Renal and Urinary Tract Pharmacology

Question 1

what are the primary pharmacological interventions with the renal system and urinary tract?

Answer 1

increasing urine output
decreasing urine output (rare)
maintaining renal perfusion
control of bladder and urethral tone

Question 2

what does water follow in its movement?

Answer 2

sodium
other osmotic agents

Question 3

why would we want to increase urine flow?

Answer 3

achieve blood volume contraction
protect kidney function

Question 4

what is the mechanism of action of diuretics?

Answer 4

osmotic effects of water-permeable segments
specific interactions with enzymes
interactions with specific membrane transport proteins
interactions with hormone receptors in renal epithelial cells

Question 5

how do osmotic diuretics (mannitol) work?

Answer 5

disrupt the osmotic gradient generated by the re-absorption of sodium

Question 6

what do you need for osmotic diuretics to be effective?

Answer 6

intact tubular wall

Question 7

what are the clinical indications of mannitol?

Answer 7

prophylaxis or treatment of acute kidney injury
not for reducing edema
reduction of CSF (cerebral edema) or intraocular pressures (must have intact blood-brain barrier)

Question 8

what is the efficacy and natriuresis of osmotic diuretics?

Answer 8

variable efficacy
N/A natriuresis

Question 9

what are the adverse effects of mannitol?

Answer 9

acute expansion of ECF/plasma volume (cardiac decompensation, edema)

Question 10

what are the contraindications of mannitol?

Answer 10

anuric kidney failure
marked dehydration
pulmonary congestion/edema
intracranial hemorrhage

Question 11

what is the over-all effect of carbonic anhydrase inhibitors?

Answer 11

low
compensation in the loop of henle and distal convoluted tubule
as body bicarbonate stores become depleted, diuretic effect is lost

Question 12

what are carbonic anhydrase inhibitors used for?

Answer 12

primarily for glaucoma: topical use more common

Question 13

what are carbonic anhydrase inhibitors contraindicated in?

Answer 13

hepatic cirrhosis

Question 14

what is the most common diuretic in veterinary medicine?

Answer 14

furosemide: all species

Question 15

what do loop diuretics do?

Answer 15

inhibit Na/K/2Cl cotransporter in the thick ascending limb of the loop of henle

Question 16

what are the loop diuretics?

Answer 16

furosemide
torsemide

Question 17

what can furosemide do?

Answer 17

block majority of sodium reabsorption in loop
only small amount of Na that flows through can be reabsorbed in rest of tubule
“high ceiling diuretic”

Question 18

what is the half-life of furosemide?

Answer 18

short: 1-1.5 hours in dogs/cats, 3 hours in horses/cattle

Question 19

what is the oral bioavailability of furosemide?

Answer 19

good except in horse

Question 20

what are the adverse effects of furosemide?

Answer 20

ototoxicity
do not use in those with liver failure- may precipitate coma
hypokalemic metabolic alkalosis

Question 21

why does furosemide cause hypokalemia?

Answer 21

higher amount sodium going down the tubule, so later excretes potassium in exchange for absorbing sodium
aldosterone (increases because of decreased blood volume) enhances Na/K exchange

Question 22

what are the clinical indications of furosemide?

Answer 22

reduce blood volume
prevent exercise-induced pulmonary hemorrhage in racehorses
acute kidney injury

Question 23

why would you want to reduce blood volume?

Answer 23

heart failure
edema
decreases hydrostatic pressure and increases oncotic pressure

Question 24

why does torsemide not have as much of an effect on potassium as furosemide?

Answer 24

may also act as an aldosterone antagonist

Question 25

what do thiazide diuretics do?

Answer 25

inhibit Na/Cl cotransport in the distal convoluted tubule

Question 26

what are some thiazide diuretics?

Answer 26

chlorothiazide hydrochlorothiazide trichlomethiazide

Question 27

what are the clinical indications of thiazides?

Answer 27

edema: adjunctive if furosemide alone does not cut it nephrogenic (ADH-resistant) diabetes insipidous

Question 28

what is a potassium-sparing diuretic?

Answer 28

spironolactone- aldosterone antagonist

Question 29

what does spironolactone do?

Answer 29

blocks aldosterone receptor

Question 30

when is spironolactone most effective?

Answer 30

in presence of hyperaldosteronism

Question 31

what are the adverse effects of spironolactone?

Answer 31

hyperkalemia

Question 32

what are the clinical indications of spironolactone?

Answer 32

used in conjunction with other diuretics, especially if refractory edema may provide additional survival benefits in congestive heart failure veterinary product sold as a combination with benazepril (angiotensin converting enzyme inhibitor)

Question 33

is spironolactone used as a sole agent?

Answer 33

rarely

Question 34

what should you treat edema due to liver disease with?

Answer 34

aldosterone antagonist

Question 35

what are some antidiuretic agents?

Answer 35

vasopressin desmopressin

Question 36

what are some agents that affect renal hemodynamics?

Answer 36

dopamine NSAIDs: inhibit prostaglandin production renin angiotensin aldosterone system modifying agents

Question 37

angiotensin II I receptors are abundant in the ________________________

Answer 37

efferent arterioles

Question 38

_____________, which is regulated by angiotensin II, can promote kidney damage

Answer 38

aldosterone

Question 39

what do AT1 receptors do?

Answer 39

induce vasoconstriction direct profibrotic and proinflammatory actions of angiotensin II, promoting kidney damage

Question 40

by ________________________, or blocking its effects (____________________), we can reduce proteinuria and hypertension

Answer 40

angiotensin II (ACE inhibitors) AT1 blockers

Question 41

what is Telmisartan (AT1 receptor blocker) shown to do?

Answer 41

reduce systemic hypertension and proteinuria in cats not shown to change outcomes yet

Question 42

what do we manipulate when we control bladder and urethral tone?

Answer 42

bladder: sympathetic/parasympathetic urethral sphincter: sympathetic/parasympathetic, musculoskeletal

Question 43

why would you want to achieve blood volume contraction?

Answer 43

edema heart failure hypertension

Question 44

what two drugs interact with specific enzymes to produce their diuretic effects?

Answer 44

dichlorphenamide dorzolamide

Question 45

what drugs interact with specific membrane transport proteins to diurese?

Answer 45

furosemide thiazidees

Question 46

what drugs interact with hormone receptors in renal epithelial cells to diurese?

Answer 46

spironolactone potassium-sparing diuretics ACE inhibitors indirectly

Question 47

what is natriuresis?

Answer 47

sodium loss in urine

Question 48

what is the efficacy and natriuresis of thiazide diuretics?

Answer 48

moderate 5%

Question 49

what is the efficacy and natriuresis of loop diuretics?

Answer 49

high 20-25%

Question 50

do osmotic diuretics, such as mannitol, directly affect sodium movement?

Answer 50

no

Question 51

why should you monitor central venous pressure in an animal you a treating with mannitol?

Answer 51

if it goes up, you are fluid overloading

Question 52

why should you not give mannitol if a patient is dehydrated?

Answer 52

exacerbates tissue/cellular dehydration

Question 53

what is lost in urine with carbonic anhydrase inhibitors?

Answer 53

sodium bicarbonate

Question 54

why is the over-all effect of carbonic anhydrase inhibitors low?

Answer 54

compensation in the loop of henle and distal convoluted tubule as body bicarbonate stores become depleted, diuretic effect is lost

Question 55

what is dorzolamide and what is it used for?

Answer 55

carbonic anhydrase inhibitor topical for glaucoma

Question 56

what are the adverse effects of carbonic anhydrase inhibitors?

Answer 56

hyperchloremic metabolic acidosis CNS toxicity with large doses contraindicated in hepatic cirrhosis teratogenic

Question 57

what is lost in urine with loop diuretics?

Answer 57

sodium potassium chloride

Question 58

with furosemide, you need to ________________________ to have an effect

Answer 58

achieve a threshold concentration

Question 59

furosemide abolishes lumen-positive voltage and thus ________________ reabsorption as well

Answer 59

calcium and magnesium

Question 60

how is torsemide cleared?

Answer 60

hepatic primarily

Question 61

what are the adverse effects of thiazides?

Answer 61

not many clinically significant hyperglycemia hypochloremic alkalosis

Question 62

how do ACE inhibitors work with diuresis?

Answer 62

decrease release of aldosterone not diuretic but similar effects

Question 63

when does hyperaldosteronism often occur?

Answer 63

cardiac failure liver disease nephrotic syndrome

Question 64

what is the veterinary product of spironolactone sold as a combination with?

Answer 64

benazepril: angiotensin converting enzyme inhibitor

Question 65

how do NSAIDs affect renal hemodynamics?

Answer 65

inhibit prostaglandin production: renal blood flow is dependent on prostaglandins when an animal is hypotensive

Question 66

what does dopamine do with renal hemodynamics?

Answer 66

vasodilation

Question 67

what do AT1 receptors induce?

Answer 67

vasoconstriction direct profibrotic and proinflammatory actions of angiotensin II

Question 68

what is Telmisartan?

Answer 68

AT1 receptor blocker vasodilation in glomerular efferent arterioles, drop in blood pressure, increased renal blood flow, reduces proteinuria