Renal - EMILY Flashcards
What ion controls the movement of water into and out of the nephron?
Sodium
What are some reasons we’d use diuretics?
-To mobilize tissue fluid
-To reduce blood volume
-To protect kidney function
What are the 5 major classes of diuretics?
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazide diuretics
- Potassium sparing diuretics
What is the ultimate goal of using diuretics?
Increase excretion of sodium followed by water
All diuretics (except for osmotic diuretics) inhibit specific ________ that play a role in renal tubular _________ reabsorption
Targets; sodium
The biggest impact on modifying sodium absorption occurs where?
The loop of Henle
Carbonic anhydrase inhibitors act mainly in the:
Proximal convoluted tubule
Osmotic diuretics act mainly in the:
Descending limb of the loop of Henle
Loop diuretics act mainly in the:
Thick ascending limb of the loop of Henle
Thiazide diuretics act mainly in the:
Distal convoluted tubule
Potassium-sparing diuretics act mainly in the:
Collecting duct
All diuretics (except spironolactone) are active in the tubular _______
Lumen
What must diuretics reach to be effective?
Adequate concentration in the urine
What is the primary MOA of carbonic anhydrase inhibitors?
Interacts with enzymes
What is the primary MOA of osmotic diuretics?
Osmotic effects in water-permeable regions of the nephron
What is the primary MOA of loop diuretics?
Interact with specific membrane transport proteins
What is the primary MOA of thiazide diuretics?
Interact with specific membrane transport proteins
What is the primary MOA of potassium-sparing diuretics?
Interact with hormone receptors
What 2 drugs are carbonic anhydrase inhibitors? Which ones work systemically and which or topical?
Acetazolamide (systemic)
Dorzolamide (topical)
Carbonic anhydrase inhibitors are (non-competitive/competitive) and (reversible/irreversible)
Non-competitive; reversible
What condition are carbonic anhydrase inhibitors (specifically acetazolamide) usually used for?
Acute glaucoma management in dogs to reduce production of aqueous humor
Acetazolamide has self-limiting diuretic effects: T or F?
True. Systemic acidosis makes H+ available in the cell again
Which carbonic anhydrase inhibitor should be used in cats first? Why?
Dorzolamide, because cats are more susceptible to the adverse effects of carbonic anhydrase inhibitors so topical would eliminate systemic effects
What are some adverse effects of acetazolamide?
-Drowsiness and disorientation
-Hypersensitivity
-Hypokalemia and metabolic acidosis
-Worsening of hepatic disease/encephalopathy
What drug is an osmotic diuretic?
Mannitol
What is the MOA of mannitol?
Mannitol increases the osmolarity of the fluid in the nephron when it’s in there, which makes the osmolarity similar to interstitial fluid and reduces passive water diffusion out of the nephron. This means that less sodium is reabsorbed, so more water is excreted.
How is mannitol administered?
As an IV solution
What are the pharmacokinetics of mannitol?
-Mostly not metabolized*
-Half-life is dose-dependent
-Rapid elimination by the kidneys
What are the pharmacodynamics of mannitol?
-Increased cardiac output
-Decreased rigidity of RBC membranes (enhanced blood flow)
-Reduced hematocrit
What are the 2 main therapeutic indications for mannitol?
- Increased intracranial pressure
- Renal failure (not recommended for anuric patients though)
What are some considerations for using mannitol?
-Give IV only
-Use a test dose
-Is the tissue barrier intact? (Nephrotoxic agents and renal ischemia damage make osmotic diuretics ineffective)
What are the adverse effects of mannitol?
-Hypertonic dehydration**
-Cardiac arrhythmias due to electrolyte loss
-Acute hyponatremia
-CHF or pulmonary edema
-Volume overload in oliguric patients
-Hyperosmolar state/osmotic compensation
What is the most commonly used loop diuretic in vet med?
Furosemide
What is the MOA of loop diuretics?
They block the action of the Na+/K+/2Cl symporter in the thick ascending limb of the loop of Henle and prevents normal concentration of urine
How does furosemide activate the RAAS?
It alters the chloride equilibrium leading to renal hypotension
Furosemide has a _______ onset and a _________ duration of action
Rapid; short
Which organ is the major site of action, metabolism and excretion of furosemide?
Kidney
What is furosemide used for?
-Mobilizing edema of cardiac, renal or hepatic origin
-Reducing exercise-induced pulmonary hemorrhage in race horses
-Renal failure
-Hypercalcemia
What are the pharmacodynamics of furosemide?
-Potassium-wasting
-Has hemodynamic effects (decreased pulmonary artery pressure; increased renal blood flow and GFR)
What are the pharmacokinetics of furosemide?
-Primarily excreted by the kidneys
-Can be given IV or orally to dogs
-Usually given IV to horses
What are the main adverse effects of furosemide?
-Volume depletion and hyponatremia
-Electrolyte abnormalities
-Cardiac effects
-Renal effects in at-risk patients
-Many drug interactions
When should you reduce the furosemide dose being given and why?
When also giving ACE inhibitors at the same time. This increases the risk of renal damage due to hypotension/ischemia
What is the MOA of thiazide diuretics?
-Inhibit Na/Cl co-transporters in the distal convoluted tubule
-Increase Ca2+ reabsorption
Which 3 drugs are thiazide diuretics?
- Chlorothiazide
- Hydrochlorothiazide
- Trichlormethiazide
What are the pharmacodynamics of thiazide diuretics?
-Moderate diuresis
-Blood pressure reduction in hypertensive individuals
What are the pharmacokinetics of thiazide diuretics?
-Incomplete GI absorption in vet species
-Extensively protein-bound**
–>Not filtered at glomerulus
—>Get into tubules via proximal tubular secretion
-Renal excretion (+/- biliary)
What are the adverse effects of thiazide diuretics?
-Potassium wasting (increased risk of arrhythmias)**
-Hyperglycemia
-Hypercalcemia
-Hyponatremia
-Hypochloremia
-Sulfonamide hypersensitivity
What type of patients is the use of thiazide diuretics contraindicated in?
Patients with severe renal disease or hepatic disease
What are 2 types of potassium-sparing diuretics?
- Mineralocorticoid receptor antagonists
- Epithelial sodium channel blockers
Which drug is a mineralocorticoid potassium-sparing diuretic?
Spironolactone
Which 2 drugs are epithelial sodium channel blockers (potassium-sparing)?
- Amiloride
- Triamterene
What is the MOA of spironolactone?
Blocks binding of aldosterone in late distal tubule and collecting duct. This reduces sodium absorption and potassium excretion.
What is the MOA of epithelial sodium channel blockers?
They block sodium channels in the luminal epithelium and prevent sodium reabsorption
What is spironolactone usually administered with and why?
A thiazide or loop diuretic to increase diuresis while sparing potassium
Spironolactone is most effective in the presence of what?
Hyperaldosteronism (happens in cardiac failure, liver disease, and nephrotic syndrome)
Why should you use spironolactone with an aldosterone antagonist in patients with liver failure?
Secondary hyperaldosteronism (due to decreased aldosterone metabolism) causes increased sodium and water retention and acsites
What is the main adverse effect of potassium-sparing diuretics?
Hyperkalemia
Why shouldn’t you use potassium-sparing diuretics with ACE inhibitors?
Can cause hyperkalemia
What is the purpose of using diuretic combinations?
-To achieve adequate diuresis while minimizing adverse effects
-To increase efficacy in acute renal failure
-To treat refractory edema
