(THER) Diuretics Flashcards
(81 cards)
1
Q
What does it mean when we say a drug is natriuretic?
A
It increases Na+ excretion
2
Q
SIte of action for Acetazolamide (and other Carbonic Anhydrase inhibitors)
A
PCT
3
Q
Site of action for Mannitol (and other osmotic diuretics)
A
PCT, as well as thin descending limb and CT [in presence of ADH])
4
Q
Site of action for Furosemide (and others in its class)
A
Thick ascending limb of the loop of Henle
(They are known as loop diuretics)
5
Q
Site of action for the Thiazides
A
DCT
6
Q
Site of action for the K+-sparing diuretics
A
CT
7
Q
Site of action for ADH antagonists
A
The CT
8
Q
The primary therapeutic goal of diuretic use is to ________ _________
A
Reduce Edema
9
Q
Except for __________ and some __________ diuretics generally exert their effects from the _________ side of the nephron.
A
Spironolactone; ADH antagonists; luminal
10
Q
How does mannitol get into the tubule fluid as compared to most of the other diuretics?
A
Mannitol: via filtration at the glomerulus
Others: via secretionacross the proximal tubule
11
Q
How does carbonic anydrase inhibition cause diuresis?
A
By blocking the function of carbonic anhydrase, you decrease HCO3- reabsorption and therefore increase the amount which makes it to the distal nephron. Na+ is the most abundunt cation present in proximal tubule fluid and thus accompanies HCO3-. At the distal tubule, Na+ is reabsorbed but bicarb holds the water in the tube and you pee it out.
12
Q
Name the carbonic anhydrase inhibitors (4)
A
- Methazolamide
- Acetazolamide
- Dichlorphenamide
- Dorzolamide
Princess is MADD about CA (california)
13
Q
Name the osmotic diuretic (1)
A
Mannitol
14
Q
Name the Loop Diuretics (4)
A
- Furosemide
- Bumetanide
- Torsemide
- Ethacrynic acid
15
Q
Name the Thiazides (5)
A
- Metolazone
- Indapamide
Chlorthalidone
- Hydrochlorothiazide
- Chlorothiazide
MI CHC (chick) has nice Thiaz (thighs)
16
Q
Potassium-sparing Diuretics (4)
A
- Amiloride
- Triamterene
- Eplerenone
- Spironolactone
I took a SEAT on my potASSium
17
Q
Name the ADH antagonists (5)
A
- Demeclocyline
- Lithium
- Tolvaptan
- Conivaptan
- Mozavaptan
18
Q
MOA of Carbonic Anhydrase Inhibitors
A
Inhibit CA in luminal membrane of proximal tubule, reducing proximal HCO3-reabsorption.
19
Q
MOA of the Osmotic Diuretics
A
Act primarily on the proximal tubule to reduce the reabsorption of H2O and solutes including NaCl
20
Q
MOA of the Loop Diuretics
A
Inhibit the Na+/ K+/ 2Cl- cotransport system in the thick ascending limb of Henle’s loop (ALH)
21
Q
MOA of the Thiazides
A
Inhibit NaCl cotransport in early distal convoluted tubule (DCT).
22
Q
MOA of the K+-sparing diuretics (2)
A
- Spironolactone & eplerenone competitively block the actions of aldosterone on the collecting tubules.
- Amiloride and triamterene reduce Na+ entry across the luminal membrane of the principal cells of the collecting tubules.
23
Q
MOA of ADH Antagonists
A
Prevent ADH induced water reabsorption in the principal cells of the collecting tubule.
24
Q
Main indications for use of Carbonic Anhydrase (3)
A
- To reduce intraocular pressure in glaucoma.
- To lower [HCO3-]p in “mountain sickness”.
- To raise urine pH in cystinuria.
25
What are some other uses for CA Inhibitors other than their main indications? (3)
1. Hypokalemic periodic paralysis.\*
2. Adjunctive therapy in epilepsy.
3. Solid hypoxic tumors?
**PET**
26
Main indications for Osmotic diuretics
1. To treat or prevent Acute Renal Failure (ARF).
27
What are some other uses for Osmotic Diuretics other than its main one? (2)
1. To reduce intra-cranial or intra-ocular pressure.
2. To enhance urinary excretion of chemical toxins.
28
Main Indications for Loop Diuretics (4)
1. Acute Pulmonary Edema.
2. Hypertension.
3. Congestive heart failure (CHF)—in the presence of renal insufficiency or for immediate effect).
4. ARF, CRF, ascites, and nephrotic syndrome
29
Other use for loop diuretics other than main indication
Hyercalcemia
30
Main indications for thiazides (3)
1. Hypertension.
2. Edema due to CHF, hepatic cirrhosis, renal disease.
3. Idiopathic Hypercalciuria (renal calculi).
31
What is another use for thiazides other than the main indication?
Nephrogenic Diabetes Insipidus (prevent further urine dilution from taking place in the DCT).
32
Main Indications of K+-Sparing Diuretics (2)
1. Chronic liver disease: to treat secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites (spironolactone, eplerenone).
2. To prevent the hypokalemic effects of other diuretics.
33
Name alternative uses for K+-sparing diuretics. Which specific drugs are involved?
Primary hyperaldosteronism (Conn's syndrome)— spironolactone, eplerenone.
34
Main Indications for ADH Antagonists (2)
1. SIADH
2. Euvolemic or hypervolemic hyponatremia
35
Name alternative use for ADH antagonist
CHF
36
AE of CA Inhibitors (3 main ones)
1. Metabolic acidosis (due to HCO3- depletion with prolonged treatment)
2. Hypokalemia (acute effect)
3. Drowsiness, fatigue, CNS depression, and paresthesia.
37
AE of Osmotic Diuretics (4)
1. Acute expansion of ECF volume and increased risk of pulmonary edema
2. Hhyponatremia (with impaired renal function)
3. Hypernatremia (prolonged use with normal GFR).
4. Nausea and vomiting; headache.
38
AE of Loop Diuretics (4 general ones)
1. Hypokalemia hypomagnesemia; hyponatremia; **hypovolemia**
2. Hyperuricemia\*
3. Metabolic alkalosis
4. Ototoxicity and diarrhea (mainly with ethacrynic acid)
39
AE of Thiazides (6)
1. Hypokalemia; hyponatremia; hypovolemia;
2. Hyperuricemia due to enhanced urate reabsorption\* and hypercalcemia due to enhanced Ca2+ reabsorption
3. Metabolic alkalosis
4. Hyperglycemia (insulin resistance); hyperlipidemia.
5. Hypersensitivity (fever, rash, purpura, anaphylaxis);
6. Interstitial nephritis
40
AE of K+-sparing diuretics (Spironlactone?Amiloride?Triamterene?)
* **_Spironolactone_**: **hyperkalemia**, gynecomastia, hirsutism; menstrual irregularities; testicular atrophy (with prolonged use).
* _Amiloride_: **hyperkalemia**, glucose intolerance in diabetic pts.
* **_Triamterene_**: **hyperkalemia**; megaloblastic anemia in pts with liver cirrhosis.
**HYPERKALEMIA**
41
AE of ADH Antagonists (which drugs have which effects?)
* _Lithium, doxycycline_: nephrotoxic
* _Tolvaptan, conivaptan, mozavaptan_: hypernatremia, thirst, dry mouth, hypotension, dizziness
42
ACE inhibitors interact with which diuretics? What can occur as a result?
**K+-sparing diuretics**
Increaed hyperkalemia and resultant cardiac arrhythmias
43
Aminoglycosides interact with which diuretics? What can occur as a result?
**Loop diuretics**
Ototoxicity and nephrotoxicity
44
Anticoagulants interact with which diuretics? What can occur as a result?
**Thiazide and Loop diuretics**
Increased anti-coagulant activity with _loop_
Decreased anti-coagulant activity with _thiazide_
45
B-blockers interact with which diuretics? What can occur as a result?
**Thiazide and Loop Diuretics**
Hyper- glycemia, lipidemia, uricemia
Increased plasma levels of propanolol
46
Carbamazepine/ chloropropamide interact with which diuretics? What can occur as a result?
**Thiazide diuretics**
Increased risk of hyponatremia
47
Digoxin interacts with which diuretics? What can occur as a result?
**Thiazide and Loop diuretics**
Hyopokalemia and increaed digoxin binding/toxicity
48
NSAIDs interact with which diuretics? What can occur as a result?
**Thiazide and Loop Diuretics/ K+ sparing diuretics**
Reduced diuretic effect. Increaed risk of salicylate toxicity with high doses of salicylates (_thiazide/ loop d.)_
Increased risk of hyperkalemia (_K+ sparing d._)
49
Quinidine interacts with which diuretics? What can occur as a result?
**Loop and thiazide d.**
Polymorphic V. Tach (torsade de pointes)
50
Sulfonylureas interact with which diuretics? What can occur as a result?
**Loop diuretics**
Hyperglycemia
51
Steroids interact with which diuretics? What can occur as a result?
**Thiazide and Loop d.**
Increased risk of hypokalemia
52
Contraindication for acetazolamide
**Cirrhosis** (increased urine pH reduces NH3 secretion and thereby increases serum NH3)
53
What are the difference in the (4) CA Inhibitors
* **Dichlorphenamide**: about 30x more potent than **acetazolamide**
* **Methazolamide**: about 5x more potent than acetazolamide
* **Dorzolamide**: topical preparation for ocular use (no systemic effects)
54
Mannitol route
IV
55
Contraindications for Mannitol
1. CHF
2. Renal failure
3. Pulmonary edema
56
How does K+ in the lumen of the nephron affect diffusion of other positvely charged ions?
The positive charge repels the Ca2+ and Mg2+, increasing their paracellular diffusion and reabsorption.
57
What is the most efficacious diuretic class?
**Loop diuretics**
They can cause excretion of up to 20% of the filitered Na+
58
Which diuretics are the only ones which cause vasodilation?
Loop diuretics
59
Which diuretic is the only one to cause otoxicity?
Loop diuretics
| (furosemide)
60
Key points about Bumetanide
**Loop diuretic**
–About 40X more potent than furosemide
–Shorter half-life than furosemide: ~ 1 hr
–50% metabolized by the liver
61
Key points about torsemide
**Loop diuretic**
–Longer half-life than furosemide: ~ 3 hrs
–Longer duration of action, too: ~ 5-6 hrs
–Better oral absorption than furosemide
–80% metabolized by the liver
62
Key points about ethacrynic acid
**Loop Diuretic**
–_Last resort_; used only when others exhibit hypersensitivity
–No CA inhibition
–Nephrotoxic and ototoxic
63
What AE are unique to thiazides?
Hyperglycemia and hyperlipidemia
64
How do thiazides prevent kidney stones?
By reducing ca2+ excretion
65
What is the most efficacious thiazide? It is the only one used if pt has ________ \_\_\_\_\_\_\_\_\_
Metolazone. Only one used if pt has renal insufficiency.
66
How is _Amiloride_ secreted into the nephron?
Via the organic base transporter
67
Difference between _amiloride_ and _triamterene_
_Triamterene_ is 10x less potent than amiloride and has a shorter half-life
68
Which ADH antagonists affect which vasopressin receptors?
_V2 receptor antagonists_: tolvaptan, mozavaptan, and lixivaptan
_V1a and V2 receptor antagonist: conivaptan_
69
Combination of what (2) diuretics will cause a powerful urination of Na+ (and as such can be a powerful diuresis)?
Loop and thiazides
70
Edema associated with hepatic cirrhosis is resistant to what type of diuretics? Which are effective?
Resistant to loop
Spironolactone is effective
71
Why is spironolactone abetter option for CHF than thiazide or loop diuretics?
You risk hypokalemia with these, but do not have that with spironolactone.
72
What diuretics are indicated in right heart failure (chronic)?
Oral loop diuretics
73
What diuretics are indicated in left heart failure (acute)?
This is a life-threatening situation and _IV loop diuretics are indicated_
74
Which ADH inhibitor has signficant efficacy in acute heart failure symptoms?
Tolvaptan
75
Why is Tolvaptan particularly useful for issues of hyponaturemia, in comparison to furosemide?
It is tremendously **sodium sparing**
76
For pts with signficant hypertension who are prescribed multiple drugs, which diuretic will almost always be one of them?
Thiazide diuretic
77
In what ay are thiazides useful for patients with calcium oxalate stones (kidney stones)?
Thiazide diuretics can decrease calcium concentrations in the urine by promiting calcium reabsorption in the distal convoluted tubule.
78
Which diuretic can be used in cases of hypercalcemia? Which should be avoided?
**Loop diuretics** may be used with hydration to increase calcium excretion.
_Thiazides_ ought to be avoided, as they increae clacium reabsorption
79
What are some causes for Diuretic resistance?
1. NSAID co-administration
2. CHF
3. Nephrotic syndrome
4. Hepatic cirrhosis/ renal failure
5. Therapeutic sta
80
For what patients do you use combined Loop + Thiazide Diuretics? What issues can you run into with this combination?
Only in patients refractory to one or the other. May be to robust and lead to K+ wasting.
81
What is the benefit of combined K+ sparing + loop or thiazide diuretics? (2)
Prevents hypokalemia
Allows you to avoid renal insufficiency
