Anti-HPN: Diuretics

Question 1

Diuretics MOA

Answer 1

Increase urinary excretion of Na+ (natriuresis) and water (aquaresis) = Diuretics
Site of action: Kidney Tubule

Question 2

Proximal Convoluted Tubule (PCT)

Answer 2

Main site of HCO3- reabsorption
Reabsorption of Na ions
Water permeable

Question 3

Thick Ascending Limb (TAL)

Answer 3

Reabsorption of Na+, K+ and Cl-
Secondary reabsorption of Mg, Ca (divalent cations)
Water impermeable

Question 4

Distal Convoluted Tubule (DCT)

Answer 4

Reabsorption of Na+, Cl-
Reabsorption of Ca (mediated by PTH)
Water impermeable

Question 5

Collecting Duct (DT)

Answer 5

Reabsorption of Na+
Secretion of K+

Question 6

Diuretics Drugs

Answer 6

a. PC
* Carbonic Anhydrase Inhibitors (CAIs)
* Osmotic Diuretic (Mannitol)
* Methylxanthine (Caffeine)
* Acidifying salts (NH4Cl)

b. TDL: Osmotic diuretic (Mannitol)

c. TAL: Loop Diuretics

d. DCT: Thiazide diuretics

e. CD: Potassium Sparing Diuretics

Question 7

Thiazide Diuretics MOA

Answer 7

Inhibits Na+ / Cl- Transporter in early distal convoluted tubule

↑ Na, K excretion ↓ Calcium excretion

Question 8

First line for hypertension and management of Nephrogenic Diabetic Insipidus

Answer 8

Thiazide Diuretics

Others:
Management of nephrolithiasis
Adjuncts in the management of CHF

Question 9

Thiazide Diuretics

Answer 9

a. Benzothiazides
* HCTZ, chlorothiazide

b. Thiazide-like
* Metolazone, Indapamide, Chlorthalidone

Question 10

Side Effects of Thiazide Diuretics

Answer 10

HyperGLUC
Gycemia
Lipidemia
Uricemia
Calcemia

Hypokalemia

Question 11

MOA of Loop Diuretics

Answer 11

Inhibit Na+/K+/2Cl– transporter in thick ascending limb of loop of Henle.

Question 12

Loop Diuretics is also called

Answer 12

High Ceiling Diuretics - produces dose-dependent diuresis

Question 13

Loop Diuretics

Answer 13

i. Sulfonamide-like Compounds
* Furosemide
* Bumetanide

ii. Sulfonylurea
* Torsemide

iii. Phenoxyacetate
* Ethacrynic acid

Question 14

Clinical Uses of Loop Diuretics

Answer 14

Adjuncts in the management of pulmonary congestion in CHF
Management of oliguric and anuric Acute renal failure
Management of anion poisoning

Question 15

Side Effects of Loop Diuretics

Answer 15

• Electrolyte-imbalance (hypo-)
• Sulfonamide associated AE: Ototoxicity: increased risk (+) aminoglycosides, cisplatin
• Metabolic Associated AE: HyperGLU: glycemia, lipidemia, uricemia

Question 16

Furosemide

Answer 16

4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid

Question 17

Potassium-Sparing Diuretics

Answer 17

a. Aldosterone Antagonist (↑ K+ Secretion, ↓ Na+ reabsorption)
* Spironolactone, Eplerenone

b. Epithelial Na+ Channel Blockers
(ENaC)
* Amirolide, Triamterone

Question 18

Clinical Uses of K-sparing Diuretics

Answer 18

Prevention of diuretic-induced hypokalemia
Adjuncts in the management of CHF
Management of hyperaldosteronism-induced HTN

Question 19

DOC in px with hepatic cirrhosis

Answer 19

Spironolactone

Question 20

Adverse Effects of K-Sparing Diuretics

Answer 20

• Hyperkalemia
• Spironolactone:
  > Anti-androgen
  > Gynecomastia
  > Decreased libido
  > Hirsutism
• Triamterene: increased chance of renal
  stone formation

Question 21

Carbonic Anhydrase Inhibitors (CAIs)

Answer 21

-Zolamides
* Acetazolamide
* Dorzolamide
* Brinzolamide
* Diclorphenamide

• sulfonamide-like compounds
• active moiety: Sulfonamoyl (SO2-NH2)

Question 22

First line management of Open-angle glaucoma and altitude Sickness

Answer 22

Carbonic Anhydrase Inhibitors
(-zolamide)

Question 23

MOA of Carbonic Anhydrase Inhibitors

Answer 23

Inhibits carbonic anhydrase in proximal convoluted tubule of the kidneys & ciliary bodies of the eyes

Question 24

Effects of Carbonic Anhydrase Inhibitors (CAIs)

Answer 24

• PCT - short-lived natriuretic effect (NMT 3
  days)
• Continuous loss of HCO3 - metabolic acidosis
• Eyes - decreased intraocular pressure
  (IOP)

Question 25

Clinical Uses of Carbonic Anhydrase Inhibitors (CAIs)

Answer 25

First line in the management of open angle glaucoma Presurgical tx in acute angle closure glaucoma Management of metabolic alkalosis Management of acute mountain sickness Management of catamenial seizure (Seizure during mens)

Question 26

Adverse Effects of Carbonic Anhydrase Inhibitors (CAIs)

Answer 26

Increases risk of metabolic acidosis Sulfonamide associated AE: rashes/ dermatitis (SJS & TEN) Hematologic: hemolytic anemia, aplastic anemia, neutropenia Hypersensitivity reaction

Question 27

Contraindications of Carbonic Anhydrase Inhibitors (CAIs)

Answer 27

Patient with COPD Patient with chronic liver disease = ENCEPHALOPATHY

Question 28

Osmotic Diuretics

Answer 28

Mannitol Glycerol

Question 29

MOA of Osmotic Diuretics

Answer 29

Creates osmotic gradient in water permeable regions of the kidney tubule

Question 30

Clinical Uses of Osmotic Diuretics

Answer 30

Management of increased intracranial pressure

Question 31

Side Effects of Osmotic Diuretics

Answer 31

Hyponatremia followed by hypernatremia Headache Nausea, vomiting Dehydration Massive loss of water (hypovolemia)