DIURETICS  DOA: 3-5 hours.

 Drugs that increase the renal excretion of  t1/2: 90 minutes.

solutes and water.
 Plasma CHON binding:Strong.
 Drugs that increase the excretion of sodium
and water from the body by an action on the  MOA: Inhibits the NA/K/Cl transport system
kidneys. in the luminal membrane of the thick
ascending limb of the loop of
Henle.

CLASSIFICATION LOOP OR HIGH-CEILING DIURETICS

 Drugs acting directly on the nephron  ADR

 Loop diuretics  Hypokalemic metabolic alkalosis
 Thiazide diuretics  Ototoxicity
 Potassium-sparing diuretics  Hyperuricemia
 Drugs acting indirectly by modifying the  Hypomagnesemia, hypocalcemia
content of the filtrate  Allergic reactions, nausea, deafness
 Osmotic diuretics  Hypovolemia, hypotension
 Carbonic anhydrase inhibitors  CLINICAL USES
THERAPEUTIC INDICATIONS  Acute pulmonary edema and other
edematous conditions
 Edematous states  Acute hypercalcemia, hyperkalemia
 Congestive heart failure  Acute renal failure
 Hepatic cirrhosis  Anion overdose: Bromide,
 Renal disease fluoride, and iodide
 Idiopathic edema
 Non-edematous states THIAZIDE DIURETICS
 HPN
 Nephrolithiasis  Short-acting (up to 12 hours)
 Hypercalcemia  Chlorothiazide, hydrochlorothiazide
 Diabetes insipidus
 Intermediate-acting (12-24 hours)
LOOP OR HIGH-CEILING DIURETICS  Bendroflumethazide, benzthiazide,
cyclothiazide, hydroflumethiazide,
 Anthranilic derivatives with sulfonamide metolazone, quinethazone,
substituent (furosemide, bumetanide) or trichlormethiazide
aryloxyacetic acid without a sulfonamide  Long-acting (> 24 hours)
component (ethacrynic acid).  Chlorthalidone, indapamide,
 AGENTS: Ethacrynic acid, furosemide, methyclothiazide, polythiazide
bumetanide, Chlorthalidone, Indapamide, and Metolazone:
muzolimine, piretanide, Thiazide-like diuretics à with sulfonamide residue
torsemide. and same MOA.
 PHARMACOKINETICS
 Administered by: Oral or Structural Features
parenteral route.
 Peak effect: 30-60 minutes.
  Benzene ring with a sulfonamide group at  Nephrogenic diabetes insipidus
position 7 and halogen at position 6.
 Saturation of 3,4 double bonds à increased POTASSIUM-SPARING DIURETICS
potency (hydrochlorothiazide).  AGENTS: Spironolactone (steroid analogue
 Lipophilic substituents at position 3 or antagonist of aldosterone), eplerenone,
methyl groups at position 2 à enhanced triamterene, amiloride (pteridine orpyrazine
potency and prolonged activity derivative).
(cyclothiazide).  PHARMACOKINETICS
 Replacement of sulfonyl group in position 1  Spironolactone: Oral, t1/2 of 10
by carbonyl group à prolonged activity minutes, canrenone (active
(quinethazone). metabolite) à t1/2 of 16 hours.
 Thiazides without the sulfonamide group  Triamterene: Oral, DOA of 12-16
(diazoxide) à anti-HPN activity without hours, metabolized in liver, excreted
diuretic activity. through the urine (unchanged).
 Amiloride: Oral, DOA of 24 hours,
THIAZIDE DIURETICS excreted through the urine
(unchanged).
 PHARMACOKINETICS
 Administration: Oral. POTASSIUM-SPARING DIURETICS
 Onset of action: Within 12
hours.  MOA
 Peak effects: 4-6 hours.  Spironolactone: Competes with
 Duration of action: 8-12 hours. aldosterone for receptor sites à
 Excretion: Tubular inhibition of sodium-retaining action
secretion. of aldosterone (distal tubule).
 MOA: Inhibits NaCl cotransporter in the  Triamterene/Amiloride: Blocks
luminal side of the distal convoluted tubule. sodium transport channels à
decreased sodium reabsorption and
potassium excretion.
 SOA: Collecting tubule
 ADR:
 Hyperkalemia, hyperchloremic
metabolic acidosis
 Gynecomastia, menstrual disorders,
testicular atrophy
 Peptic ulcer, acute renal failure,
kidney stones, increased uric acid

THIAZIDE DIURETICS

 ADR
 Hypokalemic metabolic alkalosis
 Hyperuricemia, impaired
carbohydrate tolerance
 Hypercholesterolemia, hyponatremia
 Sulfonamide-type allergic reactions
 Weakness, fatigue, paresthesia,
headache, restlessness POTASSIUM-SPARING DIURETICS
 Male impotence, encephalopathy
 NAV, bloating, constipation  CLINICAL USES
 CLINICAL USES  Primary hyperaldosteronism
 HPN  Secondary hyperaldosteronism due
 CHF to hepatic cirrhosis complicated by
 Nephrolithiasis due to idiopathic ascites
hypercalciuria
 To prevent potassium loss in
combination with potassium-losing
diuretics
 As adjunct with thiazides and loop
diuretics to treat HPN
 CONTRAINDICATIONS
 Oral potassium administration à
fatal hyperkalemia
 Liver disease
 ACE inhibitor or b-blocker
OSMOTIC DIURETICS
 AGENTS: Mannitol, urea, glycerin, sorbitol.
 ADMINISTRATION: Intravenous.
 Duration of Action: 1-2 hours.
 MOA: Prevents the normal absorption of
water by interposing a counteracting
osmotic force.
 SOA: Proximal tubule, descending limb of
Henle’s loop, collecting tubule.
 ADR: Extracellular volume expansion
manifested
by headache, NAV; dehydration,
hyponatremia.
 CLINICAL USES: Short-term treatment of
glaucoma; cerebral edema associated with
tumors and neurosurgical procedures
(decreases ICP); to prevent development of
renal failure associated with severe
traumatic injury, CV and other complicated
procedures; renal extraction of bromide,
barbiturates, salicylates, etc. in overdosage.
CARBONIC ANHYDRASE INHIBITORS
 AGENTS: Acetazolamide,
dichlorphenamide, dorzolamide,
methazolamide.
 Given orally except for dorzolamide which is
used topically for glaucoma.
 MOA: Inhibits the enzyme that catalyzes
the dehydration of carbonic acid à reduced
sodium bicarbonate absorption.
 SOA: Proximal tubule.
 Duration of action: 8-12 hours.
 ADR: Metabolic acidosis, potassium
depletion, renal stones, drowsiness and
paresthesia, sulfonamide allergy, GI upset,
BM depression.
 CLINICAL USES: Glaucoma, urinary
alkalinization,
metabolic alkalosis, acute mountain
sickness, epilepsy (adjuvant).
 CONTRAINDICATION: Hepatic cirrhosis à
decreased
ammonia excretion.
POTENTIAL DRUG INTERACTIONS
 b-blocker + thiazide à Increased blood
glucose,
urates, and lipids
 Digitalis glycosides + thiazide/loop diuretic
à
Hypokalemia
 ACE inhibitor + K-sparing diuretic à
Hyperkalemia,
cardiac effects
 Aminoglycosides + loop diuretic à
Ototoxicity,
nephrotoxicity
 Adrenal steroids + thiazide/loop diuretic à
Enhanced hyperkalemia
 Chlorpropamide + thiazide à Hyponatremia
 Loop diuretic/thiazides + NSAID à
decreased effects of diuretic
SUMMARY
 LOOP DIURETICS
 Used for conditions associated with
moderated or severe HPN or fluid
retention (HF, cirrhosis, nephrotic
syndrome).
 They are sulfonamides except
ethacrynic acid.
 THIAZIDES
 Used to treat mild to moderate HPN,
mild heart failure, chronic calcium
stone formation, and nephrogenic
diabetes insipidus.
 Most important toxicity is potassium
wasting.
 They are sulfonamides.
 POTASSIUM-SPARING DIURETICS
 Used for prevention of potassium
wasting by other diuretics.
 Spironolactone and eplerenone are
particularly effective in treating heart
failure and other high-aldosterone
conditions.
 The major toxicity is hyperkalemia.
  Eplerenone has no anti-androgen
effects.
 They are not sulfonamides.

 CARBONIC ANHYDASE INHIBITORS

 Used as therapy for galucoma and
altitude sickness and to reduce
metabolic alkalosis.
 May cause hepatic encephalopathy.
 They are sulfonamides and are cross-
allergenic with other sulfonamides.
 OSMOTIC DIURETICS
 Used to treat acute glaucoma and to
protect the kidney from solute
overload caused by crush injury or
chemotherapy.
 Mannitol is the major osmotic
diuretic.

VASOPRESSIN
(ADH, anti-diuretic hormone)

 A peptide hormone released by the posterior

pituitary in response to rising plasma tonicity
or falling BP.
 Possesses antidiuretic and vasopressor
properties.
 A deficiency of the hormone results in
diabetes insipidus.
 MOA: Activates 2 subtypes of G-protein-
coupled receptors: 1. V1 receptors – on
vascular smooth muscle cells; mediate
vasoconstriction.
2. V2 receptors – on renal tubule
cells; reduce diuresis through increased water
permeability and water resorption in the
collecting tubules.
 Administered IV or IM.
 t ½ of circulating vasopressin: 15
minutes.
 ADR: Headache, nausea, abdominal
cramps, agitation, and allergic reactions;
hyponatremia, seizures, vasoconstriction.
 ADH agonist: Desmopressin
 ADH antagonists: Conivaptan, Tolvaptan