Osteoporosis Pharm Flashcards
What are 3 broad classes of drugs used for osteoporosis?
1) Vitamin D
2) Anti-resorptive agents
3) Anabolic agents
What is the most cost effective way to diagnose osteoporosis?
1) Have you ever had a fragility fracture
2) Look for kyphosis and height loss
What are 4 antiresorptive agents used for osteoporosis?
1) Bisphosphonates (eg. risedronic acid, alendronic acid, zoledronic acid)
2) RANK ligand inhibitors (eg. denosumab)
3) Oestrogen agonist/antagonist (eg. raloxifene)
4) Calcitonins
What are 2 anabolic agents used in osteoporosis?
1) PTH therapies (eg. Teriparatide)
2) Sclerostin inhibitors (eg. romosozumab)
What is Colecalciferol usually formulated with?
1) Calcium carbonate
2) Alendronic acid
Vitamin D is a ________-soluble vitamin.
Fat-soluble
What is the moa of colecalciferol?
1) Converted in liver to calcifedol
2) Calcifedol converted in kidney to active form calcitriol
3) Calcitriol:
i) ↑Ca absorption in gut
ii) maintains [Ca] and [PO4] optimal for bone mineralisation
iii) regulates PTH levels
What are 3 AEs of colecalciferol?
1) Hypercalcemia
2) Hypercalciuria
3) GI discomfort (N&V, constipation)
Rare:
4) Allergic rxn (eg. rash, pruritus)
What are 3 contraindications for colecalciferol?
1) Hypercalcemia
2) Hypervitaminosis D
3) Severe renal impairment
What are 4 DDIs of colecalciferol?
1) Thiazide diuretics
- ↑risk of hyperCa
2) Corticosteroids
- ↓Ca abs → ↓Vit D efficacy
3) Orlistat, Bile acid sequestrants
- ↓fat abs → ↓Vit D abs
4) Anticonvulsants
- ↑Vit D metabolism → ↓efficacy
What is the moa of bisphosphonates?
↑osteoclast cell death → ↓bone loss
What are 3 examples of bisphophonates and how are they administered?
1) Risedronic acid (Oral)
2) Alendronic acid (Oral)
3) Zoledronic acid (IV)
Oral bisphosphonates must be taken __________________.
Oral bisphosphonates:
- on empty stomach
- >240ml of water
- wait >30mins before taking food
What are 4 AEs of oral bisphosphonates?
1) Atypical femoral fractures (prolonged use)
2) Severe bone/joint/muscle pain
3) Upper GI mucosal irritation
4) Ocular effects (eg. iritis, uveitis)
5) HypoCa
6) Osteonecrosis of jaw and external auditory canal
Oral:
7) Nausea
8) Abdo pain
9) Heartburn-like symptoms
IV:
10) Flu-like symptoms
What are 4 contraindications of bisphosphonates?
1) HypoCa
2) Abnormalities of oesophagus that delay emptying
3) Severe renal impairment
4) Pregnancy
5) Lactation
What is the moa of Denosumab?
Human mAb α-RANKL → prevent development of osteoblasts → ↓bone resorption
How and how often is denosumab administered?
SQ every 6mths
- Co-administer 1000mg Ca + >400 IU Vit. D daily
What are 4 AEs of denosumab?
1) Muscle/back/bone/joint pain
2) N&V
3) Constipation or diarrhoea
4) Slight tiredness
5) ↑cholesterol
Rare:
6) Atypical femur fractures
7) Osteonecrosis of the jaw
Which 2 osteoporosis drugs CANNOT be discontinued without transition to another osteoporosis drug?
1) Denosumab
2) PTH therapies (eg. teriparatide)
What are 2 contraindications of denosumab?
1) HypoCa
2) Pregnancy
What are 5 factors that support the decision to treat a px for osteoporosis?
1) High fracture risk (FRAX)
2) Past fracture
3) Low BMD (T score <2.5)
4) >65 y/o
5) High risk of falls/bone loss
Which osteoporosis drug should be avoided in a px with reflux esophagitis?
Oral bisphosphonates
Which osteoporosis drug is safe for px with renal impairment?
Denosumab
What Ix have to be performed before giving SQ denosumab or IV bisphosphonate therapy?
1) Check creatinine and 25-OH Vit. D levels
2) Replete Vit. D
3) Give Ca supplement if renal impairment
What is the moa of raloxifene?
Selective oestrogen receptor modulator
- mixed oestrogen receptor agonism and antagonism
- mimics effects of oestrogen on bone density in postmenopausal women
What are 2 main AEs of raloxifene?
1) Breast cancer (some ↑risk some ↓risk)
2) Blood clots
3) Hot flashes
What are 2 indications for raloxifene?
1) Bone health in younger women
2) Women whose other menopausal symptoms also require treatment
What is the moa of calcitonin?
1) ↓blood Ca → ↓PTH effects
2) Inhibit osteoclastic bone resorption
How can calcitonin be administered?
1) Nasal spray
2) IV
3) SQ
4) IM
What are 3 AEs of calcitonin?
1) Red streaks on skin
2) Injection site rxn
3) Warmth & redness of face, neck, arms, upper chest
What are 2 contraindications of calcitonin?
1) Hypersensitivity
2) HypoCa
What is the moa of romosozumab?
Humanised mouse mAb α-sclerostin
- removes sclerostin inhibition of canonical Wnt signalling pathway that regulates bone growth → ↑ bone formation + ↓bone resorption
What is the main indication for romosozumab?
Women at high risk of fracture/intolerant to other osteoporosis therapies
How is romosozumab administered?
SQ once monthly for 12 mths
What are 3 AEs of romosozumab?
1) MI
2) CV death
3) Stroke
4) Transient HypoCa
5) HS rxn
Rare:
6) Osteonecrosis of the jaw
7) Atypical femur fractures
What are 3 contraindications of romosozumab?
1) Hypersensitivity
2) Uncorrected hypoCa
3) Hx of MI/stroke within 1 year
How is Teriparatide administered?
once daily for max 24mths in lifetime
What are 4 AEs of Teriparatide?
1) Serious calciphylaxis
2) Worsening of previous stable cutaneous calcification
3) Transient orthostatic hypotension
4) Transient and minimal hyperCa
What is the moa of teriparatide?
PTH analogue → ↑bone formation and bone strength
What are 4 AEs of Teriparatide?
1) Hypersensitivity
2) Pre-existing hyperCa
3) Skeletal malignancies/bone metastases
4) Metabolic bone diseases (eg. Paget’s disease, hyperparathyroidism)
5) Unexplained ↑ALP
6) Previous implant/external beam radiation therapy to skeleton
7) Hereditary disorders predisposing to osteosarcoma
8) Severe renal impairment
9) Pregnancy
