Physiology and Therapeutics: Calcium Balance Flashcards
(30 cards)
What are examples of primary osteoporosis?
- type I –> post menopausal
- type II –> senile
What is the most common cause of secondary osteoporosis?
glucocorticoids can also lead to aseptic necrosis of the hip
What affects calcium distribution?
- Higher pH (alkalosis) increases calcium binding to albumin → less ionized Ca²⁺
- Lower pH (acidosis) reduces binding → more ionized Ca²⁺
What is calmodulin?
an intracellular protein that binds calcium and helps it participate in cell signaling pathways, especially those regulating enzyme activity, muscle contraction, and cell growth
How does PTH increase serum calcium levels?
- bone resorption
- decreased renal calcium excretion
- increase calcitriol synthesis
What is Renal Osteodystrophy?
when chronic kidney disease leads to significant bone loss
- CKD/renal failure → decreased vit D or hyperparathyroidism
What are thee typical treatments for patients with renal osteodystrophy?
- vitamin D analog (Calcitrriol, Eldecalcitol)
- cinacalcet
- denosumab
What are the adverse effects of Calcitriol (eldecalcitol)?
- ectopic calcification
- cardiac arrhythmias
- hypertension
- hypercalcemia
What is Cinacalcet and what does it do?
a calci-mimetic that suppresses PTH secretion by increasing the sensitivity of calcium-sensing receptors to extracellular calcium
What are the main uses of Cinacalcet?
- Secondary hyperparathyroidism in CKD patients on dialysis
- Hypercalcemia in parathyroid carcinoma (e.g., desensitization)
What are key pharmacokinetics and adverse effects of Cinacalcet?
- Rapid absorption, 93–97% protein bound
- Metabolized by CYP3A4, CYP2D6, CYP1A2
- Do NOT use in liver impairment, can cause upset stomach, vomiting, weakness, chest pain
What is Denosumab used for?
- Post-menopausal women or men at high fracture risk
- Women on aromatase inhibitor therapy (e.g. breast cancer)
- Men on androgen deprivation therapy for nonmetastatic prostate cancer
What is the mechanism of action of Denosumab?
an IgG2 monoclonal antibody that blocks RANKL, preventing activation of RANK receptors on osteoclasts → inhibits bone resorption, increases bone mass and strength
What are the adverse effects of Denosumab?
- Musculoskeletal pain, hypercholesterolemia, cystitis
- Increased infection risk
- Pancreatitis reported in trials
What are the treatments used to block osteoclast activity?
- bisphosphates (most common)
- Calcitonin
- estrogen or testosterone
What is Paget’s Disease (osteitis deformans)?
chronic bone disorder involving abnormal bone remodeling:
- Excessive bone resorption (breakdown)
- Followed by disorganized, excessive bone formation
What are signs and symptoms of Paget’s Disease?
- Bone deformities: Bowing of legs, skull enlargement
- Fractures & joint problems: Stress fractures, arthritis
- Neurological complications: deafness, spinal cord compression, facial droop, loose teeth
- Other issues: High-output heart failure, chronic pain
What are the treatments for Paget’s Disease?
- bisphosphonates
- calcitonin
- NSAIDs for pain
What are Bisphosphonates and what must be considered when taking them?
Analogs of pyrophosphate in which P-O-P bond has been replaced by P-C-P bond that binds hydroxyapatite crystals and reduces dissolution
- should be taken on empty stomach with a full glass of water and remain upright for at least 30 minutes after taking
What are the common types of bisphosphonates?
- Etidronate- can lead to osteomalacia by impairing new bone formation
- Alendronate
- Ibandronate
- Risedronate sodium or risedronic acid
- Zoledronic acid
What is the MOA for Risedronic Acid and its clinical uses?
- binds bone hydroxyapatite –> taken into osteoclasts –> release of risedronic acid –> apoptosis through inhibition of farnesyl pyrophosphate synthase
- Osteoporosis in men and post-menopausal women, Paget’s disease, Glucocorticoid-induced osteoporosis
What are the adverse effects of Risedronic Acid?
- Back pain
- arthralgia
- abdominal pain
- dyspepsia
- can increase esophagitis
What is the MOA for Recombinant calcitonin (elcatonin) and what is it used to treat?
- inhibits osteoclast mediated bone resorption
- Paget’s or other hypercalcemia causing diseases
What are the adverse effects of Recombinant calcitonin (elcatonin)?
- Should not be combined with bisphosphonates –> hypocalcemia
- May increase the rate of excretion of Lithium thus decreasing its efficacy
