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1. CV Pharmacology
Diuretic Agents
Reading/eNotes:
Renal Pharmacology
Clinical:
e-Medicine article
Hypokalemia
IllustrationHot-LinkedtoRenalPhysioandPharm/Pharm2000
Prepared and presented by
Marc Imhotep Cray, M.D.
Basic Medical Sciences & CK Teacher

2. 2
Illustration shows where some types
of diuretics act, and how

3. 3
Diuretic Agents
 Drugs that accelerate the rate of urine
formation
 Result: removal of sodium and water

4. 4
Sodium
As goes sodium so goes water
 20 to 25% of all sodium is reabsorbed
into the bloodstream in the loop of Henle
 5 to 10% in the distal tubules,
 3% in collecting ducts
 If not absorbed, it is excreted with
the urine

5. 5
Diuretic Agents
1. Carbonic anhydrase inhibitors
2. Loop diuretics
3. Osmotic diuretics
4. Potassium-sparing diuretics
5. Thiazide and thiazide-like diuretics

6. 6
Carbonic Anhydrase Inhibitors
(CAIs)
1. acetazolamide (Diamox)
2. methazolamide
3. Dichlorphenamide
 MOA: these agents block formation of
H+ and HCO3- from CO2 and H2O.
 The end result is that bicarbonate is
excreted in the urine. (see notes page for more)

7. 7
Carbonic Anhydrase Inhibitors:
Mechanism of Action
 The enzyme carbonic anhydrase helps to
make H+ ions available for exchange with
sodium and water in the proximal tubules
 CAIs block the action of carbonic
anhydrase, thus preventing the exchange of
H+ ions with sodium and water

8. 8
 Inhibition of carbonic anhydrase reduces H+
ion concentration in renal tubules
 As a result, there is increased excretion of
bicarbonate, sodium, water, and potassium
 Reabsorption of water is decreased and urine
volume is increased
Carbonic Anhydrase Inhibitors:
Mechanism of Action

9. 9
Carbonic Anhydrase
Inhibitors: Therapeutic Uses
 Adjunct agents in the
long-term management
of open-angle
glaucoma
 Used with miotics to
lower intraocular
pressure before ocular
surgery in certain cases
 Also useful in the
treatment of:
 Glaucoma
 Edema
 Epilepsy
 High-altitude
sickness

10. 10
 Acetazolamide is used in the management of
edema secondary to CHF when other
diuretics are not effective
 CAIs are less potent diuretics than loop
diuretics or thiazides—metabolic acidosis
they induce reduces their diuretic effect in 2
to 4 days
Carbonic Anhydrase
Inhibitors: Therapeutic Uses

11. 11
Carbonic Anhydrase Inhibitors:
Side Effects
hyperchloremic metabolic acidosis
Drowsiness
Anorexia
Paresthesias
Hematuria
Urticaria
Photosensitivity
Melena

12. 12
Loop Diuretics
 bumetanide (Bumex)
 ethacrynic acid (Edecrin)
 furosemide (Lasix)

13. 13
Loop Diuretics:
Mechanism of Action
 Act directly on the ascending limb of
the loop of Henle to inhibit sodium
and chloride reabsorption
 Increase renal prostaglandins,
resulting in the dilation of blood vessels
and reduced peripheral vascular resistance

14. 14
Loop Diuretics: Drug Effects
 Potent diuresis and subsequent loss of fluid
 Decreased fluid volume causes:
 Reduced BP
 Reduced pulmonary vascular resistance
 Reduced systemic vascular resistance
 Reduced central venous pressure
 Reduced left ventricular end-diastolic pressure
 Potassium depletion

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Loop Diuretics: Therapeutic
Uses
 Edema associated with CHF or hepatic
or renal disease
 Control of hypertension

16. 16
Loop Diuretics: Side Effects
Body System Effect
CNS
Dizziness
headache
tinnitus
blurred vision
GI
Nausea/vomiting, diarrhea

17. 17
Loop Diuretics: Side Effects
Body System Effect
Hematologic Agranulocytosis,
neutropenia,
thrombocytopenia
Metabolic Hypokalemia,
hyperglycemia,
hyperuricemia

18. 18
Osmotic Diuretics
 mannitol (Resectisol, Osmitrol)

19. 19
Osmotic Diuretics:
Mechanism of Action
 Work in the proximal tubule
 Nonabsorbable, producing an osmotic
effect
 Pull water into the blood vessels and
nephrons from the surrounding tissues

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Osmotic Diuretics: Drug
Effects
 Reduced cellular edema
 Increased urine production, causing
diuresis
 Rapid excretion of water, sodium, and
other electrolytes, as well as excretion
of toxic substances from the kidney
 Reduces excessive intraocular pressure

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Osmotic Diuretics:
Therapeutic Uses
 Used in the treatment of patients in the
early, oliguric phase of ARF
 To promote the excretion of toxic
substances
 Reduction of intracranial pressure
 Treatment of cerebral edema

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Osmotic Diuretics: Side
Effects
 Convulsions
 Thrombophlebitis
 Pulmonary congestion
Also headaches, chest pains, tachycardia,
blurred vision, chills, and fever

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Potassium-Sparing Diuretics
 Do not share any obvious chemical similarities,
except for steroid-structure, of the aldosterone
antagonists
 Those in clinical use include:
 Epithelial sodium channel blockers:
 Amiloride
 Triamterene
 Aldosterone antagonists:
 Spironolactone
 Eplerenone

24. 24
Potassium-Sparing Diuretics:
Mechanism of Action
 Work in collecting ducts and distal
convoluted tubules
 Interfere with sodium-potassium
exchange
 Competitively bind to aldosterone
receptors
 Block the reabsorption of sodium and
water usually induced by aldosterone

25. 25
Potassium-Sparing Diuretics:
Drug Effects
 Prevent potassium from being pumped into
tubule, thus preventing its secretion
 Competitively block aldosterone receptors
and inhibit its action
 Excretion of sodium and water
is promoted

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Potassium-Sparing Diuretics:
Therapeutic Uses
spironolactone and triamterene
 Hyperaldosteronism
 Hypertension
 Reversing potassium loss caused by
potassium-losing drugs
amiloride
 Treatment of CHF

27. 27
Potassium-Sparing Diuretics:
Side Effects
Body System Effect
CNS Dizziness, headache
GI Cramps, nausea,
vomiting, diarrhea
Other Urinary frequency,
weakness
**hyperkalemia

28. 28
Potassium-Sparing Diuretics:
Side Effects
spironolactone
 gynecomastia, amenorrhea, irregular
menses

29. 29
Thiazide and Thiazide-Like
Diuretics
 hydrochlorothiazide (Esidrix, HydroDIURIL)
 chlorothiazide (Diuril)
 trichlormethiazide (Metahydrin)
 chlorthalidone (Hygroton)
 metolazone (Mykrox, Zaroxolyn)

30. 30
Thiazide and Thiazide-Like
Diuretics: Mechanism of Action
 Inhibit tubular resorption of sodium and chloride ions
 Action primarily in the ascending loop of Henle and
early distal tubule
 Result: water, sodium, and chloride are excreted
 Potassium is also excreted to a lesser extent
 Dilate the arterioles by direct relaxation

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Thiazide and Thiazide-Like
Diuretics: Drug Effects
 Lowered peripheral vascular resistance
 Depletion of sodium and water

32. 32
Thiazide and Thiazide-Like
Diuretics: Therapeutic Uses
 Hypertension
(one of most prescribed group of agents)
 Edematous states
 Idiopathic hypercalciuria
 Diabetes insipidus
 Adjunct agents in treatment of CHF, hepatic
cirrhosis

33. 33
Thiazide and Thiazide-Like
Diuretics: Side Effects
Body System Effect
CNS Dizziness, headache,
blurred vision, paresthesias,
decreased libido
GI Anorexia, nausea, vomiting,
diarrhea

34. 34
Thiazide and Thiazide-Like
Diuretics: Side Effects
Body System Effect
GU Impotence
Integumentary Urticaria, photosensitivity
Metabolic Hypokalemia, glycosuria,
hyperglycemia

35. 35
Additional Resources
 Drug Monitor - Diuretics
 Diagram at cvpharmacology.com
 Renal Physiology And Disease