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PBL Pharm Block 3 > 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 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)

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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
[-VAPTAN] therapeutic considerations
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
Acetazolamide MOA
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
Acetazolamide clinical applications
High-altitude sickness (prophylaxis), heart failure, epilepsy, glaucoma, hyperuricemia/gout (alkalizes urine and increase excretion of organic anions (uric acid, ASA, etc))
28
Acetazolamide adverse effects
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
Acetazolamide contraindication
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
Mannitol MOA
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
Mannitol clinical applications
Cerebral edema, increased intraocular pressure, prophylaxis of oliguria in acute renal failure
32
Mannitol adverse effects
Thrombophlebitis, acidosis, seizure, urinary retention, pulmonary edema; also hypotension, palpitations, fluid/electrolyte imbalance, N, D, rhinitis
33
Mannitol contraindications
Anuria, severe dehydration, After administration of mannitol: heart failure, pulmonary congestion, renal dysfunction
34
Mannitol therapeutic considerations
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
Loop Diuretics MOA
Reversibly/competitively inhibits NKCC2 (Na/K/Cl co-transported) in luminal thick ascending limb; reduces lumen-positive transepithelial potential difference
36
Loop Diuretics Names (4)
Furosemide, Bumetanide, Torsemide, Ethacrynic acid
37
Loop Diuretics clinical applications
HTN; acute pulmonary edema; edema due to heart failure, cirrhosis, or renal dysfunction; hypercalcemia; hyperkalemia
38
Loop Diuretics adverse effects
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
Loop Diuretics contraindications
Hypersensitivity to sulfonamides (but can still use Ethacrynic acid); Anuria
40
Loop Diuretics therapeutic considerations
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
Thiazide Diuretics MOA
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
Thiazide Diuretics names (7)
HydrochloroTHIAZIDE, BendroflumeTHIAZIDE, HydrolumeTHIAZIDE, PolyTHIAZIDE, Chlorthalidone, Metolazone, Indapamide
43
Thiazide clinical applications
HTN, edema associated w/ heart failure, cirrhosis, renal dysfunction, corticosteroid Tx, and estrogen Tx
44
Thiazide adverse effects
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
Thiazide contraindications
Anuria, hypersensitivity to sulfonamides, co-administration with drugs that prolong QT interval (quinidine, stall) b/c it predisposes to torsades de pointes
46
Thiazide therapeutic considerations
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
Spironolactone & Eplerenone Class & MOA
Potassium-Sparing Diuretics: Binds to, and prevents, nuclear translocation of the mineralocorticoid receptor -> inhibits aldosterone action
48
Spironolactone & Eplerenone clinical applications
HTN (especially obesity-related HTN); Edema b/c of heart failure, cirrhosis, or nephrotic syndrome; Hypokalemia; Primary aldosteronism; Spironolactone only: acne, female hirsutism
49
Spironolactone & Eplerenone adverse effects
Hyperkalemic metabolic acidosis, GI hemorrhage, agranulocytosis, SLE; also gynecomastia, dyspepsia, lethargy, abnormal menstruation, impotence, rash
50
Potassium-Sparing Diuretics contraindications
Anuria, Hyperkalemia, Acute renal insufficiency
51
Amiloride & Triamterene Class & MOA
Potassium-Sparing Diuretics: competitive inhibitor of principal cell apical membrane ENaC sodium channel
52
Amiloride & Triamterene clinical applications
HTN, Liddle's syndrome
53
Amiloride & Triamterene adverse effects
Hematopoietic diseases, nephrotoxicity (triamterene), hyperkalemic metabolic acidosis; also orthostatic hypotension, hyperkalemia, dyspepsia, HA
54
Spironolactone & Eplerenone therapeutic considerations
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
Amiloride & Triamterene therapeutic considerations
Drug of choice for Liddle's syndrome (genetic HTN from gain-of-function mutations in beta/gamma subunits of ENaC sodium channel
56
[-PRIL] Types
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

PBL Pharm Block 3 (14 decks)

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