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
Why are osmotic diuretics used as prophylaxis for acute renal failure?
Renal protection may be conferred by:
- Removal of obstructing tubular casts
- Dilution of nephrotoxic substances
- Reduced swelling of tubular elements
Why are osmotic diuretics used to treat cerebral edema?
Osmotic pressure pulls edematous fluid off the brain and into the vasculature
Specifically, the intracellular volume is reduced*
What is dialysis disequilibrium syndrome?
- 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
What are the adverse effects of osmotic diuretics?
- ECF expansion leading to PULMONARY EDEMA in patients with HF
- Hyponatremia–>nausea, vomiting, and headache
- Hypernatremia–>loss of water in excess electrolytes
What are the contraindications to osmotic diuretics? If applicable, which osmotic diuretic is contraindicated?
1) Anuria due to renal disease–>all
2) Impaired liver function–>urea
3) Active cranial bleeding–>urea and mannitol
4) Hyperglycemia–>glycerin
List the osmotic diuretics.
1) Mannitol
2) Glycerin
3) Isosorbide
4) Urea
What is the mechanism of action of NKCC inhibitors i.e. Loop Diuretics?
- Inhibit Na+-K+-2Cl- cotransporter in the thick ascending limb
- Na+ stays in the tubular lumen and is excreted
What is the effect of IV NKCC inhibitor use?
Venodilation i.e.
1) Decreased right atrial pressure
2) Decreased pulmonary capillary wedge pressure
Effects occur in MINUTES
What happens to Ca++ and Mg++ with NKCC inhibitors?
- Increased fractional Ca++ and Mg++ excretion
This is due to the loss of the normal lumen-positive transepithelial potential that would PROMOTE Ca++ reabsorption
What are the indications for NKCC inhibitors?
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
What are the adverse effects of NKCC inhibitors?
1) Hypokalemia*****
2) Hyponatremia
3) Hypocalcemia
4) Hypomagnesia
5) Ototoxicity
6) Hyperuriciemia
List the NKCC inhibitors.
Furosemide
Bumetanide
Ethacrynic acid
