Diuretics Flashcards
Indications for diueretics
Tx of HTN, mobilization of edematous fluid from HF, cirrhosis, kidney disease. Also maintain urine flow so used to prevent renal failure
4 functional regions of the kidney
Glomerulus, proximal convoluted tubule, loop of Henle, distal convoluted tubule (plus collecting duct)
Three basic functions kidney
Cleaning and maintaining ECF, pH, excretion of wastes
Fluid through kidneys
125mL/minute or 180L/day (Volume of ECF is 12.5L so entire amount is filtered every 100 minutes)
Reabsorption of solutes is what kind of transport
Active
PCT
65% sodium and chloride reabsorbed at proximal convoluted tubule
Almost all bicarb and k+ here
Descending limb, loop of henle
Freely permeable to water. Water is drawn into interstitial space, and increases tonicity from 300mOsm/L to 1200mOsm/L
Ascending limb loop of Henle
In thick segment 20% sodium and chloride is reabosrbed. Not permeable to water so returns to 300mOsM/L
Early distal convoluted tubule
10% sodium and chloride reabsorbed here. Water follows passively
Late distal and collecting duct
Exchange of sodium for potassium under influence of aldosterone.
Final concentration of urine regulated by ADH
Aldosterone sodium/potassium exchange
Stimulates reabsorption of Na+ from DCT, and causes K+ to be secreted.
Aldosterone stimulates cells of distal nephron to synthesize more pumps which retain sodium and boot potassium
4 classes of diuretics
Loop (high-ceiling) eg lasix
Thiazide
Osmotic
K+ sparing (divided into aldosterone antagonists and nonaldosterone antagonists)
Loop diuretics
Site of action is loop of henle (hence the name)
Furosemide
Furosemide
Thick segment of ascending loop, blocks reabsorption of sodium and chloride. This prevents passive reabsorption of water
Pharmacokinetics of furosemide
Oral diuresis begins in 60 minutes persists for 8 hours
IV begins in 5 and lasts for two hours
CAN produce renal flow with a low GFR (good for pts with severe renal impairment)
No benefit in adding a second loop, but benefits in adding a thiazide
Adverse effects of furosemide
Hyponatremia, hypochloremia, dehydration.
Dehydration can promote thrombosis and embolism.
Hypokalemia
Hypotension from both fluid loss and relaxation of smooth muscle
Ototoxicity - hearing impairment. Rare and transient with lasix
Hyperglycemia from inhibition of insulin
Hyperuricemia (gout)
Dangerous in pregnancy
Reduced HDL and raises LDL (still drop risk of coronary mortality by 25%)
Hypomagnesia and hypocalcemia
NSAIDS and lasix
NSAIDS reduce effectiveness as lasix uses renal flow secondary to prostaglandins to work
Lasix dose
20-80mg a day starting. Max 600mg
Thiazides
Also increase renal excretion of NaCl, K+ and water
Principal difference is max diuresis is significantly lower
Are not effective with decreased renal flow like loops are
Thiazide MOA
Early distal convoluted tubule. 10% NaCl reabsorbed here so lower ceiling than loops.
GFR needs to be more than 20mL/min to work
Works in 2 hours peaks at 4-6, persist for 12
Thiazide for diabetes insipidus
Increased urine output in DI, for an unknown reason thiazides reduce this.
These drugs promote renal reabsorption of calcium (loops excrete it) and can be used for osteoporosis
Sides of thiazides
HypoNaCl and dehydation Hypokalemia Hyperglycemia Hyperuricemia Increase LDL and total cholesterol CAN be used with other ototoxic drugs unlike loops
Diuretics and digoxin
Hypokalemia and dig is dangerous so loops and thiazides are badness
K+ sparing diuretics
Modest effect on urine output
Spironolactone
Blocks aldosterone in distal nephron (aldosterone increases Na reabsorption decreases K+)
Blocks NEW proteins but does not stop existing so takes up to 48 hours to work
Adverse effects of K+ spironolactone
Hyperkalemia
Steroid derivative and can cause gyno, mesntral problems, impotence, hirsutism and deepening of voice
Which are the osmotic diuretics
Mannitol, glycerin and isosorbide
MOA mannitol
Six-carbon sugar Freely filtered at glomerulus Undergoes minimal tubular reabsorption Minimal metabolism Has no direct effects on biochemistry of cells
Mannitol pharmacokinetics
Can’t be taken orally, won’t be absorbed. Diuresis begins 30-60 minutes after admin and lasts 6-8 hours
Mannitol uses
Prevent renal failure. Since it is not reabsorbed it makes water keep running through in severely dehydrated patients
Reduction of ICP and intraocular pressure
Adverse mannitol effects
Edema as it leaves vascular system at capillary beds (except in the brain)
Headache, N/V, fluid/lyte imbalances
