Pharmacology Flashcards
What is the site of action of mannitol?
proximal tubule
What is the mechanism of mannitol?
Osmotic diuretic. Incr tubular fluid osmolarity, Incr urine flow.
What are the clinical uses of mannitol?
Drug overdose, elevated intracranial/intraocular
pressure.
What are the side effects of mannitol?
Pulmonary edema, dehydration.
Contraindicated in anuria, HF.
What is the site of action of acetazolamine?
Proximal tubule
What is the mechanism of action of acetazolamide?
Carbonic anhydrase inhibitor. Causes self-limited NaHCO3
diuresis and decreases total body bicarb stores.
What are the clinical uses of acetazolamide?
Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor
cerebri.
What are the side effects of acetazolamide?
Hyperchloremic metabolic acidosis,
paresthesias, NH3
toxicity, sulfa allergy.
What class of drugs are bumetanide and torsemide?
Loop diuretics
What is the mechanism of action of loop diuretics?
- Inhibit cotransport
system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle. 2. Abolish hypertonicity of
medulla, preventing concentration of urine. - Stimulate PGE release (vasodilatory effect
on afferent arteriole); inhibited by NSAIDs.
4. Increase Ca 2+ excretion. Loops Lose Ca2+.
What are the clinical uses of loop diuretics?
Edematous states (HF, cirrhosis, nephrotic
syndrome, pulmonary edema), hypertension,
hypercalcemia.
What are the side effects of loop diuretics?
Ototoxicity, Hypokalemia, Dehydration, Allergy
(sulfa), Nephritis (interstitial), Gout.
(OH DANG!)
What is the site of action of ethacrynic acid?
thick ascending loop
What is the mechanism of action of ethacrynic acid?
Phenoxyacetic acid derivative (not a
sulfonamide). Essentially same action as
furosemide.
What is the clinical use of ethacrynic acid?
Diuresis in patients allergic to sulfa drugs.
What are the side effects of loop diuretics?
Similar to furosemide; can cause
hyperuricemia; never use to treat gout.
What class of drug is chlorthalidone?
Thiazide diuretic
What class of drug is hydrochlorothiazide?
Thiazide diuretic
What is the site of action of thiazide diuretics?
DCT
What is the mechanism of action of thiazide diuretics?
Inhibit NaCl reabsorption in early DCT
, decr diluting capacity of nephron. Incr Ca
2+ excretion.
What is the clinical use of thiazide diuretics?
Hypertension, HF, idiopathic hypercalciuria,
nephrogenic diabetes insipidus, osteoporosis.
What are the side effects of thiazide diuretics?
Hypokalemic metabolic alkalosis,
hyponatremia, hyperGlycemia,
hyperLipidemia, hyperUricemia,
hyperCalcemia. Sulfa allergy.
(hyperGLUC)
What is the side of action of K+ sparing diuretics?
collecting duct
What is the mechanism of action of spironolactone and eplerenone?
Spironolactone and eplerenone are competitive
aldosterone receptor antagonists in cortical
collecting tubule.
What is the mechanism of action of triamterene and amiloride?
Triamterene and amiloride
act by blocking
Na+ channels in the cortical collecting tubule (ENaC).
What are the clinical uses for K+ sparing diuretics?
Hyperaldosteronism, K+ depletion, HF.
What are the side effects of K+ sparing diuretics?
Hyperkalemia (can lead to arrhythmias),
endocrine effects with spironolactone (e.g.,
gynecomastia, antiandrogen effects).
Which diuretics increase urine sodium? (possibly causing hyponatremia)
All diuretics except acetazolamide.
Which diuretics increase urine K+? (possibly causing hypokalemia). Why?
Loop diuretics, thiazide diuretics.
Increased distal sodium delivery, where sodium reabsorption is exchanged from K+ excretion
What is the effect of carbonic anhydrase inhibitors on blood pH?
Acidemia. Decreases bicarb reabsorption in the PCT.
What is the effect of loop diuretics on blood pH? How does this occur?
Alkalemia.
1) volume contraction –> AT2 –> Greater Na+/H+ exchange in PCT, greater bicarb reabsorption.
2) K+ loss leads to K+ exiting all cells (via H+/K+ exchanger), driving H+ into cells and out of blood
3) In low K+ state, H+ rather than K+ is exchanged for Na+ in cortical collecting tubule –> alkalosis with paradoxical aciduria
What is the effect of K+ sparing diuretics on blood pH?
Acidemia.
Aldo blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells (via K+/H+ exchanger) in exchange for H+ leaving
What is the effect of thiazide diuretics on blood pH?
Alkalemia. Same mechanism as loop diuretics; Contraction alkalosis, K+ loss leading to K+ cell exit/H+ cell entry, and low K+ state leading to H+ exchange instead of K+ in collecting tubule.
What is the effect of loop diuretics on Ca2+ ?
Increase urine Ca2+, due to decreased paracellular transport (hypocalcemia)
What is the effect of thiazide diuretics on Ca2+?
Enhanced Ca2+ absorption in DCT –> hypercalcemia.
What is the mechanism of ACEis?
Inhibit ACE , Decr AT II , decr GFR by preventing
constriction of efferent arterioles. Levels
of renin incr as a result of loss of feedback
inhibition. Inhibition of ACE also prevents
inactivation of bradykinin, a potent vasodilator.
What is the clinical use of ACEis?
Hypertension, HF, proteinuria, diabetic
nephropathy. Prevent unfavorable heart
remodeling as a result of chronic hypertension.
Why are ACEis used for slowing the progression of diabetic nephropathy?
Decr intraglomerular
pressure slows GBM thickening.
Toxicity of ACEis?
Cough, Angioedema (contraindicated in C1
esterase inhibitor deficiency), Teratogen (fetal
renal malformations), Incr Creatinine (decr GFR),
Hyperkalemia, and Hypotension. Avoid in
bilateral renal artery stenosis, because ACE
inhibitors will further decr GFR –> renal failure.
What is the mechanism of ARBs?
Selectively block binding of angiotensin II to AT1
receptor. Effects similar to ACE inhibitors, but
ARBs do not increase bradykinin.
What is the clinical use of ARBs?
Hypertension, HF, proteinuria, or diabetic nephropathy with intolerance to ACE inhibitors (e.g.,
cough, angioedema).
What are the toxicities of ARBs?
Hyperkalemia, renal function, hypotension; teratogen.
What is the mechanism of aliskiren?
Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I.
What are the clinical uses of aliskiren?
HTN
What are the toxicities of aliskiren?
Hyperkalemia, renal function, hypotension. Contraindicated in diabetics taking ACE inhibitors
or ARBs.
