1. 1) BIS PHOSPHATES
1.1. An analogue of pyrophosphate (P-O-P)-->(P-C-P)
1.2. MOA - Have affinity for calcium in bone ,Accumulate at site of bone resorption taken up by OC by endocytosis promote apoptosis of OC , inhibit formation of OC --Stimulating OB activity
1.3. CLASSIFICATION
1.3.1. a) First generation - ETIDRONATE , simple side chain , least potent , rare use
1.3.2. b)Second generation - ALENDRONATE Not to lie down or take food for 30 mins. With NSAIDS ---> increase gastric irritation
1.3.2.1. have AMINO / NITROGENOUS RING substitution , more potent , high efficacy
1.3.3. c)Third generation - RISENDRONATE --- more potent than alendronate
1.4. PHARMACOKINETICS - Orally , poorly absorbed *nearly 50% of dose accumulated at site of resorption and remain for months/years *absorption - imapaired by food (milk) *free drug - excreted unchanged by kidney
1.5. S/E - gastric irritation , esophagitis , headache , body ache , initial fall in serum Ca+
1.6. C/I - gastroesophageal reflux , peptic ulcer , renal impairment
1.6.1. 2nd , 3rd generation more effective in preventing POSTMENOPAUSAL OSTEOPOROSIS in women ALENDRONATE equally or more effective than RALOXIFENE
1.7. USES
1.7.1. a) OSTEOPOROSIS
1.7.2. b) PAGET'S DISEASE
1.7.2.1. Due to abnormal OC function *Arrest OSTEOLYTIC LESIONS and DECREASE BONE PAIN *CALCITONIN further increase efficacy
1.7.3. c) HYPERCALCAEMIA OF MALIGNANCY
1.7.3.1. PAMIDRONATE (60-90 mg) - IV OVER 2-4 Hr ZOLENDRONATE (4 mg) - IV over 6-12 Hr for 2 days
1.7.4. d) OSTEOLYTIC BONE METASTASIS
1.7.4.1. Parenteral PAMIDRONATE /ZOLENDRONATE *Arrest osteolytic lesion and decrease bone pain
2. 2) COMPOUNDS RELATED TO ESTROGEN
2.1. these are SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERM)
2.2. RALOXIFENE on binding to estrogen receptor
2.2.1. AGONIST -- bone , CVS
2.2.2. ANTAGONIST -- mammary tissues , uterus
2.2.3. BA-2% , Widely distributed in in tissues and converted to active metabolite ( in liver ,lungs ,bone , spleen , uterus , kidney )
2.2.4. CHOLESTYRAMINE -- reduce enterohepatic cycling by 60% WARFARIN -- reduce prothrombin time by 10%
3. 3) PTH
3.1. stored in vesicles *Secretion regulated by plasma Ca+ conc. through GPCR
3.2. when plasma Ca+
3.2.1. increase -- release increase
3.2.2. decrease -- release inhibit
3.3. VITAMIN D INHIBIT expression of PTH gene reducing PTH production
3.4. ACTIONS
3.4.1. a) BONE - increase resorption of bone
3.4.2. b) KIDNEY - increase Ca+ resorption from DCT and regulate its excretion
3.4.3. c) INTESTINE - Enhances formation of calcitonin indirectly increases Ca+ absorption
3.4.4. d) Decrease Ca+ level in milk ,saliva and ocular lens
4. 4) CALCITONIN
4.1. PARAFOLLICULAR 'c' cells of thyroid gland *synthesis and secretion by Ca+
4.2. MOA - Target site - OB *Binds to GPCR (activation)--> increase cAMP and intracellular Ca+
4.3. plasma conc. of Ca+
4.3.1. increase - release increase
4.3.2. decrease - release decrease
4.4. ACTIONS
4.4.1. 1) Target cell - OC , KIDNEY ,BRAIN
4.4.2. 2) Inhibit bone resorption by direct action on OC
4.4.3. 3) Hypocalcaemic action last for approximately 8 Hr.
4.4.4. 4) Inhibit PCT resorption of Ca+ and Phosphate by action on kidney
4.4.5. 5) Renal Ca+ is decreased.
4.5. PHARMACOKINETICS
4.5.1. Plasma T 1/2 - 4-12 Min.
4.5.2. can be given by SC / IM
4.6. S/E
4.6.1. *Nausea ,Vomiting ,Facial Flushing . *Tingling sensation in fingers ,Joint pain.
4.7. USES
4.7.1. Paget's disease ,postmenopausal and corticosteroid induced osteoporosis