Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Clinical Correlate

Osmotic diuretics are contraindicated in CHF and pulmonary edema because they draw water from the cells and increase the filling pressures of the heart.

Hypokalemia and Alkalosis

Diuretics that block Na+ reabsorption at segments above the collecting ducts will increase sodium load to the collecting tubules and ducts (“downstream”). This results in increased loss of K+ → hypokalemia, and in the case of both loop and thiazide diuretics the associated loss of H+ results in alkalosis.

OSMOTIC DIURETICS

λMannitol (IV) inhibits water reabsorption throughout the tubule.

λIt increases urine volume.

λUses:

−↓ IOP in glaucoma

−↓ intracerebral pressure

−Oliguric states (e.g., rhabdomyolysis)

λSide effects: acute hypovolemia

CARBONIC ANHYDRASE INHIBITORS

Figure III-1-2. Actions of Carbonic Anhydrase Inhibitors

λDrugs: acetazolamide and dorzolamide

λMechanism: carbonic anhydrase inhibition, results in:

−↓ H+ formation inside PCT cell

−↓ Na+/H+ antiport

−↑ Na+ and HCO3− in lumen

−↑ diuresis

λUses:

−Glaucoma

−Acute mountain sickness

−Metabolic alkalosis

Figure III-1-3. Actions of Loop Diuretics on the Thick Ascending Loop (TAL)

λDrugs: furosemide, torsemide, and ethacrynic acid

λMechanism: Na+/K+/2Cl− transporter inhibition, results in:

−↓ intracellular K+ in TAL

−↓ back diffusion of K+

−↓ positive potential

−↓ reabsorption of Ca2+ and Mg2+

−↑ diuresis

λUses:

−Acute pulmonary edema

−Heart failure

−Hypertension

−Refractory edemas

−Anion overdose

−Hypercalcemic states

Note

Allergies to SulfonamideContaining Drugs

Cross allergenicity with:

λCarbonic anhydrase inhibitors

λAll loop diuretics, except ethacrynic acid

λThiazides

λSulfa antibiotics

λCelecoxib

Clinical Correlate

An important difference between loops and thiazides is that loops promote calcium excretion, while thiazides decrease calcium excretion.

Clinical Correlate

Thiazides also hyperpolarize both smooth muscle cells (vasodilation) and pancreatic beta cells (decrease insulin release)

THIAZIDES

Figure III-1-4. Actions of Thiazides on the

Distal Convoluted Tubule (DCT)

λDrugs: hydrochlorothiazide, chlorthalidone, and indapamide

λMechanism: Na+/Cl− transporter inhibition, results in:

−↑ luminal Na+ and Cl− in DCT

−↑ diuresis

λUses:

−Hypertension, CHF

−Nephrolithiasis (calcium stones)

−Nephrogenic diabetes insipidus

λSide effects:

−Sulfonamide hypersensitivity

−Hypokalemia and alkalosis

−Hypercalcemia

−Hyperuricemia (actively secreted by the OAT)

K+-SPARING AGENTS

Collecting duct

Principal cell

Figure III-1-5. Actions of Potassium-Sparing

Agents on Collecting Tubules

λDrugs:

− Spironolactone: aldosterone-receptor antagonist º Uses:

Hyperaldosteronic state Adjunct to K+-wasting diuretics

Antiandrogenic uses (female hirsutism) Congestive heart failure

º Side effects:

Hyperkalemia and acidosis Antiandrogen

−Amiloride and triamterene: Na+-channel blockers

ºUse: adjunct to K+-wasting diuretics, lithium-induced nephrogenic diabetes insipidus (amiloride)

ºSide effects: hyperkalemia and acidosis

Clinical Correlate

Combining K+-sparing diuretics with

ACEIs or ARBs may cause hyperkalemia.

Note

Eplerenone is a selective aldosterone receptor blocker devoid of antiandrogenic effect.