1-4 and 5 Flashcards
Which two drugs have a black box warning that state they cause myelination disorders?
Tolvaptan/Mozvaptan (V2 Receptor Antagonists)
Which drug class does Conivaptan belong to?
V1a/V2 Receptor Antagonists
Which drug class is best use for treating hypervolemic-hyponatremia due to SIADH?
Vasopressin Receptor Antagonists
Clinical indications for Vasopressin agonists?
1) Diabetes insipidus
2) Nocturia
What part of the kidney is critical for conserving water?
Collecting duct
When plasma Osm increases, so do vasopressin levels. How does this affect water permeability?
Increases water permeability by enhancing AQP2 localization in membrane
What is the major receptor in renal tissue (specifically: in the principal cells of the collecting duct and thick ascending limb)?
V2
How does vasopressin lead to translocation of AQP2 on membrane surface?
-Rise in cAMP and PKA
What drug class binds to NPR receptors, thereby triggering conversion of GTP to cyclic GMP?
Natriuretic Peptides (AMP, CMP, Urodilatin)
True or False: In the Natriuretic Peptide pathway, both cGMP and PKG inhibit the CNG (cyclic nucleotide gate channel) directly
True
True or False: In the Natriuretic Peptide pathway, PKG prevents Na exit via Na/K ATPase
True
___ is a recombinant BMPknown to inhibit cyclic nucleotide gated cation channel (CNGC)
Nesiritide
Regarding natriuretic peptides, what channel allows for Na/K/NH4 entry and is controlled by cGMP?
CNGC (cyclic nucleotide gated cation channel)
Where do Natriuretic Peptides act?
Inner medullary collecting duct
What drug is a MR specific antagonist with reduced non-specific effects?
Eplerenone
True or False: Since Thiazides can interfere w/other steroid receptors, they can cause impotence, hirsuitism, menstrual irregularities, etc.
False - Since MR Antagonists can interfere w/other steroid receptors, they can cause impotence, hirsuitism, menstrual irregularities, etc.
What drugs prevent aldosterone induced increased expression of ENaC mRNA and protein
A. Spironolactone/Eplerenone
B. Amiloride
A. Spironolactine/Eplerenone
How do MR Antagonists decrease mRNA expression of ENaC and promote degradation of ENaC
They stop NEDD 4/2 from being phosphoryalted - therefore ENaC is degraded
By inhibiting aldosterone, aldosterone cannot bind to MR, enter nucleus, and upregulate ENa
Delete me
True or False: Hypokalemia is an AE of K Sparing Diuretics
False - hyperkalemia
____ is one of the aldosterone induced proteins
ENaC
How does the aldosterone-MR complex produce proteins?
Enters nucleus, homodimerizes, binds to responsive elements in DNA
Which two drugs block ENaC channels?
Which two drugs are MR antagonists?
ENaC: Amiloride/Triamterene
MR Antagonists: Spironolactone/Eplerenone
Amiloride and Triamterene are known to cause _____
hyperkalemia
(worsened by NSAID’s, ACE Inhibitors, and Trimethoprim)
Amiloride and Triamterene are contraindicated in what patient population?
Those with hypoaldosteronism
True or False: By inhibiting ENaC in late DCT and Collecting Duct, Triamterene and Amiloride spares K loss
True
True or False: Mineralcorticoid Receptor antagonists bring about decreased expression of ENaC
True
What cell types of the cortical collecting duct do K+ sparing diuretics and aldosterone act on?
Principal cells
Role of Principal Cells?
Reabsorb water and sodium; promote K secretion
Thiazides and ____ can cause polymorphic ventricular tachy
Quinidine
Indapamide, Chlorthalidone, and Metolazone belong to what drug class?
Thiazides
What differentiates Na/Cl symporter inhibitors from Loop Diuretics?
-Thiazides have minimal effect on GFR, renin release, or RAAS activation because they act at a site PAST macula densa cells
Where are Na/Cl- symporters located?
Distal Convoluted Tubule
Describe the epithelium in the DCT?
Tight, minimal water permeability
What type of diuretics may cause ototoxicity?
Loop Diuretics
- Interference of ionic conductance
True or False: Loop Diuretics can lead to sympathetic reflex and, ultimately, RAAS pathway activation
True
How does inhibition of Na/K/2Cl Symporter affect potential difference across epithelial cells?
Reduces potential difference
- Could cause decrease calcium and magnesium reabsorption
Where do osmotic diuretics act?
Loop of henle and PCT (water permeable membranes)
___ acts an an inert agent, increasing Osm and promoting water loss in lumen
Mannitol
True or False: Loop of Henle is site of action for osmotic and loop diuretics
True
Systemic metabolic acidosis is associated with which drug class?
CA Inhibitors
What are two examples of CA Inhibitors?
1) Acetazolamide
2) Methazolamide
What do CA Inhibitors prevent?
1) CO2 uptake - decreases carbonic acid break down
2) indirectly decreases amount of sodium reabsorbed from luminal fluid
In the lumen/brush border, H2CO3 decomposes rapidly to CO2 and water in the presence of which CA Enzyme?
CA Type 4
Which CA Enzyme acts within the cytoplasm to breakdown carbonic acid into HCO3 and H+?
CA Type II
True or False: Carbonic Anhydrase plays a role in HCO3 reabsorption and acid excretion
True
Where are CA enzymes primarily located?
PCT
Denser microvilli are found in the apical membrane of the ___ tubule, which allows for greater solute absorption
The collecting duct contains ___ epithelia
proximal
tight
How do diuretics treat HTN?
- Promotes diuresis/natriuresis
- Decrease hypervolemia/hypernatremia
- Decrease pre-load
How are diuretics used to treat heart failure?
Reduce edema and congestion
