Renal pharm

Question 1

Fractional elimination of water (FEw) = ?

Glomerular filtration rate (GFR) = ?

Answer 1

EF (water) = Plasma creatinine/urin creatinine

EFw = Pc/Uc = Pin/Uin

GFR = Uc*V/Pc

Question 2

fractional elimination of sodium = ?

Answer 2

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 ….

Question 3

What is fractional reabsorption?

Answer 3

1-FE (fractional elimination) = the percent solute that is retained e.g. 99% for Na

Question 4

What factors regulate potassium secretion ?

Answer 4

dietary consumption of K+
Aldosterone
pH of blood
flow rate of tubular fluid ?
[Na] in tubular fluid

Question 5

What will cause potassium to be secreted?

What is formula for total excretion?

Answer 5

Aldosterone
Alkalosis 
Diuretics that block TAL Na reabsorption
Dilute tubular fluid
High dietary K+

Excretion = filtered - reabsorbed + secreted

Question 6

What will decrease K+ secretion?

Answer 6

acidosis

Question 7

What part of the nephron do thyazide diuretics act on? which recetpors?

Answer 7

Na/Cl- co-transporters in the distal tubule

Question 8

What are some examples of thyazide diuretics?

Answer 8

hydrochlorothiazide
chlorothiazide
chlorothalidone
indapamide 
metolazone

Question 9

Explain the relationship between thiazide diuretics and calcium?

Answer 9

Thiazide diuretics trigger calcium reabsoption….

Question 10

When is urine dilute vs concentrated with respect to the ratio of Uosmolarity:Posmolarity (U/P)

Answer 10

(U/P)osm 1, the urine is concentrated or hypertonic.

Question 11

What is the free water clearance when urine is isotonic? Hypotonic? Hypertonic?

Answer 11

zero!
Positive
Negative

Question 12

Where does aldosterone act along the nephron? What does it do? How does it do it?

Answer 12

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

Question 13

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?

Answer 13

Amiloride and triamterine

Inhibit sodium reabsorption and also K+ secretion, so called “K+ sparing” diuretics

Question 14

What is spironolactone? What does it do? Where does it act? When would it be ineffective?

Answer 14

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!)

Question 15

Where do thiazide diuretics act along the nephron? What is the mechanism of action?

Answer 15

Early distal convoluted tubule

inhibit the Na+/Cl- co-transporter

Question 16

What is desmopressin? How would free water clearance be affected? Osmolarity of urine?

Answer 16

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

Question 17

What does lithium do to the urine?

Answer 17

aquatic diuretic - blocks actions of ADH somehow…

Question 18

What is democlocycline?

Answer 18

aquatic diuretic - blocks actions of ADH somehow…

Question 19

what is fluoride (methoxy flurane)?

Answer 19

aquatic diuretic - blocks actions of ADH somehow…

Question 20

What drug would you use to treat ADH secreting “Oat-cell” carcinoma of the lung?

Answer 20

democlocycline

Question 21

What is Lixivaptan? What is it used for?

Answer 21

ADH receptor antagonist (diuretic) FDA approved for treatment of euvolemic hyponatremia

Question 22

What does isosorbide do?

Answer 22

cause diuresis by increasing the osmolarity of the glomerular filtrate sufficiently enought to prevent water AND solute reabsorption

Question 23

What are 4 extra-renal uses of diuretics?

Answer 23

(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.

Question 24

What section of the nephron would a carbonic anhydrase inhibitor act on?

Answer 24

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

Question 25

What part of the nephron would aminophylline and theophylline act on? What would be the consequence and what is the mechanism of action?

Answer 25

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!

Question 26

What drugs could be used along with a loop diuretic (i.e. a diuretic that blocks Na+ reabsorption in the TAL)?

Answer 26

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

Question 27

Do loop diuretic dilute or concentrate the urine? What is the consequence of loop diuretics on free water clearance?

Answer 27

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

Question 28

What are 4 loop diuretics ?

Answer 28

furosemide, bumetanide, torsemide,
ethacrynic acid (dichlorophenoxyacetic acid)

Question 29

Where do these drugs act? What do they do?

chlorothiazide, hydrochlorothiazide

Answer 29

Early distal tubule - block Na/Cl- reabsorption cause K+ secretion

Question 30

What is the affect of thiazide diuretics on urine concentration?

Answer 30

concentrates urine so less total urine is produced (takes longer to rid someone of volume expansion)

Question 31

What would you treat a patient with who had central diabetes insipidus? Nephrogenic diabedes insipidus?

Answer 31

desmopressin

Thiazide diuretic - concentrates urine, you don’t pee as much

Question 32

What would you treat someone with who has syndrome of inappropriate ADH

Answer 32

SIADH have excess ADH (so can’t dilute urine) - use democlocycline, lithium, vaptan

Question 33

efflux of what two ions from peritubular epithelial cells establishes the positive membrane potential in the thick ascending limb?

Answer 33

K+ (luminal efflux) and Cl- (basolateral eflux)

Question 34

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

Answer 34

true - can rescue pulmonary edema

Question 35

what are chlorthalidone, metolazone, quinethazone and indapamide?

Answer 35

Thiazide like diuretics

Question 36

What consequence is there to blocking N/CL- reabsorption at the early distal tubule with a thiazide diuretic?

Answer 36

can’t dilute the urine properly so it takes longer to return someone from volume expanded state

Question 37

What are potantial complications for use of thiazide diuretics?

Answer 37

contraction alkalosis,
hyperuricemia,’
hypomagnesemia
increased BUN (with or without an increase in serum creatinine).
hypokalemia (may induce diabetes mellitus)

Question 38

What would you use to treat idiopathic hypercalciuria? Why?

Answer 38

Thiazide diuretic - cause reabsorption of Ca2+ so less goes into urinary system and so can’t form kidney stones!