Prepared by Dr Rasol . M. Hasan

BackgroundPrimary effect of diuretics is to increase solute

excretion, mainly as NaCl

Certain disease states may cause blood volume to increase outside of narrowly defined limitsHypertensionCongestive heart failureLiver cirrhosisNephrotic syndromeRenal failure

Dietary Na restriction often not enough to maintain ECF and to prevent edema diuretics needed

REVIEW OF KIDNEY STRUCTURE

NEPHRON SITES OF ACTION OF DIURETICS

TYPES OF DRUGS*Drugs that modify salt excretion1)Carbonic anhydrase inhibitors2)Loop diuretics3)Thiazide diuretics.4)K+ sparing diuretics.5)Osmotic diuretics. *Drugs that modify water excretion1)ADH agonists2)ADH antagonists.3)Osmotic diuretic.

SITE OF DRUG ACTIONS CARBONIC ANHYDRASE INHIBITORS (work in

proximal tubule)LOOP DIURETICS (ascending limb of loop)THIAZIDE DIURETICS (distal convolutedtubule)POTASSIUM-SPARING DIURETICS (collecting

tubule) OSMOTIC (proximal tubule, descending loop of Henle,

collecting duct)

NEPHRON SITES OF ACTION OF DIURETICS

Sites of diureticsProximal.c.tubule= 60-70%Ascending loop Henle= 20-30%Distal c. tubule = 5-8%Cortical collecting ducts = 2-5%

TYPES AND NAMES OF DIURETICS

Osmotic agents Mannitol Proximal tubule

Descending loop

Collecting duct

Carbonic anhydrase inhib.

Acetazolamide,dorzolamide,brinz

Proximal tubule

Thiazides Hydrochlorothiazide,metolazone

Distal convoluted tubule

Loop diuretic Ethacrynic acid

Furosemide,Bumetanide,Toresa

Loop of Henle

K+ - sparing Spironolactone

Amiloride,triamterene

Eplerenone

Collecting tubule

GENERAL BACKGROUND OF DIURETICS

Pattern of excretion of electrolytes (how much of which type) depends on class of diuretic agent

Maximal response is limited by site of action

Effect of two or more diuretics from different classes is additive or synergistic if there sites or mechanisms of action are different

CARBONIC ANYDRASE INHIBITORS

Block carbonic-anhydrase in the cytoplam and brush borders.

C.anhyd.Inh plays an imp. role in the secretion of CSF and aqueous humor.

Major renal effect is BICARBONATE DIURESIS.

Useful for treating glaucoma and metabolic alkalosis.

CNS--acidosisHyperventilation->Protect against High altitude Sickness.

LOOP DIURETICSGenerally cause greater diuresis than

thiazides; used when they are insuffficientInhibit co-transport of Na+,K+ and Cl- AND

excrete Ca+,and Mg+.Short Acting (4 hours)Efficacy of these durgs decreases with

NSAIDS.and (e.g. probenecid).

THIAZIDE DIURETICSActive by Oral Route.Inhibit NaCl transport in early segments of

DCT.Magnitude of effect is lower because work on

distal convoluted tubule (only recieves 5-8% of filtrate)

Cause decreased Ca excretion hypercalcemia reduce osteoporosis

POTASSIUM-SPARING DIURETICS

Have most downstream site of action (collecting tubule)

Reduce K loss by inhibiting Na/K exchangeNot a strong diuretic because action is

furthest downstreamOften used in combination with thiazide

diuretics to restrict K loss.

OSMOTIC DIURETICSNo interaction with transport systemsAll activity depends on osmotic pressure

exerted in lumenBlocks water reabsorption in proximal tubule,

descending loop, collecting ductResults in large water loss, smaller

electrolyte loss can result in hypernatremia,and hyperkalemia.

ADH AGONISTS & ANTAGONISTSAGONISTS facilitates reabsorption from the

collecting tubules.Reduces urine volume and increase its

concentrationANTAGONISTS oppose the action of ADH.Can cause significant water retention &

dangerous hyponatremia.

THERAPEUTIC USES:CARBONIC ANHYDRASE INHIBITORS

Cystinuria (increase alkalinity of tubular urine)Glaucoma (decrease ocular pressure)Acute mountain sicknessMetabolic alkalosis

LOOP DIURETICSHypertension, in patients with impaired renal

function Congestive heart failure (moderate to severe) Acute pulmonary edema Chronic or acute renal failure Nephrotic syndrome Hyperkalemia Chemical intoxication (to increase urine flow)

THIAZIDE DIURETICSHypertension Congestive heart failure (mild) Renal calculi Nephrogenic diabetes insipidus Chronic renal failure (as an adjunct to loop

diuretic) Osteoporosis

POTASSIUM-SPARING DIURETICS

Chronic liver failure with ascitesCongestive heart failure, when hypokalemia is a problem

OSMOTIC AGENTS Reduce pre-surgical or post-trauma intracranial

pressure Prompt removal of renal toxins

Reduces intraocular pressure in Acute Glaucoma.

ADH AGONISTS..Pituitary Diabetes Insipidus

ANTAGONISTS…SIADH

Adverse Effects Diuretics Symptoms

HYPOVOLEMIA loop diureticsthiazides

lassitudethirstmuscle crampshypotension

HYPOKALEMIA acetazolamidesloop diureticsthiazides

muscle weaknessparalysisarrhythmia

HYPERKALEMIA triamterenesSpironolactoneAmiloride

arrhythmiamuscle crampsparalysis

HYPONATREMIA thiazidesfurosemides

CNS symptomscoma

METABOLIC ALKALOSIS,

loop diureticsthiazides

arrhythmiaCNS symptoms

ADVERSE EFFECTS

METABOLIC ACIDOSIS

acetazolamides Kussmaul respirationsmuscle weakness neurological symptoms,lethargy coma seizures Stupor

HYPERCALCEMIA thiazides gout tissue calcificationfatigue depression confusion anorexia

HYPERURICEMIA loop diureticsthiazides

Gout

Thanks for your attention