T9 pharmacology of parathyroid drugs

primary hyperparathyroidism - Ca2+ & PTH levels

raised, not suppressed

secondary hyperparathyroidism - Ca2+ & PTH levels

low, raised

tertiary hyperparathyroidism - Ca2+ & PTH levels

raised, not suppressed

primary hyperparathyroidism - definitive treatment

parathyroidectomy

candidates for parathyroidectomy

calcium > 1 mg/dL, T-score < -2.5, kidney stones, creatinine clearance <60 mL/min, calcium >400 mg/day, age < 50 years

primary hyperparathyroidism - management

correct dehydration, increase renal calcium excretion, inhibit bone resorption

primary hyperparathyroidism - avoid what

thiazides → increase Ca2+ resorption

primary hyperparathyroidism - drugs

saline hydration, furosemide, bisphosphates, plicamycin, calcitonin, estrogens, gallium nitrate

saline hydration - uses

first line for acute hypercalcemia

loop diuretics - drug name

furosemide

furosemide - mechanism

inhibit Na+/K+/2Cl- in loop of henle → increase Ca2+ & Mg2+ excretion

furosemide - onset

4 hours (fast)

furosemide - side effects

hypokalemia, hypomagnesemia, volume depletion

bisphosphates - drug names

alendronate, ibandronate, zoledronate

bisphosphates - mechanism

inhibit osteoclast activity and bone resorption & promote osteoblast to inhibit osteoclast formation

bisphosphates - side effects

jaw necrosis, hypophosphatemia, flu-like symptoms

etidronate - mechanism

impairs osteoclast function

pamidronate

impairs osteoclast function

plicamycin - mechanism

inhibits RNA synthesis and osteoclast activity

plicamycin - uses

people who failed bisphosphate or intolerant, refractory hypercalcemia

plicamycin - side effects

thrombocytopenia (decrease platelet count), hemorrhage

plicamycin - contraindications

liver/kidney failure, pregnancy, coagulopathy, bone marrow supression

calcitonin - mechanism

inhibit osteoclasts, increase renal calcium excretion

calcitonin - onset

2-4 hours (fast)

calcitonin - side effects

hypersensitivity, nausea, vomit

calcitonin - other drugs

salcatonin

estrogens - mechanism

inhibit cytokines that activate osteoclasts

estrogens - onset

2 months (long time)

estrogens - side effects

hot flashes, leg cramps, nausea

estrogens - uses

last choice

estrogens - other drugs

raloxifene & estradiol

gallium nitrate - mechanism

antitumor agent → inhibit osteoclast activity

gallium nitrate - uses

hypercalcemia of malignancy

gallium nitrate - side effects

nephrotoxicity

gallium nitrate - contraindications

renal insufficiency / patients with high serum creatinine

secondary hyperparathyroidism - cause

chronic kidney disease

secondary hyperparathyroidism - CKD leads to

decrease phosphate excretion → increase phosphate levels

secondary hyperparathyroidism - increase phosphate leads to

decrease vitamin D activation → decrease calcitriol

secondary hyperparathyroidism - decrease calcitriol leads to

decrease calcium absorption in gut

secondary hyperparathyroidism - result

hypocalcemia → triggers increase PTH secretion

secondary hyperparathyroidism - management

treatment of CKD, calcium supplementation, correcting vitamin D deficiency, cinalcalcet

secondary hyperparathyroidism - drug name

cinacalcet

cinacalcet - mechanism

allosteric activator of CaSR on parathyroid chief cells → increase sensitivity to extracellular Ca2+ → suppress PTH secretion → inhibit bone resorption

cinacalcet - uses

CKD patients on dialysis

hypocalcemia - symptoms

CATS → convulsions, arrhythmias, tetany, spasm and stridor, numbness

neuromuscular irritability

low calcium → lowers threshold for nerve firing → nerves more hyperexcitable

hypoparathyroidism - drugs

calcium IV, calcium oral, vitamin D (calcitriol), thiazide diuretics

calcium IV - mechanism

increase serum calcium

calcium IV - uses

severe symptomatic hypocalcemia

calcium IV - side effects

cardiac arrhythmias (if infused too rapidly)

calcium oral - mechanism

increase serum calcium

calcium oral - uses

mild/moderate hypocalcemia, maintenance therapy

calcium oral - side effects

hypercalcemia, hypercalciuria → kidney stones

vitamin D (calcitriol) - mechanism

increase intestinal absorption of calcium by promoting calcium-binding protein synthesis

thiazide diuretics - mechanism

reduce urinary calcium excretion

preparation of calcium - most preferred

calcium carbonate (40% Ca2+)

7-dehydrocholesterol - becomes

cholecalciferol (vitamin D3)

cholecalciferol (vitamin D3) - becomes

calcidiol

25 hydroxylase

convert cholecalciferol (vitamin D3) → calcidiol & ergocalciferol (vitamin D2) → calcidiol

1alpha hydroxylase

convert calcidiol → calcitriol