Diuretics Flashcards
What are diuretic drugs typically used to treat?
Edema (localized or generalized0
What are the main classes of diuretic drugs?
Osmotic diuretic Loop direct Thiazides diuretics Potassium -sparking Carbonic-anhydrase inhibitor
What is the MOA of osmotic diuretics?
Filtered at glomerulus and poorly reabsorbed in nephron -> water stays in nephrons with the drug -> urine volume increased
what is the osmotic diuretic?
Mannitol
How is mannitol administered?
IV (can crystallized at room temp)
Does mannitol enter the CNS or eye?
Nope
What drug is used to manage acute cerebral edema and acute glaucoma?
Mannitol
Osmotically draws water out of these compartment back to the circulating blood
When is use of mannitol contraindicated?
If BBB or BOB is disrupted and mannitol enters this compartment –> worsen edema
What is the MOA of loop diuretics?
Inhibit Na/K/2Cl cotransporter at the luminal membrane of the tick ascending Loop of Henle
Sodium is not reabsorbed -> water stays in the nephron –> increased urine
Loops diuretics inhibit reabsorption of _________ and increases _______ loss, in addition to its effect on sodium and water.
Ca and Mg; K and H
What is the drug of choice to treat pulmonary edema/acute pulmonary edema ?
Furosemide
What drugs is used for treatment of exercise induced pulmonary hemorrhage in horse?
Furosemide
What diuretic drug would be useful in treatment of hypercalcemia ?
Furosemide
What are adverse effects to furosemide use?
Fluid and electrolyte imbalances (cats more sensitive than dog)
Chronically -> metabolic ALKALOSIS, hypocalcemia, hypomagnesium, hyponatermia, hyperuricemia
Ototoxicity (esp in cats)
When is use of furosemide contraindicated?
Dehydrated patients
What is the MOA of thiazide diuretics
Inhibiting Na/Cl symporter in the early part of the distal convoluted tubule -> less Na and Cl reabsorption -> less water reabsorbed -> diuretics
Which has more diuretic effect, thiazide or loop diuretic?
Loop diuretic (25% of water reabsorption in the loop vs 5% in distal convoluted tubule j
Are thiazide diuretics potassium wasting or potassium sparing?
Potassium wasting -> can lead to hypokalemia
What are side effects of this aside diuretics?
Inhibit conversion of proinsulin to insulin -> hyperglycemia
Fluid and electrolyte imbalances (less severe than furosemide )
T/F: furosemide and hydrochlorothiazide decrease calcium absorption, therefore hypercalcemia can be a side effect
F
Furosemide decreases calcium -> hypocalcemia
Hydrochlorothiazide increase calcium -> hypercalcemia
What drug can be used to treat edema, treat nephrogenic diabetes insipidus, and manage calcium oxalate urolithiasis?
Hydrochlorothiazide
What are precautions to using hydrochlorothiazide ?
Fluid and electrolyte imbalances
Dehydration
Hyponatermia, hypokalemia, hypomagnesemia, hyperuricemia, metabolic ALKALOSIS
Hypercalcemia
Hyperglycemia
Spironolactone is what type of drug?
Potassium-sparing diuretic
What is the MOA of spironolactone?
Reduce aldosterone-mediated Na/K exchange in late distal convoluted tubule -> Na/Cl loss and K reabsorption
What drug is sometimes used to manage ascites or treat mineralocortocoid producing tumors?
Spironolactone
What are precautions to using spironolactone ?
Can lead to HYPERkalemia especially if used in combination with ACE inhibitors
Metabolic ACIDOSIS
Block androgens
Block mineralocorticoids
In what patients is spironolactone contraindicated?
Addison’s disease (hypoadrenocorticism) -> blocks mineralocorticoids
What type of drug in amiloride?
Potassium-sparing diuretics
What is the MOA of amilordie ?
Block Na reabsorption in distal convoluted tubule and in the collecting duct -> Na blocked -> reduced the net driving force for K secretion
What are cautions to using amiloride?
HYPERkalemia
Metabolic acidosis
What drug is a carbonic anhydrase inhibitor?
Acetazolamide
What is the MOA of acetazolamide?
Reversible inhibition of carbonic anhydrase (CA) in proximal convoluted tubule and collecting duct -> inhibit exchange of Na for H
What is the main use of carbonic anhydrase inhibitors
Decrease aqueous humor production in eye -> decrease IOP for treatment of glaucoma
What are the topical carbonic anhydrase inhibitors used for glaucoma treatment?
Dorzolamide
Brinzolamide
Sulfonamides derivatives
When should acetazolamide not be used ?
Significant renal/hepatic disease
Hypoadrenocorticism, hyponatremia, hypokalemia, or hyperchloremic acidosis, other electrolyte imbalances
Acetazolamide can increase ammonia levels. What drug can bind these ions for excretion?
Lactulose
Explain RAAS
Low BP or hyponatremia-> renin (juxtaglomular cells) -> covert angiotensinogen to angiotensin I -> vasoconstriction and aldosterone release -> aldosterone increase water reabsorption
How is renin secretion inhibited?
Local or systemic hypertension
Antigotenin II (pos feedback)
ADH, increased Na
B-adrenergic blockers
What is the function of angiotensin II ?
Vasoconstriction
Stimulate aldosterone secretion
Positive feedback to inhibit renin
What are the ACE- inhibitors?
Enalaril
Benazepril
How are enalapril and benazepril administered?
Oral
How are Enalapril and Benazepril excreted?
Enalapril - 95% at kidney
Benazepril - 45% kidney and 55% liver
What are the indications to using ACE-inhibitors?
Secondary physiological effects of chronic heart failure
Systemic hypertension
Protein losing neuropathy
What are cautions to using ACE inhibitors
In animals with renal insufficiency> lower doses
Not in critically ill renal failure patients
Monitor
Hyperkalemia
What is the action of ADH in the body?
Normally secreted in response to decreased vascular volume -> work on V2 receptors in collecting ducts -> increase water reabsorption through aquaporins -> increase vascular volume
What are the two types of diabetes insipidus?
Central ->. Decreased secretion of ADH (pituitary)
Nephrogenic -> ADH is secreted but kidney is not responding
What is the hallmark of diabetes insipidus?
PU/PD Hyposethenuric urine (more dilute than plasma)
What do we use to treat central DI?
Desmopressin - synthetic ADH analog
What can be used in a dose-dependent manner to increase plasma factor VIII to manage von Willebrands disease?
Desmopressin
How is desmopressin administered?
Topically on conjunctiva
Can desmopressin be administered orally?
Yes. But is broken down in GI tract -> low oral bioavailability -> dose needs to be much higher if given orally
Do you do a water deprivation test to determine central vs neprhogenic DI?
NO
Dr. BOOTS SAYS NO!
How can you determine central vs nephrogenic DI?
Give desmopressin
- > concentrated urine = central
- > still no concentration = nephrogenic
How do you treat nephron DI?
Thiazides diuretics (hydrochlorothiazide) -> help reduce clinical symptoms (polyuria) upregulate aquaporin in collecting duct
