Renal pharm Flashcards
Fractional elimination of water (FEw) = ?
Glomerular filtration rate (GFR) = ?
EF (water) = Plasma creatinine/urin creatinine
EFw = Pc/Uc = Pin/Uin
GFR = Uc*V/Pc
fractional elimination of sodium = ?
When in ballance FEw=FEna=1%
When positive water balance (more water in plasma) than FEw >1% but FEna = 1%
FEna doesn’t deviate from 1% with changes in water elimination because of compensation from distal convoluted tubule and collecting duct take up left-over sodium
Except with a drug..? Loop diuretics ….
What is fractional reabsorption?
1-FE (fractional elimination) = the percent solute that is retained e.g. 99% for Na
What factors regulate potassium secretion ?
dietary consumption of K+ Aldosterone pH of blood flow rate of tubular fluid ? [Na] in tubular fluid
What will cause potassium to be secreted?
What is formula for total excretion?
Aldosterone Alkalosis Diuretics that block TAL Na reabsorption Dilute tubular fluid High dietary K+
Excretion = filtered - reabsorbed + secreted
What will decrease K+ secretion?
acidosis
What part of the nephron do thyazide diuretics act on? which recetpors?
Na/Cl- co-transporters in the distal tubule
What are some examples of thyazide diuretics?
hydrochlorothiazide chlorothiazide chlorothalidone indapamide metolazone
Explain the relationship between thiazide diuretics and calcium?
Thiazide diuretics trigger calcium reabsoption….
When is urine dilute vs concentrated with respect to the ratio of Uosmolarity:Posmolarity (U/P)
(U/P)osm 1, the urine is concentrated or hypertonic.
What is the free water clearance when urine is isotonic? Hypotonic? Hypertonic?
zero!
Positive
Negative
Where does aldosterone act along the nephron? What does it do? How does it do it?
Acts on the late portion of the distal convoluted tubule and the early collecting duct.
increases sodium reabsorption, K+ secretion
binds intracellular receptors to initiate tracription of mRNA for K+ channels, Na+ channels and Na/K+ -ATPase
What drugs target the sodium channel in the luminal membrane of the late distal tubule and collecting duct? What is a secondary function that forms the basis for their classification?
Amiloride and triamterine
Inhibit sodium reabsorption and also K+ secretion, so called “K+ sparing” diuretics
What is spironolactone? What does it do? Where does it act? When would it be ineffective?
Competitive antagonist of aldosterone
prevents sodium reabsorption/K+ secretion in the late distal convoluted tubule and early collecting duct.
When someone is eating a high sodium diet (aldosterone would be low, so nothing to compete with!)
Where do thiazide diuretics act along the nephron? What is the mechanism of action?
Early distal convoluted tubule
inhibit the Na+/Cl- co-transporter
What is desmopressin? How would free water clearance be affected? Osmolarity of urine?
alologue/agonist for ADH/vasopressin receptors (AV2R - arganin-vasopressin 2 receptors - Gs coupled==> increase PKA»cAMP»>AQP2 transcription/insertion in luminal membrane)
decrease free water clearance (more negative) concentrating the urine
What does lithium do to the urine?
aquatic diuretic - blocks actions of ADH somehow…
What is democlocycline?
aquatic diuretic - blocks actions of ADH somehow…
what is fluoride (methoxy flurane)?
aquatic diuretic - blocks actions of ADH somehow…
What drug would you use to treat ADH secreting “Oat-cell” carcinoma of the lung?
democlocycline
What is Lixivaptan? What is it used for?
ADH receptor antagonist (diuretic) FDA approved for treatment of euvolemic hyponatremia
What does isosorbide do?
cause diuresis by increasing the osmolarity of the glomerular filtrate sufficiently enought to prevent water AND solute reabsorption
What are 4 extra-renal uses of diuretics?
(1) a hemodynamic effect improving the control of hypertension by increasing vascular wall compliance;
(2) decrease CSF volume and pressure preventing damage to
brain tissue;
(3)decrease intraocular fluid volume and pressure preventing
ocular damage in glaucoma;
(4) improve localized imbalances in lung fluid
distribution in children with respiratory disease.
What section of the nephron would a carbonic anhydrase inhibitor act on?
Proximal convoluted tubule - decreaases sodium and bicarinate reaborption
Urine would have more Na HCO3- and K+
K+ is due to later compensation and Na reabsorption coupling to K+ secreation
What part of the nephron would aminophylline and theophylline act on? What would be the consequence and what is the mechanism of action?
Proximal tubule
MOA is through inhibiting the Na/H+ exchanger
outcomes is decreased Na/bicarb reabsroption and increased Na/bicarb in urine
Low potency because of downstream compensation!
What drugs could be used along with a loop diuretic (i.e. a diuretic that blocks Na+ reabsorption in the TAL)?
Amiloride and triamterine
directly block Na reabsorption channels on the late distal tubule and early collecting duct so Inhibit compensatory sodium reabsorption and K+ secretion
Do loop diuretic dilute or concentrate the urine? What is the consequence of loop diuretics on free water clearance?
dilutes the urine and increases free water clearance
reason is because 25% of solutes are removed from tubular fluid in the TAL are essential for maintaining countercurrent multiplication that establishes the high osmotic gradient in the medulla which is what permits ADH to remove water from tubuler fluid - loop diuretic blocks this - thus fluid delivered to collecting duct faces a deminished gradient and water stays in the urine
What are 4 loop diuretics ?
furosemide, bumetanide, torsemide, ethacrynic acid (dichlorophenoxyacetic acid)
Where do these drugs act? What do they do?
chlorothiazide, hydrochlorothiazide
Early distal tubule - block Na/Cl- reabsorption cause K+ secretion
What is the affect of thiazide diuretics on urine concentration?
concentrates urine so less total urine is produced (takes longer to rid someone of volume expansion)
What would you treat a patient with who had central diabetes insipidus? Nephrogenic diabedes insipidus?
desmopressin
Thiazide diuretic - concentrates urine, you don’t pee as much
What would you treat someone with who has syndrome of inappropriate ADH
SIADH have excess ADH (so can’t dilute urine) - use democlocycline, lithium, vaptan
efflux of what two ions from peritubular epithelial cells establishes the positive membrane potential in the thick ascending limb?
K+ (luminal efflux) and Cl- (basolateral eflux)
T/F in addition to causing diuresis, loop diuretics can increase the vascular wall compliance of veins via the production of prosteglandins at the kidney
true - can rescue pulmonary edema
what are chlorthalidone, metolazone, quinethazone and indapamide?
Thiazide like diuretics
What consequence is there to blocking N/CL- reabsorption at the early distal tubule with a thiazide diuretic?
can’t dilute the urine properly so it takes longer to return someone from volume expanded state
What are potantial complications for use of thiazide diuretics?
contraction alkalosis,
hyperuricemia,’
hypomagnesemia
increased BUN (with or without an increase in serum creatinine).
hypokalemia (may induce diabetes mellitus)
What would you use to treat idiopathic hypercalciuria? Why?
Thiazide diuretic - cause reabsorption of Ca2+ so less goes into urinary system and so can’t form kidney stones!
