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What are the three thiazide diuretics?
What are the three high ceiling diuretics?
ethacrynic acid
What are the three potassium-sparing diuretics?
What is the Mechanism of action of thiazide diuretics?
Thiazides inhibit Na+ reabsorption in distal tubules and also in cortical diluting segment of loop of Henle.

This results in a decrease in extracellular fluid volume.
What is the percent absorption for chlorothiazide, hydrocholorthiazide, and chlorthalidone?
Chlorothiazide - 10%
Hydrocholorthiazide - 60-80%
Chlorthalidone - 100%
How long do the thiazides take for diuresis to occur?
Diuresis is seen in 1-2 hours of oral administration. Chronic administration produces complete effect in 2-3 days.
What is the half life of the thiazides?
Chlorothiazide - 1.5 hr
Chlorthalidone - 44.0 hr

Chlorthalidone and Metolazone are highly protein bound and have greater lipid solubility. This results in low renal clearance and a prolonged diuretic action.
Describe the elimination of the thiazides.
Thiazides are eliminated via kidneys - mostly unchanged by filtration and secretion.
What are the side effects and drug interactions of thiazides?
Side effects:
Hypokalemia, hyperuricemia, and metabolic alkalosis

Thiazides inhibit tubular secretion of uric acid which leads to increased Uric acid which may rarely lead to gout)

Probenecid ( uric acid levels)
Allopurinol ( synthesis)
Drug Interaction:
Thiazides decrease lithium clearance which can lead to toxicity.
What do thiazide diuretics increase and decrease the urinary secretion of?
and volume of urine

What is the bodily effect of the hypokalemia induced by thiazide diuretics?
hypokalemia reduces insulin secretion and may lead to hyperglycemia.
How do High ceiling (loop) diuretics get their name?
High ceiling - because peak effect is much greater than other agents.
Loop - because the site of action is in the thick ascending limb of the loop of Henle.
Describe the onset and duration of thiazide diuretics.
These diuretics are the most potent agents. They have very rapid onset and short duration of action. [Thus less convenient for chronic use.]
What is the mechanism of action of loop diuretics?
Loop diuretics inhibit a coupled Na+/K+/2Cl- transport system driven by Na+, K+ ATPase at luminal border of ascending limb of loop of Henle - Thus inhibit sodium reabsorption.
About 20% - 30% of Na+ is reabsorbed in the Loop. – When Na+ reabsorption in proximal tubule is inhibited, the loop increases its rate of Na+ reabsorption.
Describe the pharmacokinetics of loop diuretics including absorption, onset of action, plasma protein binding, elimination, and what other medication can decrease the effect of loop diuretics.
Absorption Rapid
Onset of action (IV/Oral) 5/30 min
Plasma protein binding Extensive
Elimination via kidneys Filtration
Ethacrynic acid, Furosemide Bile (30%)

NSAIDs decrease the effect of loop diuretics.
What molecules have incresed and decreased secretion with the use of loop diuretics?
Na, K, Ca, and volume of urine.
What are the side effects of loop diuretics?
Loss of fluid and electrolytes
Ototoxicity Dose related in renal insufficiency
What is the Mechanism of action of potassium-sparing diuretics?
A competitive inhibitor of aldosterone
Is effective only when mineralocorticoids are present.
Aldosterone antagonists inhibit Na+ reabsorption and K+ secretion in distal tubule.

Decreases K+ excretion in Na+-K+ exchange process in distal tubule and the collecting duct.
What is the The site and mechanism of action of amiloride, triamterene and spironolactone?
Amiloride and triamterene block the Sodium channels on the lumenal side of the collecting duct.
Spironolactone is an aldosterone receptor antagonist.
Decsibe the absorption, onset of action, peak effects, and metabolism of spironolactone.
Absorption Poor
Onset of action Delayed  
Peak effects Several days
Metabolism Rapid and extensive
Metabolized to canrenone an active metabolite
Describe the absorption, onset of action, peak effect, and elimination of triamterene and amiloride.
Triamterene and amiloride are orally effective

Absorption Rapid

Onset of action 2-4 hr

Peak effect Several days

Triamterene (Metabolites) Urine (80%) Amiloride (unchanged) Urine
What molecules and have incresed or decreased urinary secretion when using potassium-sparing diuretics?
Increased urinary secretion:
Na, Ca, and volume of urine

Clinical use of potassium-sparing diuretics
Primary hyperaldosteronism
Hypertension/CHF - with thiazides

Side effects
Gynecomastia, impotence
Contraindication: High K+ diet K+ supplements
what is the carbonic anhydrase inhibitor?
what is the mechanism of action of carbonic anhydrase inhibitors (acetazolamide)
Inhibit intracellular carbonic anhydrase (distal tubules and collecting ducts). Intracellular enzyme inhibition decreases H+ production and secretion which is necessary for HCO3 reabsorption.
what are the changes in composition of urine in induced by acetazolamide?
Increased urinary secretion of:
and Volume of Urine
What are the clinical uses of acetazolamide?

Petit mal seizure (Mechanism is not known, inhibition of CA or the resulting acidosis)
What are five properties of the osmotic diuretics?
water soluble
freely filtered at the glomerulus
poorly reabsorbed
pharmacologically inert
osmotically impair tubular fluid reabsorption
What are three properties of mannitol and what is the mechanism?
Is a six-carbon sugar
It is not absorbed from GI
Must be given intravenously

Water molecules surround these osmotic diuretics and the bound water is eliminated
What are the five clinical uses of mannitol?
maintain kidney function during hypotension and decresed glomerular filtration

prevent kidney tubular damage by maintaining urine flow uder circulatory collapse and absent glomerular filtration

reduce cerebral edema prior to neurosurgery

reduce intraocular pressure

promote elinimation of ingested toxic substances.

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