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Flashcards in Pharmacology and Pathophys Deck (21)
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What is the most dangerous adverse effect of amphotericin B?

Nephrotoxicity - decreases GFR and directly toxic to tubular epithelium

results in anemia and electrolyte abnormalities:
- hypokalemia
- hypomagnesemia
due to increase in membrane permeability of distal tubule


Consequences of hypokalemia? ECG findings?

weakness and arrhythmias

- T-wave flattening
- ST-segment depression
- prominent U waves
- premature atrial and ventricular contractions

profound hypokalemia can cause ventricular tachycardia or fibrillation


Pt with bipolar with excessive thirst and frequent urination?

lithium-induced nephrogenic diabetes insipidus

Lithium reduces ability of kidneys to concentrate urine primarily by antagonizing the action of ADH in the collecting tubules and ducts.


Pt undergoing treatment for acute leukemia develops oliguria and crystal obstruction? X-ray findings? Risk factors for precipitation? Treatment?

Uric acid stones
RadioLUCENT (not visible on X-ray)

risk factors: acidic pH, low urine volume, arid climate

Treatment: alkalinization of urine, hydration, allopurinol


Renal artery stenosis results in hyperplasia and hypertrophy of?

Juxtaglomerular cells - modified smooth muscle cells of the afferent arteriole

Juxtaglomerular apparatus:
- Macula densa cells in the distal tubule sense hypoperfusion
- Juxtoglomerular cells synthesize and secrete renin (will undergo hypertrophy and hyperplasia to allow for greater renin production)


Diuretic that increases serum calcium? What part of the loop does it act on?

Thiazide (hydrochlorothiazide)

acts at early distal tubule to block Na+/Cl- symporters and thus inhibit NaCl reaborption, increasing excretion of Na+, Cl-, and H2O


Diuretic that decreases calcium? What part of the loop does it act on?

Loop diuretics (furosemide)

inhibits cotransport system (Na/K/2Cl) of thick ascending limb of loop of Henle
also stimulates PGE release to vasodilate afferent arteriole and increase drug delivery


Pt on IV high dose acyclovir develops high serum creatinine - how prevented?

aggressive IV hydration
(could also slow rate of infusion)

acyclovir nephrotoxicity:
excreted in urine via glom. filtration and tubular secretion
if concentration exceeds solubility, crystallization, crystalluria, renal tubular damage.


What is calcineurin? What agents inhibit calcineurin activation? Primary toxicity?

Calcineurin - protein phosphatase that is activated upon stimulation of appropriate cell receptor that dephosphorylates NFAT (nuclear factor of activated T cells)

NFAT enters nucleus and binds to IL-2 promoter
IL-2 stimulates the growth and differentiation of T cells

Cyclosporine and tacrolimus inhibit calcineurin activation (used as immunosuppressants in transplant)
Both calcineurin inhibitors are highly nephrotoxic!


What diuretics promote the maximum amount of diuresis in the shortest amount of time? Why/mechanism? Side effects?

Loop diuretics
most potent class of diuretics and thus are the agent of choice in acute settings (used for edema in many different settings!)

Bind/inhibit Na/K/2Cl symporters in thick ascending limb of loop of Henle to block Na and Cl resorption to decrease medullary concentration gradient and increase Na, Cl, and H2O excretion.
Normally only a small portion of filtered sodium reaches the distal tubules, so diuretics that work beyond the loop of Henle are not as efficacious.

Common side effects: hypokalemia, hypomagnesemia, hypocalcemia


Pt with CHF complains of breast enlargement? Other drugs in this class?

(competitive aldosterone receptor antagonist in cortical collecting tubule)
structurally similar to steroids - can have antiandrogen effects, gynecomastia

K-sparing diuretics:
- epleronone (also competitive aldosterone receptor antagonist; newer, more selective, may have less endocrine effects)
- triamterene (blocks ENaC Na channel in CCT)
- amiloride (blocks ENaC Na channel in CCT)


What is mannitol, where does it act, and what conditions is it used for? Side effects and contraindications?

osmotic diuretic
primarily works in the proximal tubule and descending limb of the loop of Henle to promote diuresis

Used to reduce intracranial or intraocular pressure (e.g., cerebral edema with increase intracranial pressure); also drug overdose

Side effects: pulmonary edema (!) and dehydration
(pulls fluid from interstitial space into vascular space or tubular lumen - increased blood volume can increase hydrostatic pressure and precipitate pulmonary edema, worsen CHF)

Contraindications: CHF, anuria


79yo pt on digoxin therapy develops visual abnormalities, nausea, anorexia?

Cholinergic toxicities of digoxin - nausea, vomiting, diarrhea, blurry yellow vision (Van Gogh)

Due to age-related decline in renal function and clearance.
Elderly pts exhibit age-related renal insufficiency, even with normal creatinine levels (derived from muscle, which also declines with age)

Digoxin predominantly cleared by kidneys - need reduced dose.


Pt with calcium oxalate stones - best diuretic to prevent recurrent stone formation?

increases calcium reabsorption from the nephron, thus decreasing urine Ca2+ excretion and helping to prevent stone formation


Pt with chronic renal insufficiency gets UTI, treatment with gentamicin, loses hearing -- what diuretic?

Loop diuretic ototoxicity, occurs with:
- higher dosages
- rapid IV administration
- concurrent use with other ototoxic agents (aminoglycosides, salicylates, cisplatin)


Name the toxicities of loop diuretics.

Hypokalemia (also hypocalcemia, hypomagnesemia)
Allergy (sulfa)
Nephritis (interstitial)


What are the side effects of ACE inhibitors? What is their suffix?


Creatinine increase (decreased GFR due to inhibition of efferent arteriole constriction)


What is the drug of choice for mucormycosis? Mechanism? What should be monitored?

Amphotericin B
binds ergosterol in fungal cell membranes to form holes

Notorious for renal toxicity:
severe hypokalemia and hypomagnesemia commonly seen during therapy and often require daily supplementation


What does acetazolamide do? What conditions is it used for? Toxicities?

carbonic anhydrase inhibitor
catalyzes reactions necessary for NaHCO3 reabsorption
CA inhibition blocks NaHCO3 and water reabsorption in the proximal tubules
(self-limited NaHCO3 diuresis and decreases total body HCO3 stores)

Used for:
- glaucoma
- urinary alkalinization
- metabolic alkalosis
- altitude sickness
- pseudotumor cerebri

Side effects:
- hyperchloremic metabolic acidosis (ACIDazolamide)
- paresthesias
- NH3 toxicity
- sulfa allergy


Describe the mechanism of acetazolamide in the treatment of glaucoma.

Relieves intraocular pressure in open-angle and angle-closure glaucoma.

CA is presents in various tissues, including the eyes.
In eye tissues, CA modulates HCO3- formation in the aqueous humor -- inhibition of CA will decrease HCO3- and aqueous humor formation.


What diuretic improves overall survival in heart failure patients?

benefits more likely due to more direct inhibition of aldosterone activity on the heart than to its mild diuretic effect

(Loop diuretics and others can improve symptoms of CHF significantly but have not been shown to improve survival)