Renal and Urinary Tract Pharmacology Flashcards
what are the primary pharmacological interventions with the renal system and urinary tract?
increasing urine output
decreasing urine output (rare)
maintaining renal perfusion
control of bladder and urethral tone
what does water follow in its movement?
sodium
other osmotic agents
why would we want to increase urine flow?
achieve blood volume contraction
protect kidney function
what is the mechanism of action of diuretics?
osmotic effects of water-permeable segments
specific interactions with enzymes
interactions with specific membrane transport proteins
interactions with hormone receptors in renal epithelial cells
how do osmotic diuretics (mannitol) work?
disrupt the osmotic gradient generated by the re-absorption of sodium
what do you need for osmotic diuretics to be effective?
intact tubular wall
what are the clinical indications of mannitol?
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)
what is the efficacy and natriuresis of osmotic diuretics?
variable efficacy
N/A natriuresis
what are the adverse effects of mannitol?
acute expansion of ECF/plasma volume (cardiac decompensation, edema)
what are the contraindications of mannitol?
anuric kidney failure
marked dehydration
pulmonary congestion/edema
intracranial hemorrhage
what is the over-all effect of carbonic anhydrase inhibitors?
low
compensation in the loop of henle and distal convoluted tubule
as body bicarbonate stores become depleted, diuretic effect is lost
what are carbonic anhydrase inhibitors used for?
primarily for glaucoma: topical use more common
what are carbonic anhydrase inhibitors contraindicated in?
hepatic cirrhosis
what is the most common diuretic in veterinary medicine?
furosemide: all species
what do loop diuretics do?
inhibit Na/K/2Cl cotransporter in the thick ascending limb of the loop of henle
what are the loop diuretics?
furosemide
torsemide
what can furosemide do?
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”
what is the half-life of furosemide?
short: 1-1.5 hours in dogs/cats, 3 hours in horses/cattle
what is the oral bioavailability of furosemide?
good except in horse
what are the adverse effects of furosemide?
ototoxicity
do not use in those with liver failure- may precipitate coma
hypokalemic metabolic alkalosis
why does furosemide cause hypokalemia?
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
what are the clinical indications of furosemide?
reduce blood volume
prevent exercise-induced pulmonary hemorrhage in racehorses
acute kidney injury
why would you want to reduce blood volume?
heart failure
edema
decreases hydrostatic pressure and increases oncotic pressure
why does torsemide not have as much of an effect on potassium as furosemide?
may also act as an aldosterone antagonist
what do thiazide diuretics do?
inhibit Na/Cl cotransport in the distal convoluted tubule
what are some thiazide diuretics?
chlorothiazide
hydrochlorothiazide
trichlomethiazide
what are the clinical indications of thiazides?
edema: adjunctive if furosemide alone does not cut it
nephrogenic (ADH-resistant) diabetes insipidous
what is a potassium-sparing diuretic?
spironolactone- aldosterone antagonist
what does spironolactone do?
blocks aldosterone receptor
when is spironolactone most effective?
in presence of hyperaldosteronism
what are the adverse effects of spironolactone?
hyperkalemia
what are the clinical indications of spironolactone?
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)
is spironolactone used as a sole agent?
rarely
what should you treat edema due to liver disease with?
aldosterone antagonist
what are some antidiuretic agents?
vasopressin
desmopressin
what are some agents that affect renal hemodynamics?
dopamine
NSAIDs: inhibit prostaglandin production
renin angiotensin aldosterone system modifying agents
angiotensin II I receptors are abundant in the ________________________
efferent arterioles
_____________, which is regulated by angiotensin II, can promote kidney damage
aldosterone
what do AT1 receptors do?
induce vasoconstriction
direct profibrotic and proinflammatory actions of angiotensin II, promoting kidney damage
by ________________________, or blocking its effects (____________________), we can reduce proteinuria and hypertension
angiotensin II (ACE inhibitors)
AT1 blockers
what is Telmisartan (AT1 receptor blocker) shown to do?
reduce systemic hypertension and proteinuria in cats
not shown to change outcomes yet
what do we manipulate when we control bladder and urethral tone?
bladder: sympathetic/parasympathetic
urethral sphincter: sympathetic/parasympathetic, musculoskeletal
why would you want to achieve blood volume contraction?
edema
heart failure
hypertension
what two drugs interact with specific enzymes to produce their diuretic effects?
dichlorphenamide
dorzolamide
what drugs interact with specific membrane transport proteins to diurese?
furosemide
thiazidees
what drugs interact with hormone receptors in renal epithelial cells to diurese?
spironolactone
potassium-sparing diuretics
ACE inhibitors indirectly
what is natriuresis?
sodium loss in urine
what is the efficacy and natriuresis of thiazide diuretics?
moderate
5%
what is the efficacy and natriuresis of loop diuretics?
high
20-25%
do osmotic diuretics, such as mannitol, directly affect sodium movement?
no
why should you monitor central venous pressure in an animal you a treating with mannitol?
if it goes up, you are fluid overloading
why should you not give mannitol if a patient is dehydrated?
exacerbates tissue/cellular dehydration
what is lost in urine with carbonic anhydrase inhibitors?
sodium bicarbonate
why is the over-all effect of carbonic anhydrase inhibitors low?
compensation in the loop of henle and distal convoluted tubule
as body bicarbonate stores become depleted, diuretic effect is lost
what is dorzolamide and what is it used for?
carbonic anhydrase inhibitor
topical for glaucoma
what are the adverse effects of carbonic anhydrase inhibitors?
hyperchloremic metabolic acidosis
CNS toxicity with large doses
contraindicated in hepatic cirrhosis
teratogenic
what is lost in urine with loop diuretics?
sodium
potassium
chloride
with furosemide, you need to ________________________ to have an effect
achieve a threshold concentration
furosemide abolishes lumen-positive voltage and thus ________________ reabsorption as well
calcium and magnesium
how is torsemide cleared?
hepatic primarily
what are the adverse effects of thiazides?
not many clinically significant
hyperglycemia
hypochloremic alkalosis
how do ACE inhibitors work with diuresis?
decrease release of aldosterone
not diuretic but similar effects
when does hyperaldosteronism often occur?
cardiac failure
liver disease
nephrotic syndrome
what is the veterinary product of spironolactone sold as a combination with?
benazepril: angiotensin converting enzyme inhibitor
how do NSAIDs affect renal hemodynamics?
inhibit prostaglandin production: renal blood flow is dependent on prostaglandins when an animal is hypotensive
what does dopamine do with renal hemodynamics?
vasodilation
what do AT1 receptors induce?
vasoconstriction
direct profibrotic and proinflammatory actions of angiotensin II
what is Telmisartan?
AT1 receptor blocker
vasodilation in glomerular efferent arterioles, drop in blood pressure, increased renal blood flow, reduces proteinuria
