Renal

Acetazolamide and methazolamide inhibit carbonic anhydrase on the proximal tubule’s brush border and inside its cells, so filtered bicarbonate escapes into the urine: an alkaline urine, a normal-anion-gap (hyperchloremic) metabolic acidosis, and a diuresis that fades as plasma bicarbonate falls. Mannitol is filtered and barely reabsorbed, so it raises the osmolality of plasma and tubular fluid — it dehydrates the brain and eye, but expands the circulation before it leaves.

Anions secreted into the tubule that block NKCC2 in the thick ascending limb, the segment that reclaims about a quarter of filtered sodium and builds the medullary gradient. Bioavailability, metabolic route, half-life and the one non-sulfonamide agent tell the four drugs apart. (on the Cardiovascular pages)

Competitive blockers of the Na-Cl cotransporter (NCC) in the distal convoluted tubule. The same site explains calcium retention, the dilution defect behind hyponatremia, and the hypokalemia-driven fall in insulin release; thiazide-like agents last longer and keep working at low GFR. (on the Cardiovascular pages)

Two routes to the same channel: mineralocorticoid-receptor antagonists (spironolactone, eplerenone) and ENaC blockers (amiloride, triamterene). Both shut down electrogenic sodium entry in the aldosterone-sensitive distal nephron, so K⁺ and H⁺ secretion fall. (on the Cardiovascular pages)

Vasopressin (ADH) acts on two receptors: V2 on the collecting duct (Gs → cAMP → aquaporin-2 insertion → water reabsorption) and V1 on vascular smooth muscle (Gq → calcium → vasoconstriction). Desmopressin is a V2-selective analog with little pressor effect — it replaces ADH in central diabetes insipidus, distinguishes central from nephrogenic DI, and releases von Willebrand factor and factor VIII; its defining risk is water intoxication. Vasopressin itself is a V1 pressor for vasodilatory shock.

Antagonists of vasopressin’s V2 receptor in the collecting duct, which signals through Gs, cAMP and aquaporin-2. Blocking it causes aquaresis — free-water loss without sodium loss — which raises serum sodium in euvolemic and hypervolemic hyponatremia and lowers the cAMP that drives cyst growth in ADPKD. Conivaptan also blocks the vascular V1a receptor.

Potassium sets the resting membrane potential and shifts between cells and plasma with insulin, β-adrenergic stimulation and pH; both extremes show on the ECG. Magnesium is the cofactor that lets cells hold potassium and the drug that reverses torsades, but in excess it blocks the neuromuscular junction. Calcium stabilizes the heart in hyperkalemia, and tonicity decides where an IV fluid’s water goes.

Potassium binders trap potassium in the gut lumen so it leaves in the stool, and each one’s chemistry predicts its signature problem: SPS releases sodium and is not selective, patiromer also binds magnesium, and SZC carries sodium and raises gastric pH. All act over hours, so in hyperkalemia they are the removal step, not the rescue.

Empagliflozin and dapagliflozin block SGLT2, the proximal-tubule transporter that reclaims most filtered glucose, so glucose and sodium leave in the urine. The glucosuria lowers blood glucose; the natriuresis lowers cardiac preload and intraglomerular pressure — the basis of the heart-failure and kidney indications — while the same glucose-rich urine and ketone shift explain genital infections, Fournier’s gangrene and euglycemic ketoacidosis. (on the Cardiovascular pages)

Competitive inhibitors of the zinc metallopeptidase ACE (kininase II): less angiotensin II, more bradykinin. Prodrug status, the sulfhydryl group, renal versus hepatic handling and the one IV agent tell the four drugs apart. (on the Cardiovascular pages)

Selective AT1-receptor antagonists: angiotensin II is still made — renin and angiotensin II even rise — but cannot reach AT1. Prodrug activation, losartan’s active metabolite and uricosuric effect, and olmesartan’s enteropathy tell the drugs apart. (on the Cardiovascular pages)

Two ways to quiet the detrusor: antimuscarinics block the Gq-coupled M3 receptor through which acetylcholine contracts it, and the β3 agonists mirabegron and vibegron stimulate the Gs-coupled β3 receptor that relaxes it during storage. Among the antimuscarinics, M3 selectivity (darifenacin), quaternary structure (trospium) and the shared active metabolite 5-HMT (tolterodine, fesoterodine) set their differences. (on the Autonomics pages)