Renal - Pharmacology Flashcards
Pg. 546-549 in First Aid 2014 Pg. 499-502 in First Aid 2013 Sections include: -Diuretics: site of action -Mannitol -Acetazolamide -Loop diuretics -Ethacrynic acid -Hydrochlorothiazide -K+-sparing diuretics -Diuretics: electrolyte changes -ACE inhibitors
Draw a nephron, labeling the tubules and depicting the reabsorption and/or secretion of the following substances in each of the tubules: (1) Ca2+ (2) 2Cl- (3) Mg2+ (4) K+ (5) Na+ (6) H2O (7) NaHCO3 (8) H+ (9) NaCl. Now, label the site of action for each of the following diuretics: (1) Acetazolamide (2) ADH antagonists (3) Loop diuretics (4) Mannitol (5) Potassium-sparing diuretics (6) Thiazides.
See p. 546 in First Aid 2014 or p. 499 in First Aid 2013 for visual
What is the mechanism of mannitol? Include its major effect and 3 effects that follow from that.
Osmotic diuretic, increase tubular fluid osmolarity, producing increased urine flow, decrease intracranial/intraocular pressure
What are 2 things for which mannitol is used clinically?
(1) Drug overdose (2) Elevated intracranial/intraocular pressure
What are 2 toxicities associated with mannitol?
(1) Pulmonary edema (2) (Intravascular) dehydration
What are 2 clinical contexts/conditions in which mannitol is contraindicated?
(1) Anuria (2) CHF
What is the mechanism/drug type of acetazolamide? What are 2 related effects that stem from this mechanism?
Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total-body HCO3- stores.
What are 5 things for which acetazolamide is clinically used?
(1) Glaucoma (2) Urinary alkalinization (3) Metabolic alkalosis (4) Altitude sickness (5) Pseudotumor cerebri
What are 4 toxicities associated with acetazolamide?
(1) Hyperchloremic metabolic acidosis (2) Paresthesias (3) NH3 toxicity (4) Sulfa allergy; Think: “‘ACID’azolamide causes ACIDosis”
Name two loop diuretics. What kind of loop diuretic is each.
(1) Furosemide: Sulfonamide loop diuretic (2) Ethacrynic acid: Phenoxyacetic acid derivative (not a sulfonamide)
What is the mechanism of loop diuretics (e.g., furosemide, ethacrynic acid)? What are 3 effects of this mechanism?
Inhibits cotransport system (Na+, K+, 2Cl-) of thick ascending limb of loop of Henle; (1) Abolishes hypertonicity of medulla, preventing concentration of urine (2) Stimulates PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs. (3) Increase Ca2+ excretion; Think: “Loops Loose calcium”
Which effect of loop diuretics (e.g., furosemide, ethacrynic acid) do NSAIDs inhibit?
Loop diuretics stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs.
What are 3 clinical uses for furosemide?
(1) Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema) (2) Hypertension (3) Hypercalcemia
What are 6 toxicities associated with furosemide?
(1) Ototoxicity (2) Hypokalemia (3) Dehydration (4) Allergy (sulfa) (5) Nephritis (interstitial) (6) Gout; Think: “OH DANG!”
What is a clinical use for ethacrynic acid?
Diuresis in patients allergic to sulfa drugs
How do the toxicities of ethacrynic acid relate to those of furosemide? What is one contraindication of ethacrynic acid, and why?
Similar to furosemide (OH DANG); can cause hyperuricemia; never use to treat gout
What kind of diuretic is hydrochlorothiazide? What is its mechanism? What are 2 effects of this mechanism?
Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, (1) reducing diluting capacity of the nephron. (2) Decreasing Ca2+ excretion.
What are 5 clinical uses for hydrochlorothiazide?
(1) Hypertension (2) CHF (3) Idiopathic hypercalciuria (4) Nephrogenic diabetes insipidus (5) Osteoporosis
What effect does furosemide/ethacrynic acid versus hydrochlorothiazide have on calcium?
LOOP DIURETICS: Increase Ca2+ excretion; HYDROCHLOROTHIAZIDE: Decrease Ca2+excretion
What are 7 toxicities associated with hydrochlorothiazide?
(1) Hypokalemic metabolic acidosis (2) Hyponatremia (3) HyperGlycemia (4) HyperLipidemia (5) HyperUricemia (6) HyperCalcemia (7) Sulfa allergy; Think: “HyperGLUC(emia)”
What are 4 examples of K+-sparing diuretics?
(1) Spironalactone and (2) eplerenone (3) Trimaterene (4) Amiloride; Think: “The K+ STAys”
What is the mechanism of sprinolactone? What other diuretic shares this mechanism?
Spironolactone and eplerenone are competitive aldosterone receptor antagonists in the cortical collecting tubule
What is the mechanism of triamterene? What other diuretic shares this mechanism?
Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT
Again, what are 4 examples of K-+sparing diurectics? What are 3 clinical uses for K+-sparing diuretics?
(1) Spironalactone and (2) eplerenone (3) Trimaterene (4) Amiloride; Think: “The K+ STAys”; (1) Hyperaldosteronism (2) K+ depletion (3) CHF
What are 2 toxicities associated with K+-sparing diuretics?
(1) Hyperkalemia (can lead to arryhythmias) (2) Endocrine effects with spironolactone (e.g., gynecomastia, antiandrogen effects).
What is the effect of nearly all diuretics on urine NaCl? What side effect may this have? Name a diuretic that is an exception to the norm in the case of urine NaCl effect.
All diuretics except acetazolamide increase urine NaCl; Serum NaCl may decrease as a result
What are 2 diuretics that increase urine K+? What side effect may this have?
Increase with loop and thiazide diuretics; Serum K+ may decrease as a result
Name 2 diuretics/renal drugs that decrease blood pH, causing acidemia, and briefly describe their mechanism behind this.
Decrease blood pH (acidemia): (1) Carbonic anhydrase inhibitors - decrease HCO3- reabsorption. (2) K+ sparing - Aldosterone blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchange) in exchange for H+ exiting cells
Name 2 diuretic/renal drugs the increase blood pH, causing alkalosis. Also, briefly describe 3 mechanisms behind this.
Increase blood pH (alkalemia): (1) Loop diuretics and (2) thiazides cause alkalemia through several mechanisms: (1) Volume contraction –> increase AT II –> increase Na+/H+ exchange in proximal tubule –> increase HCO3- reabsorption (“contraction alkalosis”) (2) K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells (3) In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule, –> alkalosis and “paradoxical aciduria”
What 2 diuretics/renal drugs affect urine Ca2+? What are those effects, and what are the mechanisms behind them?
Increase Urine Ca2+ with loop diuretics: decrease paracellular C2+ reabsorption –> hypocalcemia; Decrease Urine Ca2+ with thiazides: Enhanced paracellular Ca2+ reabsorption in distal tubule
What are 3 examples of ACE inhibitors?
(1) Captopril (2) Enalapril (3) Lisinopril
What is the mechanism of ACE inhibitors? What effects does this have on GFR, renin, and unrelated metabolism?
Inhibit angiotensin-converting enzyme (ACE) –> decrease angiotensin II –> decrease GFR by preventing constriction of efferent arterioles; Levels of renin increase as a result of loss of feedback inhibition; Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator
What drugs have effects similar to ACE inhibitors? How do they differ from ACE inhibitors?
Angiotensin II receptor blocks (-sartans) have effects similar to ACE inhibitors but do not increase bradykinin –> no cough or angioedema.
What are 4 clinical uses for ACE inhibitors?
(1) Hypertension (2) CHF (3) Proteinuria (4) Diabetic renal disease
What prevention do ACE inhibitors provide in the context of chronic hypertension?
Prevent unfavorable heart remodeling as a result of chronic hypertension
What are 6 toxicities associated with ACE inhibitors?
(1) Cough (2) Angioedema (3) Teratogen (fetal renal malformations) (4) Creatinine increase (decrease GFR) (5) Hyperkalemia (6) Hypotension; Think:” Captopril’s CATCHH”
In what condition/context are ACE inhibitors contraindicated, and why?
Avoid in bilateral renal artery stenosis, because ACE inhibitors will further decrease GFR –> renal failure
