kaplan flashcards
think of :
sites of action
electrolyte balances/results of diaretics
:)
What is absorbed at the PCT? (proximal convoluted tubule)
60% Na+
and two anions to maintain electroneutrality:
>95% HCO3-
45% Cl-
Which diuretics work at the PCT?
- CA anhydrase inhibitors
2. Osmotic diuretics (work along the entire tubule, but proximal tubule is most efficient part of the nephron)
What is absorbed at the TAL? (thick ascending loop)
25% Na+
Which diuretic work at the TAL?
- Loop diuretics: block salt reabsorption in the loop of Henle
How does ADH work?
Works in early collecting duct to retain free water
if the receptors work well, it will place aquaporin channels and water will be retained because of the concentration gradient that was enstated in the medulla by salt re-absorption
What is hepato-renal syndrome?
liver through urea cycle detoxifies ammonia to produce the milder form which is urea ;
this means that when the liver fails then so will the kidney; without urea there would be no way to concentrate the urine through the action of ADH
How much Na is retained at the DCT? (distal convoluted tububle)
10% Na
PTC dependend CA2+ re-absorption
Where do thiazide diuretics work?
DCT (distal convoluted tubule)
Where does aldosterone work?
at the early collecting duct
How much Na+ is reabsorbed at the collecting duct?
<5% Na+ re-absorption
Which drugs work on the early collecting duct?
K+ sparing diuretics
Aldosterone antagonists
How does the kidney adapt when given a diuretic?
adapt or die:
if a drug was to block Na re-absorption proximally, then the kidney would adapt to increase Na+ re-absorption distal to the medication;
this in turn would result in better Na retention by aldosterone but at the expense of K+ and H+
as the diuretics result in hypovolemia (water follows Na?)
hypokalemia( due to aldosterone action distal to the drug’s site of action)
alkalosis (through loss of H+)
unless the drug is a K+ sparking diuretic there should be hypokalemia with diuretics
What are names of some osmotic diuretics?
mannitol, glycerin, isosorbide, urea
What is the moa, uses, and side effects of mannitol?
IV; inhibits water reabsorption throughout the tubule because it’s filtered freely but not reabsorbed; traps water in the tubule and increases urine volume
decreases fluid load in :
glaucoma acute attack
decrease ICP
reopen kidney function in toxic acute tubular necrosis (rhabdomyosis) ; increase excretion of toxins in the kidney
side effect: acute hypovolemia
When thinking of the other diuretics…
they don’t increase diuresis, but rather increase Na+ excretion
How do carbonic anhydrase inhibitors work?
prevent reabsorption of Na+ in the PCT
a little bit of physiology: Na+ is exchanged for for H+ on the luminal side by Na/H antiport; from the luminal side soidum will only come into the PCT cell if it has a proton to be exchanged with; this proton is coming from the intracellular CA; this H is release in the PCT; it will not change the pH because the H is immediately recycled with the actual HCO3 which has been freely filtered just like the other salts; it needs to become carbonic acid through the enzyme CA on the extracellular side (luminal side) to make it CO2 and H2O which is freely permeable between membranes; that same CO2 and H2O are the substrates for intracellular CA which produces the H needed for Na exchange and the HCO3 which goes back into the blood as a buffer
What is the mechanism of acetazolamide?
CA inhibitor; will prevent the proton from being made and without the proton, then NA cannot enter the PCT and will built inside the lumen -> diuretic since it enhances sodium excretion and water follows
What happens to the HCO3- when using acetazolamide?
since the H+ cannot be released into the lumen, the HCO3 depended on the H+ to be reabsorbed so you will loose HCO3- along with Na+
consequence: huge change in pH causing metabolic acidosis
What are the names of carbonic anhydrase inhibitors?
acetazolamide, dorzolamide
Summarize the action of CA inhibitors. do it…do it now…
4 things
- decrease H+ formation inside the cell
- decrease H+/Na+ antiport
- increase Na+ and HCO3- in the lumen
- increase diuresis
What are the medical uses of CA inhibitors?
What are some side effects?
glaucoma, acute mountain sickness and metabolic alkalosis
side effects: metabolic acidosis, hypovolemia, hypokalemia, hypercholoremia(think of Na and Cl cotransporters distal to the drug’s site of action)…compensation , sulfonamide HS
*causes hypokalemia yet acidosis…whaaattttt!!…..it makes sense though *
Explain the mechanism of using acetazolamide in acute mountain sickness
when you go into altitude, you have a decrease in atm pressure, decrease in alveolar oxygen resulting in hypoxemia
respiratory centers cause hyperventilation due to low oxygen; hyperventilation causes a decrease in PCO2 causing respiratory alkalosis
also: pulmonary vasoconstriction in the lung to divert the blood to better ventilated areas; this increases hydrostatic pressure in capillaries resulting in edema,
acetazolamide will drain the edema and will treat the alkalosis
What is classic of a CA inhibitor drug?
Hyperchloremic acidosis
