Renal Pharmacology & The Urinary System, Pt. 2 Flashcards
What are the 3 most common high ceiling diuretics? Where do they act?
- Furosemide*
- Bumetanide
- Ethacrynic acid
(most common, highly effective)
acts at Henle’s loop (mTAL), binding and impairing the function of NKCC and reducing 25% of sodium reabsorption
What are 3 common effects of Furosemide? What effect does it have at low doses?
- increased sodium and chloride excretion in urine and out of the ECF
- blocks tubuloglomerular feedback
- disrupts countercurrent multiplier system (blocked NKCC decreases osmolality of interstitial fluid, interrupting its opposite flow of the blood from the vasa recta)
antioxidant free radical scavenger
How does Furosemide travel to and absorb into the kidneys? Where is it well absorbed? In what species is there an exception?
high plasma protein binding —> not filterable, enters via active secretion into the lumen to affect apical NKCC
GIT
horses - slowly absorbed, IV administration recommended
What are 4 possible side effects of Furosemide? In what animals is usage not recommended?
- excretion of calcium, magnesium, and potassium causes decrease of concentrations in the blood
- lethargy
- decreased appetite
- ototoxicity - inner ear endolymph affected by impaired electrolyte transport
pregnant or lactating animals
What is the primary indication of Furosemide usage?
general edema - udder, pulmonary, liver disease, cardiovascular
What is a common usage of Furosemide in horses? How does this disease develop?
lowers pulmonary vascular pressure to treat exercise-induced pulmonary hemorrhage
- exercise causes cardiac output to increase 6-8x
- increased left atrial pressure causes pulmonary hypertension
- blood vessels dilate to decrease resistance and eventually rupture
What are some common signs of exercise-induced pulmonary hemorrhage? What breed is it especially common in?
- pulmonary hypertension
- edema
- rupture of pulmonary capillaries
- intra-alveolar hemorrhage
- presence of blood in the airways
Thoroughbreds
What are 6 other indications of Furosemide?
- udder edema
- diuresis with acute renal failure
- hypertension
- hydrocephalus
- ascites from liver failure
- hypercalcemia (decreases Ca reabsorption)
What are the 2 types of potassium-sparing diuretics? Where do they act?
- Na+ channel blockers (ENaC) - Amiloride, Triamterene
- mineralocorticoid receptor antagonist - Spironolactone, Eplerenone
late DT and CD
What are the 2 common ENaC blockers used as potassium-sparing diuretics? What is their mechanism of action? What makes them less effective?
- Triamterene
- Amiloride
impairs the electrogenic sodium reabsorption late in the DT and CD (ENaC), causing less potassium to leave the cell
limited elimination of sodium at this point in the kidney - commonly combined with other diuretics
What is a possible side effect of Triamterene and Amiloride? In what patients is usage contraindicated?
hyperkalemia
- hyperkalemia
- NSAID treatment —> nephrotoxicity
What aldosterone antagonist is commonly used as a potassium-sparing diuretic? What is its mechanism of action? What additional effect does it have?
Spironolactone
antagonizes cytoplasmic aldosterone receptors in the late DT and CD responsible for molecular ENaC and Na/K ATPase production
calcium excretion in the urine
What makes Spirinolactone distribution unique?
does not require active secretion at the PT to reach its site of action —> diffused into cells from the blood to act on the cytoplasmic MR
What are 7 side effects of Spironolactone? When is usage contraindicated?
- hyperkalemia
- metabolic acidosis
- gastritis
- diarrhea
- drowsiness
- lethargy
- ataxia
gastric ulcers
What are 5 common indications of Spironolactone?
- ascites
- diuretic
- heart failure
- primary hyperaldosteronism
- hepatic insufficiency
What is a common drug combined with Spironolactone? When is this usage indicated?
Hydrochlorothiazide
diuretic, antihypertensive
What 3 conditions commonly use diuretics for treatment? What diuretics are used in each?
- CHF - thiazide and loop diuretics (check potassium!)
- liver cirrhosis resulting in ascites and hyperaldosteronism - Spironolactone
- nephrotic syndrome (hypoalbuminemia, proteinuria, edema) - Furosemide
What commonly affects the efficacy of diuretics used in nephrotic syndrome?
- less protein binding of the drug and reduced distribution to action site
- binding to albumin in the tubular lumen reduces action
(aldosterone antagonists not indicated —> decreases renal response)
What stimulates the ADH-thirst system? What are the 2 outcomes?
increased ECF osmolality or decreased blood volume stimulates hypothalamic osmoreceptors
- ADH release - stimulates water reabsorption by the kidneys (concentrates urine)
- stimulates thirst center - promotes fluid intake
What are the 3 classes of ADH receptors? Where are they located? How do they work?
- V1a - glomerulus, renal medulla
- V1b - inner medulla
- V2 (AQP2) - mTAL, DCT, CD; responds to ADH
tunnel-like channels that use asparagine to recognize water and repel other ions based on size and charge
What drugs act as ADH stimulants? Inhibitors?
STIMULANTS = vinca alkaloids, cyclophosphamide, tricyclic antidepressants, isoproterenol
INHIBITORS = ethanol, mineralocorticoids, glucocorticoids
What is the therapeutic treatment for diabetes insipidus centralis? How can it be used as a diagnostic? What should be monitored?
recombinant ADH, Desmopressin acetate (off-label for increasing von Willebrand factor)
- centralis = responsive
- nephrogenic = no response
USG
What test is used for diagnosing the type of diabetes insipidus?
Carter-Robbins test
- water is administered, where a functional kidney will dilute urine
- NaCl is later administered, where a functional kidney will concentrate urine
- with diabetes insipidus centralis, urine concentration will not change, but will be concentrated upon ADH administration (Desmopressin)
When do uroliths form? What is the most common treatment?
concrement-forming substances reach a concetration above the metastable range and solubility threshold
solubilization/dissolving crystals by altering urine pH below the metastable range
What are the 4 most common types of uroliths in domestic species?
- calcium oxalate (50%)
- calcium phosphate/magnesium ammonium phosphate (30%)
- uric acid/urate (25-30%)
- xanthine/cystine (<5%)
What is cystine urolithiasis? When do they form?
oxidized form of cysteine formed when cysteine dimerizes by forming a disulfide bond
solubility decreases as urine acidity increases —> soluble in ammonia, insoluble in acetic acid
What is the structure of cystine crystals?
hexagonal and flat colorless crystals
What is the most common kidney stone in dogs and cats? What is its structure like? In what urine does it form?
magnesium ammonium phosphate (struvite) - also in rabbits and guinea pigs
long, flat, colorless coffin lid
forms in alkaline urine with a pH of 7-9 —> soluble in acetic acid
What is the second most common kidney stone in cats? What is its structure like? In what urine does it form?
calcium oxalate (also in dogs and horses)
short, square, colorless envelope shape
produced in acetic, neutral, and alkaline urine —> insoluble in acetic acid
What is the shape of urate crystals? In what urine does it form?
(sodium/ammonium urate) red round or amorphous shapes —> red-colored urine
acidic or neutral urine in large amounts
What are the 3 causes of urolithiasis?
- PRE-RENAL - increased filtration of stone-producing substances (hypercalcinuria, phosphaturia), increased mobilization from bone (increased PTH or calcitriol)
- RENAL - abnormal renal reabsorption, ADH release (enhanced urine concentration)
- POST-RENAL - pH of urine (phosphates dissolved in acidic urine, uric acid dissolved in alkaline urine)
What are the 4 major effects of urolithiasis?
- urinary tract blockage
- stretching of ureters (renal colic)
- growth of pathogens (NH3 formation by bacteria further alkalinizes urine)
- hydronephrosis
How can acute cases of urolithiasis be treated?
surgical removal
What are 3 possible treatments of cystine urolithiasis?
- dietary management (low methionine and cyteine diet)
- solubilization
- urine alkalinization (sodium bicarbonate, potassium citrate)
What is the most common treatment of calcium oxalate urolithiasis?
difficult to treat - stimulation of calcium absorption by thiazide diuretics or potassium citrate
What are 3 possible treatments of urate urolithiasis?
- low protein diet
- urine alkalization by sodium bicarbonate or potassium citrate
- Allopurinol - xanthine oxidase inhibitor
