Diuretics Flashcards
How does the kidney regulate extracellular fluid volume?
by changing ionic concentrations and water levels in the body
What percentage of Na, K, Ca, Mg, Cl, bicarbonate, and water are resorbed by the kidney?
greater than 95%
How many liters does the kidney filter per day?
180
How often does the total blood volume get filtered through the kidney?
every 40 minutes
What does the kidney eliminate?
urea, creatinine, drugs, and toxicants
Urine is _____ of plasma.
ultrafiltrate
What are some other functions of the kdiney?
production of renin, erythropoietin, and glycogen storage
What is occurring at step 1?
Active transport coupled to ATP hydrolysis
What is happening at steps 2 and 3?
simple diffusion
What is happening during steps 4-7?
movement via ion channels
What is happening in step 8?
counter-transport (antiport)
What is happening in steps 9-10?
co-transport (symport)
Some of these transporter sites (in the renal tubule cells) serve as ______ of various class of diuretic drugs.
pharmacological targets
Generally, what do diuretics do?
increase the water and salt elimination rate in urine
Diuretics ______ renal excretion of mainly Na+ and water.
incrrease
Diuretics ______ extracellular fluid volume.
decrease
Diuretics ______ blood pressure and ______ cardiac function.
normalize, improve
Diuretics _____ normal tissue perfusion and organ function.
restore
Diuretics _____ the clearance of poisons, drug, and metabolites.
enhance
Diuretics ______ clearance of debris from the nephrons.
increase
What are the indications for diuretic use?
edema, hypertension, and ‘others’ (will address others in another card)
What is edema?
an increase in interstitial fluid volume
What are three causes of generalized edema?
congestive heart failure, nephrotic syndrome, and hepatic diseases
How does congestive heart failure cause generalized edema?
Decreased cardiac output -> renal hypofunction -> RAS activation -> Na and H20 retention -> edema
How does nephrotic syndrome cause generalized edema?
Protein loss in urine → decreased plasma oncotic pressure → increased interstitial fluid → edema
How do hepatic diseases cause edema?
Decreased aldosterone or protein synthesis -> increased Na and H20 retention -> edema
What some types of local edema?
cardiogenic pulmonary edema, cerebral edema, ocular edema, and udder edema
What can cause cardiogenic pulmonary edema?
cardiomyopathy, valve and septal defects
What are the ‘other’ indications for diuretics?
glaucoma, Ca urolithiasis, hypercalcemia, hypo and hyperkalemia, metabolic acidosis/alkalosis, nephrogenic diabetes insipidus
What are the 5 major classes of diuretics?
osmotic diuretics, loop diuretics, thiazides diuretics, K+ sparing diuretics, and ‘others’
What are the ‘others’ diuretics?
Carbonic anhydrase inhibitors: Methylxanthines, acidifying salts
The site of action of diuretics can ______ the efficacy of the specific class of diuretics?
influence
What is the primary site of action of osmotic diuretics?
proximal tubule and descending loop
What is the mechanism of action of osmotic diuretics?
Osmotic diuretics are filtered into the nephron at the glomerulus but cannot be reabsorbed therefore forming an osmotic gradient. - the osmotic activity of these agents prevents water and ion reabsorption
What are the osmotic diuretics we discussed in class?
mannitol, glycerin, and isosorbide
How and when is mannitol used?
They are most commonly used by IV route only; used in short-term and emergency situations
How is glycerin given and at what percentage?
orally, used up to 50% solution
How is isosorbide given and at what percentage?
orally, used up to 50% solution
What are the therapeutic uses for osmotic diuretics?
cerebral edema, acute glaucoma, renal failure, and poisonings
What specific osmotic diuretic is used to treat cerebral edema?
Mannitol - it is very effective for reducing intracranial pressure
What osmotic diuretics are used to treat acute glaucoma?
mannitol and glycerin
When is mannitol and glycerin used in acute glaucoma cases?
For acute glaucoma attacks before and after opthalamic surgery
If you have a diabetic patient with acute glaucoma and chose to use an osmotic diuretic, what is your drug of choice?
isosorbide
What is the choice osmotic diuretic to be used in the case of renal failure and why?
Mannitol (with furosemide) to increase glomerular filtration volume and maintain urine flow - also used to treat ischemia or nephrotoxin
What is the choice osmotic diuretic for poisonings?
Mannitol
What patients is mannitol not recommended for?
patients with pulmonary edema or with cerebral hemorrhage
Why is mannitol not recommended for patients with pulmonary edema?
because it can extract water from intracellular compartments and expand in the extracellular fluid in the lung
Why is mannitol not recommended in animals with cerebral hemorrhage?
because it can increase fluid buildup resulting in intracranial pressure
What should be monitored when using osmotic diuretics?
fluid and electrolyte balance
What is the most powerful and widely used diuretic?
loop diuretics
What are the mechanisms of action of loop diuretics?
Reduce ion reabsorption by inhibiting the Na/K/2Cl cotransporter in the luminal membrane of the thick ascending loop of Henle
Also inhibit Ca and Mg reabsorption due to change in luminal positive potential
What is the ancillary action of loop diuretics?
increase prostaglandin (PGE2) release
What does increased prostaglandin do?
increased renal blood flow, decreased left ventricular pressure, decreased pulmonary edema
What are the loop diuretics we discussed in class?
furosemide (Lasix), torsemide, bumetanide, and ethacrynic acid
Furosemide causes Na and water excretion by __-fold in dogs.
17
Torsemide is ____ as potent as furosemide.
twice
Bumetanide is _____ times more potent than furosemide.
25-40
True or False: Ethacrynic acid is the most commonly used loop diuretic in animals.
False - it is not used in animals
How are loop diuretics metabolized?
They are strongly bound to plasma proteins and do not pass into the glomerular filtrate. They reach the site of action by being secreted into convulated tubule by organic acid transport.
Rapid onset - IV route w/in 5 minutes and within 1hr after oral dosing. diuresis 3-6 hour
Excretion: 80% of unmetabolized drug is excreted in urine; 20% as glucuronide
What are the therapeutic uses of loop diuretics?
edema, heart failure, antihypertensive, acute renal failure, hypercalcemia of malignancy, vitamin D toxicosis, hyperkalemic state, treatment of post-parturient udder edema, exercise-indused pulmonary hemorrhage
In cases of acute renal failure, what is furosemide paired with?
mannitol
How do loop diuretics help treat hypercalcemia?
increased urinary Ca secretion
When are loop diuretics used in the case of hyperkalemia?
if mannitol is ineffective
What are the adverse effects of loop diuretics?
fluid and electrolyte imbalance, oxotoxicity, dehydration, hyperuriemia, hypocalcemia, muscle weakness, metabolic alkalosis, CNS depression
What are symptoms associated with hypokalemia?
dizziness, muscular weakness, cardiac arrhythmias, tetany, respiratory arrest, and coma
How can loop diuretics cause ototoxicity?
they can cause deafness due to electrolyte imbalances in the endolymph of the inner ear
Loop diuretics exacerbate ototoxicity and nephrotoxicity of _________ antibiotics and cisplatin.
aminoglycoside
What do loop diuretics cause when combined with corticosteroids or amphotericin B?
increased hypokalemia
What reduces the diuretic response of loop diuretics?
NSAIDS
How does furosemide interact with probenecid or sulfinpyrazone?
it inhibits the uricosuric effects
What are the contraindications for using loop diuretics?
hepatic dysfunction, gout, and diabetes mellitus
