Exam I - Diuretics Flashcards
Drug List
Carbonic Anhydrase Inhibs
Acetazolamide
Drug List
Osmotic Diuretics
Mannitol
Drug List
Loop Diuretics
Furosemide
inhibit TAL Na/K/2Cl
Drug List
Thiazides
Hydrochlorathiazide
inhib DCT Na/Cl
Drug List
K-Sparing
Amiloride
inhib late DCT ENaC
Drug List
ARB/K-sparing
Spironolactone
(block Aldosterone by
inhib DCT Na/K)
Drug List
ADH antags
Tolvaptan
Diuretic Braking
-Physiological compensation
for lost Na
-^symp, ^RAAS, ^ADH
-new steady state reached
ECFV Body Fluid
- 44% interstitium
- 17% plasma
- 17% bone
- 17% dens conn tiss
- 5% transcellular
Diuretics target what ECFV?
-plasma
-interstitial
(these compartments equilibrate)
Edematous Indications
- CHF
- Pulm Edema
- Nephrotic Dz
- Hepatic Cirrhosis
Hypertensive Indications
- Essential
- Renovasc HTN (hypoperfusion)
- Renal HTN (poor excretion)
- Hyperaldosteronism
Right-sided HF
Pathophysiology/Clin
- systemic edema
- ascites
- nocturia
- hepatomegaly
Left-sided HF
Pathophysiology/Clin
- pulm edema
- SOB
- Wheezing
Renal Handling Na+
Nephron Reabsorption
Percentages
- 67% PCT
- 25% TAL
- 4% early DCT
- 3% late DCT
Renal Handling Na+
Nephron Reabsorption
Channels
- PCT: glc/AA/phosph symport
- PCT: H+ antiport
- TAL: Na/K/2Cl symport
- DCT: Na/Cl symport
- DCT: Na/K antiport
Carbonic Anhydrase
Function
- drives HCO3->H2CO3-> H2O/CO2
- intracellularly and in PCT
- increases intracellular H+ for H+/Na+ antiport
Carbonic Anhydrase Inhibitors
Mechanism
-CAIs secreted into PCT
-inhibs CA both
intra/extracellularly
-reduces available H+ for Na+/H+ antiport
-Na+ therefore left in PCT lumen
Carbonic Anhydrase Inhibitors
Systemic Effects
- Alkalinized urine
- Activates TGF
- decr. Plasma HCO3 (decr. pH), Cl
Carbonic Andydrase Inhibitors
Indications
- decr intraocular pressure
- metabolic alkalosis
- acute mountain sickness
- resp alkalosis prophylaxis
Carbonic Anhydrase Inhibitors
Adverse
- hyperchloremic metabolic acidosis
- renal stones
Loop Diuretics
Mechanism
- secreted into PCT
- Blocks TAL Na/K/2Cl symport
- Abolishes corticomedullary gradient
Loop Diuretics
Adverse
- abolish osmotic gradient
- increase renal blood flow
- increased excretion of all ions
- hypokalemia (arrhythmias)
- HoTN
- Hyperuricemia
- Ototoxicity
Loop Diuretics
Indications
-Edema of renal/pulm/cardiac/hepatic origin
Thiazides
Mechanism
- Secreted into PCT (anion transporter)
- Inhibit Na/Cl contransporter in DCT
- Do NOT abolish corticomedullary gradient
- Ca2+ sparing
Thiazides
Adverse
- hypokalemia (combat with ACEI co-rx)
- metablolic alkalosis
- hypovolemia (and further hypokalemic exacerbation)
- hypercalcemia/glycemia (DM)/lipidemia/uricemia
- HoTN
Thiazides
Indications
- hypercalciuria
- Nephrogenic diabetes insipidus
- HTN, CHF
Loop/Thiazide
K+ loss
Cells responsible
- CD principle cells
- via apical K+ channels
Loop/Thiazide
H+ loss
Cells responsible
- CD intercalated cells
- via H+/K+ exchange
K-sparing ARBs
Mechanism
- do NOT need to be secreted; act on basolateral membrane
- canrenone is active metabolite
- complexes with and inactivates mineralocorticoid receptor in DCT
- inhibits Na/K antiporter in CD
K-sparing ENaC blockers
Mechanism
- secreted into PCT by cation transporter
- block luminal ENaC Na+ reabsorption in late DCT/CD
- downregs complimentary K+ secretion/excretion
- effects are independent from aldosterone
K-Sparing ENaC blockers
Adverse
-hyperkalemia (esp w/ renal dz)
K-Sparing ENaC blockers
indications
-adjunct to loop/thiazide tx to preserve K+
K-Sparing ARBs
adverse
- hyperkalemia (contra’d in chronic renal insufficiency)
- gynecomastia :( (antiandrogenic)
- menstrual irregularities
Osmotic Diuretics
Mechanism
- freely filtered at glomerulus
- osmotic gradient favors water in tubules
- acts on water permeable segments (PT, TDLH, CD)
- incr renal blood flow
Osmotic Diuretics
Adverse
- Mg2+ wasting
- Hyperkalemia
Osmotic Diuretics
Indications
-reduce intracranial/intraocular P before/after surgery
ADH antagonists
Mechanism
-binds V2 ADH receptor on CD basolateral membrane
ADH antagonists
Adverse
-hypernatremia
ADH antagonists
Indications
-SIADH
Is EtOH diuretic?
- Yes!
- Why? Interferes with Aquaporins in CD
Diuresis not optimal?
What shoud you do?
- synergistic additive effects of co-rx loop + thiazide
- co-rx should be given with close hemodynamic monitoring
Diuresis causing hypokalemia?
What should you do?
-co-rx with K-sparing diuretic
Is caffeine diuretic?
- Yes!
- Why? it’s a methylxanthine; blocks PCT Na reabsorption
