Diuretics Flashcards
What ions are usually excreted when using a diuretic? (2) What ion may be spared?
Sodium, Chloride
Potassium
Where in the nephron is majority of water, potassium and sodium reabsorbed, and urine is isoosmotic with the blood?
The PCT
In what part of the nephron are organic acids actively secreted into the urine? What is the driving force for this secretion?
PCT
Sodium/K+ ATPase on basolateral surface
What 2 parts of the loop of henle are urea impermeable? What part is NaCl impermeable? What part is water impermeable?
Urea - Descending thin, ascending thick
NaCl - Descending thin
Water - Ascending thick
Where is the macula found? What is its function? What is the name for the phenomenon it is critical for?
End of thick ascending limb
Sense osmolality of urine
Tubuloglomerular feedback
What is actively transported out of the distal convoluted tubule? Describe fluid in the DCT relative to blood [hypo, hyper, iso-tonic]? What molecules are unable to pass through DCT? (2)
NaCl is actively transported out of DCT
Fluid is hypotonic
Urea and Water
The DCT is considered the [concentrating/diluting] segment of the nephron
Diluting
Under what circumstance is water able to leave the collecting ducts?
Only is vasopressin is present
What is the only area of the nephron that is permeable to urea?
The collecting ducts
What is the vasa recta? What two molecules escape the nephron and exit via the vasa recta to return to circulation?
Network of blood vessels surrounding the nephron
NaCl enter vasa recta, water follows
What is a diuretic?
increases solute excretion to increase the volume of urine
What is an aquaretic?
Increase water but not solute excretion
What is a natriuretic?
Increases excretion of sodium
What is a saluretic?
Increases the excretion of sodium and chloride
What is a kaliuretic?
Increases the excretion of potassium
What are 2 conditions that diuretics are used to treat?
Hypertension
Edema
What are the primary and secondary sites of action of carbonic anhydrase inhibitors?
Primary - PCT lumen
Secondary - distal collecting duct
What is the major effect of carbonic anhydrase inhibitors in the nephron?
Cause excretion of sodium bicarbonate. Usually sodium bicarb is reabsorbed to acidify urine, blocking carbonic anhydrase prevents that process
What is carbonic anhydrase inhibitors expected to cause? Metabolic acidosis / alkalosis?
They cause acidosis, so can be used to treat metabolic alkalosis
Carbonic anhydrase inhibitors affect the secretion of the following ions: Na, K, H, HCO3 and H2PO4. Which are increased and which are decreased?
Na, K, HCO3 and H2PO4 increased. H decreased (can't acidify urine, stays in system)
What is the example of the carbonic anhydrase inhibitor provided? Why is it regarded as a potassium wasting drug?
Acetazolamide
A lot of Na+ reaches the distal nephron, K+ exchanged to absorb in. Exchanged K+ is excreted
What are 4 uses of acetazolamide?
Open angle glaucoma
Presurgical pressure reduction in glaucoma
Altitude sickness
Treating diuretic induced metabolic alkalosis
What are 4 side effects of acetazolamide?
Metabolic acidosis
Allergy
Kidney stones
Bone marrow depression, paresthesia, tingling
What patients should not use acetazolamide?
Liver cirrhosis - Renal ammonia returns to system, can worsen cirrhosis
What is the mechanism of osmotic diuretics? What is the effect on the medullary salt gradient? What is the primary site of action in the nephron?
Draws water from tissues into blood, increase renal blood flow
It washes out the gradient
Loop of Henle
What is the effect of osmotic diuretics on ADH activity?
Prevents the action of ADH (water reabsorption) because salt gradient is disrupted
Osmotic diuretics increase the excretion of essentially all ions. What is the exception?
Hydrogen (acid)
What are the 2 examples of osmotic diuretics provided?
Glycerin
Mannitol
What are 4 uses of osmotic diuretics?
Acute renal failure
Acute tubular necrosis
Dialysis disequilibrium (too much solute removal)
Mannitol - Reduce brain swelling before neurosurgery
What are 3 adverse effects associated with osmotic diuretics?
Hyponatremia
Hyponatremia and dehydration
Hyperglycemia (Glycerin metabolism)
What are 3 populations that should be cautious about using osmotic diuretics?
Pulmonary congestion - Can become pulmonary edema
Patients with Anuria
Patients with intracranial bleeding (Mannitol)
What is the primary site of action of the loop diuretics? How do they enter the urine?
Thick ascending limb of loop of Henle
Organic ion transporters in proximal tubules
What is the specific transporter inhibited by the loop diuretics? What is its effect on the medullary ion gradient? What is its effect on urine volume and concentration?
Na, K, Cl Symporter
Diminishes the ion gradient
Increases urine volume, Increased concentration
What is the effect of loop diuretics on ion excretion? Which are spared?
All ion excretion is increased. None are spared
What are the 4 examples of loop diuretics provided? Which is uniquely metabolized in the kidney (glucuronidation)?
Furosemide (Glucuronidation in kidney)
Bumetanide
Ethacrynic acid
Torsemide
Among the loop diuretics, which is also a weak carbonic anhydrase inhibitor and can increase venous capacitance? Being able to increase venous capacitance makes this drug useful for what 2 conditions?
Furosemide
Heart failure, pulmonary edema
How do loop diuretics circumvent limits of salt excretion i.e. referred to as high ceiling diuretics?
Prevent salt transport into the macula, therefore no tubuloglomerular feed back to alter excretion rates
What are 4 uses of loop diuretics?
Acute pulmonary edema
Congestive heart failure
Nephrotic Syndrome
Edema and ascites from cirrhosis
What class of diuretic is likely to cause hyponatremia, hypokalemia, volume depletion and metabolic alkalosis?
Loop diuretics
Regarding mechanism, how thiazide diuretics work?
They block the sodium chloride symporter. No effect on potassium symport
How do the thiazide diuretics get to the urine? What part of the nephron do they act on?
Enter urine via organic ion transporters in proximal tubule
Act in distal convoluted tubule
What is the difference between the symporters targeted by loop diuretics and thiazide diuretics?
Loop - Na, Cl, K symporter
Thiazide - Na, Cl symporter
What is the source of energy for the NaCl symporter?
basolateral Na+/K+ antiporter
What is the one ion whose excretion is decreased during use of thiazide diuretics? Why?
Calcium excretion is decreased
Activity of the Na-Ca antiporter
Why are thiazide diuretics not limited by tubuloglomerular feedback? What can happen to plasma calcium with prolonged use of thiazide diuretics?
They act distal to the macula
Plasma calcium can go up
What are the two examples of thiazide diuretics provided? What is the example of thiazide like provided (1)?
Thiazide - Hydrochlorothiazide and Chlorothiazide
Thiazide like - Metolazone
How does half life influence the use of thiazide and thiazide like diuretics?
Long half like (metolazone) - Hypertension
Short half life (Hydrochlorothiazide and Chlorothiazide) - acute diuresis
What are 4 uses of thiazide diuretics?
Hypertension
Edema from CHF
Nephrogenic diabetes
Calcium nephrolithiasis
Hypotension, hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia and hyperuricemia. These are all potential side effects of _
Thiazide diuretics
What patient population should not use thiazide diuretics? What drug class decreases diuretic response? What drug increases the effective dose?
People with sulfonamide sensitivity
NSAIDs
Probenecid
What are the 2 examples of inhibitors of renal sodium channels provided? Where do the function? What is their net effect?
Amiloride and Triamterene
Distal convoluted tubule, collecting duct
Slight increase in sodium excretion, Potassium SPARING
Renal sodium channel blockers are diuretics that decrease the secretion of most ions. What are the 2 exceptions i.e. what 2 ions are secreted more with sodium channel blockers?
Sodium and chloride
Where is triamterene metabolized?
Liver
What is the effect of amiloride and triamterene on potassium reabsorption?
Strongly increases K+ reabsorption
How can the effects of the renal sodium channel blockers be enhanced?
Co-admin with loop or thiazide diuretics. This also reduces the loss of potassium
In what sub-population are the renal sodium channels particularly effective? Why? What syndrome is it used to treat? How can it be used in cystic fibrosis
5% African Americans
They have a mutation in ENaC beta subunit
Liddle syndrome
Used to clear mucus in CF patients (aerosol)
What are 2 serious side effects of renal sodium channel blockers? What class of drug may reduce their diuretic efficiency?
Hyperkalemia (can lead to cardiac arrhythmia/death)
Megaloblastic anemia (triamterene)
NSAIDs
What are the 2 examples of mineralocorticoid antagonists provided? How do they work? Where do they work?
Spironolactone and Eplerenone
They antagonize the mineralocorticoid receptor (Aldosterone)
Distal convoluted tubule and collecting duct
What is they function of aldosterone? How does it work? What is a major trigger for its signalling?
Salt and water retention, increased secretion of K+ and protons
Induces transcription of proteins that activate silent sodium channels to increase sodium retention
Dehydration
In addition to the renal sodium channel blockers, what other group of drugs are potassium sparing?
Mineralocorticoid receptor antagonists
Mineralocorticoid receptor blockers are diuretics that decrease the secretion of most ions. What are the 2 exceptions i.e. what 2 ions are secreted more with mineralocorticoid receptor blockers?
Sodium and chloride
To mitigate the great increase in potassium secretion by loop and thiazide diuretics, what is usually coadministered with these drug?
Mineralocorticoid antagonists
Renal sodium channel blockers
What are 3 uses for spironolactone?
Primary hyperaldosteronism Secondary hyperaldosteronism (heart failure, cirrhosis, ascites, nephrotic syndrome) Ascites and edema
What is the major side effect associated with the use of mineralcorticoid antagonists? What is a second concern regarding other hormones?
Hyperkalemia
Can cross react with other steroid receptors (feminization, menstrual irregularities)
What class of drug decrease the diretic effect of mineralocorticoid receptor blockers
NSAIDs (same effect on renal sodium channel blockers)
Because of its ability to cause diarrhea, gastritis, gastric bleeding, for what group of patients is mineralocorticoid receptor blockers contra-indicated?
Patients with peptic ulcers
What is a draw back from the prolonged use of spironolactone?
Development of malignancies
What are the 2 examples of antidiuretic drugs provided? How are they related?
Vasopressin (ADH) and Desmopressin (DDAVP)
DDAVP is synthetic analog of vasopressin
What receptor subtypes do vasopressin and desmopressin bind?
Vasopressin - V1 and V2
Desmopressin - V2 mainly
What is arginine vasopressin?
Synthetic intranasal or subQ form of vasopressin
What is the effect of activating the V1 subtype of the vasopressin receptor?
Reduced medullary blood flow, increased medullary salt gradient and more water reabsorption
What is the effect of activating the V2 subtype of the vasopressin receptor? (3)
- More aquaporins in membrane
- More urea permeability (distal duct)
- Increased Na, K and Cl symporter activity (thick ascending limb)
What is vasopressin used for?
Diabetes insipidus
What are 2 side effects of vasopressin?
Coronary artery constriction
Water intoxication
What is the effect of chlorpropamide?
Increases the secretion of ADH
Beyond its use as a diuretic, what is another use for amiloride?
Used to treat lithium induced diabetes insipidus, blocks sodium channel uptake of lithium
What causes the pain associated with gout? What are 3 drugs that can be used to treat it?
Presence of urate crystals in tissues and joints
Probenecid, allopurinol, colchicine
What is the mechanism of action of allopurinol?
Blocks conversion of xanthine to uric acid by inhibiting xanthine oxidase
What is the effect of colchicine?
Blocks neutrophil activity
What is the biphasic effect of uricosuric agents?
First - decrease uric acid secretion
Second - In lumen, block uric acid reabsorption, increased excretion rate
What are 2 major considerations / side effects of probenecid?
Increased risk of kidney stones
Interferes with renal excretion of several drugs (e.g. thiazide diuretics)
