Diuretics II Flashcards
What are some K-sparing diuretics? Structure?
Triametrene [Dyrenium] & Amiloride [Midamor]organic bases and are not structurally related to aldosterone.
How do K sparing diuretics work?
They block ENaC sodium channels to inhibit Na reabsorption in DCT and CD
What are the effects of K sparing diuretics?
•Increase Urinary excretion of Na+ (weak effect).•inhibit the secretion of K+ and H+ (K-sparring)
Clinical uses of K sparing diuretics?
•Diuretics. Combined with HCTZ [Dyazide] to increase their effectiveness and decrease K+ excretion.
Side effects of K sparing diuretics?
-Hyperkalemia, -Megaloblastic anemia in patients with cirrhosisTriamterene rarely forms kidney stones
Responses to diuretics (thiazides in particular) are seen at lower doses, which produce a small but optimal natriuretic effect; higher doses should be avoided because of increase risk of side effects.
Responses to diuretics (thiazides in particular) are seen at lower doses, which produce a small but optimal natriuretic effect; higher doses should be avoided because of increase risk of side effects.The antihypertensive effect of thiazides plateaus at 25mg of HCTZ.A single morning dose of HCTZ will provide sustained effect, while reducing K+ wastage during the nighttime.
T or F. Most popular drugs for treatment of mild or moderate hypertension.
T.
What diuretics may be effective in patients with impaired renal function?
Metolazone and indapamide However, most of these compounds are usually ineffective when GFR lower than 30 mL/min and/or serumcreatinine above 2.5 mg/dL.
T or F. Patients with “volume dependent” hypertension (notably African Americans and elderly, with low renin levels) show better responses.
T.
A poor response to thiazides may reflect what?
Either an overwhelmingload of dietary sodium or impaired renal capacity to excrete sodium
When are loop diuretics used?
More efficient diuretics than the thiazides. Used in patientswith severe hypertension unresponsive to thiazides,especially with renal insufficiency, cardiac failure or cirrhosis.Due to their high efficacy, these diuretics (furosemide inparticular) is administered I.V. in acute pulmonary edema.
Why do loop diuretics require more monitoring than thiazides?
They cause excessive natriuresis leading to more side effects thanthiazides. Therefore, they require more frequent monitoring.
What is a common cause of diuretic resistance?
Co-administration of NSAID (such as aspirin, Motrin.) with loop diuretics
When are K+ sparing diuretics particularly useful?
Useful in patients at risk of K+ depletion and in patients with hyperuricemia.
Spironolactone is the diuretic of choice in what disease?
cirrhosis and canbe titrated up to 400 mg/day in very rare cases. If GFR is
Other uses of spirolactone?
Equipotent to Thiazides as antihypertensives, useful toenhance the natriuretic effects of other diuretics.Available combination formulations include:Spironolactone+Hydrochlorothiazide; Triameterene+Hydrochlorothiazide = [Dyazide] a very popularantihypertensive diuretic.
Contraindications for spirolactone?
They are contraindicated in significant renal insufficiencyGFR
When is ADH released?
•Elevation in plasma osmolarity > 280 mOsm/Kg.•Depletion of extracellular volume•Other: pain, nausea hypoxia
What does ADH bindings to the VI receptor cause?
Binding of vasopressin to V1R activates Gq-PLC-IP3 pathway and mobilizes Ca2+ causing vasoconstriction of vascular smooth muscle
Where are ADH V2 receptors located?
in principal cells in renal collecting ducts (CD)
What does ADH bindings to the V2 receptor cause?
activates Gs-cAMP, PKA.• PKA increases rate of insertion of water channel containing vesicles (WCV’s) into the apical membrane of CD.• PKA phosphorylates the water forming channel aquaporin- 2, which are then inserted as tetramers into the apical membrane.• Aquaporin channels increase the permeability of CD to water.• PKA also phosphorylates the urea transporter (termedVRUT or UT1), and increases the permeability of CD to urea.• This in concert with the TALH and the multiplierconcentrates urine, up to 4 times the osmolarity of plasma.
What is the difference between central and nephrogenic DI?
Impaired water conservation caused by:• Inadequate AVP secretion (Central DI)• insufficient kidney AVP response (nephrogenic DI).
What are some causes of central DI?
• Head injury, surgery or trauma in the pituitary or hypothalamus, tumors, CNS ischemia etc.• Autosomal dominant (chrom 20) cause a gradual loss of AVP.
What are some causes of nephrogenic DI?
• Acquired: obstructive renal disease, Drugs: Lithium, clozapine.• Genetic: X-linked caused by gene encoding V2R that result in frame shift, truncated receptor or single amino acid mutations.
