Diuretics Flashcards
3 mechanism for how drugs can be delived to renal sites
- Glomerula filtration
- PT secretion (organic anion transporter proteins, oatp & mdr1 gene product (p-glycoprotein 170))
- By diffusion
Order of nephron segment from most to least Na reabsorbtion
PT>LOH>DT>CD
5 big catagoriesof diuretics
- Osmotic diuretics
- Carbonic anhydrase inhibitors
- Thiazide diuretics
- Loop diuretics
- Potassium sparing diuretics
Osmotic diuretics are __ but not ___
Enhece Na & K excretion vial
Filtered but not reabsorbed
SOlute drag
Mannitol
Indications
Mechanism
SE
Indications
- Glaucoma
- Cerebral edema
- Pigment related AKI
- Trying to shrink intracellualr volume
Mechanism
- Solute drag and prevents H2O reabsorbtion
SE
- Osmotic diuresis
Increased tubular flow rates wast Na & K
Sulfanilamide & Acetazolamide
Class
Indications
Mechanism
SE
Class
Carbonic anhyrdase inhibitors
Indications • Alkanline urine (trap agents, tumor lysis syndrome to trap urate or salicylic acid (drug toxicity) • Open angle glaucoma Mountain sickness • Metabolic alkalosis • Familial hypokalemia
Mechanism
• Blocks bicarbonate re absorption in PT
• Na stays in PT
• Increase Na, HCO3 flow in kidney and excretions
- Distal tubule
- CA inhibition decreases H+ availability so urinary K is secreted
SE
• Metabolic acidosis that will then stop action of diuretics
• Ca stones (alkalinized urine)
• Familial Hypokalemic Periodic Paralysis
• Hypersensitivity to sulfonamide residues
Hydrochlorothiazde
Class
Indications
Mechanism
SE
Class
Thiazide diuretics
Indications • HTN • Increase bone density in elderly women • Reduce nonfatal and fatal MI • Edema • Ca nephrolithiasis • Nephrogenic diabetsis insipidus (volume contraction reduces water delivary to distal sites where inadequate vasopressin effect)
Mechanism
• Blocks NaCl in distal tubule
• Leaves them behind in the tubule
• Blocks ability to maxially dilute the urine
• Ca reabsorption made easier
• More Na for ENAC, negative charge in the lumen, hypokalemia)
• Volume depletion increases Ca reabsorption
SE • Hypercalcemia • Hypocalcium urea • Hyponatremia (can’t produce urine that is less diluete than the serum) • Hypokalemia • Hyponatremia • Hypercalcemia • Hypersensitivity reactions (sulfa) Unknowm Mechanism • Hyperuricemia • Hyperglycemia • Hyperlipidemia • Make gout and diabetes worse
Furosomide
Class Indications Mechanimsm Dosing SE
Class
Loop diuretics
Indications
• CHF
• Acute pulmonary edema
• Edema from cardiac, hepatic, renal causes
• HTN refractory to other diuretics (Not 1st choice because short action peiod of 6 hours)
Saline to treat hyper Ca
Mechanism
• Block Na K 2Cl in LoH
• Block urinary concentrating and diluting ability compensatory
• Increase distal Na delivery so K excretion
• Increase Ca and Mg Excretion
Compare to THZ
• More Na in urine
Dosing
• As GFR falls have to use higher doses of furosemide (CKD & nephrotic syndrome)
• Furosomide (Lasics)
o 25-50% bioavbility (oral) high variability and some patients don’t absorb it in tthe gut, edema in gut
o 95% plasma bound
o 50% renal excretion unchanged (oatp-mediated)
o Urine concentratin correlates with natriuretic effect
o Short half life compared to others in class but 6 hours of diuresisi
SE • Electrolyte abnormalities o Volume depletion o Hypokalemia o Excess Ca and Mg • Similar to Bartlets syndrome o Congetital Na/K/Cl defect • Ototoxicity (at high doses – irreversible) • Hyperuricemia • Hypersensitivy reatcion
Which loop diuretic can be used for patients with sulfa allergies and what is its side effect?
Ethacrynic acid
alternative for patients with sulfa allergies, expensive & GI distress
Amiloride
Class
Indications
Mechanism
SE
Class
- sparing diuretic
Indications
- Used in combination with thiazide/loop diuretics to prevent hypokalemia
- Liddle’s disease
- In combination with Li to block upake into PC & inhibit Li-induced diabetes insipidus
Mechanism
- Na blocker in ENaC
- Inhibit Na re-absorption by PC in late distal tubules & collecting ducts
- Decrease K excretions by acting either at ENaC or Indirectly antagonize of aldosterone at mineralocorticoid receptor
SE
- Headache
- Dizziness
- Nausea
- Vomiting
- GI distress & diarrhea
- Dehydration/ dry mouth/muscle craps…
Spironolactone Class Indications Mechanism SE
Class
- Aldosterone antagonist
- K sparing diuretic
Indications
• Primary Hyperaldosteronism (NOT Liddle’s disease, cirrhotic edema, nephrosis & heart failure), ENaC open regardless so not aldosterone antagonism
• Combination with thiazides to reduce K wasting
• CHF with loop diuretics & ACE inhibitors
• In combination with Li
Mechanism
- Competiive antagonism of mineralocorticoid receptor (MR)
- Block MR induced ENaC, Na/K ATPase& sgk (ser.thr kinase that activates ENaC) expression,
SE
• Hyperkalemia
• Endocrine abnormalities (gynecomastia impotence)
What drug will not cause the endocrine abnormalites of spirolactan be used instead of spironolacto
Eplerenone
4 reasons for limited or short lasting effect of diuretics “Braking Syndrome)
o High Na intake
o Volume depletion activates RAAS (Na retention, AII, catecholamines, aldosterone , resitance to ANP)
o Decrease renal clearance
o DCT hypertrophy
Management of Braking Syndrome
o Increase dose (careful of diuretics)
o Use loop or thiazide diuretics in combination)
o Restrict fluid/Na
o Aldosetrone agonist
o Avoid vasodilator that impairs renal perfusion
