Where does loop diuretics take action and what does it do?
selective inhibition of NaCl reabsorption in thick ascending limb of Loop of Henle
What are the consequences of loop diuretics?
- inhibits K going back into the urine to create that positive potential to reabsorb Mg and Ca and thus, Mg and Ca are not reabsorbed back into the blood
- induce activity of PGE2 which inhibits activity of macula densa and cannot decrease GFR
What effect does NSAIDs have on loop diuretics?
reduce efficacy
Where does thiazide diuretics take action and what does it do?
inhibit NaCl transport in distal convoluted tubule
What are the consequences of thiazide diuretics?
- Slight increase of blood calcium levels
- induce expression of COX2
How does thiazide diuretics increase Ca levels?
- Volume depletion causes active Na reabsorption in proximal convoluted tubule which causes passive Ca reabsorption
- Distal convoluted tubule blocks reabsorption of Na into the convoluted tubule which causes Na/Ca exchange on the basolateral membrane
- Usually not a problem unless there is secondary condition that also causes hypercalcemia
What effect does NSAIDs have on thiazide diuretics?
reduce efficacy
Where does potassium-sparing diuretics take action and what does it do?
prevent Na absorption, decrease K secretion in collecting tubules
drugs that are loop diuretics
- furosemide
- torsemide
drugs that are thiazide diuretics
hydrochlorothiazide
drugs that are potassium-sparing diuretics
- spironolactone
- eplerenone
- triamterene
How does spironolactone and eplerenone work?
Direct antagonism of aldosterone receptors
What does aldosterone do?
- binds to mineralocorticoid receptors
- they stimulate Na reabsorption through ENaC
- aldosterone also stimulates Na/K
In which patients would spironolactone or eplerenone be best?
if patient has excessive mineralocorticoids or high aldosterone levels
How does triamterene work?
Prevent Na absorption via ENaC –> Na/K inhibits on basolateral side
What is triamterene commonly paired with?
HCTZ
What are the adverse effects of loop diuretics?
- Hypomagnesemia
- Hypocalcemia
- Hypokalemic metabolic alkalosis
- Ototoxicity
- Hyperuricemia
- Drug allergy
- Dehydration
What are the causes of ototoxicity?
Directly due to electrolyte changes
How is hyperuricemia caused in loop diuretics?
Less blood volume leads to increased uric acid concentration and increased uric acid reabsorption in proximal tubule
Why is allergy a concern in loop diuretics?
it is a sulfonamide
What are the adverse effects of thiazide diuretics?
- Slight increase in blood calcium levels
- Hyperuricemia
- Hypokalemic metabolic alkalosis
- Decreased glucose tolerance
- Hyponatremia
- Drug allergy
Why is allergy a concern in thiazide diuretics?
contains sulfa
How is hyperuricemia caused in thiazide diuretics?
- Competes with uric acid for secretion
- usually seen in men under 60
What is the effect on glucose by thiazide diuretics? (with respect to adverse effects)
- Decreased glucose tolerance –> hyperglycemia possible at higher doses of HCTZ
- HCTZ hyperpolarize beta cells –> decrease release of insulin –> increased blood sugar
- Hyperpolarization caused by HCTZ stimulation of potassium sensitive ATP-ase channels in beta cells –> worse in hypokalemic conditions
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Appendix A Product List84
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Diuretics36
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Hypertension - Sharpe78
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Therapeutics of Hypertension119
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Pathophysiology of Dyslipidemia and Atherosclerosis24
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Therapeutics of Dyslipidemia28
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Dyslipidemia drugs68
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Pathophysiology of Hypertension26
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Pathophysiology of Vascular Diseases, Venous16
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Therapeutics of Venous Vascular Diseases62
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Pathophysiology of Arterial Vascular Disease24
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Pharmacotherapy of Peripheral Artery Disease38
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Hospital Course of Treatment for ACS64
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Therapeutics of Coronary Artery Disease129
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Anticoagulants45
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Heart Failure - Big Picture10
