Diuretics Flashcards
Diuretics
increase urine production by acting on the kidney (Pig. 3.1). Most agents
affect water balance indirectly by altering electrolyte reabsorption or secretion. Osmotic agents
affect water balance directly.
NAtiuretic Diuretics
produce diureaia, associated with increased sodium (N1+)
excretion, which results in a concomitant loss of water and a reduction in extracellular volume
Adverse effects
Hypo-kalemia, natremia, chloremia and acid-base disturbances
Carbonic Anhydrase inhibitors
Acetezolamide
Dichlorphenamide
Methazolamide
CAI MOA
Carbonic Anhydrase of PCT is reversibly inhibited leading to reduced absorbtopn of sodium and bicarb- increase excretion of Na, HCO3 and H2O
Indications of CAI
Rarely used as diuretis
Indicated in reducing ocular pressure in glaucoma
alkaline urine to enhance uric acid and cystine secretion
Acute mountain sickness prophylaxis
Adjuvant therapy for Epilepsy
Adv Eff and ContraI
Metabolic acidosis- depletion of HCO3, decrease in Ca and risks formation if calculi, K+ wasting
drowsiness and parasthesia
precaution in Sulfa allergy as they are sulfonamide derivatives
contraindicated in cirrhosis
Loop diuretics
furosemide, bumetanide, torsemide, and ethacrynic acid
MOA of LD
Loop diuretics Inhibit active sodium chloride (NaCl) reabsorption in the
thick ascending limb of the loop of Henle by inhibiting the activity of NAKCC2 symporter.
Diuresis occurs in 5min after administration IV and 30 min oral
why are Loop diuretics referred as high ceiling
Because of the high capacity for NaCl reabsorption in this segment, agents active at this
site markedly increase water and electrolyte excretion
LD also reduces the
lumen positive potential, mg+2 and Ca excretion is increased
The block the kidney’s ability to concentrate urine by interfering with an important step in
the production of a hypertonic medullary interstitium.
Loop diuretics cause increased renal prostaglandin production, which accounts for some of
their activity. Nonsteroidal anti-inftammatory drugs (NSAlDs) can reduce the effectiveness
of loop diuretics.
Uses for LD
CHF- reduces acute PE when along with Thiazides
treat hypertension in renal failure patients
acute hypercalcemia due to hyper PTH or malignancy
Adv eff of LD
a. Loop diuretics produce hypotension and volume depletion.
b. They can cause hypokalemia due to enhanced secretion ofK+. They may also produce alkalo1i1 due to enhanced H• secretion. Mgz+ wasting can occur with chronic use.
The risk of cardiac glycoside (digoxin) toxicity increases in the presence of hypokalemia.
Loop diuretics can cause dose-related ototoxicity, more often in individuals with renal impairment. These effects are the most pronounced with ethacrynic acid.
These agents should be administered cautiously in the presence of renal disease or with the use of other ototoxic agents, such as aminoglycosides.
All loop diuretics, except ethacrynic acid, are
Sulfonamides- caution in sulfa allergy
Thiazide and thiazide-like diuretics
chlorothiazide and hydrochlorothiazide. Chlorothiazide is the only
thiazide available for parenteral use.
Thiazide-like drugs
Metolazone, chlorthalidone, and indapamide
They have properties similar to thiazide diuretics but may be effective in the presence
of renal impairment.
MOA of TZD
Thiazide diuretics inhibit active re. absorption of NaCl in the distal
convoluted tubule by blocking the NCC cotransporter
This results in the net
excretion of sodium and an accompanying volume of water. Diuresis occurs within 1 to 2 hours
a. They decrease the diluting capacity of the nephron.
b. These agents increase excretion of Na+, Cl-, K+, and, at high doses, bicarbonate (HC03 -). They
also reduce excretion of Ca+
Uses of TZDs
TZDs inhibit NaCl reabsorption in DCT by blocking NCC.
diuresis occurs in 1-2 hours
decrease the diluting capacity of the nephron.
These agents increase excretion ofNa+, Cl-, K+, and, at high doses, bicarbonate (HC03 -). They also reduce the excretion of Ca
Adv eff of TZDs
a. Thiazide diuretics produce electrolyte imbalances such as hypokalemia, hyponatremia, and
hyperalcemia. Potassium supplementation may be required.
b. The risk of cardiac glycoside (dlgoxin) toxicity increases in the presence of hypokalemia.
c. These agents often elevate Serum urate, presumably as a result of competition for the organic anion carriers (which also eliminate uric acid). Gout-like symptoms may appear
d. Thiazide diuretics can cause hyperglycemia (especially in patients with diabetes), hypertriglyceridemia, and hypercholesterolemia.
e. These agents are sulfonamide derivatives; therefore, precaution must be used in patients with a sulfa allergy
K+ Sparing
spironolactone, eplerenone, amiloride, and triamterene
MOA of K+ sparing
Potassium-sparing diuretics reduce Na+ reabsorption and K excretion by antagonizing the
effects of aldosterone In the collecting tubule.
Spironolactone and Eplerenone inhibit the actions of
aldosterone- binds to mineralocorticoid receptor and prevents subsequent cellular events of K+ and H+ secretion and Na+ reabsorption
An important action is a reduction in the blo·synthesis of epithelial Na• channel (ENaC) in the principal cells of the collecting duct
These K+ agents are active only when
endogenous mineralocorticoid is present; the effects
are enhanced when hormone levels are elevated.
Eplerenone
highly selective for the mineralocorticoid receptor
Spironolactone has anti-androgenic activities
binds to other nuclear receptors such as the androgen receptor or
progesterone receptor. this may lead to additional side effects.
Therapeutic effects are achieved only after several days
Amiloride and triamterene bind to and block the
ENaC and thereby decrease absorption of
Na• and excretion of K• in the cortical collecting tubule, independent of the presence of mineralocorticoids
2-4 hours to produce action after oral-admin
Spironolactone and eplerenone are
not potent diuretics when used alone, combination with thiazide and LD to treat hypertension, CHF, and refractory edema
They are also used to Induce diuresis in clinical situations associated with hyperaldosteronism, such as in adrenal hyperplasia
Amiloride and triamterene
manage CHF, cinhosis, and edema caused by secondary hyperaldosteronism. They are available in comblnadon products containing thiazide or
loop diuretics to treat hypertension
Often times, they are used as an adjunct to other diuretic agents to prevent K• loss
adv effects and contraindications
All potassium-sparing diuretics can cause hyperkalemia.
(1) Precaution must be taken since this can lead to cardiac arrhythmias.
(2) The risk is increased in patients with chronic renal insufficiency and in those who take medications that inhibit renin (NSAIDs) or angiotensin U (angiotensin-converting
enzyme inhibitors).
b. Hyperchloremic metabolic acidosis may occur due to inhibition ofH• and K• secretion.
c. Spironolactone is associated with gynecomastia in men and can also cause menstrual abnormalities in women.
Osmotic Diuretics
Mannitol, Water
MOA of ODs
Mannitol is easily filtered at the glomeruli but poorly reabsorbed. It increases the osmotic pressure of the glomerular filtrate, which inhibits reabsorption of water and electrolytes and increases wine output
Uses of ODs
a. Mannitol is commonly used to reduce intracranial pressure due to trauma and to reduce intraocular pressure prior to a surgical procedure.
b. It is used in prophylaxis of acute renal failure resulting from physical trauma or surgery.
Even when filtration is reduced, sufficient mannitol usually enters the tubule to promote urine output
Adv eff and Contraind.
a. The osmotic forces that reduce intracellular volume ultimately expand extracellular volume;
therefore, precautions must be taken in patients with CHF or pulmonary congestion.
b. The volume expansion may cause adverse effects such as headache and nausea
Agents that influence the action of antidiuretic hormone (ADH) (vasopressin)
Agents that influence the action of ADH will influence the permeability of the luminal surface of the medullary collecting duct to water by causing water-specific water channels
(aquaporin 1) to be inserted into the plasma membrane
Under conditions of dehydration, ADH
levels increase to conserve body water.
Agents that elevate or mimic ADH
antidiuretic effect
Agents that lower or antagonize ADH
diuretic effect
Vasopressin binds to three receptors
Va: Vasculature
V1b: Brain
V2: collecting ducts
Vasopressin and vasopressin analogs
vasopressin and desmopressin (DDAVP).
Uses of Vasopressin and its analogs
(1) These agents are useful in die management of central diabetes insipidus.
(2) Desmopressin Is also used to treat nocturnal enuresis.
(3) Studies have suggested that vasopressin and its analogs are useful to maintain blood pressure in patients with septic shock and to increase clotting factor VIII In some patients with type I von WWebrand disease.
adv. effects of contra
These drugs can produce serious cardiac-related adverse effects and they should be used with caution 1n individuals with coronary artery disease. Hyponatremia occurs in about 5% of patients.
ADH antagonist
conivaptan (a mixed V1a and V2 antagonist) and tolvaptan (a V2
selective antagonist)
Convitapan
approved for the treatment of hypervolemic hyponatremia and
syndrome of inappropriate ADH (SIADH).
Tolvaptan
approved for treating hyponatremia
associated with CHF, cirrhosis. and SIADH. These agents may be more effective in treating
hypervolemia in heart failure than diuretics.
adv eff of ADH antagonist`
nausea and xerostomla. Rapid correction of hyponatremia (> 12 mBq/L/24 h) may cause osmotic demyelination
osmotic demyelination
lethargy, confusion, behavioral
disturbances, movement disorders, paresis, or seizures.
Nonreceptor antagonists of ADH
demeclocycline and lithium carbonate
They may be useful in the treatment of SIADH.
adv eff of Demeclocycline
(a) It may cause photosensitivity.
(b) Dose-dependent nephrogenic diabetes insipidus is common with use (reversible on discontinuation).
{c) It may lead to tooth discoloration or tissue hyperpigmentation in children
K+ loss
No: K+ sparing
Yes: HCO3- loss
HCO3- loss
No: Ca+2 loss
Yes: CAI
Ca+2 loss
No: Thiazide
Yes: loop
CAIs
acetolazamide
dichlorophenamide
methazolamide
LDs
Bumetanide
Ethacrynic acid
Furosemide
Torsemide
TZD
Chlorothiazide
Hydrochlorothiazide
Methylclothiazide
TZD like
Chlorthalidone
Indapamide
Metolazone
K+ sparing
Amiloride
Eplerenone
Spironolactone (Aldactone, CaroSpir)
Triamterene
Osmotic
Mannitol
Urea
ADH antagonist
Desmopressin
Vasopressin
Vasopressin anta
Conivaptan
Demeclocycline
Lithium Carbonate
Tolvaptan
