Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

12. Pharmacology > Diuretics > Flashcards

Diuretics Flashcards

1
Q

Typical features of excessive diuresis on the metabolic/electrolyte profile include __________

A

o ↓K+
o ↓Na+
o ↓Cl-
o ↓Mg2+
o Metabolic alkalosis (↓H+)
o Hypovolemia → prerenal azotemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What is meant by the term progressive nephron blockade

A
  • Different tubular site of action → additive effect
    o Thiazides
    o Loop diuretics
    o K+ sparing agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are potential complications of high-dose diuresis in the animal with CHF

A
  • ↓ intravascular volume and ventricular filling → ↓ CO → ↓ tissue perfusion
    o ↑ activation of RAAS and ∑ nervous system
  • More common with diuretic combination → synergy (loop + thiazide diuretic)

o Metabolic alkalosis (↓H+)
o Hypovolemia → prerenal azotemia
Electrolytes derangements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How are the mechanisms leading to diuretic resistance

A
  • Late or as early as after 1 dose
  • Mechanism:
    o Repetitive diuretic administration → ↓ intravascular volume → ↓ renal blood flow → RAAS stimulation → ↑ reabsorption of Na+ in other part of tubular system
     Hypertrophy of distal nephron  from aldosterone induced growth
     ↓ Na+ diuresis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Goals of diuretics

A

alter physiologic renal mechanism
* ↑ urine flow and Na+ excretion
o ↑ renal plasma flow → usually CI in CHF since ↑ venous pressures
o Alter nephron function → ion transport
* In CHF: control pulmonary/peripheral symptoms and signs of congestion
o Rarely used with non congested HF → induce renin activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Diuretics should always be combined to what type of drugs

A

ACEi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Loop diuretics

A

Furosemide
Torsemide
Bumetanide
Ethacrynic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Furosemide: molecule

A

Sulfonamide derivative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Furosemide: MOA

A

o Inhibit Na+/K+/2Cl- cotransporter in ascending loop of Henle
 Can ↑ Na+ fractional excretion up to 23% of filtered load

o Venodilation: ↓ preload w/I 5-15min
 Can help dyspnea prior to diuresis action
 Reactive vasoconstriction may follow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Furosemide: site of action

A

intraluminal
 Drug excreted by proximal tubule
 Inhibition of Cl, Na, K and H+ transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Furosemide: pharmacoK/D

A

o Oral absorption: 10-100%, average 50%
o Short action duration: 4-5h → frequent doses needed for sustained diuresis
o > earlier absolute Na+ loss (vs thiazide)
 24h Na+ loss is ↓
o Highly protein bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Furosemide: dosage

A

o ↑ if impaired renal function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Furosemide: indications

A

o Diuretic of choice for severe CHF or acute edema 3 reasons
 ↑ fluid clearance for similar natriuresis (compared to thiazides)
 Work despite renal impairment
 ↑ dose → ↑ diuretic response
* High ceiling diuretics
o After initial IV doses → PO is continued for standard diuretic tx
 Usually twice daily low doses
o Effect limited with ↓CO → ↓ renal perfusion → ↓ delivery of furosemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Furosemide: contra indications

A

o CHF w/o fluid retention
 ↑ aldosterone levels
 ↓ LV function
o Anuria → exclude dehydration and hypersensitivity to furosemide/sulfonamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Furosemide: side effects

A

o HypoK+
 Depend on doses and degree of diuresis
 Electrolyte monitoring necessary with IV furosemide
 ↑ risk with high doses

o Hypovolemia and hyperuricemia
 Risk of prerenal azoetmia
 ↓ risk with lower doses

o Hyperosmolar nonketotic hyperglycemic state
o Photosensitive skin eruptions
o Blood dyscrasias
o Ototoxicity: dose related
 Electrolyte disturbance of endolymphatic system
 Avoided with oral doses <1000mg/day
o Excreted in milk (nursing mothers)
o ↑ risk of gout

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Furosemide: diuretic resistance

A

o Braking: ↓ diuretic response after 1st dose
 RAAS activation → restore diuretic loss of blood volume
o Long term tolerance: ↑ Na+ reabsorption from distal nephron hypertrophy
 ↑ aldosterone → ↑ growth of nephron cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Furosemide: drug interaction

A

o Aminoglycosides → ototoxicity
o Probenecid (uric acid reducer) → block secretion of diuretic into urine in proximal tubule
o NSAIDs → ↓ renal response
 Interfere with formation of vasodilatory PGE
o Salicylate (aspirin) → excretion inhibited by furosemide
 Predispose to salicylate poisoning
o Steroids → predidspose to hypoK+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hyperosmolar nonketotic hyperglycemic state

A

 Reported in Hu
 Related to total body K+ depletion
* Transient postprandial ↓ K+ → impairs effect of insulin →intermittent hyperglycemia
 Can precipitate diabetes
* ↓ hypoK+ should ↓ risk of glucose tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Bumetanide: effect/site of action

A

Similar to furosemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Bumetanide: dose

A

o Higher dose can cause significant electrolyte disturbances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Bumetanide: pharmocoK/D

A

o Oral absorption: 80% or ↑
o 10-50x more potent vs furo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Bumetanide: side effects

A

o Similar to furosemide
 ↓ ototoxicity
 ↑ renal toxicity
* Avoid combination with other nephrotoxic drug (ie aminoglycosides)
* Renal failure: reported myalgia in Hu

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Torsemide: dose/pharmacoK/D

A

longer duration of action
o IV dose: onset 10min, peak 1h
o PO dose: onset 1h, peak 1-2h, duration 6-8h
 Absorption: 80-100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Torsemide: side effect and CI

A

similar to furosemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Ethacrynic acid: molecule
non-sulfonamide diuretic o Used in patients with sulfonamide sensitivity
25
Ethacrynic acid: dose/pharmaco/side effects
* Similar to furosemide for dose, duration, side effects but ↑ ototoxicity
26
Thiazide diuretics
Hydrochlorothiazide/Chlorothiazide/Bendrofluazide/Hydroflumethiazide
27
Thiazide diuretics: use
Combination with loop diuretics for chronic CHF
28
Thiazide diuretics: major difference vs loop diuretics
o Longer duration of action o Different site of action o Low ceiling diuretics → max response at low dosage o ↓ capacity to work with renal failure
29
Thiazide diuretics: MOA
o Inhibit Na+/Cl- co-transporter in distal part of nephron  ↑ Na+ excretion by 1-8% of filtered load  ↑Na+ and Cl- reaching distal tubule → stimulate H+ and K+ secretion * Especially with activated RAAS  ↑ active excretion of K+ o Block nephron site where hypertrophy occurs from loop diuretic  Synergetic combination  Long term diuretic therapy
30
Thiazide diuretics: dose
PO: onset 1-2h, last 16-24h
31
Thiazide diuretics: indications
o Hypertension: low dose diuretic used as initial agent  Lower doses → ↓ biochemical alterations → full antihypertensive  Variable response rate: depend on age, race, Na+ intake o Congestive heart failure: higher doses necessary
32
Thiazide diuretics: contra indications
o HypoK+ → may precipitate arrhythmias o Ventricular arrhythmias o Co-therapy with pro-arrhythmic drug o Pregnancy: can cross placental barrier → neonatal jaundice o Renal dysfunction  Can be exacerbated by thiazides  Thiazides are ineffective when GFR <30ml/min
33
Thiazide diuretics: side effects
rare o Sulfonamide-type immune side effects  Intrahepatic jaundice  Pancreatitis  Blood dyscrasia  Angiitis  Pneumonitis  Interstitial nephritis  Photosensitive dermatitis o Metabolic side effects: similar to loop diuretics and dose dependent  HypoK+ → can combine with K+ retaining agents (ACEi, ARBs, aldosterone blockers) * Ventricular arrhythmias * Avoid hypoK+: o K+ sparing diuretic o K+ supplementation: do not correct hypo Mg2+  HypoMg2+ → can provoke arrhythmias with QT prolongation  HypoNa+  Diabetogenic effects  ↓ urate excretion → ↑ risk of gout  HyperCa2+ → ↑ proximal tubular reabsorption
34
Thiazide diuretics: drug interactions
o Steroids → Na+ retention  Antagonize effects of thiazides o NSAIDs → blunt response o Antiarrhythmics prolonging QT interval (class Ia or III)  Precipitate Torsade de Pointes if hypoK+
35
Thiazide-like agents: molecule
Different structure * Chlorthalidone * Indapamide * Metolazone o Efficacy despite ↓ renal function
36
K+ sparing diuretics
Amiloride and triamterene Spironolactone and Eplerenone Angiotensin Converting Enzyme inhibitor and Aldosterone Receptor blockers
37
K+ sparing agents: effect on arrhythmias
* ↓ incidence of ventricular arrhythmias
38
Risk K+ sparing agents
hyperK+: o ↑ if  Preexisting renal dz  Diabetes  concurrent administration of nephrotoxic agent o Mechanism:  Prolonged solute driven water loss  Diuretic driven angiotensin aldosterone activation  Negative effect of diuretic on nephron fct
39
Amiloride and triamterene: potency
* Weak diuretics alone
40
Amiloride and triamterene: MOA
o ↓ Na+ reabsorption in distal and collecting tubules  Indirectly ↓ K+ loss o Amiloride: act on renal epithelial Na+ channel o Triamterene: inhibits Na+/H+ exchanger
41
Amiloride and triamterene: advantages
o Na+ loss w/o major K+ or Mg2+ loss  Amiloride also help retain Mg2+ o K+ retention independent of aldosterone
42
Amiloride and triamterene: side effects
o HyperK+ = contra-indication o Acidosis
43
Spironolactone: MOA
inhibit action of aldosterone in distal tubule cell o Aldosterone blockers  Block mineralocorticoid R binding aldosterone, cortisol and deoxycorticosterone  K+ sparing
44
Eplerenone: MOA
inhibit action of aldosterone in distal tubule cell o Eplerenone: more specific blocker of mineralocorticoid R  Avoid gynecomastia and sexual dysfct in 10% of patients with spiro
45
Effect of Spironolactone and Eplerenone
* Mild diuretic effect since [aldosterone] is normally low o Probably more effective in CHF when [aldosterone] ↑
46
Spironolactone and Eplerenone: pharmaco, structure, site of action
Rapidly metabolized in active product = canrenone o Structure similar to aldosterone → competitive binding on distal tubule site
47
Spironolactone and Eplerenone: Advantage
no reflex sympathetic activation
48
Angiotensin Converting Enzyme inhibitor and Aldosterone Receptor blockers: diuretic effect
* Anti aldosterone effect → mild K+ sparing diuretics
49
Aquaretics: MOA
AVP-2 R antagonists in kidneys (aquaporin-2) in renal collecting ducts o Promote solute free water clearance  ↑ urine volume and ↓ osmolality  ↑ serum Na+ o Chronic CHF: associated w ↑ plasma [vasopressin]  Fluid retention and hypoNa+  Arginine Vasopressin (AVP) act on * V1 R → regulate vascular tone * V2 R → regulate fluid retention
50
Aquaretics: drugs
vaptans o Tolvaptan o Conivaptan o Satavaptan o Lixivaptan
51
Minor diuretics
Carbonic anhydrase inhibitors Ca2+ channel blockers Dopamine A1-adenosine receptor antagonists
52
Carbonic anhydrase inhibitors: drug
* Acetazolamide * Weak diuretics
53
Carbonic anhydrase inhibitors: MOA
↓ H+ secretion in proximal renal tubule o ↑ loss of bicarbonate → ↑ loss of Na+
54
Ca2+ channel blockers: effect
* Mild direct diuretics
55
Dopamine: effect and MOA
* Direct and indirect diuretic action * Mechanism: only if fluid retention o Dopamine stimulates agonists receptors on renal tubular  → opposes aldosterone effects
56
A1-adenosine receptor antagonists: effect and MOA
* ↑ urine flow and natriuresis * Mechanism: o Dilation of afferent arteriole → ↑ GFR o ↑ response to loop diuretics
57
Prevention of excessive diuresis/complications
* ↓ dosage * Dietary changes o K+ supplementation  Co administration of Cl- required to fully correct K+ in hypoK+ hypoCl- alkalosis * KCl: slow release tablets can cause GI ulcerations, not liquid formula o Na+ restriction
58
Causes of diuretic resistance
o Inadequate dose o Nonadherence: not taking drug, high Na+ intake o PharmacoK factors  Gut edema: slow absorption  Impaired secretion in tubule lumen: CKD, age, drugs (NSAID, probenecid) o Hypoproteinemia o Hypotension o Nephrotic syndrome o Antinatriuretic drugs: NSAID, antihypertensives o ↓ renal blood flow o Nephron remodelling o Neurohormonal activation
59
What are the benefits of IV furosemide over those of oral furosemide (at least 3)
* Anti-inflammatory * Venodilation * Transient bronchodilator effect * Fast acting: onset 5min, peak 20-30min, ½ life 15min, duration 2h o PO: onset 30-60min, peak 1-2h, duration 6h * ↓ bioavailability of PO → ↓GI absorption (especially with edema) * ↓ stress during administration in dyspneic dogs
60
Why might torsemide be preferable to furosemide?
* More potent drug * Longer duration of action: longer ½ life * ↑ bioavailability * Likely achieve greater diuresis vs furosemide * Decreased susceptibility to diuretic resistance * Adjunctive aldosterone antagonist properties

12. Pharmacology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions