DIURETICS

IKE HUSEN

Depart. Of Pharmacology and Therapy
Medical School - Universitas Padjadjaran
Learning Objectives:
Describe Mechanism of action (MoA) related to
its pathophysiology
Describe MoA related to its effects leading to
indications & related to adverse effects leading
to contraindications


References:
Katzung
Lippincotts

DIURETICS
Increase the rate of urine formation

Major clinical uses :
Abnormal fluid retention (edema)
Hypertension (decreased blood volume)
I. OSMOTIC DIURETICS
MOA :

Freely filtered at the glomerulus
Limited reabsorbed by the renal tubule
Pharmacology inert & resistant to metabolic
alteration
urine output
(water & small amount of Na)
Carry water into
tubule
Including:
- Manitol
- Urea
- Glycerin
Preparation:
Intravenous
Indication:
- Increased of the intracranial pressure
- Glaucoma

Contraindication:
- CHF
- Pulmonary oedema
Toxicity
- ECF expansion:
- Complicate CHF
- Produce pulmonary oedema
- Hypersensitivity reactions
- Urea : irritating to tissues, thrombosis or
pain if extravasations occurs
- Headache, nausea and vomiting

II. CARBONIC ANHYDRASE INHIBITORS
>< bicarbonic reabs. (prox tubule)

hyperchlor. mtbl acidosis
I: - Mbtl alkalosis-
- Urinary alkalinization
- Acute mountain sickness
(patof.: pH & edema crbr)
reabs. NaCl diuretic effect (after several days)

excr. K+ hypokalemia
>< excr. NH+ CI: cirrh. Hepatis
SOA: ciliary body H. aqueous formation


pH & vol I: Glaucoma
Adverse effects

- Metabolic acidosis (mild)
- Potassium depletion
- Renal stone formation
- Drowsiness
- Paresthesia may occur
Prototype:
Azetazolamide

Prep: - Bumetamide
- Furosemide
- Etacrinic acid

RBF (furosemide) I: ARF

Furosemide & etacrinic acid:
>< NaCl reabs. Effect diuretic
(thick asc.tub)

I: Edematous state:
- Pulmonary congestion
- CHF (LV filling press.)
III. LOOP DIURETICS
>< KCl reabs. SE: hypokalemic mtbl alkalosis
(H secretion in collect. tub d.t
delivery salt & water)

I: hyperkalemic acidosis

due to (+) electrical potential:
Excr. Mg SE: hypomagnesia
Excr. Ca I: hypercalcemia
(major Ca reabs. At distal tubule doesnt promote
hypocalcaemia)

Other SE:

- Ototoxic
- Hyperuricemia ( uric ac. Reabs in prox
tub. d.t hypovol)
- Allergy Rx Furosemide & bumetamide
cross-reactivity w/ sulfonamide


IV. THIAZIDES
>< NaCl reabs. SE: Hyponatremia
(distal tub)
SE:
Excr. K - hypokalemic mtbl alkalosis
- hyperuricemia
- hyperglycemia (in individual
who potency to have it d.t impaired
pancreatic release of insulin)
- hyperlipidemia (prolonged use)

Reabs. Ca (exchange Ca-Na)
Other SE:
- Allergic Rx
- Weakness, paresthesias
- Impotence (hypovol)

Prep. :
- Chlorothiazide
- Hydrochlorothiazide
- Chlorthalidone
- Thiazide analog: metolazone, indapamide
Indication:
- Hypertension
- CHF
- Nephrolithiasis d t hypercalciuria
- Nephrogenic diabetes insipidus
- Diabetes insipidus

Contraindication:
- Cirrh. Hepatic
- borderline RF
- CHF
V. Potassium-sparing Diuretics
a. aldosteron formation (spironolacton)
b. Sodium-channel blockers (triamteren & amiloride)
>< Na reabs (collecting tub.)

>< K secretion hyperkalemia

>< H secretion hyperchloremic mtbl acidosis
Other SE:
- Gynaecomastia, impotence, BPH
(d t synthetic steroid- spironolacton)
- Kidney stones

Indication:
- Diuretic
- Secondary hyperaldosteronism

Contraindication:
- CRF
- ACE inhibitors & -blockers
- Liver disease