Cardiovascular Pharmacology Flashcards
Explain the complication of hyperuricemia due to dieuretics
Some diuretics bind to a receptor on the apical side of the cell so they have to use the organic acid and base secreting systems to cross the cell. Uric acid also uses the same system so the diuretics will outcomete uric acid → hyperuricemia
Function of the thick ascending loop of Henle:
Na/K/Cl reabsorption secondary to reabsorption of Ca and Mg.
(NK2Cl transporter)
Where can you find ENaC transporters in the nephron?
At the cortical collecting duct (Na reabsorption, K and H SECRETION)
_____ and _____ are secreted in the CD
H+ and K+
What are some non edematous states that diuretics can be useful to treat?
- HTN
- hypercalcemia
- Diabetes insipidus
What happens to the urine output in a patient given a diuretic to treat diabetes insipidus?
- ↓ urine output (all others cases they diuretic will ↑ urine output)
What are 6 families of diuretics?
- loop diuretics: furosemide
- thiazides: hydrochlorothiazide, chlorthalidone, metolazone
- potassium sparing diuretics: spironolactone, eplerenone, triamterene, amiloride
- Carbonic anhydrase inhibitors: acetazolamide
- osmotic agents: mannitol
- ADH antagonists: conivaptan
Which class of diuretics acts at the proximal tubule?
Carbonic anhydrase inhibitors (acetazolamide)
Thiazides exert their effects on the _____
DCT
Where do K sparing diuretics work?
Collecting duct (same as ADH antagonists)
________ work at all areas of the nephron
Osmotic agents
___________ diuretics are the most efficacious in removing Na and CL from the body and act on _______
Furosemide (-emide) which is a loop diuretic;
Ascending limb of loop of Henle
Where in the nephron can you expect to see the triple co transporter Na/K/2Cl on the luminal side?
Ascending loop of Henle
What is the use of the ROMK channel on the __________ side of the tubular cells in the loop of Henle?
Luminal;
Because there is no way from K to exit the cell (lumen → cell and blood → cell) the ROMK channel on the luminal side takes the K form the cell and pushes it into the lumen
What is the MOA of loop dietetics?
Block NKCC2 triple co transporter on the luminal side on the ascending limb of the loop of Henle
Normally at the luminal side of the ascending limbo of loop of Henle there is a ___________ potential that facilitates _______________
Positive;
Absorption of: Na, Ca, Mg
Loop diuretics changes the luminal potential from ___ to ____ which results in _________
Positive → negative
SECRETION of: Na, Ca, Mg
Loop diuretics ______ renal vascular resistance resulting in _______ and _______
- ↓; increased renal blood flow and ↑ prostaglandin synthesis
Ototoxicity is a AE of which kind of diuretic?
Loop diuretic
What are some AE ‘s of loop diuretics?
- ototoxicity
- allergic reactions
- hyperuricemia
- acute hypovolemia
- K depletion
- hypomagnesemia
Loop diuretics will cause ↑ urinary excretion of:
- Na
- K
- Mg
- Ca
- urine volume
What are the 3 drugs that are thiazides and where do they act on?
- hydrochlorothiazide
- chlothalidone
- metolazone
Act on the distal tubule
What class of diuretics would you give to prevent renal stones or in patients with hypercalciuria?
Thiazides (hydrochlorothiazide, chlorthalidone, metolazone) because they INHIBIT calcium excretion
What is the MOA of thiazides?
BLOCKS the activity of the Na/Cl symporter on the luminal side
Will you high or low levels of potassium in the urine in someone taking thiazides?
Higher levels of potassium because when thiazides work on the distal tubule there is ↑ Na in thelumen so the CD will try to compensate and reabsorb some of the Na but exchanges Na for K (Na absorption in return for K excretion)
How does the blocking of NCC transporter affect the movement of calcium?
Blocking of the absorption of Na on the luminal side will then cause ↑ activity of the Ca/Na antiport on the basolateral side becuase it will push Na into the cell and calcium into the blood
On the luminal side there is a calcium channel that brings calcium from the lumen into the cell so ↑ activity fo the Na/Ca transporter will ↑ calcium absorption
What are the action of thiazides?
- ↑ Na and Cl excretion
- ↑ K excretion
- ↑ Mg excretion
- ↓ urinary calcium excretion
- ↓ peripheral vascular resistance due to ↓ blood volume
Long term effects of thiazides are due to _________
↓ peripheral vascular resistance; NOT due to ↑ in urine output
How long can a patient expect to see the effects of taking a thiazides?
1-3 weeks
Which thiazide drug has a long duration of action so that you only have to take it once a day
Chlorthalidone
__________ is the most potent thiazide
Metolazone
Metolazone is a ___________
The most potent thiazide
Hyperglycemia/ hypoglycemia is an adverse effect of thiazides
Hyperglycemia
Reasoning: release of insulin in K+ dependent and thiazides can cause hypokalemia thus hindering release of insulin
Patient has HTN and is given a diuretic but now has ↑ glucose levels. What kind of drug was he given?
Thiazide diuretic
What are some unique adverse effects of thiazides?
- hyperglycemia
- hyperlipidemia
- hypersensitivity
- sexual dysfunction
Sexual dysnfucntion is a major complaint after taking what type of diuretic?
Thiazide
Thiazides cause ↑ urinary excretion of:
- Na
- K
- Mg
- urine volume
K sparing drugs are given for the diagnosis and treatment of ______
Primary hyperaldosteronism
K sparing diuretics act mainly on _________
Collecting tubule, specifically on aldosterone which inc. ENaC and ROMK on the luminal side
What is the mechanism of action of aldosterone in the collecting tubule?
It ↑ EnaC (Na absorption) and also ↑ ROMK (K secretion)
ENaC and ROMK are on the luminal side
What is the MOA of K sparing diuretics?
Blocks the effects of aldosterone on ENaC (Na absorption) and on ROMK (K secretion) in the collecting duct
Gastric upset and peptic ulcers is an adverse effect of ________
K sparing diuretics (spironolactone, eplerenone)
What are some adverse effects of K sparing diuretics
- peptic ulcers and gastric upset
- anti androgen endocrine effects
- hyperkalemia
- nausea, lethargy and mental confusion
Which K sparing diuretic drugs work SOLELY on the Na channel?
- amiloride
- triameterene
What is the benefit of drugs like amiloride and triameterene vs sprionolactone?
↓ Na reabsorption and ↓ K excretion in the K sparing diuretics that act on only the sodium channels
___________ is a carbonic anhydrase inhibitor that acts on the _________
Acetazolamide; Proximal Tubule
What are some clinical applications of carbonic anhydrase inhibitors?
- glaucoma
- epilepsy
- mountain sickness prophylaxis
- metabolic alkalosis
these inhibitors cause the movement of HCO3 into the urine
What is the MOA of acetazolamide?
Acetazolamide is a carbonic anhydrase inhibitor that acts on the proximal tubule
Blocks carbonic anhydrase and this causes ↓ absorption of water and Na because carbonic anhydrase catalzyues the breakdown of H2CO3 into H and HCO3 and the H ion is transported out into the lumen via a Na/H exchanger (H pushed into lumen and Na pushed into cell from the lumen)
Acetazolamide inhibits _________ carbonic anhydrase
Intracellular
What is the effect of acetazolamide on the urinary pH?
Will ↑ pH because HCO3 is retained in the lumen
Adverse effects of carbonic anhydrase inhibitors:
- metabolic acidosis
- hyponatremia
- hypokalemia (due to the body’s compensatory mechanism to try to reabsporb more sodium in exchange of K)
- crystalluria (due to ↑ bicarbonate in the urine ↑ PH)
Hyperkalemia is an AE when giving what type of diuretic?
K sparing diuretics
What diuretic is given for glaucoma, prophylaxis for mountain sickness and epilepsy?
Acetazolamide; (carbonic anhydride inhibitor that is usually not used as a diuretic)
Mannitol _______ osmotic pressure of the plasma and effects Na excretion ________
↑; indirectly
What is the effect of mannitol on urine volume?
INCREASES
Mannitol is given via _____
IV
Osmotic diuretics are contraindicated in _______ and _______
CHF and pulmonary edema
___________ is an ADH antagonist
Conivaptan;
What are some clinical uses for conivaptan?
It is an ADH antagonist so use it for:
- euvolemic or hypervolemic hyponatremia
- SIADH
What’re some adverse effects of conivaptan?
- infusion site reactions
- thirst
- atrial fibrillation
- GI and electrolyte disturbances
- nephrogenic diabetes insipidus
