DIURETICS
Prof. Hanan Hagar
Pharmacology Department
Classification of diuretics
Carbonic Anhydrase Inhibitors
Loop Diuretics
Thiazides
Potassium-Sparing Diuretics
Osmotic Diuretics
SITES OF ACTION OF DIURETICS
Thiazide diuretics
Mechanism of action:
acts via inhibition of Na/Cl
co-transporter on the luminal
membrane of distal convoluted
tubules
Efficacy: Moderate 5% natriuresis
Drugs as:
hydrochlorothiazide -metolazone
Distal convoluted tubules
Mechanism of action of thiazide diuretics
Pharmacokinetics:
Given orally, slow of onset
long duration of action (40 h)
are secreted by active tubular
secretory system of the kidney
may interfere with uric acid
secretion and cause
hyperuricemia
Pharmacological effects:
urinary NaCl excretion
urinary K excretion
(Hypokalemia)
urinary magnesium excretion
urinary calcium excretion
calcium re-absorption
(hypercalcemia)
uric acid in blood
(hyperuricemia).
glucose in blood (hyperglycemia)
Thiazide diuretics
Uses:
Treatment of essential
hypertension (cheap-well
tolerated)
Treatment of mild heart failure
(to reduce extracellular volume).
Uses:
Nephrolithiasis due to
hypercalciuria (to increase calcium
re-absorption and decrease renal
calcium stones)
Nephrogenic diabetes insipidus
(decrease blood volume and GFR)
Adverse effects:
Fluidand electrolyte imbalance
Hyponatremia
Hypovolemia (volume depletion)
Hypokalemia
Metabolic alkalosis.
Hyperuricaemia (gout)
Hypercalcemia
Hyperglycaemia
Potassium sparing diuretics
Drugs:
Spironolactone.
Triamterene.
Amiloride.
given by oral administration
Mechanism of action
Act in collecting tubules and
ducts by inhibiting Na re-
absorption and K & H secretion
(K-sparing effect) by either:
Inhibition of Na influx through
Na channels in the luminal
membrane (triamterene –
amiloride).
Mechanism of
action
Or by antagonizing cytoplasmic
aldosterone receptors
(mineralocorticoid receptors
Spironolactone).
Spironolactone : is a synthetic
steroid that acts as a competitive
antagonist for aldosterone.
COLLECTED TUBULES (CT)
Pharmacodynamics:
urinary Na excretion
urinary K excretion
(hyperkalemia)
H secretion (acidosis)
Therapeutic uses:
Drug of choice for patients with
hepatic cirrhosis
Inmineralocorticoid
hypersecretion e.g. Conn’s
syndrome
Therapeutic uses:
Secondary hyperaldosteronism:
(CHF, hepatic cirrhosis,
nephrotic syndrome).
Treatment of hypertension
(combined with thiazide or loop
diuretics to correct for
hypokalemia).
Adverse Effects
Hyperkalaemia.
Metabolic acidosis.
Gynaecomastia
GIT upset and peptic ulcer
Contraindications:
Hyperkalaemia: as in chronic renal
failure, K+ supplementation, -
blockers or ACE inhibitors.
liver
disease (dose adjustment is
needed).
Osmotic diuretics
Mannitol
Poorly absorbed
Given intravenously.
Not metabolized
Excreted by glomerular
filtration without being
re-absorbed or secreted within
30-60 min.
Mannitol
Acts in proximal tubules &
descending loop of Henle by
osmotic effect.
Retains water within the
tubules (water diuresis).
Has a secondary effect on
reducing sodium re-
absorption.
Therapeutic
Uses:
Cerebral edema (increased
intracranial pressure).
Glaucoma.
Acute renal failure due to
shock, trauma, drug toxicities
(maintain urine flow- preserve
kidney function).
Adverse Effects:
Extracellularwater expansion
(extracts water from cells)
Dehydration
Hypernatremia
Headache, nausea, vomiting
Adequate water replacement
is required.
Therapeutic applications of
diuretics of hypertension:
Treatment
o Thiazide diuretics
o used alone or in combination with beta-
blockers at low-dose (fewer side effects)
o In presence of renal failure, loop diuretic
is used
Edema States Thiazide diuretic is used
in mild edema with normal renal
function
o Loop diuretics are used in cases with
impaired renal function
Congestive Heart failure
Thiazides may be used in only mild cases
with well-preserved renal function
Loop diuretics are much preferred in
severe cases especially when GF is
lowered
In life-threatening acute pulmonary
edema, furosemide is given IV
Renal failure
Thiazides are used till GFR ≥ 40-50 ml/min
Loop diuretic are used below given values,
with increasing the dose with as GFR goes
down.
Diabetes inspidus
Large volume(>10 L/day) of dilute urine
thiazide diuretics reduces urine volume
Hepatic cirrhosis with ascites
Spironolactone is of choice.
Diuretics Mechanism of Effects
action
CA inhibitors Inhibition of Urinary Na HCO3, K
Acetohexamide NaHCO3 Urinary alkalosis
Dorzolamide
reabsorption in Metabolic acidosis
PCT
Osmotic diuretic Osmotic effect in Urine excretion
Mannitol PCT & DLH Little Na
Loop diuretics Na/K/2Cl Urinary Na, K, Ca, Mg
Furosemide transporter in
TAL the most
effective
Thiazide Na and Cl Urinary Na, K, Mg
diuretics cotransporter in BUT↓ urinary Ca
DCT (hypercalcemia)
hydrochlorothiazide
Metabolic alkalosis
K-sparing competitive ↑ Urinary Na
diuretic antagonist of ↓ K, H secretion
.Spironolactone aldosterone in Metabolic acidosis
Diuretics Uses
CA inhibitors Glaucoma, epilepsy
Acetohexamide Mountain sickness
Dorzolamide (topically)
for glaucoma
Osmotic diuretic • Cerebral edema
Mannitol • Acute renal failure
Loop diuretics Acute pulmonary edema (Drug of
Furosemide choice)
Heart failure
Hyperkalemia, Hypercalcemia
Thiazide diuretics Commonly used
Hypertension, heart failure,
hydrochlorothiazide
hypercalciuria, kidney stones,
diabetes inspidus
K-sparing diuretic Hepatic cirrhosis
.Spironolactone (Drug of choice)
Diuretics Side effects
CA inhibitors Metabolic acidosis , Urinary alkalosis
Acetohexamide Hypokalemia
Dorzolamide
Osmotic diuretic Extracellular water expansion
Mannitol Dehydration
Hypernatremia
Loop diuretics Hypokalemia,
Furosemide hypovolemia, hyponatremia,
hypomagnesemia, hypocalcemia
Precipitate gout, alkalosis
Thiazide diuretics Hypokalemia, hyponatremia,
hypovolemia, hypomagnesemia,
hydrochlorothiazide
hypercalcemia
Alkalosis, precipitate gout
Hyperlipidemia, hyperglycemia
K-sparing Gynaecomastia
diuretic Hyperkalaemia, Metabolic acidosis.
.Spironolactone GIT upset and peptic ulcer
