Renal Pharmacology

Front 1

Cockcroft-Gault formula for estimating GFR

Back 1

Ccr = [(140-age) x lean body weight (in kg)] / (Pcr x 72)

Front 2

Aminoglycoside dosing

Back 2

Loading dose for aminoglycosides depends only on Vd, not on clearance. Typically 2 mg/kg.
Maintenance dose is GFR-adjusted, typically 2 mg/kg every 8 hours.

Front 3

Probenecid and the kidney

Cidofovir and the kidney

Back 3

Probenecid blocks renal secretion of all penicillins and cephalosporins.

Cidofovir is secreted from blood into tubular cells and into the lumen and damages the cells. Give probenecid at the same time to prevent this damage.

Front 4

Imipenem and the kidney

Cilastin and the kidney

Back 4

Imipenem is an antibiotic that's filtered and secreted from blood to renal cells.

Inipenam inside renal tubular cells is hydrolyzed to an inactive and toxic metabolite by the enzyme dehydropeptidase.

Cilastin inhibits dehydropeptidase, reducing the toxicity of imipenem.

Front 5

Proximal tubule diuretics
Examples:
Mechanism and effects:
Secondary effects:
Adverse effects:

Back 5

Carbonic anhydrase inhibitors.
Mechanism and effects: Proximal tubule reabsorbs 65% of Na. Carbonic anhydrase inhibitors block Na+/H+ exchange. Only mild potency.
Secondary effects: H+ is retained--> acidosis. Potassium is lost due to distal Na delivery-->hypokalemia. Can be used for acute mountain sickness...
Adverse effects: Acidosis, hypokalemia, teratogenesis.

Front 6

Loop diuretics
Examples:
Mechanism and effects:
Braking effect:
Secondary effects:
Adverse effects:

Back 6

Furosemide (Lasix), Bumetanide, [Torsemide, Ethacrynic acid.]
Mechanism: Ascending limb of the loop of Henle. Inhibit Na/K/2Cl transport across apical plasma membrane. Very potent.
Braking effect: Rebound sodium retention later may reduce efficacy. May need to administer multiple times a day.
Secondary effects: Increased calcium excretion, increased venous capacitance.
Adverse effects: Hypokalemia (due to transport inhibition), metabolic alkalosis (due to increased Na delivery to distal nephron and increased renin/aldosterone). Hyperuricemia, rare ototoxicity.

Front 7

Thiazide diuretics:
Examples:
Mechanism and effects:
Secondary effects:
Adverse effects:

Back 7

Hydrochlorothiazide (HCTZ), chlorthalidone, indapamide, metolazone.
Mechanism: Distal tubule cells.Inhibit Na/Cl transport across apical plasma membrane. One-a-day dosing.
Secondary effects and uses: Antihypertensive effects independent of diuretic effect! Reduced calcium excretion with long-term use.
Adverse effects: Increased Na delivery to distal nephron and increased aldosterone --> hypokalemia, hyperuricemia, hyperglycemia, hyperlipidemia, hyponatremia.

Front 8

Potassium-sparing diuretics:
Examples:
Mechanism and effects:
Secondary effects:
Adverse effects:

Back 8

Spironalactone, triamterene, amiloride.
Mechanism: Collecting duct. 3-5% of Na reabsorption via Na channels and 3Na/2K exchanger. Spironalactone is an aldosterone antagonist, triamterene and amiloride block Na channels.
Secondary effects: Spiro is helpful at reducing mortality in patients with CHF, while amiloride reduces kidney toxicity.
Adverse effects: Potentially fatal hyperkalemia, metabolic acidosis. Spironolactone-->gynecomastia, hirsutism, impotence.

Front 9

Mannitol
Effects:
Use:
Side effect:

Back 9

Osmotic diuretic.
Effect: Freely filtered, inhibits water reabsorption.
Use: Used to treat cerebral edema.
Side effect: Hyponatremia.

Front 10

Nesiritide:

Back 10

Acts like a natriuretic peptide-->natriuresis, vasodilation.

Front 11

Most frequently used/efficacious:
Add _____ in most severe cases:
_____ are used as monotherapy in mild edema and HTN.
Combinations:
Loop diuretic + thiazide
Thiazide + potassium sparing agent
ACE-inhibitor + thiazide

Back 11

Loop diuretics most frequently used.
Add thiazides in most severe cases, or use them alone for mild edema/HTN.

Loop diuretic + thiazide: Very potent!
Thiazide + potassium sparing agent: Potassium effects of thiazide are balanced, widely used for HTN.
ACE-inhibitor + thiazide: ACE-I reduces K+ loss by inhibiting RAA system. Synergistic for HTN.