EXAM #2: CV PHARM 4

Question 1

What is the most metabolically activate part of the nephron? 2nd?

Answer 1

1) PCT
- B/c of Na+ATPase
2) Thick ascending loop

Question 2

What is reabsorbed in the PCT?

Answer 2

• 65% of the filtered
  1) Na+
  2) K+
  3) Ca++
  4) Mg++
• 85% of the filtered bicarbonate
• Nearly 100% of the filtered
  1) Glucose
  2) Amino acids

Question 3

What are the primary transporters and drug targets in the PCT?

Answer 3

1) Na+/H+ exchanger

2) Carbonic anhydrase

Question 4

What diuretics work on the PCT?

Answer 4

CA inhibitors including Acetazolamide

Question 5

What is the major function of the Thin Descending Loop of Henle? What facilitates this action?

Answer 5

Passive water reabsorption, facilitated by aquaporins

Question 6

What is the effect of osmoitc diuretics on the Thin descending loop of Henle?

Answer 6

Water flux INTO the lumen of the nephron, instead of out

Question 7

What soluates are reabsorbed at the Thick Ascending Loop?

Answer 7

K+ 
Ca++ 
Mg++ 
Na+ 
Cl-

Question 8

What class of diuretics targets the Thick Ascending Loop of Henle? What are they targeting?

Answer 8

NKCC inhibitors i.e. “Loop diuretics,” which are targeting to the Na+-K+-2Cl- transporter

Question 9

What is unique about the loop diuretics?

Answer 9

Most potent class of diuretics

Question 10

What is reabsorbed in the distal convoluted tubule?

Answer 10

NaCl

Question 11

What class of diuretic works on the distal convoluted tubule? What are they targeting?

Answer 11

Thiazide diuretics, which target the Na/Cl (NCC) transporter

Question 12

What is the physiologic function of the cortical collecting tubule?

Answer 12

Na+ reabsorption coupled to K+ and H+ secretion

Question 13

What type of diuretics target the cortical collecting tubule?

Answer 13

K+ sparing diuretics

Question 14

What is the physiologic function at the medullary collecting duct? What type of diuretic targets this section of the nephron?

Answer 14

Water reabsorption is under vasopressin control; thus, the medullary collecting duct is targeted by vasopressin antagonsits

Question 15

List the three main actions of Carbonic Anhydrase (CA) in the nephron.

Answer 15

1) Reabsorption of bicarboante in the PCT
2) New bicarbonate formation
3) Secretion of NH4+

Question 16

Generally, what is the effect of blocking CA in the PCT?

Answer 16

• Decreased bicarboante reabsorption/ loss of bicarboante in the urine
• Metabolic acidosis

Question 17

Draw figure #5; the effects of CA inhibition.

Answer 17

N/A

Question 18

What are the net effects of CA inhibitors on the kidney? What is the main effected that is targeted for therapeutic action?

Answer 18

1) Diuresis

2) Metabolic acidosis*****

Question 19

What are the indications for Acetazolmide? What class of drug is this?

Answer 19

CA Inhibitor

1) Glaucoma
2) Acute mountain sickness
3) Urinary alkalinization
4) Edema

Note that CA is present in the ciliary body; blocking CA in the ciliary decreases the production of aqueous humor and decreases intraocular pressure. Also, weak acids are easily reabsorbed from acidic urine. Increasing the urine pH with a bicarbonate dump favors excretion of weak acids.

Question 20

Why is Acetazolamide used in acute mountain sickness?

Answer 20

• CA is present in the choroid plexus
• CA inhibition decreases and the pH of the CSF
• This acidosis stimulates respiratory drive and resolves the symptoms of mountain sickness

Question 21

What are the adverse effects of Acetazolamide?

Answer 21

1) Hypercholeremic metabolic acidosis
2) Renal stones
3) Renal loss of K+

Note that K+ wasting is the result of partial Na+ reabsorption in the collecting tubule; this increases the lumen negative potential and enhances K+ secretion.

Question 22

What are the contraindications for Acetazolamide?

Answer 22

Cirrhosis; urinary excretion of ammonia will decrease an may lead to the development of hyperammonemia

Question 23

What is the mechanism of action of the osmotic diuretics? What sites of the nephron do they target?

Answer 23

• PCT and Thin Desecending Limb of the Loop of Henle are freely permeable to water
• Osmotic diuretics in these areas “pull” water into the lumen of the nephron

Question 24

What are the indications for Osmotic Diuretics?

Answer 24

1) Prophylaxis for acute renal failure
2) Cerebral edema
3) Dialysis disequilibrium syndrome
4) Acute glaucoma

Question 25

Why are osmotic diuretics used as prophylaxis for acute renal failure?

Answer 25

Renal protection may be conferred by:

• Removal of obstructing tubular casts
• Dilution of nephrotoxic substances
• Reduced swelling of tubular elements

Question 26

Why are osmotic diuretics used to treat cerebral edema?

Answer 26

Osmotic pressure pulls edematous fluid off the brain and into the vasculature

Specifically, the intracellular volume is reduced*

Question 27

What is dialysis disequilibrium syndrome?

Answer 27

• Dialysis pulls electrolytes from ECF
• Fluid shifts from ECF to ICF, causing hypotension and CNS symptoms

**Osmotic diuretics pulls the water from the ECF into the vasculature to reset the ECF/ICF fluid volumes

Question 28

What are the adverse effects of osmotic diuretics?

Answer 28

• ECF expansion leading to PULMONARY EDEMA in patients with HF
• Hyponatremia–>nausea, vomiting, and headache
• Hypernatremia–>loss of water in excess electrolytes

Question 29

What are the contraindications to osmotic diuretics? If applicable, which osmotic diuretic is contraindicated?

Answer 29

1) Anuria due to renal disease–>all
2) Impaired liver function–>urea
3) Active cranial bleeding–>urea and mannitol
4) Hyperglycemia–>glycerin

Question 30

List the osmotic diuretics.

Answer 30

1) Mannitol
2) Glycerin
3) Isosorbide
4) Urea

Question 31

What is the mechanism of action of NKCC inhibitors i.e. Loop Diuretics?

Answer 31

• Inhibit Na+-K+-2Cl- cotransporter in the thick ascending limb
• Na+ stays in the tubular lumen and is excreted

Question 32

What is the effect of IV NKCC inhibitor use?

Answer 32

Venodilation i.e.

1) Decreased right atrial pressure
2) Decreased pulmonary capillary wedge pressure

Effects occur in MINUTES

Question 33

What happens to Ca++ and Mg++ with NKCC inhibitors?

Answer 33

• Increased fractional Ca++ and Mg++ excretion

This is due to the loss of the normal lumen-positive transepithelial potential that would PROMOTE Ca++ reabsorption

Question 34

What are the indications for NKCC inhibitors?

Answer 34

1) Pulmonary edema
2) CHF
3) Acute renal failure**
4) Hypercalcemia

**Often these are the only drugs capable of reducing massive edema associated with renal disease

Question 35

What are the adverse effects of NKCC inhibitors?

Answer 35

1) Hypokalemia*****
2) Hyponatremia
3) Hypocalcemia
4) Hypomagnesia
5) Ototoxicity
6) Hyperuriciemia

Question 36

List the NKCC inhibitors.

Answer 36

Furosemide
Bumetanide
Ethacrynic acid