Pharm 20 - Diuretics

Question 1

Aliskiren MOA

Answer 1

Renin inhibitor (decreases conversion of angiotensinogen to angiotensin I -> reduces substrate for ACE -> decreases arteriolar vasoconstriction, aldosterone synthesis, renal proximal tubule NaCl reabsorption and ADH release)

Question 2

Aliskiren clinical applications

Answer 2

HTN (can be used even in pts w/ renal insufficiency)

Question 3

Aliskiren adverse effects

Answer 3

Hypotension, acute renal failure, angioedema; also rash, diarrhea, cough

Question 4

Aliskiren contraindications

Answer 4

Pregnancy, hyperkalemia, Hx of angioedema, cyclosporine Tx

Question 5

Aliskiren therapeutic considerations

Answer 5

Plasma concentration and half-life increased by atorvastatin and ketokonazole, decreased by furosemide; may reduce proteinuria in chronic kidney disease.

Question 6

[-PRIL] MOA

Answer 6

ACE inhibitors

1) decrease conversion of ATI to ATII -> decreases arteriolar vasoconstriction, aldosterone synthesis, renal proximal tubule NaCl reabsorption and ADH release (same as Aliskiren)
2) Inhibit degradation of bradykinin -> increase vasodilation (unique to ACE inhibitors)

Question 7

[-PRIL] clinical applications

Answer 7

HTN, heart failure, diabetic nephropathy, MI

Question 8

[-PRIL] adverse effects

Answer 8

Angioedema (more frequrent in black pts), agranulocytosis, neutropenia; also dry cough, edema, hypotension, rash, gynocomastia, hyperkalemia, and proteinuria

Question 9

[-PRIL] contraindications

Answer 9

Pregnancy, B/L renal artery stenosis, renal failure, Hx of angioedema

Question 10

[-PRIL] therapeutic considerations

Answer 10

Dry, non-productive cough and angioedema are due to bradykinin action; 1st dose hypotension and/or renal failure more common in pts w/ B/L renal artery stenosis; hyperkalemia more common if used w/ potassium-sparing diuretics; delay progression of cardiac contractile dysfunction after MI; delay progression of diabetic nephropathy

Question 11

[-SARTAN] MOA

Answer 11

Angiotensin II Receptor Antagonists (AKA “ARBs”); antagonize action of angiotensin II at AT receptor, may also indirectly increase vasorelaxant AT2 receptor activity

Question 12

[-SARTAN] clinical applications

Answer 12

HTN, heart failure, diabetic nephropathy, MI (same as ACE inhibitors) AND prevention of stroke (reduced platelet aggregation, decreased serum uric acid, decreased atrial fibrillation, anti-diabetic effects)

Question 13

[-SARTAN] adverse effects

Answer 13

Thrombocytopenia, rhabdomyolysis, angioedema; also hypotension, diarrhea, asthenia, dizziness

Question 14

[-SARTAN] contraindications

Answer 14

Pregnancy, B/L renal artery stenosis

Question 15

[-SARTAN] therapeutic considerations

Answer 15

Can be used w/ ACE inhibitors to increase survival in heart failure; less cough/angioedema than ACE inhibitors…but less effective vasodilation too

Question 16

Nesiritide MOA

Answer 16

B-Type Naturetic Peptide (BNP); increases intracellular concentrations of cGMP by binding to guanylyl cyclase receptor NPR-A of vascular smooth muscle and endothelial cells -> smooth muscle relaxation

Question 17

Nesiritide clinical applications

Answer 17

Acutely decompensated heart failure

Question 18

Nesiritide adverse effects

Answer 18

Hypotension, arrhythmia, renal dysfunction; also headache, confusion, somnolence, tremor, pruritis, nausea

Question 19

Nesiritide contraindications

Answer 19

Cardiogenic Shock, Systolic BP < 90

Question 20

Nesiritide therapeutic considerations

Answer 20

Decreases pulmonary capillary wedge pressure and systemic vascular resistance; Improves stroke volume; Associated with fewer instances of arrhythmia than dobutamine; Risk of hypotension increased when co-asministered with ACE inhibitors; lower plasma aldosterone and endothelian-1; drug is a peptide, so it can’t be given orally

Question 21

[-VAPTAN] MOA

Answer 21

Vasopressin Receptor 2 (V2) Antagonist, prevents vasopressin-stimmulated water reabsorption via V2-coupled aquaporin channels in apical membrane of collecting duct

Question 22

[-VAPTAN] clinical applications

Answer 22

Euvolemic hyponatremia, SIADH, Heart failure, Ascites due to cirrhosis, ADPKD

Question 23

[-VAPTAN] adverse effects

Answer 23

Atrial fibrillation; also orthostatic hypotension, HTN, hypokalemia, thirst, dyspepsia, headache, polyuria

Question 24

[-VAPTAN] contraindication

Answer 24

Concurrent use of CYP3A4 inhibitors (grapefruit juice); hypovolemic hyponatremia

Question 25

[-VAPTAN] therapeutic considerations

Answer 25

Conivaptan is non-selective for V1/V2 and must be administered IV; Tolvaptan is oral and V2-selective - may be able to retard ADH-driven renal cyst growth in ADPKD

Question 26

Acetazolamide MOA

Answer 26

Carbonic Anhydrase inhibitor: noncompetitively/reversibly inhibits proximal tubule cytoplasmic carbonic anhydrase II and luminal carbonic anhydrase IV -> inhibits sodium and bicarbonate reabsorption -> more sodium bicarbonate in distal segments of nephron

Question 27

Acetazolamide clinical applications

Answer 27

High-altitude sickness (prophylaxis), heart failure, epilepsy, glaucoma, hyperuricemia/gout (alkalizes urine and increase excretion of organic anions (uric acid, ASA, etc))

Question 28

Acetazolamide adverse effects

Answer 28

Metabolic acidosis (mild/moderate with normal clinical use), sulfonamide adverse rxns (anaphylaxis, blood dyscrasia, erythema multiforme, fulminante hepatic necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis); also N/V, D, wt gain, loss of appetite, tinnitus, parethesia, somnolence, polyuria

Question 29

Acetazolamide contraindication

Answer 29

In the ciliary process of the eye, carbonic anhydrase inhibition reduces secretion of aqueous humor (reduces intraocular pressure); use of ASA increases plasma concentration -> can cause CNS toxicity

Question 30

Mannitol MOA

Answer 30

Osmotic diuretic, filtered at glomerulus but not reabsorbed; effect is greatest in proximal tubule (osmotic diuresis can also occur the same way when you use radio contrast dyes or in hyperglycemia)

Question 31

Mannitol clinical applications

Answer 31

Cerebral edema, increased intraocular pressure, prophylaxis of oliguria in acute renal failure

Question 32

Mannitol adverse effects

Answer 32

Thrombophlebitis, acidosis, seizure, urinary retention, pulmonary edema; also hypotension, palpitations, fluid/electrolyte imbalance, N, D, rhinitis

Question 33

Mannitol contraindications

Answer 33

Anuria, severe dehydration, After administration of mannitol: heart failure, pulmonary congestion, renal dysfunction

Question 34

Mannitol therapeutic considerations

Answer 34

Promotes vigorous natriuresis so monitor pt's volume status; if water loss exceeds sodium excretion -> causes hyponatremia; used mostly for emergent reduction of ICP in head trauma, brain hemorrhage, etc; sometimes used to Tx compartment syndrome

Question 35

Loop Diuretics MOA

Answer 35

Reversibly/competitively inhibits NKCC2 (Na/K/Cl co-transported) in luminal thick ascending limb; reduces lumen-positive transepithelial potential difference

Question 36

Loop Diuretics Names (4)

Answer 36

Furosemide, Bumetanide, Torsemide, Ethacrynic acid

Question 37

Loop Diuretics clinical applications

Answer 37

HTN; acute pulmonary edema; edema due to heart failure, cirrhosis, or renal dysfunction; hypercalcemia; hyperkalemia

Question 38

Loop Diuretics adverse effects

Answer 38

Hypotension, erythema multiforme, Stevens-Johnson syndrome, pancreatitis, aplastic/hemolytic anemia, leukemia, thrombocytopenia; also volume contraction alkalosis, dose-related OTOTOXICITY, hypokalemia, hypomagnesemia, hyperglycemia, rash, cramps, spasticity, HA, blurred vision, dyspepsia, glycosuria

Question 39

Loop Diuretics contraindications

Answer 39

Hypersensitivity to sulfonamides (but can still use Ethacrynic acid); Anuria

Question 40

Loop Diuretics therapeutic considerations

Answer 40

Bumetanide is most potent; co-administration with aminoglycosides increases ototoxicity and nephrotoxicity; edema due to hypoalbuminemia can be Tx w/ low dose loop diuretics

Question 41

Thiazide Diuretics MOA

Answer 41

Acts as competitive antagonist at NCC Na/Cl co-transporter in luminal membrane of distal convoluted tubule -> inhibits NaCl resporption; promotes increased transcellular calcium resorption in distal convoluted tubule

Question 42

Thiazide Diuretics names (7)

Answer 42

HydrochloroTHIAZIDE, BendroflumeTHIAZIDE, HydrolumeTHIAZIDE, PolyTHIAZIDE, Chlorthalidone, Metolazone, Indapamide

Question 43

Thiazide clinical applications

Answer 43

HTN, edema associated w/ heart failure, cirrhosis, renal dysfunction, corticosteroid Tx, and estrogen Tx

Question 44

Thiazide adverse effects

Answer 44

Cardiac arrhythmia, Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis, hepatotoxicity, SLE; also hypotension, vasculitis, photosensitivity, electrolyte abnormalities, hypokalemic metabolic alkalosis, hyperglycemia, hyperuricemia, dyspepsia, HA, blurred vision, impotence, restlessness

Question 45

Thiazide contraindications

Answer 45

Anuria, hypersensitivity to sulfonamides, co-administration with drugs that prolong QT interval (quinidine, stall) b/c it predisposes to torsades de pointes

Question 46

Thiazide therapeutic considerations

Answer 46

Can used to diminish hypercalciuria for pts at risk for nephrolithiasis and osteoporosis; HYDROCHLOROTHIAZIDE DECREASES GLUCOSE TOLERANCE (may unmask diabetes); in pts w/nephrogenic diabetes insipidus, may DECREASE urine flow

Question 47

Spironolactone & Eplerenone Class & MOA

Answer 47

Potassium-Sparing Diuretics: Binds to, and prevents, nuclear translocation of the mineralocorticoid receptor -> inhibits aldosterone action

Question 48

Spironolactone & Eplerenone clinical applications

Answer 48

HTN (especially obesity-related HTN); Edema b/c of heart failure, cirrhosis, or nephrotic syndrome; Hypokalemia; Primary aldosteronism; Spironolactone only: acne, female hirsutism

Question 49

Spironolactone & Eplerenone adverse effects

Answer 49

Hyperkalemic metabolic acidosis, GI hemorrhage, agranulocytosis, SLE; also gynecomastia, dyspepsia, lethargy, abnormal menstruation, impotence, rash

Question 50

Potassium-Sparing Diuretics contraindications

Answer 50

Anuria, Hyperkalemia, Acute renal insufficiency

Question 51

Amiloride & Triamterene Class & MOA

Answer 51

Potassium-Sparing Diuretics: competitive inhibitor of principal cell apical membrane ENaC sodium channel

Question 52

Amiloride & Triamterene clinical applications

Answer 52

HTN, Liddle's syndrome

Question 53

Amiloride & Triamterene adverse effects

Answer 53

Hematopoietic diseases, nephrotoxicity (triamterene), hyperkalemic metabolic acidosis; also orthostatic hypotension, hyperkalemia, dyspepsia, HA

Question 54

Spironolactone & Eplerenone therapeutic considerations

Answer 54

Mild diuretics when used in isolation (but potentiates loop diuretics); can be used in combination with thiazides to reduce potassium-wasting; can reduce mortality in heart failure from inhibition of cardiac fibrosis resulting from a paracrine aldosterone-signaling pathway

Question 55

Amiloride & Triamterene therapeutic considerations

Answer 55

Drug of choice for Liddle's syndrome (genetic HTN from gain-of-function mutations in beta/gamma subunits of ENaC sodium channel

Question 56

[-PRIL] Types

Answer 56

1) Captopril: active when administered, processed to active metabolite 2) Enalapril, Ramipril: ester prodrug converted in plasma to active metabolite (Enalaprilat, Ramiprilat) 3) Lisinopril: active when administered, excreted unchanged