HydrochlorothiazideMuhammad Jabar Rashid

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Content Hydrochlorothiazide

Dosage Forms & Trade Names

Pharmacokinetics Ι & ΙΙ Mechanism of action

Action

Therapeutic uses

Adverse effects

Contraindication & Drug Interaction

Pregnancy & Lactation

Overdose

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HydrochlorothiazideHCTZ, 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.

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Dosage Forms & Trade Names

Trade Names: Microzide, HydroDiuril, Hydro, Esidrix

Dosage Forms: Tablet, Capsule, Solution.

Tablet/Capsule: 12.5 mg, 25 mg, 50 mg

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Co-Diovan: Valsartan – Hydrochlorothiazide (ARB+Thiazide)

Pharmacokinetics 𝚰

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.

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Pharmacokinetics 𝚰𝚰 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

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Mechanism of action

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www.youtube.com/watch?v=oh0nAyW5r5Y

Action

Increased excretion of Na+ and Cl−.

Loss of K+.

Loss of Mg++: The mechanism for the magnesuriais 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.

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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.

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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

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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

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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.

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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.

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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

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