Renal - Pharmacology

Question 1

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.

Answer 1

See p. 546 in First Aid 2014 or p. 499 in First Aid 2013 for visual

Question 2

What is the mechanism of mannitol? Include its major effect and 3 effects that follow from that.

Answer 2

Osmotic diuretic, increase tubular fluid osmolarity, producing increased urine flow, decrease intracranial/intraocular pressure

Question 3

What are 2 things for which mannitol is used clinically?

Answer 3

(1) Drug overdose (2) Elevated intracranial/intraocular pressure

Question 4

What are 2 toxicities associated with mannitol?

Answer 4

(1) Pulmonary edema (2) (Intravascular) dehydration

Question 5

What are 2 clinical contexts/conditions in which mannitol is contraindicated?

Answer 5

(1) Anuria (2) CHF

Question 6

What is the mechanism/drug type of acetazolamide? What are 2 related effects that stem from this mechanism?

Answer 6

Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total-body HCO3- stores.

Question 7

What are 5 things for which acetazolamide is clinically used?

Answer 7

(1) Glaucoma (2) Urinary alkalinization (3) Metabolic alkalosis (4) Altitude sickness (5) Pseudotumor cerebri

Question 8

What are 4 toxicities associated with acetazolamide?

Answer 8

(1) Hyperchloremic metabolic acidosis (2) Paresthesias (3) NH3 toxicity (4) Sulfa allergy; Think: “‘ACID’azolamide causes ACIDosis”

Question 9

Name two loop diuretics. What kind of loop diuretic is each.

Answer 9

(1) Furosemide: Sulfonamide loop diuretic (2) Ethacrynic acid: Phenoxyacetic acid derivative (not a sulfonamide)

Question 10

What is the mechanism of loop diuretics (e.g., furosemide, ethacrynic acid)? What are 3 effects of this mechanism?

Answer 10

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”

Question 11

Which effect of loop diuretics (e.g., furosemide, ethacrynic acid) do NSAIDs inhibit?

Answer 11

Loop diuretics stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs.

Question 12

What are 3 clinical uses for furosemide?

Answer 12

(1) Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema) (2) Hypertension (3) Hypercalcemia

Question 13

What are 6 toxicities associated with furosemide?

Answer 13

(1) Ototoxicity (2) Hypokalemia (3) Dehydration (4) Allergy (sulfa) (5) Nephritis (interstitial) (6) Gout; Think: “OH DANG!”

Question 14

What is a clinical use for ethacrynic acid?

Answer 14

Diuresis in patients allergic to sulfa drugs

Question 15

How do the toxicities of ethacrynic acid relate to those of furosemide? What is one contraindication of ethacrynic acid, and why?

Answer 15

Similar to furosemide (OH DANG); can cause hyperuricemia; never use to treat gout

Question 16

What kind of diuretic is hydrochlorothiazide? What is its mechanism? What are 2 effects of this mechanism?

Answer 16

Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, (1) reducing diluting capacity of the nephron. (2) Decreasing Ca2+ excretion.

Question 17

What are 5 clinical uses for hydrochlorothiazide?

Answer 17

(1) Hypertension (2) CHF (3) Idiopathic hypercalciuria (4) Nephrogenic diabetes insipidus (5) Osteoporosis

Question 18

What effect does furosemide/ethacrynic acid versus hydrochlorothiazide have on calcium?

Answer 18

LOOP DIURETICS: Increase Ca2+ excretion; HYDROCHLOROTHIAZIDE: Decrease Ca2+excretion

Question 19

What are 7 toxicities associated with hydrochlorothiazide?

Answer 19

(1) Hypokalemic metabolic acidosis (2) Hyponatremia (3) HyperGlycemia (4) HyperLipidemia (5) HyperUricemia (6) HyperCalcemia (7) Sulfa allergy; Think: “HyperGLUC(emia)”

Question 20

What are 4 examples of K+-sparing diuretics?

Answer 20

(1) Spironalactone and (2) eplerenone (3) Trimaterene (4) Amiloride; Think: “The K+ STAys”

Question 21

What is the mechanism of sprinolactone? What other diuretic shares this mechanism?

Answer 21

Spironolactone and eplerenone are competitive aldosterone receptor antagonists in the cortical collecting tubule

Question 22

What is the mechanism of triamterene? What other diuretic shares this mechanism?

Answer 22

Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT

Question 23

Again, what are 4 examples of K-+sparing diurectics? What are 3 clinical uses for K+-sparing diuretics?

Answer 23

(1) Spironalactone and (2) eplerenone (3) Trimaterene (4) Amiloride; Think: “The K+ STAys”; (1) Hyperaldosteronism (2) K+ depletion (3) CHF

Question 24

What are 2 toxicities associated with K+-sparing diuretics?

Answer 24

(1) Hyperkalemia (can lead to arryhythmias) (2) Endocrine effects with spironolactone (e.g., gynecomastia, antiandrogen effects).

Question 25

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.

Answer 25

All diuretics except acetazolamide increase urine NaCl; Serum NaCl may decrease as a result

Question 26

What are 2 diuretics that increase urine K+? What side effect may this have?

Answer 26

Increase with loop and thiazide diuretics; Serum K+ may decrease as a result

Question 27

Name 2 diuretics/renal drugs that decrease blood pH, causing acidemia, and briefly describe their mechanism behind this.

Answer 27

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

Question 28

Name 2 diuretic/renal drugs the increase blood pH, causing alkalosis. Also, briefly describe 3 mechanisms behind this.

Answer 28

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"

Question 29

What 2 diuretics/renal drugs affect urine Ca2+? What are those effects, and what are the mechanisms behind them?

Answer 29

Increase Urine Ca2+ with loop diuretics: decrease paracellular C2+ reabsorption --> hypocalcemia; Decrease Urine Ca2+ with thiazides: Enhanced paracellular Ca2+ reabsorption in distal tubule

Question 30

What are 3 examples of ACE inhibitors?

Answer 30

(1) Captopril (2) Enalapril (3) Lisinopril

Question 31

What is the mechanism of ACE inhibitors? What effects does this have on GFR, renin, and unrelated metabolism?

Answer 31

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

Question 32

What drugs have effects similar to ACE inhibitors? How do they differ from ACE inhibitors?

Answer 32

Angiotensin II receptor blocks (-sartans) have effects similar to ACE inhibitors but do not increase bradykinin --> no cough or angioedema.

Question 33

What are 4 clinical uses for ACE inhibitors?

Answer 33

(1) Hypertension (2) CHF (3) Proteinuria (4) Diabetic renal disease

Question 34

What prevention do ACE inhibitors provide in the context of chronic hypertension?

Answer 34

Prevent unfavorable heart remodeling as a result of chronic hypertension

Question 35

What are 6 toxicities associated with ACE inhibitors?

Answer 35

(1) Cough (2) Angioedema (3) Teratogen (fetal renal malformations) (4) Creatinine increase (decrease GFR) (5) Hyperkalemia (6) Hypotension; Think:" Captopril's CATCHH"

Question 36

In what condition/context are ACE inhibitors contraindicated, and why?

Answer 36

Avoid in bilateral renal artery stenosis, because ACE inhibitors will further decrease GFR --> renal failure