Pharm - Prog2 - Diuretics

Front 1

What is the MOA of carbonic anhydrase inhibitors?

Back 1

Diuretic: Inhibition of carbonic anhydrase (membrane bound and cytoplasmic) in PCT. More Na, bicarb in urine; less H+ secreted

Front 2

What are the three carbonic anhydrase inhibitors?

Back 2

DAM: acetazolamide, dichlorphenamide, methazolamide (amide, sulfa derivatives)

Front 3

What is the effect of carbonic anhydrase inhibitors on urine?

Back 3

The pH increases, becomes more alkaline due to increased bicarb in urine. Effect is quick, long-lasting.

Front 4

What are the three main toxicities of carbonic anhydrase inhibitors?

Back 4

Hyperchloremic metabolic acidosis (bc lose bicarb, efficacy limiting), Renal stones (calcium salts precipitate at alkaline pH), Potassium wasting (increased load for K sec). Also, allergies with sulfa derivatives, drowsiness and paresthesias

Front 5

Where are carbonic anhydrase inhibitors contraindicated?

Back 5

Liver failure bc alkalization decreases excretion of ammonium, hyperammonemia leads to hepatic encephalopathy. Also, Na, K depletion

Front 6

What are the three main uses of carbonic anhydrase inhibitors?

Back 6

1) Glaucoma (dec aqueous humor prod). 2) Acute mountain sickness (dec pH in CNS, increases ventilation to reduce sx). 3) Metabolic alkalosis: corrects alkalosis from loop diuretics 4) Also urinary alkalization..

Front 7

What are the four loop diuretics?

Back 7

Furosemide, Bumetanide, Torsemide (sulfonamides) and Ethacrynic acid (for ppl with sulfa allergies)

Front 8

What are the three MOA's of the loop diuretics?

Back 8

1) Inhibit NaK2Cl cotransporter in TAL of loop of Henle: more Na, K, Cl excreted. Also, more Ca, Mg excreted (bc reduced +lumen potential from K exc) 2) Stimulates renin release via macula densa (vasoconstriction) (inc syn of renal PG's, inc RBF) 3) Inc systemic venous capacitance (good for heart failure)

Front 9

How are loop diuretics secreted?

Back 9

Secreted by organic acid transport system in PT of kidney, competes with uric acid secretion -- gout.

Front 10

What kind of transport mechanisms are occurring at the PCT?

Back 10

Na/H exchanger, H + bicarb --> H2CO3 by carbonic anhydrase, gets converted to carbon dioxide and water. Membrane-associated and intracellular carbonic anhydrases. 60-70% Na

Front 11

What kind of transport mechanisms are occurring at the TAL?

Back 11

Na/K/2Cl cotransporter, builds K+ gradient, creates +luminal potential, drives Mg, Ca into blood. 25% Na.

Front 12

What kind of transport mechanisms are occurring at the DCL?

Back 12

Na/Cl cotransport. PTH reabsorbs Ca for Na/Ca exchanger absorbing Ca into blood. 5%

Front 13

What kind of transport mechanisms are occurring at the DCT and CD?

Back 13

Na/K/H antiporter, dependent on tubular Na. K, H loss. Aldosterone stimulates antiport. CD: ADH/vasopressin from post pituitary regulates pores that reabsorb water. 1-2% Na.

Front 14

What is the important drug interaction with loop diuretics?

Back 14

Loop diuretics have to be transported into the urine to work-- NSAIDs and probenecid compete at the same site. NSAIDs reduce their ability to induce synthesis of renal PG's.

Front 15

What are 4 toxicities of loop diuretics?

Back 15

Ototoxicity: alter electrolyte composition of endolymph --> tinnitus, deafness, vertigo.
Ion dysreg: hypokalemia, hyperglycemia, hypocalcemia, hypomagnesemia, hyperuricemia
Lipids: Inc LDL, Dec HDL
Allergies with sulfa -- use ethacynic acid

Front 16

Where are loop diuretics CI?

Back 16

Osteoporosis (Ca excreted)

Front 17

What are the five uses of loop diuretics?

Back 17

1) Edema 2) HTN (esp reduced renal fcn states 3) Drug OD (bromide, fluoride, iodide) 4) Hypercalcemia 5) Acute Renal Failure (inc urine flow to prevent oliguria)

Front 18

Name the four thiazide diuretics.

Back 18

Hydroclorothiazide, Metolazone (still effective at lower GFR, use with loop diuretics for heart/renal failure), Chlorothiazide, Indapamide (sulfas)

Front 19

What is the MOA for thiazide diuretics?

Back 19

Inhibit NaCl symport in DCT. Excrete more NaCl, block dilute urine. Enhance Ca reabsorption in PCT, DCT (Na/Ca exchanger), Mg excretion increased

Front 20

How are thiazide diuretics secreted?

Back 20

Secreted by organic acid transport system in proximal tubule (gout, NSAID/probenecid competition)

Front 21

What are the four toxicities of thiazide diuretics?

Back 21

1) Dec glucose tolerance (diabetics) 2) Hyperlipidemia 3) Hyponatremia 4) Allergies with sulfas
Also fatigue, impotence

Front 22

What are the five uses of thiazide diuretics?

Back 22

1) HTN: DOC 2) Edema 3) Osteoporosis 4) Nephrolithiasis from hypercalciuria 5) Nephrogenic diabetes insipidus (cannot respond to ADH)

Front 23

Name the 2 aldosterone antagonists.

Back 23

Spironolactone (DOC for hepatic cirrhosis), Eplerenone, bind Ald in CD so downregulate Na/K/H antiport, K sparing. Slow onset bc regulate gene expression

Front 24

Name 2 K sparing diuretics that inhibit Na/K/H antiport at the CD.

Back 24

Amiloride, Triamterene (drug containing renal stones). More Na excreted, less K/H excreted. Secreted by organic base transport system in proximal tubule (NSAIDs inhibit but probenecids do NOT interfere)

Front 25

What effect do NSAIDs have on K sparing diuretics?

Back 25

Inhibit action bc action depends on renal PG production

Front 26

What toxicities do K sparing diuretics have?

Back 26

1) Hyperkalemia, Metabolic acidosis (K/H) 2) Hormonal disturbances (gynecomastia, menstrual irreg) 3) Peptic ulcers

Front 27

Where are K sparing diuretics CI?

Back 27

Renal failure, hyperkalemic. Don't use with other K sparing diuretics or ACE inhibitors

Front 28

What are the uses of K sparing diuretics?

Back 28

1) Combine with diuretics to prevent hypokalemia 2) Mineralocorticoid excess

Front 29

What are the 2 ADH agonists?

Back 29

Vasopressin and desmopressin, act on ADH receptors in CT

Front 30

Where are ADH agonists used?

Back 30

Central diabetes insipidus (deficiency of ADH)

Front 31

What are the three ADH antagonists?

Back 31

Conivaptan, Lithium, Demeclocycline - Inhibit ADH by reducing cAMP in response to ADH

Front 32

What are the 2 osmotic diuretics?

Back 32

Mannitol and Glycerin

Front 33

What is the MOA of osmotic diuretics?

Back 33

Increase osmolality of plasma and tubular fluid by being freely filtered at glomerulus. Causes water retention in proximal tubules and descending limb

Front 34

What are the 4 toxicities of osmotic diuretics?

Back 34

Extracellular volume expasions; Deydration/Hypernatriuremia; Hyponatremia; Glycerin causes hyperglycemia when metabolized

Front 35

Where do you use osmotic diuretics?

Back 35

Prevent anuria, increase urine volume, CEREBRAL EDEMA and GLAUCOMA (reduce intracranial and intraocular pressure)