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Pharmacology LECOM SH > Pharm 20 Diuretics > Flashcards

Pharm 20 Diuretics Flashcards

1
Q

Aliskiren MOA

A

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)

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2
Q

Aliskiren clinical applications

A

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

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3
Q

Aliskiren adverse effects

A

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

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4
Q

Aliskiren contraindications

A

Pregnancy, hyperkalemia, Hx of angioedema, cyclosporine Tx

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5
Q

Aliskiren therapeutic considerations

A

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

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6
Q

[-PRIL] MOA

A

ACE inhibitors1) 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)

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7
Q

[-PRIL] clinical applications

A

HTN, heart failure, diabetic nephropathy, MI

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8
Q

[-PRIL] adverse effects

A

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

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9
Q

[-PRIL] contraindications

A

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

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10
Q

[-PRIL] therapeutic considerations

A

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

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11
Q

[-SARTAN] MOA

A

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

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12
Q

[-SARTAN] clinical applications

A

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)

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13
Q

[-SARTAN] adverse effects

A

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

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14
Q

[-SARTAN] contraindications

A

Pregnancy, B/L renal artery stenosis

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15
Q

[-SARTAN] therapeutic considerations

A

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

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16
Q

Nesiritide MOA

A

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

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17
Q

Nesiritide clinical applications

A

Acutely decompensated heart failure

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18
Q

Nesiritide adverse effects

A

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

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19
Q

Nesiritide contraindications

A

Cardiogenic Shock, Systolic BP < 90

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20
Q

Nesiritide therapeutic considerations

A

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

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21
Q

[-VAPTAN] MOA

A

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

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22
Q

[-VAPTAN] clinical applications

A

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

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23
Q

[-VAPTAN] adverse effects

A

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

24
Q

[-VAPTAN] contraindication

A

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

25
Q

[-VAPTAN] therapeutic considerations

A

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

26
Q

Acetazolamide MOA

A

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

27
Q

Acetazolamide clinical applications

A

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

28
Q

Acetazolamide adverse effects

A

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

29
Q

Acetazolamide contraindication

A

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

30
Q

Mannitol MOA

A

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)

31
Q

Mannitol clinical applications

A

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

32
Q

Mannitol adverse effects

A

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

33
Q

Mannitol contraindications

A

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

34
Q

Mannitol therapeutic considerations

A

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

35
Q

Loop Diuretics MOA

A

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

36
Q

Loop Diuretics Names (4)

A

Furosemide, Bumetanide, Torsemide, Ethacrynic acid

37
Q

Loop Diuretics clinical applications

A

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

38
Q

Loop Diuretics adverse effects

A

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

39
Q

Loop Diuretics contraindications

A

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

40
Q

Loop Diuretics therapeutic considerations

A

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

41
Q

Thiazide Diuretics MOA

A

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

42
Q

Thiazide Diuretics names (7)

A

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

43
Q

Thiazide clinical applications

A

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

44
Q

Thiazide adverse effects

A

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

45
Q

Thiazide contraindications

A

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

46
Q

Thiazide therapeutic considerations

A

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

47
Q

Spironolactone & Eplerenone Class & MOA

A

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

48
Q

Spironolactone & Eplerenone clinical applications

A

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

49
Q

Spironolactone & Eplerenone adverse effects

A

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

50
Q

Potassium-Sparing Diuretics contraindications

A

Anuria, Hyperkalemia, Acute renal insufficiency

51
Q

Amiloride & Triamterene Class & MOA

A

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

52
Q

Amiloride & Triamterene clinical applications

A

HTN, Liddle’s syndrome

53
Q

Amiloride & Triamterene adverse effects

A

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

54
Q

Spironolactone & Eplerenone therapeutic considerations

A

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

55
Q

Amiloride & Triamterene therapeutic considerations

A

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

56
Q

[-PRIL] Types

A

1) Captopril: active when administered, processed to active metabolite2) Enalapril, Ramipril: ester prodrug converted in plasma to active metabolite (Enalaprilat, Ramiprilat)3) Lisinopril: active when administered, excreted unchanged

Pharmacology LECOM SH (24 decks)

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