Diuretics Flashcards
Drug class: Acetazolamide
Carbonic Anhydrase Inhibitor
Drug class: Mannitol
Osmotic diuretic
Drug class: Furosemide
Na+/K+/2Cl- Transporter inhibitor (Loop diuretic)
Drug class: Hydrochlorothiazide
Na+/Cl- transporter inhibitor (Thiazide diuretics)
Drug class: Amiloride
Inhibitor of ENaC (“K-sparing” diuretics)
Drug class: Spironolactone
Antagonists of mineralocorticoid receptor (Aldosterone antagonist)
Drug class: Tolvaptan
Antagonists to vasopressin (ADH)
What is diuretic braking?
Diuretics cause a temporal increase in excretion of Na+ and H2O. Compensatory mechanisms then diminish excretion, so that excretion is again equal with sodium and water intake, and a new steady state is achieved (lower fluid volume).
What are the two indications of diuretics?
- Edematous states (CHF, pulmonary edema, nephrotic syndrome, hepatic cirrhosis)
- Hypertension (essential and secondary).
Describe the mechanism of Acetazolamide:
Secreted into the PCT by organic anion transporter. By reducing the effect of CA, there is increased HCO3- and H+ in the lumen (H2CO3) and therefore reduced activity of the H+/Na+ antiporter in the PCT, and therefore reduced Na+ uptake in the PCT.
In addition, HCO3- trapped in the lumen increases electronegativity causing increased Na+ and K+ secretion in the CD, and increased Cl- reabsorption in the CD.
What are some side effects of Acetazolamide?
Increased HCO3- secretion causes increased urine pH (8). Increased solute delivery to macula densaa causes reduced gloemrular flow (lower GFR).
Potential electrolyte disturbances: metabolic acidosis due to HCO3- wasting and H+ retention. Hypokalemia and hyperchloridemia.
Acetazolamide: indication
Reducing intraocular pressure (topical preps); Urinary alkalinization (improved excretion of weak acids); to correct metabolic alkalosis.
Furosemide: mechanism
- Secreted into lumen by OATs at PCT
- Blocks activity of Na/K/2Cl- cotransporter
Result is more excretion of Na, K+, Cl-, Mg2+, H+, Ca2+. Abolishes corticomedullary osmotic gradient
Furosemide: side effects
Hypokalemia; Hypotension; also hypochloremia, metabolic alkalosis
HCTZ: mechanism
- Secreted into lumen by OATs
- Blocks activity of Na+/Cl- symporter in DCT
- Increased distal sodium delivery increases secretion of K+, H+
HCTZ: indications
Aside from usual (HTN, CHF), used to prevent renal stones (hypercalciuria) and as treatment for nephrogenenic diabetes insipidus (renal insensitivity to ADH- provide for fluid retention).
HCTZ: adverse
- Hypokalemia, metabolic alkalosis, hypercalcemia, hyperuricemia.
- Hyperglycemia in pts with diabetes/abnormal glucose tolerance
- Hyperlipidemia
Amiloride: mechanism
- Secreted into tubule by OCT in PCT
- Blocks ENaC channel in CD.
- Less Na+ in cells of the CD leads to K+ retention
* Independent of effect of Aldosterone on ENaC channels
Amiloride: Adverse
Hyperkalemia
Spironolactone: Mechanism
*NOT secreted into tuble. Active metabolite is Instead blocks the action of aldosterone on the CD by entering the basolateral side, binding to mineralocorticoid receptor in the cells of the CD. The result is less expression of ENaC channels, and less activity/expressoin of Na/K ATPase. Less Na is reabsorbed in the CD, and less K+ is wasted.
**Ineffective w/o circulating aldosterone
Spironolactone: Adverse
Hyperkalemia, gynecomastia in males, menstrual irregularities in females
Mannitol: mechanism
Pharmocologically inert. Filtered in glomerulus, not reabsorbable. Increases filtrate osmolality and decreases the osmotic gradient. Increases renal blood flow, further reducing corticomedullary gradient.
Mannitol: route, adverse
IV only (not absorbed orally).
Acute: hyponatremia (moving fluid into extracellular compartment)
Later: Hypernatremia since relatively more water is excreted. Hypomagnesemia due to increased Mg excretion. Hyperkalemia.
Mannitol: indication
Rapid reduction in intracranial and intraocular pressure before and after surgery.
Tolvaptan: mechanism
Acts as antagonist of ADH on V2 ADH receptors in basolateral membrane of the collecting duct. Result is increased urine volume and decreased osmolality.
Tolvaptan: Indication
Syndrome of inappropriate ADH.
Describe how diuretics can be used in combination for CHF:
- Give thiazide diuretic, if inadequate response…
- Switch to loop diuretic. If inadequate response…
- Increase dosage of loop. If inadequate response…
- Add thiazide diuretic to Loop. If inadequate response…
- Add K+ sparing diuretic
Describe yow to manage K+ in patients on loop diuretics
- Advise patients that Na restriction and K supplementation can help with low K levels.
- When conservative management is unsuccessfule, the patient can be placed on a K+ sparing diuretic.
