Kidney/Bone/Thyroid Flashcards
Carbonate Anhydrase Inhibitor (Acetazolamide)
Indication: metabolic alkalosis, familial hypokalemic periodic paralysis, open-angle glaucoma, mountain sicknesses
MOA: blocks HCO3 reabsorption in the proximal tubule, secondarily inhibits Na reabsorption, cause metabolic acidosis that leads to loss of diuretic effect, distally increases K excretion
ADR: hypokalemia, calcium stones due to alkalinization of urine (Ca is not paracellularly dragged in as Na reabsorption is inhibited) , hypersensitivity rxn due to sulfa residue
Osmotic Diuretic (Mannitol)
Indication: glaucoma, cerebral edema
MOA: filtered but nor reabsorbed, decreases water reabsorption, frequently enhances excretion of Na and K via solute drag
Thiazide Diuretic (HCTZ)
Indication: HTN (first-line), edema, prevention of kidney stone, nephrogenic diabetes insipidus
MOA: inhibition of NaCl symporter in distal tubule, increases Na and Cl excretion, blocks urine diluting capacity only, distally increases Na delivery therefore K excretion, volume depletion enhances proximal tubule Ca reabsorption
ADR: hypokalemia, hyponatremia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypersensitivity rxn
Pathophysiological equivalent: Gitelman Syndrome (hypochloremic metabolic alkalosis, hypokalemia, hypocalciuria)
Loop Diuretic (Furosemide)
Indication: acute pulmonary edema, edema, HTN refractory to other diuretics, used in conjunction with saline to treat hypercalcemia
MOA: inhibits Na/K/2Cl symporter in thick ascending limb of loop of henle, increases Na and Cl excretion, block urine diluting and concentrating capacity, increases therefore Na delivery therefore K excretion, increases Ca and Mg excretion
ADR: volume depletion, hypokalemia, xs Mg and Ca excretion, hyperuricemia, ototoxicity, hypersensitivity rxn
PK of furosemide: iv, po, 50% F, 95% bound to plasma albumin to site of delivery, 50% renally excreted unchanged, urine concentration correlates to natriuretic effect, shorter half-life compared to other drugs in the class (1-2hr)
Pathophysiological equivalent: Bartter Syndrome (hypokalemia, metabolic alkalosis, normo or hypotension)
Potassium Sparing Diuretic (Amiloride, Spirolactone)
Indication: in combination with thiazide or loop diuretic tomprevent hypokalemia, hyperaldosteronism (cirrhotic edema, nephrosis, heart failure), Liddle’s disease (to reduce xs Na uptake by mutated constitutively active form of ENaC), in combination with lithium to block Li reuptake into principal cell and Li-induced DI
MOA: inhibits Na reabsorption by principal cells of late distal tubule and collecting ducts decreases K excretion, act either on ENaC (Amiloride) or by antagonizing MR receptor (Spriolactone)
ADR: hyperkalemia, endocrine abnormalities (gynecomatasia, impotence)
C.f. Eplerenone: more selective antagonist of MR receptor than progesterone or androgen receptors
ACE Inhibitor/ARBs
Indicated for prevention of diabetic nephropathy and HTN with progressive renal impairment
MOA: selective renal efferent arteriole dilation, decreased glomerular capillary pressure, inhibition of angiotensin2-induced mesangial cell growth and matrix production
Desmopressin
Indication: Central DI
MOA: long acting analogue of ADH with higher selectivity to V2 versus V1, efficacy by nasal or oral route
C.f. nDI: due to inadequate response to V2, so try thiazide and amiloride (by inducing ECV contraction, enhances proximal sodium reabsorption, antagonizing diuresis somewhat)
C.f. Demeclocycline: ADH antagonist, indicated in SIADH
Nephrotoxic agents c.f. drug-induced Acute Tubular Necrosis
Gentamicin (aminoglyside), cyclosporine and tacroimus (calcineurin inhibitor), cisplatin, amphotericin, radiocontrast agents
Thyroxine (T4)
Indication: hypothyroidism
Radioactive Iodide (131I)
Indication: hyperthyroidism
C.f. Beta-blocker: indicated in pregnancy-induced hyperthyroidism, as anti-thyroid hormone and radioiodine are contraindicated
Methimazole, Propylthiouracil (PTU)
Indication: hyperthyroidism
Biphosphonate (Zoledronate, Alendronate)
Indication: hypercalcemia, osteoporosis, first-choice therapy, safe-effective
MOA: inhibition of accelerated bone resorption
PK: IV admin, single dose, prolonged effect
ADR: acute phase rxn (common, flu-like sx), potential nephrotoxicity, jaw necrosis (cancer pt, after oral surgery or infection), may even cause hypocalcemia
C.f. Zoledronate (IV) and highly potent other drugs–effects may last for months, Alendronate (po)
Calcitonin
Indication: hypercalcemia, used in severe cases along with other slower acting drugs, not front-line
Class: endogenous peptide hormone that’s secreted in response to high blood calcium
MOA: cell surface g-protein coupled receptor on osteoclasts, decreases bone resorption, increases urinary calcium excretion
PK: safe, rapid (min) but transient action, IN, analgesic effect (helpful for bone pain), synthetic salmon calcitonin–50x more potent, by SC or IM
Calcium carbonate (po), IV Calcium
Indication: mild&symptomatic hypocalcemia and acute&symptomatic hypocalcemia respectively
Calcimimetics (Cinacalet Hydrochloride)
Indication: 2’ hyperparathyroidism in chronic kidney disease, hypercalcemia in parathyroid carcinoma
MOA: allosteric regulator of CaSR
PK: po
ADR: hypocalcemia, nausea/vomiting
