiazides are secreted by the organic acid secretory system of the kidney . 5

6. Pharmacokinetics   Absorption Onset: Diuresis, ~2 hr ; hypertension, 3-4 days Peak plasma time: 1-2.5 hr Peak effect: Diuresis, 4-6 hr Bioavailability: 65-75 % Distribution Protein bound: 40-68% Vd : 3.6-7.8 L/kg Metabolism Minimally metabolized Elimination Half-life: 5.6-14.8 hr Dialyzable: Hemodialysis, no Excretion: Urine 6

7. Mechanism of action 7 www.youtube.com/watch?v=oh0nAyW5r5Y

8. Action Increased excretion of Na+ and Cl −. Loss of K +. Loss of Mg++: The mechanism for the magnesuria is not understood. Decreased urinary calcium excretion. Reduced peripheral vascular resistance: An initial reduction in blood pressure results from a decrease in blood volume and , therefore, a decrease in cardiac output . 8

9. Therapeutic uses Chronic edema Mild & moderate cardiac edema. Ascites due to cirrhosis . Hypertension : Decrease intravascular volume Decrease PVR due to decrease responsiveness of vascular smooth muscle to noradrenaline . Heart failure . Hypercalciuria : Inhibit urinary Ca2+ excretion Idiopathic hypercalciuria Calcium oxalate stones . Diabetes insipidus: Hyperosmolar urine . Nephrogenic diabetes insipidus. The urine volume of such individuals may drop from 11 L/d to about 3 L/d when treated with the drug . 9

10. Adverse effects Potassium depletion: Digoxin to ventricular arrhythmias . Hyponatremia: Elevation of ADH as a result of hypovolemia. Hyperuricemia : Decreasing the amount of acid excreted by the organic acid secretory system . Volume depletion: Orthostatic hypotension. Hypercalcemia: Inhibit the secretion of Ca2 +. Hyperglycemia: Glucose intolerance 10

11. Contraindication & Drug Interaction Contraindication: Anuria Hypersensitivity to this product or to other sulfonamide-derived drugs. Renal impairment: CrCl <10 mL/min: Avoid use. not effective with CrCl <30 mL/min unless used in combination with loop diuretic . Drug Interaction: ( Serious - Use Alternative) Amisulpride Carbamazepine Cisapride Cyclosporine Dofetilide Squill tretinoin 11

12. Pregnancy & Lactation Pregnancy Category : B Thiazides are indicated in pregnancy when edema is due to pathologic causes. Not used in dependent edema in pregnancy Lactation: Thiazides are excreted in breast milk . Because of the potential for serious adverse reactions in nursing infants , a decision should be made whether to discontinue nursing or to discontinue Hydrochlorothiazide . 12

13. Overdose Overdose signs and symptoms : hypokalemia , hyponatremia. Dehydration. hypokalemia may accentuate cardiac arrhythmias. Overdose management: Normal saline used for volume replacement. Dopamine or norepinephrine used to treat hypotension . If dysrhythmia due to decreased potassium or magnesium is suspected, replace aggressively. Emesis should be induced or gastric lavage performed. If required, give oxygen or artificial respiration for respiratory impairment . Lethal Dose: The oral LD50 of Hydrochlorothiazide is greater than 10 g/kg in the mouse and rat . 13

14. References Katzung & Trevor's Pharmacology Examination and Board Review, 10th Edition ( Katzung & Trevor's Pharmacology Examination & Board Review ), ISBN-13: 978-0071789233 Lippincott Illustrated Reviews: Pharmacology 6th edition (Lippincott Illustrated Reviews Series ), ISBN-13 : 978-1451191776 www.drugs.com www.reference.medscape.com www.nlm.nih.gov www.webmd.com www.medicinenet.com www.youtube.com/watch?v=oh0nAyW5r5Y 14

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