Flashcards in Renal - Pharmacology Deck (62):
On what three segments of the kidney nephron do osmotic agents such as mannitol exert their diuretic effects?
Proximal convoluted tubule, thin descending loop of Henle, and collecting duct
On what segment of the kidney nephron do loop agents such as furosemide exert their diuretic effects?
The ascending limb of the Loop of Henle
On what segment of the kidney nephron do thiazides exert their diuretic effects?
Distal convoluted tubule
On what segment of the kidney nephron do potassium-sparing agents exert their diuretic effects?
On what segment of the kidney nephron do antidiuretic hormone antagonists exert their effects?
In the proximal convoluted tubule, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
In the thin descending limb of the loop of Henle, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
In the thick ascending limb of the loop of Henle and the distal convoluted tubule, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
On what segment of the kidney nephron does the diuretic acetazolamide exert its effects?
Proximal convoluted tubule
What are the clinical uses of mannitol?
To treat shock, drug overdose, and elevated intracranial/intraocular pressure
What is the mechanism of action of mannitol?
Mannitol acts as an osmotic diuretic, increasing osmolarity within the renal tubules producing increased urine volume
What two toxicities are associated with mannitol?
Pulmonary edema and dehydration
In what two conditions is mannitol contraindicated?
Anuric renal failure, congestive heart failure
What four toxicities are associated with acetazolamide?
Hyperchloremic metabolic acidosis (ACIDazolamide causes ACIDosis), neuropathy, ammonia toxicity, and sulfa allergic reactions
What is the mechanism of action of acetazolamide?
It acts as a carbonic anhydrase inhibitor, causing self-limited sodium bicarbonate diuresis and a reduction in total-body bicarbonate stores
What are the four clinical uses of acetazolamide?
To treat glaucoma, metabolic alkalosis, and altitude sickness, and to cause urinary alkalinization
What are three (general) the clinical uses of furosemide?
To treat edematous states (congestive heart failure, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, and hypercalcemia
Name one loop diuretic.
Furosemide, also known as Lasix
What is the mechanism of action of furosemide?
It inhibits the sodium-potassium-chloride cotransport system in the thick ascending limb of the loop of Henle, thereby abolishing the hypertonicity of the medulla and preventing the concentration of urine
What is the effect of the diuretic furosemide on calcium handling in the kidney nephron?
Furosemide increases calcium excretion (remember: "loops lose calcium")
Name six toxicities associated with use of loop diuretics; use the mnemonic "OH DANG!"
Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), and Gout
Ethacrynic acid has a mechanism of action similar to which other drug?
Which loop diuretic is used to diurese patients who are allergic to sulfa drugs?
Name five toxicities of ethacrynic acid.
Ototoxicity, hypokalemia, dehydration, and interstitial nephritis
Serum levels of which substances are increased as a result of the effects of hydrochlorothiazide?
Glucose (hyperGlycemia), lipids (hyperLipidemia), uric acid (hyperUricemia), and calcium (hyperCalcemia) (remember: HyperGLUC)
What is the mechanism of action of hydrochlorothiazide?
It reduces the diluting capacity of the kidney nephron by inhibiting sodium chloride reabsorption in the early distal tubule
_____ (Furosemide/Hydrochlorothiazide) increases calcium excretion, whereas _____ (furosemide/hydrochlorothiazide) decreases calcium excretion.
Name four clinical uses of hydrochlorothiazide.
To treat hypertension, congestive heart failure, idiopathic hypercalciuria, and nephrogenic diabetes insipidus
Name seven toxicities associated with hydrochlorothiazide.
Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, and sulfa allergy
What are the three clinical uses of potassium-sparing diuretics?
To treat hyperaldosteronism, potassium depletion, and congestive heart failure
What is the mechanism of action of spironolactone?
It exerts its effects by competitively antagonizing the aldosterone receptor in the cortical collecting tubule
What is the mechanism of action of triamterene and amiloride?
They exert their effects by blocking sodium channels in the cortical collecting tubule
Name four potassium-sparing diuretics.
Spironolactone, triamterene, amiloride, and eplerenone (remember: the K+ STAys)
What are the toxicities of the potassium-sparing diuretics?
Hyperkalemia (leading to arrhythmias) and endocrine effects with spironolactone (gynecomastia and antiandrogen effects)
What is the mechanism by which potassium-sparing diuretics cause acidemia?
Hyperkalemia leads to potassium entering all cells via the H+/K+exchanger in exchange for H+exiting cells
Which diuretics increase potassium excretion in the urine, thus causing a potential decrease in serum potassium?
All of them, except for the potassium-sparing diuretics
Which two classes of diuretics may increase the blood pH?
Loop diuretics and thiazides
Which type of diuretics increases urine calcium excretion?
Which types of diuretic reduce urine calcium excretion and increases serum calcium?
What is the mechanism by which carbonic anyhydrase inhibitors cause acidemia?
Acetazolamide causes the kidney to excrete more bicarbonate, decreasing the body's pH
By what two mechanisms does potassium loss caused by loop diuretics and thiazide diuretics lead to alkalosis?
Potassium loss leads to potassium ions exiting the cells in exchange for hydrogen ions entering the cell, leading to alkalosis; also, in a low-potassium state, hydrogen ions (as opposed to potassium ions) are exchanged for sodium ions in the cortical collecting tubule, which leads to alkalosis
By what mechanism do loop diuretics cause increased excretion of calcium in the urine?
Loop diuretics abolish the lumen-positive potential in the thick ascending limb of the loop of Henle, causing decreased paracellular calcium reabsorption, leading to increased urinary calcium and hypocalcemia
Which two classes of diuretics may reduce the blood pH?
Carbonic anhydrase inhibitors and potassium-sparing diuretics
What mechanism underlies "volume contraction alkalosis"?
Volume contraction leads to increased angiotensin II, which causes an increased hydrogen-sodium exchange in the proximal tubule and increased bicarbonate reabsorption
By what mechanisms do thiazide diuretics decrease urinary calcium?
Volume depletion leads to enhanced paracellular calcium resorption in the loop of Henle; the increased sodium gradient in the tubule leads to increased sodium/calcium exchange and increased calcium resorption
The names of angiotensin-converting enzyme inhibitors typically end in what suffix?
The suffix -pril
What enzyme do captopril, enalapril, and lisinopril inhibit?
Losartan is an example of what class of drug?
An angiotensin II receptor antagonist
Why is renin released from the kidneys when angiotensin-converting enzyme inhibitors are used?
There is a loss of feedback inhibition (ie, the lack of angiotensin II production and subsequent aldosterone release results in a drop in blood pressure, causing renin release)
What class of diuretics can be used in place of angiotensin-converting enzyme inhibitors if cough is a problematic adverse effect?
Angiotensin II receptor antagonists such as losartan
What is the mechanism by which angiotensin-converting enzyme inhibitors can cause angioedema?
Angiotensin-converting enzyme inhibitors prevent the inactivation of bradykinin, a potent vasodilator; increased bradykinin levels can lead to angioedema in susceptible individuals
What electrolyte disturbance can result from angiotensin-converting enzyme inhibitor toxicity?
Name the adverse effects of angiotensin-converting enzyme inhibitors; use the mnemonic CAPTOPRIL.
Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems (fetal renal damage), Rash, Increased renin, and Lower angiotensin II
Angiotensin-converting enzyme inhibitors can cause acute renal failure (acute kidney injury) in patients with which condition?
Bilateral renal artery stenosis; these patients are dependent on angiotensin II to maintain their glomerular filtration rate
What are three clinical uses of angiotensin-converting enzyme inhibitors?
To treat hypertension and congestive heart failure and to slow the progression of diabetic renal disease
What exogenous substance can be used to calculate the glomerular filtration rate and why?
Inulin, because it is freely filtered and is neither reabsorbed nor secreted
Clearance of what endogenous substance approximates glomerular filtration rate?
How is the glomerular filtration rate calculated if inulin is used?
Glomerular filtration rate = the urine concentration of inulin times the urine flow rate divided by the plasma inulin concentration (Uinulin × V/Pinulin)
Creatinine clearance slightly _____ (overestimates/underestimates) the glomerular filtration rate because creatinine is _____ (secreted/reabsorbed) by the renal tubules.
Overestimates; secreted; the plasma concentration of creatinine is slightly lower than it would be from filtration alone
What is the value of normal glomerular filtration rate?
Approximately 100 mL/min
What is the formula for calculating the glomerular filtration rate that relates glomerular capillary and Bowman's space pressures?
Glomerular filtration rate = Kf[(Pgc - Pbs) - (πgc - πbs)]; where Kfis the filtration constant; Pgc is glomerular capillary pressure; Pbs is Bowman's space pressure; πgc is glomerular capillary colloid osmotic pressure; and πbs is Bowman's space colloid osmotic pressure (normally close to a value of 0)