Flashcards in Diuretics Deck (89)
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1
PCT
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here
1. responsible for 60-70% of total reabsorption of NA
2. carries out isosmotic reabsorption of AA, glucose & many cations
3. major site for reabsorption of Sodium Chloride& Bicarb
b) NHE3: apical membrane Na/H exchange via NHE3
Na/K ATPase is present in the basolateral membrane to maintain intracellular Na & K
c) Carbonic Anhydrase: bicarbonate is reabsorbed poorly through luminal membrane so it is converted to CO2 & H2O by Carbonic Anhydrase
2
TAL
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here
1. responsible for absorption of 20-30% of Na
2. pumps out Na, K, Cl into interstitium
3. major site for Mg & Ca reabsorption: positive potential in lumen allows Mg2+ and Ca2+ to be reabsorbed via paracellular pathway
b) NKCC2: reabsorption of Na, Cl & K via Na+/K+/2Cl- cotransporter
3
DCT
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here
1. reabsorption of 5-8% of Na
2. actively pumps Na & Cl out of lumen via Na+/Cl- cotransporter NCC
3. Ca also reabsorbed under control of PTH
b) NCC: actively pumps Na & Cl out of lumen (Na+/Cl- cotransporter)
c)
4
CD
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here
1. reabsorption of 2-5% of Na--last tubular site for Na reabsorption
2. controlled by aldosterone, occurs via channels & is accompanied by equal loss of K or H ions
3. primary site of acidification of union & K excretion
4. Cl- reabsorbed via paracellular pathway because of negative lumen potential
b) ENaC: inward diffusion of Na via the epithelial sodium channel ENaC leaves lumen negative potential--> drives reabsorption of Cl- & efflux of K+
5
Carbonic Anhydrase Inhibitors
1. acetazolamide
2. dorzolamide
6
Loop Diuretics
1. Furosemide
2. Bumetanide
3. Torsemide
7
Thiazides
1. Hydrochlorothiazide
8
Potassium Sparing Diuretics
1. aldosterone antagonists: spironolactone & eplerenone
2. Na channel Blockers: amiloride & triamterene
3. ADH antagonists: Lithium & demeclocycline
9
Osmotic Diuretics
Mannitol
10
Acetazolamide
Carbonic Anhydrase inhibitor
11
Where do Carbonic Anhydrase Inhibitors Act
the PCT
12
Acetazolamide MOA & Effects & uses
inhibit CA both in the brush border & intracellular CA in PCT
Effects:
1. Bicarbonate diuresis-->metabolic acidosis results
2. Increased Na is presented to the CCD, where it is absorbed so more K is excreted-->causes significant K loss in urine--> HYPOKALEMIA
3. CA inhibition in ciliary epithelium -->reduced secretion of aqueous humor
Uses:
1. glaucoma
2. urinary alkalinization for acidic drug toxicity
3. tx acute mountain sickness
4. significant metabolic alkalosis
13
drug used in high altitude sickness (mountain sickness)
acetazolamide (CA inhibitor)
acidosis of CSF results in hyperventilation
14
Uses of CA inhibitors
1. glaucoma
2. urinary alkalinization for acidic drug toxicity is salicylates
3. tx acute mountain sickness
4. significant metabolic alkalosis
15
Adverse Effects of Carbonic Anhydrase Inhibitors
1. cross algernicity with other sulfonamides
2. hyperchloremic metabolic acidosis
3. renal stones: alkalization of urine by these drugs may cause Ca to precipitate -->renal stones
4. Hypokalemia
16
How can CA inhibitors be used to treat glaucoma
CA inhibition in the ciliary epithelium -->reduced secretion of aqueous humor
17
Where do Loop Diuretics act?
Thick ascending limb
18
Furosemide
Loop Diuretic
19
Furosemide MOA & Effects & uses & ADR
Loop Diuretic, acts in TAL
1. Inhibits NKCC2 (Na+/K+/2Cl- cotransporter)-->produce massive NaCl diuresis-->Edema fluid is rapidly excreted & blood volume is significantly reduced.
The Loop of Henle is the diluting segment, so blocking its function-->reduced ability to dilute urine
2. also results in loss of lumen positive potential-->decreased reabsorption of ions like Ca & Mg-->Ca excretion is significantly increased
3. More Na is presented to the CD-->it's reabsorbed in exchange for K+ & H+-->hykalemic alkalosis
Uses:
1. Tx of edematous states including HF & ascites
2. *tx of acute pulmonary edema (LVF)
3. mild to moderate CHF
4. severe hypercalcemia
5. seen commonly in malignancy (so we give large doses of furosemide with fluids & electrolytes)
ADR:
1. *Hypokalemia--usually given with K sparing drugs
-------->Hypokalemic metabolic alkalosis
2. Hypomagnesemia
3. Hypocalcemia
4. Hypovolemia
5. *Ototoxicity--> don't combine with other ototoxic drugs i.e. aminoglycosides
6. cross hypersensitivity with sulfa drugs--> i.e. if allergic to sulfa drugs don't use bc may also be allergic
20
Uses of Loop Diuretics
1. Tx of edematous states including HF & ascites
2. *tx of acute pulmonary edema (LVF)
3. mild to moderate CHF
4. severe hypercalcemia
5. seen commonly in malignancy (so we give large doses of furosemide with fluids & electrolytes)
21
ADR of Loop Diuretics
1. *Hypokalemia--usually given with K sparing drugs
-------->Hypokalemic metabolic alkalosis
2. Hypomagnesemia
3. Hypocalcemia
4. Hypovolemia
5. *Ototoxicity--> don't combine with other ototoxic drugs i.e. aminoglycosides
6. cross hypersensitivity with sulfa drugs--> i.e. if allergic to sulfa drugs don't use bc may also be allergic
22
Site of action of Thiazides
Distal Convoluted Tubule
23
Hydrochlorothiazide
MOA
Uses
ADR
Thiazide, acts in Distal convoluted tubule
MOA: inhibits Na/Cl transporter (NCC) in early segment of distal convoluted tubule
Uses:
1. HTN (Mild-moderate essential HTN)
2. Chronic renal calcium stone (bc reduce urine Ca concentration)
ADR:
1. severe hyponatremia
2. hypokalemia
3. cross hypersensitivity w sulfonamides
4. hyperuricemia-->gout
(direct competition of thiazides for rate transport)
5. Hyperlipidemia-->increase serum CH & LDL 5-10%
6. Hyperglycemia due to diminished insulin secretion in patient with preexisting type 2 diabetes
24
Effects of Thiazides
1. sustained Na & Cl Diuresis
reduction in transport of Na into tubular cell reduces intracellular Na -->promotes Na/Ca exchange
------->results in increased reabsorption of Ca from urine -->urine Ca content is decreased
2. Reduces BP
initially decrease CO bc decrease blood volume, but later decrease TPR bc decrease Na concentration & Na is responsible for maintaining vessel stiffness.
25
Uses of Thiazides
1. HTN (Mild-moderate essential HTN)
2. Chronic renal calcium stone (bc reduce urine Ca concentration)
26
Thiazides ADR
1. severe hyponatremia
2. hypokalemia
3. cross hypersensitivity w sulfonamides
4. hyperuricemia-->gout
(direct competition of thiazides for rate transport)
5. Hyperlipidemia-->increase serum CH & LDL 5-10%
6. Hyperglycemia due to diminished insulin secretion in patient with preexisting type 2 diabetes
27
Potassium sparing Diuretics act in the
Collecting Duct
28
Downside of Potassium sparing diuretics & compensation
Weak therefore rarely used alone; Exception = hyperaldosteronism
29
Spironolactone
Aldosterone antagonist; K+ sparing diuretic
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