test 6 part 2 Flashcards
Diuretics
Increase the volume of urine excreted
Proximal convoluted tubule reabsorption
Almost 100%: glucose, amino acids, metabolites
65%: H2O, Na, Cl, K, bicarbonate
Proximal convoluted tubule secretion
H+
Organic acids and bases
Catecholamines
Drugs/toxins
Descending loop of henle
- H2O reabsorbed
Ascending loop of henle reabsorbed
Impermeable to water!
25%: Na, Cl, K
Ca, bicarbonate, magnesium
Ascending loop of henle secreted
H+
Early Distal convoluted tubule
Impermeable to water!
5%: Na, Cl, K reabsorbed
Late distal tubule and cortical collecting tubule reabsorbed
H2O in the presence of Antidiuretic hormone (ADH) Principal cells - Na+ Intercalated cells - Bicarb, K+, and H+
Late distal tubule and cortical collecting tubule excreted
Principal cells
- K+
Intercalated cells
- Bicarb, K+, and H+
Medullary collecting duct reabsorbed
10%: Na, H2O (when ADH present)
Urea
Medullary collecting duct secreted
H+
Common uses of diuretics
Hypertension Edema associated with Congestive heart failure Liver cirrhosis Corticosteroid therapy Renal dysfunction
Types of diuretics
Thiazide Loop Potassium-Sparing Carbonic Anhydrase Inhibitors Osmotic
Thiazide diuretics
Most widely used
Affect distal convoluted tubule
All have same Emax, different potencies
Effective orally
1-3 weeks for stable blood pressure reduction
- “low ceiling diuretics” = giving more than therapeutically required won’t do anything
Thiazide diuretics affect which transporter
- Na/Cl cotransporter on luminal membrane
- in distal convoluted tubule
Thiazide diuretics enter lumen where and how
- Secreted into the lumen in the proximal tubule via the organic acid secretory system
Thiazide diuretic actions
Increased excretion of Na and Cl
Very hyperosmolar urine
Unique to thiazides
Loss of K+ (Na/K countertransport mech on luminal side)
Sodium concentration in filtrate is high when it reaches distal tubule
More K+ is exchanged for Na+
Loss of Mg2+ (supplementation of Mg2+ required with chronic use)
Decreased excretion of calcium
Increased reabsorption in distal convoluted tubule
Reduced PVR
Over time volume status returns but PVR remains low
Thiazide diuretics therapeutic uses
Hypertension
Heart failure
Hypercalciuria
Diabetes insipidus
Thiazide diuretics adverse effects
Potassium depletion Hyponatremia Hyperuricemia Volume depletion Hypercalcemia Hyperglycemia
Loop diuretics
Major action on ascending Loop of Henle
Act on luminal side
Highest efficacy in removing Na+ and Clfrom
the body
Produce copious amounts of urine
Oral or IV
Rapid onset, short duration (2-4 hours)
- greatest diuretic effect
Loop diuretics act on what transporter
- Na/2Cl/K cotransporter luminal membrane
- ascending loop of henle
Loop diuretics and renal blood flow
Quick response
May increase renal blood flow due to prostaglandin synthesis
NSAIDS inhibit renal prostaglandin synthesis and can reduce the diuretic action
Loop diuretics therapeutic uses
Peripheral and pulmonary edema (HF)
Emergency situations (Acute pulmonary edema)
Hypercalcemia
Hyperkalemia
- Diuretic of choice even in patients with compromised renal function
Loop diuretics perfusion uses
Remove extra fluid on CPB
Treat hyperkalemia
Help maintain urine production and renal function
Adult pump dose of loop diuretics
20-40 mg bolus
Loop diuretics adverse effects
Ototoxicity Hyperuricemia Acute hypovolemia Potassium depletion Hypomagnesemia
Potassium-sparing diuretics: aldosterone antagonists
Block aldosterone action
Mediator proteins that normally stimulate the Na+/K+ pump are not produced
Retention of K+
Excretion of Na+
Potassium-sparing diuretics: aldosterone antagonists therapeutic uses
Diuresis
Low efficacy in removing Na+ from body
Useful for retention of K+
Given in conjunction with thiazide or loop diuretics
Secondary hyperaldosteronism
Hepatic cirrhosis
Nephrotic syndrome
Heart failure
Resistant hypertension
Ascites
Polycystic ovary syndrome (high androgen levels)
Potassium-sparing diuretics: aldosterone antagonists adverse effects
Gynecomastia in male patients
Menstrual irregularities in female patients
Hyperkalemia
Mental confusion
Potassium-sparing diuretics: Sodium channel blockers
- the Na/K counterstransport blocked
Not very efficacious
Used in combination with other diuretics for potassium sparing effects
Prevent the loss of potassium that occurs with thiazide and loop diuretics
Potassium-sparing diuretics: Sodium channel blockers adverse effects
Increased uric acid
Renal stones
K+ retention
Carbonic Anhydrase inhibitors
Much less efficacious than thiazide or loop diuretics
Often used for other pharmacologic actions
Inhibits carbonic anhydrase of proximal tubule
Carbonic Anhydrase inhibitors therapeutic uses
Glaucoma
Correction of metabolic alkalosis
Mountain sickness
Osmotic diuretics - Mannitol (osmitrol)
Alcohol and a sugar (similar to xylitol or sorbitol)
Not absorbed orally
IV
Osmotic diuretics - Mannitol (osmitrol) mechanism of action
Elevates blood plasma osmolality
Enhanced flow of water from tissues into the plasma
Elevates tubular filtrate osmolality
Filtered, but not reabsorbed
Facilitates water excretion
Reduces water reabsorption
Inhibits reabsorption of sodium, chloride, and other solutes
Osmotic diuretics therapeutic uses
Reduce intracranial pressure Acute renal failure Shock Drug toxicity Trauma Maintaining urine flow preserves long term kidney function!