Diuretics Flashcards
nephron
functional unit of kindey
four regions of nephron
1) glomerulus
2) proximal convoluted tubule
3)loop of Henle
4) distal convoluted tubule
where does nephron fluid flow into
collecting ducts
upper portion of nephron is in
renal cortex
lower portion of nephron is located in
renal medulla
why are the nephron located different parts of the kidney (upper and lower)
allows different urine concentrations
kidneys main functions
1) cleansing ECF and maintenance of ECF volume and composition
2) maintenance of acid-base balance
3) excretion of metabolic waste and foreign substances (toxins, drugs, etc.)
filtration
small molecules in plasma undergo filtration
- large particles excluded
reabsorption
movement of fluids and molecules from nephron to peritubular capillaries
how do diuretics primarily work?>
interfering with reabsorption
active secretion (requires energy)
movement of fluids and molecules from peritubular capillaries back to nephron
what are the kidneys 2 pumps for active secretion?
1) transports organic acids
2) transports organic bases
Pathway of renal fluid through nephron
proximal convoluted tubule
loop of Henle
early distal convoluted tubule
distal convoluted tubule
percentages of sodium/chloride reabsorbed at specific sites
proximal convoluted tubule- 65%
- by the end of proximal tubule, Na/Cl only solutes that remain
ascending limb of Henle loop
20%
-not permeable to water
= osmolarity returns to orig. filtrate of 300mOsm/L
Early distal convoluted tubule
10%
-water follows passively
distal convoluted tubule and collecting tubule
1% - 5%
What important processes happen at late distal and collecting ducts?
1) exchange of sodium for potassium
- under influence of aldosterone
2) Determines final concentration of urine
- regulated by antidiuretic hormone
What does aldosterone stimulate?
stimulates linked process of sodium reabsorption and secretion of potassium
Basic mechanism of how diuretics work
Blockage of Sodium/ Chloride reabsorption
- creates increased osmotic pressure within nephron –> prevents passive reabsorption of water
- diuretics cause both sodium/chloride and water to be retained in nephron
–> excretion of both in urine - increase in urine flow directly related to AMOUNT of na/cl BLOCKED
where do drugs blocking na/cl in the nephron have the most profound diuresis
earliest in nephron (proximal, loop)
how much will diuretics increase urine output by?
1.8L for every 1 % blocked
blocking a small amount of solute effect has a
profound effect on fluid and electrolyte composition in the body
diuretics adverse impact on ECF
- hypovolemia
-acid/base imbalance
-altered electrolyte levels
how can effects be minimized while using diuretics
-use short acting diuretics
–> allow kidneys to function in a drug free manner between periods of diuresis
Four classifications of diuretics include
1) Loop diuretics (furosemide)
2) Thiazide diuretics (hydrochlorothiazide)
3) Osmotic diuretics (mannitol)
4) Potassium-sparing diuretics (aldosterone antagonists and agonists)
Loop Diuretics
Most effective
site of action: loop of Henle
Loop Diuretic drug
Furosemide (fur-oh-semide)
Furosemide mechanism
-Bind reversible to a carrier protein that stops it from reabsorbing NA/CL
- potentially 20% of na/cl reabsorption can be blocked here
Pharmakinetics of Furosemide
PO- diuresis within 60 min, lasts for 8 hrs
- use when rapid onset diuresis NOT REQUIRED
IV- within 5 min
-critical situations (pulmonary edema)
metabolism: hepatic
excretion: renal
Adverse effects of Loop Diuretics
Hyponatremia, dehydration
- dry mouth, unuasual thirst, low urine output
- initiate therapy with low doses and monitor weight loss
Hypotension
- (1) from loss of water
- (2) relaxation of venous smooth muscle
- reduced venous return to heart –> monitor BP
Hypokalemia: low levels of Na
-if serum levels fall below 3.5 mEq/L fatal dysrhythmias may occur
- CONSUME K rich foods
Ototoxicity
- hearing impairment/ severity depends on different loop diuretics
Loop Diuretic drug interactions
Dioxin: drug used for heart failure/ cardiac dysrhythmias
- loop diuretics cause hypokalemia
–> increases risk of ventricular dysthymias
Ototoxic: combined with furosemide should be avoided
therapeutic uses of loop diuretics
hypertension
pulmonary edema
cardiac edema
major difference between max diuresis with thiazides and loop diuretics is that
maximal diuresis is lower with thiazides
Thiazide drug name
Hydrochlorothiazide (hydro-chlora-thi-a-zide)
Mechanism of Thiazides
Blocks Na?Cl reabsorption in early segment of distal tubule
- only 10% reabsorbed her = change in urine flow is lower
therapeutic uses of thiazides
FIRST choice for ESSENTIAL hypertensin
- can often by treated with thiazides alone
FIRST choice for EDEMA treatment associated with mild to moderate heart failure
What responses do Potassium-Sparing Diuretics Ellicit
(1) MODEST increase in urine production
(2) Substantial Decrease in Potassium excretion
- usually used in combination to counteract K loss
Drug name for Potassium-Sparing Diuretics
Spironolactone (spira-no-lack-tone)
Mechanism of Potassium- Sparring Diuretics
Blocks action of aldosterone in distal convoluted tubule and collecting duct
Aldosterone acts to increase na/cl reabsorption and increase secretion/excretion of K+
Inhibition of Aldosterone = increased reabsorption of potassium back into interstitial fluid
Potassium- Sparring diuretics adverse effects
Hyperkalemia
- fatal dysrhythmias
Endocrine effects
- spironolactone is a steroid derivative
–> menstrual irregularities, impotence, deepening of voice
—> BLOCKS TESTOSTERONE/ ESTROGEN effects
Therapeutic uses of potassium-sparring diuretics
hypertension and edema
- used with combination with other diuretics
COUNTERACT POTASSIUM-WASTING EFFECTS of other diuretics
HEART FAILURE- reduces mortality in sever heart failure patients
Potassium- Sparring Diuretics drug interactions
don’t combine with ingestion of potassium supplements and other products high in potassium
Mannitol
osmotic diuretic
mechanism of action of mannitol
after IV admin. mannitol is filtered by glomerulus into nephron
- undergoes minimal reabsorption
-creates an increased osmotic pressure in nephron
RESULTS - inhibits passive reabsorption of water
Degree of diuresis directly related to mannitol in tubular filtrate
Pharmacokinetics of mannitol
IV- diuresis begins in 30-60 min
lasts 6-8 hours
excreted intact in urine
Therapeutic uses of mannitol (2)
Prophylaxis of Renal failure
- if blood flow to kidney is decreased= great reduction in filtrate volume
- low filtrate volume = most na/cl reabsorbed (water follows)
- urine production ceases
- kidney failure occurs
- mannitol reduces risk because it is not reabsorbed in nephron
–> preserves urine flow
Reduction of Intracranial pressure (ICP)
- mannitol’s presence in brain blood vessels (cannot pass through BBB)
- creates osmotic force that draws fluid from brain into blood
= reduction ICP
