diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action...
TRANSCRIPT
![Page 1: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/1.jpg)
Diuretics1) the role of different portions
of the nephron in ion exchange;
2) the sites of action and pharmacology of diuretics;
3) the therapeutic applications of diuretics
![Page 2: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/2.jpg)
A diuretic -
is any drug that elevates the rate of bodily urine excretion (diuresis).
All diuretics increase the excretion of water from the body.
![Page 3: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/3.jpg)
![Page 4: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/4.jpg)
Classification /due to location of action/
1. Diuretics which increase glomerular filtration rate
/Xanthines/Caffeine,
Theophyllinum
Euphyllinum
![Page 5: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/5.jpg)
2. Proximal convoluted tubule diuretics
2.1. Osmotic diuretic Mannitol
2.2. Carbonic anhydrase (CA) inhibitors
Diacarbum (acetazolamide)
![Page 6: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/6.jpg)
3. Loop (of Henle) diureticsFurosemidum
Bumetanidum
Ethacrynic acid
4. Distal convoluted tubule diuretics/Thiazides and thiazide-like drugs/
Hydrochlorothiazidum
![Page 7: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/7.jpg)
5. Collecting duct diuretics5.1. Antagonist of aldosterone
Spironolactonum
5.2. Agents inhibit the Na+ channel in the apical membrane
Amiloridum
Triamterenum
![Page 8: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/8.jpg)
Indications:
Hypertension CHF, Nephrotic syndrome Poisonings
![Page 9: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/9.jpg)
Proximal convoluted tubule diuretics
The proximal tubule (PT) determines the rate of Na+ and H2O delivery to the more distal portions of the nephron
A wide variety of transporters couple Na+ movement into the cell to the movement of amino acids, glucose, phosphate, and other solutes
![Page 10: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/10.jpg)
MannitolMechanism of Action
o Mannitol is a non-metabolizable osmotic diuretic and is filtered into the tubular space where it markedly increases tubular fluid osmolality.
o This results in impared reabsorption of fluid with a resultant increased excretion of water (some Na+ accompanies)
![Page 11: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/11.jpg)
![Page 12: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/12.jpg)
Pharmacokinetics of Mannitol:
o Given only i.v. and acts within 10 min; o if given p.o. it causes an osmotic diarrhea
(not well absorbed from gut). o In pts with normal renal function t1/2 is
approx. 1.2 hr.
![Page 13: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/13.jpg)
Indications:
prophylaxis against renal dysfunction, e.g. major surgical procedure
Contraindications: CHF,
chronic renal failure
![Page 14: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/14.jpg)
![Page 15: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/15.jpg)
Carbonic anhydrase (CA) inhibitors
![Page 16: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/16.jpg)
![Page 17: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/17.jpg)
Carbonic anhydrase (CA) inhibitors Mechanism of Action:
If CA activity is inhibited, HCO3- reabsorption is reduced and exits the proximal tubule in much larger amounts.
In the distal nephron, Na+ is largely reabsorbed (unlike HCO3-) and is exchanged for K+. Therefore acetazolamide primarily causes an increase in urinary HCO3-, K+, and water excretion.
![Page 18: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/18.jpg)
CA Inhibitors: Adverse Side Effects
hypokalemia metabolic acidosis
![Page 19: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/19.jpg)
Loop Diuretics
![Page 20: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/20.jpg)
Loop Diuretics: Mechanism of Action
block the Na+/K+/Cl- co-transporter in the apical membrane of the thick ascending limb of Henle's loop. Therefore, loop diuretics increase urinary water, ions excretion.
cause dilation of the venous system and renal vasodilation - effects that may be mediated by prostaglandins.
![Page 21: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/21.jpg)
![Page 22: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/22.jpg)
Loop diuretics: Pharmacokinetics
- act within 20 min and t1/2 is approx. 1-1.5 hr.
- are rapidly absorbed from the gut and can be given i.v.
- are the most potent available and can cause excretion of up to 20% of the filtered Na+.
![Page 23: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/23.jpg)
Clinical uses of loop diuretics
acute pulmonary oedema chronic heart failure cirrhosis of the liver complicated by
ascites nephrotic syndrome renal failure.
![Page 24: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/24.jpg)
Loop diuretics Adverse Side Effects
hypokalemia metabolic alkalosis hypomagnesemia hyperuricemia dehydration (hypovolemia), leading to
hypotension dose-related hearing loss (ototoxicity)
![Page 25: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/25.jpg)
Thiazides: Mechanism of Action
They inhibit Na+ and Cl- transport in the cortical thick ascending limb and early distal tubule.
They have a milder diuretic action than do the loop diuretics because this nephron site reabsorbs less Na+ than the thick ascending limb.
![Page 26: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/26.jpg)
Thiazides
![Page 27: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/27.jpg)
Thiazides: Pharmacokinetics
All are well absorbed from the gut. Onset of action is within approx. 1 hr;
effects can be long lasting but vary with the drug used (6-48 hr).
![Page 28: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/28.jpg)
Clinical uses of thiazide diuretics
Hypertension. Mild heart failure (loop diuretics are
usually preferred). Severe resistant oedema (together
with loop diuretics).
![Page 29: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/29.jpg)
Thiazides have a week antihypertensive
effect because reduce arterial wall sensitivityto NA (noradrenaline) and AT (Angiotensin).
They potentiate significantly the effectof other antihypertensive drugs.
![Page 30: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/30.jpg)
Thiazide Adverse Side Effects
hypokalemia metabolic alkalosis dehydration (hypovolemia), leading to
hypotension hyponatremia hyperglycemia in diabetics hyperuricemia (at low doses) Erectile dysfunction
![Page 31: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/31.jpg)
Symptoms of hypokalemia
muscle weaknessparalysisarrhythmia
![Page 32: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/32.jpg)
Potassium sparing diuretics
These agents are often given to avoid the hypokalemia
They should never be given in the setting of hyperkalemia
(diabetes mellitus, multiple myeloma, renal insufficiency)
![Page 33: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/33.jpg)
SpironolactoneMechanism of Action
It is a competitive antagonist of aldosterone.
Therefore it blocks aldosterone-stimulated Na+ reabsorption and K+ and H+ excretion in the late distal tubule and collecting duct.
![Page 34: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/34.jpg)
Potassium sparing diuretics
![Page 35: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/35.jpg)
![Page 36: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/36.jpg)
SpironolactonePharmacokinetics:
Given orally, spironolactone takes up to 2 days to be effective with a t1/2 approx. 20 hr.
![Page 37: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/37.jpg)
Amiloride and triamtereneMechanism of Action
inhibit the Na+ channel in the apical membrane of the late distal tubule and collecting duct.
Because K+ and H+ secretion in this nephron segment are driven by the electrochemical gradient generated by Na+ reabsorption, K+ and H+ transport into the urine is reduced.
![Page 38: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/38.jpg)
![Page 39: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/39.jpg)
Clinical uses of potassium-sparing diuretics (e.g. amiloride, spironolactone) in heart failure, where either of these
improves survival in primary hyperaldosteronism (Conn's
syndrome) in resistant essential hypertension
(especially low-renin hypertension) in secondary hyperaldosteronism caused
by hepatic cirrhosis complicated by ascites.
![Page 40: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/40.jpg)
K+-sparing diuretics Adverse Side Effects
hyperkalemia metabolic acidosis gynecomastia (aldosterone antagonists) gastric problems including peptic ulcer
![Page 41: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/41.jpg)
![Page 42: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/42.jpg)
Arctostaphylos uva-ursi L. (Bearberry)
![Page 43: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/43.jpg)
Stipites Cerasorum(Cherry)
![Page 44: Diuretics 1) the role of different portions of the nephron in ion exchange; 2) the sites of action and pharmacology of diuretics; 3) the therapeutic applications](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649ea35503460f94ba7ee7/html5/thumbnails/44.jpg)
Equisetum arvense(Common horsetail)
Containssilicates with diureticand urolitholytic effects.