Diuretics Flashcards
Carbonic Anhydrase inhibitor
Acetazolamide
Osmotic diuretic
Mannitol
Loop diuretics (Na/K/2Cl transporter inhibitor)
Furosemide (lasix)
Na/Cl tranporter inhibitor
Hydrochlorothiazide
ENaC inhibitors (K sparing diuretics)
Amiloride
Antagonist of mineralocorticoid receptor
Sprionalactone
Vasopressin (ADH) Antagonist
Tolvaptan
Diuretic Braking
The process by which the body adapts to diuresis. Diuretics cause a temporal increase in Na and H2O excretion. Compensatory mechanisms decrease excretion, creating a new steady state.
Mechanisms of diuretic braking
Increased sympathetic activity, renin-angiotensin- aldosterone system, ADH release. During Diuresis, a new steady state is reached at a LOWER VOLUME.
Clinical Indications for diuretic therapy
Edema, Hypertension
Location of action of classes of diuretics in the nephron
PT - Osmotic TDLH - K sparing TALH - Loop DCT - Na/Cl blockers CD - ENaC, Mineralocorticoid antagonists, ADH antagonists, Osmotic
Carbonic anhydrase inhibitors mechanism of action.
If you inhibit luminal carbonic anhydrase, you can’t split H2CO3 into H2O and CO2 so it can diffuse into the epithelium of the PCT. This means that you can’t use the Na/H exchanger to pump Na out of the lumen.
Now you have more HCO3- in the lumen, making it more negatively charged. This keeps cations, like Na+ in the lumen.
What happens to urine and plasma if you are on a carbonic anhydrase inhibitor? Why?
You are excreting more HCO3-, so your urine pH and HCO3- increases. Plasma HCO3- decreases and chloride goes up.
Uses of Acetazolamide (CAI)
Reducing intraocular pressure, alkalizing urine to help excrete weak acids, metabolic alkalosis, to pee off the bicarbonate.
Mechanism of loop diuretics
Inhibits Na/K/2Cl SYMPORTER. This causes the positive luminal potential to deminish, decreasing cation reabsorbtion. It also causes hypochloremia, because you can’t reabsorb Cl. Excretion of ALL IONS, except Ca2+ increases, leading to plasma hypochloremia and HYPOKALEMIA.
Furosemide ADME and adverse effects
PO or IV, acts in 5 minutes, excreted in urine and metabolized.
Adverse - hypokalemia, hypotension. Can cause cardiac arrythmias including Torsades,and V-Fib.
Thiazide diuretics mechanism of action and location.
Inhibition of Na/Cl co-transporter, act in DCT.
What happens to urine and plama if you’re on HCTZ?
Urine is hyperosmolar. DECREASED excretion of Ca2+. Plasma HYPOKALEMIC and alkalotic.
Uses of HCTZ
Htn, CHF, Hypercalciuria - prevents renal stones, Nephrogenic diabetes insipidus collecting duct. This actually causes fluid concervation.
How does HCTZ help in nephrogenic diabetes insipidus?
This is a wierd one - Decreased plama volume lowers GFR, leading to REABSORBTION of Na in PT, reducing the amount of Na that reaches the collecting duct.
Adverse effects of HCTZ
Electrolyte imbalance Metabolic alkalosis Hypokalemia, Hypercalcemia Hyperuricemia Hypotension (volume) Hyperglycemia Hyperlipidemia
How do loops and thiazides lead to loss of potassium and H+?
Pumping more Na into the lumen pushes more K into the cells
Principal cells - secrete more K through channels.- higher luminal K
alpha intercalated cells - Higher luminal K causes a more active H+/K exchange - push H+ into the lumen.
ENaC Blockers mechanism of action
Blockade of sodium channels in collecting duct, independent of aldosterone. Bound to plasma proteins and secreted by organic base transporters directly into the PCT
What happens to urine in ENaC blocker use? What problem could this cause?
Decreased K+ excretion, hyperkalemia.
Spironolactone mechanism of action
Blocks aldosterone by forming an inactive receptor complex in the collecting duct, decreasing sodium retention.
Spironolactone ADME
PO- Induces P450, takes hours- days to work. Only effective if the patient has circulating aldosterone.
What happens to urine on spironolactone?
Increased Na, Cl, H20, decreased K+
Indications for spironolactone use
In conjunction with thiazide/loops to prevent hypokalemia,
hyperaldosteronism.
Osmotic diuretics ADME/mechanism
Inert - freely filtered and poorly absorbed. Increase tubular osmolarity and renal blood flow, draws more water into the filtrate osmotically.
Urine and plasma effects of osmotic diuretics
Urine - Increased volume and electrolytes, decreased osmolality, INCREASED Magnesium.
Plasma - first, hyponatremia as mannitol draws fluid into vasculature, then hypernatremia as more water is excreted.
Adverse effects of osmotic diuretics
Pulmonary edema, CHF, HA, Nausea, vomiting. Chronic - dehydration, hypernatremia, hyperkalemia.
ADH antagonists mechanism of action
Antagonist to ADH at V2 ADH receptors in CD.
ADH antagonists ADME and indications
Hepatic activation via CYP3A4, renal and fecal excretion. Used for Systemic Inappropriate ADH (SIADH)
Combination therapy - what drugs play well together?
Loop and Thiazide are synergistic
K Sparing can prevent hyponatremia if used with a loop or thiazide.
