Drugs for bone metabolism Flashcards
What are the main cells in bones? role?
Osteoblasts = bone forming cells –> from bone marrow precursors
Osteoclasts = bone resorbing cells (from macros and monocytes
Osteocytes = derive from osteoblasts, embed in bone formation
What happens when Ca2+ drops in the body? (general)
parathyroid cells –> synthesise and secrete PTH –> conserve Ca2+
What happens when Ca2+ inc in the body? (general)
high plasma Ca2+ —> binding of Ca2+ to CaSR –> activates GPCR –> activates PLC –> inhibits further PTH secretion
What is the effect of PTH secretion from the parathyroid on the rest of the body? (kidney, digestive, bone)
Kidney = dec excretion of Ca2+
Gut = inc Ca2+ absorption
Bone = mobilisation of Calcium from bone
What is the effect of calcitonin on bone?
Produced by thyroid gland in response to Ca2+, dec rate of bone turn over
- bind to receptors on osteoclasts --> Inhibit bone resorption - Inhibits resorption of Ca2+ in PCT of kidney
What is the natural antagonist of the actions of PTH and VIT D?
Calcitonin
What are the indications for Ca2+ use and what are some ADRs?
Indications = Ca2+ def, adjuvant for osteoporosis, osteomalacia, rickets, acute hypocalcaemia and hypocalcaemia tetany
ADRs = belching, flatulence, abdominal distension, constipation, hypercalcaemia, alkalosis, hypophosphatemia
How is active vitamin D formed?
7-dehydro-cholesterol + UVB –> Vit D3 (cholecalciferol) —>Vit D3 goes to liver and is made into 25(OH)D3 (calcifediol) –> travels to kidney –> formed into 1,25(OH)2D3 (calcitriol) –> calcitriol enters blood
What are the effects of vit D? (available forms)
Reg Ca homeostasis and bone metabolism
Inc intestinal absorption and renal reabsorption of calcium and phosphorus
Promotes bone mineralisation
Available forms = ergocalciferol D2, cholecalciferol D3, calcitriol
What are the indications, C/I, effects of cholecalciferol (D3) & ergocalciferol (D2)? (time of action, strength)
Slow onset of 4-8 wks, prolonged duration of action
D3 may be more effective than ergocalciferol in inc and maintaining serum 25(OH)D3
Indications = prevent/tx vit D def due to improper diet or sunlight
- combine w/ bisphosphonates for osteoporosis req Vit d
C/I = renal impairment
What are the indications, C/I, effects of Calcitriol? (time of action, strength)
Active vit D metabolite, rapid onset (!-3 days) and short duration <1wk
Indications = hypocalcaemia in hypoparathyroidism, renal dialysis, tx of osteoporosis, prevention of corticosteroid induced OP
ADRs = N/V, constipation, freq urination, headache, thirst
What are the relevant bisphosphonates?
*End in -dronate
Pamidronate
Alendronate
Etidronate
Risedronate
Zolidronate
*PACERZ
What is the MOA of the bisphosphonates? (indications?)
Bind strongly to bone surface –> inhibit osteoclast ATP dependent enzymes, induce osteoclast apoptosis –> deplete osteoclasts/osteoclast activity
Indications = for postmenopausal OP (1st line), paget’s disease, hypercalcaemia of malignancy
What are the ADRs of bisphosphonates?
Oesophagitis = TAKE WITH FULL GLASS WATER 30min BEFORE FOOD, DONT LIE DOWN FOR 30MIN AFTER —> acidic drug
- oesophageal erosions, ulcers (alendronate), gastritis, duodenitis, glossitis, iritis, scleritis, rash
N/V/D/C, muscle pain, osteonecrosis of jaw
What jaw related side effect can be seen with bisphosphonate use?
Osteonecrosis of jaw due to IV bisphosphonate
Risk associated w/ dose and type of bisphos, hx of trauma, dental surgery, dental infection
What two drugs influence the parathyroid horomone?
Teriparatide
Cinacalcet
What is the MOA of teriparatide? (ADRs)
active fragment of human PTH –> promote bone formation and inc BMD
ADRs = N, headache, dizziness, leg cramps, arthralgia, hyperuriciaemia,
Which parathyroid hormone drug can only be used for a max of 18 months in a lifetime? Why?
Teriparatide
Due to risk of osteosarcoma
What are the indications and C/I for teriparatide?
C/I = paget’s disease, hyperparathyroidism
Indication = postmeno OP, or primary OP in men
What is the MOA of cinacalcet? (ADRs)
Inc sensitivity of CaSR on PT gland for Ca2+ —> dec sec of PTH –> dec serum Ca2+
ADRs = hypocalcaemia, N/C, anorexia, dizziness, reduced testosterone, seizures, angioedema
What is raloxifene used for? What does it do? (generally)
Used in postmeno OP
ER agonist –> bone mass and lipid
ER antagonist –> other oestrogen receptive in tissues (breast and uterus)
What is strontium ranelate used for? What does it do? (generally)
Similar to Ca2+, bone seeking role
- Inc bone formation = inc osteoblast precursor - Reduce bone resorption = alter osetoclast ultrastructure, dec resorbing activity
Indication = severe postmenopausal osteoporosis, severe osteoporosis in men
What is Calcitonin/salcatonin used for? What does it do? (generally)
Action = inhibits bone resorption and inc urinary excretion of ca2+
Indication = hypercalcaemia (IV infusion)
Treat for shortest possible time –> long term is associated w/ malignancies
What is denosumab used for? What does it do? (generally)
Action = dec bone destruction and inc bone mass and strength
- anti-receptor activator of nuclear factor k B ligand [RANKL] antibody
Indications = post menopausal women w/ OP at high facture risk
