Flashcards in Diuretics Deck (89):
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
30
Amiloride & Triamterene
K+ Sparing Diuretics that directly block Na channels in CD
31
How do K+ Sparing Diuretics work
Inward diffusion of Na via epithelial sodium channel levels a lumen-negative potential which drives reabsorption of Cl- & efflux of K+
32
Spironolactone MOA, Effects, Uses, ADR
Antagonist of Aldosterone in Collecting Duct
MOA: by binding & blocking the aldosterone receptor-->reduce expression of genes controlling synthesis of epithelial Na ion channels & Na/K ATPase-->this increases sodium excretion bc less Na is being reabsorbed
Effects:
1. increases Na excretion
2. Decreases K+ & H+ ion excretion (bc whenever Na is reabsorbed K is exchanged & excreted
3. may cause hyperkalemic metabolic acidosis
Uses:
1. Hypokalemia causes by loop diuretics & thiazides
2. Aldosteronism (occurs in cirrhosis; also seen in Conn's syndrome & with late HF
ADR:
1. Hyperkalemia-->can cause cardiac arrest
2. Extreme caution needed when given with ACE-inhibitors bc both inhibit aldosterone
3. gynecomastia (painful, enlargement of breast in males) hirsutism (excess body hair growth), loss of libido & impotence
--->all from anti-androgenic effects
33
gynecomastia (painful, enlargement of breast in males) hirsutism (excess body hair growth), loss of libido & impotence
all from anti-androgenic effects of spironolactone
34
Osmotic diuretics work where
PCT (where majority of isosmotic reabsorption occurs)
35
Mannitol
Osmotic diuretic; acts in PCT; given by IV
freely filtered in glomerulus but poorly reabsorbed, so it remains in the lumen
Holds water by virtue of its osmotic effect
36
Mannitol Effects & uses
Effects:
1. urine volume is increased
2. Can decrease intracranial pressure by osmotically extracting water fro tissue into blood
3. similar effect in eye (reduces IOP)
Uses:
1. Cerebral Edema
2. Glaucoma
37
Amiloride
K+ sparing diuretic used in lithium-induced diabetes insidious bc prevents lithium's action on CD (Li acts like & replaces Na)
38
Dorzolamide MOA
inhibition of CA in PCT
39
Urinary Electrolytes in Acetazolamide
Increase Na
Increase K
VERY increased HCO3
40
Urinary Electrolytes in Dorzolamide
Increase Na
Increase K
VERY increased HCO3
41
Blood Chemistry & pH in Acetazolamide
1. hypokalemia
2. acidosis (low pH)
3. Hyperchloremia
42
Blood Chemistry & pH in Dorzolamide
1. hypokalemia
2. acidosis (low pH)
3. Hyperchloremia
43
Ethacrynic acid MOA
Inhibition of Na/K/2Cl cotransporter in TAL
44
Furosemide MOA
Inhibition of Na/K/2Cl cotransporter in TAL
45
Torsemide MOA
Inhibition of Na/K/2Cl cotransporter in TAL
46
Urinary Electrolytes in Ethacrynic acid
1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3
47
Urinary Electrolytes in Furosemide
1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3
48
Urinary Electrolytes in Torsemide
1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3
49
Blood Chemistry & pH in Ethacrynic acid
1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia
50
Blood Chemistry & pH in Furosemide
1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia
51
Blood Chemistry & pH in Torsemide
1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia
52
Hydrochlorthiazide MOA
Inhibition of Na/Cl cotransporter in DCT
53
Indapamide MOA
Inhibition of Na/Cl cotransporter in DCT
54
Metolazone MOA
Inhibition of Na/Cl cotransporter in DCT
55
Thiazides
1. Hydrochlorthiazide
2. Indapamide
3. metolazone
56
Loop Diuretics
1. Furosemide
2. Torsemide
3. Ethacrynic acid
57
K+ sparing Diuretics
1. Amiloride (blocks Na channels in CD)
2. Triamterene (blocks Na channels in CD)
3. Spironolactone (blocks aldosterone receptors in CD)
58
Thiazides Urinary Electrolytes
1. Increased Na, K, Cl
2. Decreased Ca
59
Thiazides Blood Chemistry & pH
1. hypokalemia
2. alkalosis (increased pH)
3. HYPERcalcemia
4. Hyperuricemia
5. Hyper glycemia
60
Loop Diuretics Blood Chemistry & pH
1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia
61
Loop Diuretics Urinary Electrolytes
1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3
62
K+ Sparing Diuretics Urinary Electrolytes
1. Small amounts of Na
2. decreased K
63
K+ Sparing Diuretics Blood Chemistry & pH
1. Hyperkalemia
2. acidosis (decreased pH)
64
Diuretics that result in acidosis (pH)
1. CA inhibitors: acetazolamide & dorzolamide
2. K+ sparing diuretics
65
Diuretics that result in alkalosis (pH)
1. Loop Diuretics
2. Thiazides
66
MOA of Spironolactone
Blocks Aldosterone receptors in CD
67
MOA of triamterene
Blocks Na channels in CD
68
MOA of Amiloride
Blocks Na channels in CD
69
Best Diuretic for edema
Furosemide
70
Best for HTN & as anti-diuretic
Thiazides
71
Best to tx nephrolitiasis with hypocalcemia
thiazides
72
best to treat glaucoma
acetazolamide & mannitol
73
best to treat cerebral edema
mannitol--NEVER USED IN CF
74
Increases risk of HYPERkalemia seen with K sparing diuretics
1. NSAIDS
2. Beta blockers
3. ACE-I
75
Reduces Digoxin toxicity
K sparing diuretics
76
Increases Digoxin toxicity
loop & thiazides
77
reduces efficacy of diuretics by inhibiting secretion into renal tubule
Probenecid
78
DOC in CCF
Thiazide
79
DOC in Hepatic ascites
Thiazides with K+ supplements or
Thiazides with K+ sparing diuretics
80
DOC in Pulmonary Edema of Cardiac origin (LVF)
Loop Diuretics
81
DOC in increased intracranial pressure
osmotic diuretics
82
DOC in renal edema--nephrotic syndrome
Thiazide & K-sparing or
loop & K-sparing
83
DOC in Chronic Renal Failure
Loop Diuretics
84
DOC in acute renal failure
osmotic diuretics
85
Vasopressin & Desmopressin
What?
MOA
Effects
Used to Tx
Antidiuretic Hormone Agonists
MOA:
1. facilitates H20 reabsorption from CD by activation of V2 receptors (Gs)
2. increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption
Effects: reduce urine volume & increase it's concentration
Used: in Neurogenic (pituitary) Diabetes Insipidus
86
DOC in Neurogenic (pituitary) Diabetes Insipidus
Vasopressin or Desmopressin
87
Demeclocycline
ADH Antagonist
MOA:
1. oppose the actions of ADH & other peptides with act on V2 receptors
2. such peptides are secreted by certain tumors (i.e. small cell carcinoma of the lung) and cause significant water retention & hyponatremia
This is syndrome of inappropriate ADH secretion (SIADH)
Remember: V2 receptors act through Gs-->increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption
88
Conivaptan
ADH antagonist
MOA:
1. oppose the actions of ADH & other peptides with act on V2 receptors
2. such peptides are secreted by certain tumors (i.e. small cell carcinoma of the lung) and cause significant water retention & hyponatremia
This is syndrome of inappropriate ADH secretion (SIADH)
Remember: V2 receptors act through Gs-->increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption
89