Kap Pharm Urinary drugs
Terms
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% Na filtered
PCT
TAL
DCT
CT -
PCT>60
TAL<25
DCT<10
CT<4 -
Where do the CA inhibitors work?
Osmotic?
Thiazides?
K sparing?
Loops?
Aldosterone antagonists? -
CA inhibitors - proximal convoluted tubule
Osmotic - proximal convoluted tubule and the thin descending limb and also in the coll. duct
Thiazides - distal convoluted tubule
K sparing - collecting tubule
Loops - Thick ascending limb of Loop
Aldosterone antagonists - collecting duct - What is the main example of a CA inhibitor?
- azolamide
- What are the osmotic diuretic drugs?
- mannitol
- What is the mechanism of osmotic diuretics
- draws water to it anywhere it is in the body and thus can be used to decrease intraocular pressure and intracerebral pressure
- how is mannitol given
- IV
- What are the carbonic anhydrase inhibitors?
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acetazolamide
dorzolamide - How is most sodium reabsorbed in the proximal tubule?
- NA/H pump - where the H protons being pumped out originate from Carbonic anhydrase
- What are the two things that CA inhibitors are giong to effect the absortpion of?
- Na and bicarbinate
- What are the uses of CA inhibitors?
- GLAUCOMA (carbonic anhydraese is in the eye and needed to form aqueous humor), mountain sickness, metabolic alkalosis, elimination of acidic drugs
- What is the target for loop diureteics?
- 2Cl, Na, K cotransporter on the luminal membrane of TAL
- How is Mg and Ca reabsorbed?
- the K buildup in the cells via the Cl, Na, K transporter and the Na/K pump causes some of the K to diffuse across the luminal membrane and create a positive potential across this membrane. This postive potential drives the reabsorption of Mg anc Ca in the spaces between the cells and the Thick ascending limb
- What is the mechanism for a look diuretic?
- in addition to the direct consequence of having more Cl, Na, and K in the urine, the loss of positive potential on the luminal membrane due to K will result in loss of absorption of Mg and Ca also. Thus you will have more Na, Cl, K, Mg, and Ca in the urine
- What are the results of loop diuretics.
- the increase in Na in the collecting duct wil lead to hypokalemia (loss of K) and alkalosis (loss of H)
- What are the loop diuretic drugs?
- furosemide and ethacrynic acid
- how do loop diuretic get into the lumen?
- filtered and secreted in proximal tubule
- What are some nonintuitive adverse effects of loop diuretics?
- hyperuricemia, ototoxicity (ethacrynate>furosemide) especially with aminoglycosides, decreased clearance of lithium
- What is the target for the thiazide diuretics?
- Na/Cl co-transporter on luminal membrane of DCT
- What is the normal ionic physiology of the distal convoluted tubule?
- Normally, na is exchanged for K via a pump on the basolateral membrane, K returns to blood by back-diffusion. Ca diffuses across luminal membrane via channels (PTH regulated) and returns to blood by a Ca/Na antiporter
- What are the adverse effects of thiazide diuretics?
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increased levels of Na and Cl due to inhibition of the cotransporter leads to hypokalemiz and alkalosis due to the Na load downstream
-the lack of intracellular Na increases the activity of the Na/Ca antiporter and thus there is increased reabsorption of Ca and hypercalcemia.
so overall thiazides increase urinary levels of Na, K, and Cl, and decrease levels of Ca - What are the transporters and channels present in the collecting duct?
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Luminal side:
Na Channel
K channel
Na/ (H or K) antiporter
H energy dependent transporter (intercalated cell)
basil side:
Na/K pump
becarb/Cl antiporter (intercalated cell) - What is the mechanism of aldosterone?
- increase formatino of Na channels on luminal membrane (principal cell) and increase antivity of Na/ (k or H) exchangers
- What happens when there is increased Na concentration in the tubular lumen?
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increased intracellular positive charge leads to extrusion of K into the lumen
the Na entry increases energy dependent extrusion of H across luminal membranes (intercalated cell) - What are the ionic changes in the urine due to a K sparing diuretic?
- small increase in urinary Na but marked decrease in urinary K and H (hyperkalemia and acidosis)
- What are the K sparing agents (weak diuretics)?
- spironolactone, amiloride, and triamterene
- What is the mechanism of spironolactone?
- aldosterone receptor antagonist
- What is the mechanism of amiloride and triamterene
- Na channel blockers
- What is an unusual use of spironolactone?
- reduces hirsutism in women due to androgen clocking effect
- what are the main uses of K sparing diuretics?
- adjunctive with other diuretics to decrease K loss
- what are the negative side effects of the K sparing agents?
- spironolactone - gynecomastia
- What are the antihyperlipidemic drugs?
- bile acid sequestrants, HMG--CoA inhibitors ("statins"), niacin, and gemfibrozil
- What are the bile acid sequestrants?
- cholestyramine and colestipol
- What is the mechanism of cholestyramine and colestipol
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complex bile salts preventing reabsorption from GI tract, thus decreasing feedback inhibition of 7-alpha hydroxylase and increasing synthesis of bile salts from cholesterol
the decreased liver cholesterol leads to increased LDL receptors and decreased plasma LDL - When are the bile acid sequestrants not used?
- hypertriglyceridemias since they encrease VLDLs and TGs
- What are the HMG-CoA reductase inhibitors?
- Lovastatin and other "statins"
- What is the mechanism of the statins?
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inhibit the rate limiting step in cholesterol synthesis and thus decrease liver cholesterol, and thus increase LDL receptors, decrease plasma LDL and decrease synthesis of VLDL and apoproteinB
they cause a small increase in HDL and a decrease in TGs
they also release NO (vasodilate) and decrease synthesis of ET-1 (potent vasoconstrictor) - What are the adverse effects of the statins?
- diarrhea, myalgia, rhabdomyolysis (especialy with other antihyperlipidia drugs),
- What are the effects of niacin?
- inhibit synthesis of VLDL and apoprotein in hepatocytes, thus decreaseing VLDL, LDL, Tgs and increaseing HDL
- What is the main adverse effect of nicotinic acid (niacin)?
- flushing and pruritis
- What drug activates lipoprotein lipases?
- gemfibrozil
- What are the thiazide drugs?
- hydrochlorothiazide, indapamide, metolazone