EXAM #2: CV PHARM 4 Flashcards
What is the most metabolically activate part of the nephron? 2nd?
1) PCT
- B/c of Na+ATPase
2) Thick ascending loop
What is reabsorbed in the PCT?
- 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
What are the primary transporters and drug targets in the PCT?
1) Na+/H+ exchanger
2) Carbonic anhydrase
What diuretics work on the PCT?
CA inhibitors including Acetazolamide
What is the major function of the Thin Descending Loop of Henle? What facilitates this action?
Passive water reabsorption, facilitated by aquaporins
What is the effect of osmoitc diuretics on the Thin descending loop of Henle?
Water flux INTO the lumen of the nephron, instead of out
What soluates are reabsorbed at the Thick Ascending Loop?
K+ Ca++ Mg++ Na+ Cl-
What class of diuretics targets the Thick Ascending Loop of Henle? What are they targeting?
NKCC inhibitors i.e. “Loop diuretics,” which are targeting to the Na+-K+-2Cl- transporter
What is unique about the loop diuretics?
Most potent class of diuretics
What is reabsorbed in the distal convoluted tubule?
NaCl
What class of diuretic works on the distal convoluted tubule? What are they targeting?
Thiazide diuretics, which target the Na/Cl (NCC) transporter
What is the physiologic function of the cortical collecting tubule?
Na+ reabsorption coupled to K+ and H+ secretion
What type of diuretics target the cortical collecting tubule?
K+ sparing diuretics
What is the physiologic function at the medullary collecting duct? What type of diuretic targets this section of the nephron?
Water reabsorption is under vasopressin control; thus, the medullary collecting duct is targeted by vasopressin antagonsits
List the three main actions of Carbonic Anhydrase (CA) in the nephron.
1) Reabsorption of bicarboante in the PCT
2) New bicarbonate formation
3) Secretion of NH4+
Generally, what is the effect of blocking CA in the PCT?
- Decreased bicarboante reabsorption/ loss of bicarboante in the urine
- Metabolic acidosis
Draw figure #5; the effects of CA inhibition.
N/A
What are the net effects of CA inhibitors on the kidney? What is the main effected that is targeted for therapeutic action?
1) Diuresis
2) Metabolic acidosis*****
What are the indications for Acetazolmide? What class of drug is this?
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.
Why is Acetazolamide used in acute mountain sickness?
- 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
What are the adverse effects of Acetazolamide?
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.
What are the contraindications for Acetazolamide?
Cirrhosis; urinary excretion of ammonia will decrease an may lead to the development of hyperammonemia
What is the mechanism of action of the osmotic diuretics? What sites of the nephron do they target?
- 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
What are the indications for Osmotic Diuretics?
1) Prophylaxis for acute renal failure
2) Cerebral edema
3) Dialysis disequilibrium syndrome
4) Acute glaucoma
