Diuretics

Question 1

Carbonic Anhydrase inhibitor

Answer 1

Acetazolamide

Question 2

Osmotic diuretic

Answer 2

Mannitol

Question 3

Loop diuretics (Na/K/2Cl transporter inhibitor)

Answer 3

Furosemide (lasix)

Question 4

Na/Cl tranporter inhibitor

Answer 4

Hydrochlorothiazide

Question 5

ENaC inhibitors (K sparing diuretics)

Answer 5

Amiloride

Question 6

Antagonist of mineralocorticoid receptor

Answer 6

Sprionalactone

Question 7

Vasopressin (ADH) Antagonist

Answer 7

Tolvaptan

Question 8

Diuretic Braking

Answer 8

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.

Question 9

Mechanisms of diuretic braking

Answer 9

Increased sympathetic activity, renin-angiotensin- aldosterone system, ADH release. During Diuresis, a new steady state is reached at a LOWER VOLUME.

Question 10

Clinical Indications for diuretic therapy

Answer 10

Edema, Hypertension

Question 11

Location of action of classes of diuretics in the nephron

Answer 11

PT - Osmotic
TDLH - K sparing
TALH - Loop
DCT - Na/Cl blockers
CD - ENaC, Mineralocorticoid antagonists, ADH antagonists, Osmotic

Question 12

Carbonic anhydrase inhibitors mechanism of action.

Answer 12

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.

Question 13

What happens to urine and plasma if you are on a carbonic anhydrase inhibitor? Why?

Answer 13

You are excreting more HCO3-, so your urine pH and HCO3- increases. Plasma HCO3- decreases and chloride goes up.

Question 14

Uses of Acetazolamide (CAI)

Answer 14

Reducing intraocular pressure, alkalizing urine to help excrete weak acids, metabolic alkalosis, to pee off the bicarbonate.

Question 15

Mechanism of loop diuretics

Answer 15

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.

Question 16

Furosemide ADME and adverse effects

Answer 16

PO or IV, acts in 5 minutes, excreted in urine and metabolized.

Adverse - hypokalemia, hypotension. Can cause cardiac arrythmias including Torsades,and V-Fib.

Question 17

Thiazide diuretics mechanism of action and location.

Answer 17

Inhibition of Na/Cl co-transporter, act in DCT.

Question 18

What happens to urine and plama if you’re on HCTZ?

Answer 18

Urine is hyperosmolar. DECREASED excretion of Ca2+. Plasma HYPOKALEMIC and alkalotic.

Question 19

Uses of HCTZ

Answer 19

Htn, CHF, Hypercalciuria - prevents renal stones, Nephrogenic diabetes insipidus collecting duct. This actually causes fluid concervation.

Question 20

How does HCTZ help in nephrogenic diabetes insipidus?

Answer 20

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.

Question 21

Adverse effects of HCTZ

Answer 21

Electrolyte imbalance
Metabolic alkalosis
Hypokalemia, Hypercalcemia
Hyperuricemia
Hypotension (volume)
Hyperglycemia
Hyperlipidemia

Question 22

How do loops and thiazides lead to loss of potassium and H+?

Answer 22

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.

Question 23

ENaC Blockers mechanism of action

Answer 23

Blockade of sodium channels in collecting duct, independent of aldosterone. Bound to plasma proteins and secreted by organic base transporters directly into the PCT

Question 24

What happens to urine in ENaC blocker use? What problem could this cause?

Answer 24

Decreased K+ excretion, hyperkalemia.

Question 25

Spironolactone mechanism of action

Answer 25

Blocks aldosterone by forming an inactive receptor complex in the collecting duct, decreasing sodium retention.

Question 26

Spironolactone ADME

Answer 26

PO- Induces P450, takes hours- days to work. Only effective if the patient has circulating aldosterone.

Question 27

What happens to urine on spironolactone?

Answer 27

Increased Na, Cl, H20, decreased K+

Question 28

Indications for spironolactone use

Answer 28

In conjunction with thiazide/loops to prevent hypokalemia,

hyperaldosteronism.

Question 29

Osmotic diuretics ADME/mechanism

Answer 29

Inert - freely filtered and poorly absorbed. Increase tubular osmolarity and renal blood flow, draws more water into the filtrate osmotically.

Question 30

Urine and plasma effects of osmotic diuretics

Answer 30

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.

Question 31

Adverse effects of osmotic diuretics

Answer 31

Pulmonary edema, CHF, HA, Nausea, vomiting. Chronic - dehydration, hypernatremia, hyperkalemia.

Question 32

ADH antagonists mechanism of action

Answer 32

Antagonist to ADH at V2 ADH receptors in CD.

Question 33

ADH antagonists ADME and indications

Answer 33

Hepatic activation via CYP3A4, renal and fecal excretion. Used for Systemic Inappropriate ADH (SIADH)

Question 34

Combination therapy - what drugs play well together?

Answer 34

Loop and Thiazide are synergistic

K Sparing can prevent hyponatremia if used with a loop or thiazide.