chondroprotectives and bisphosphonates Flashcards
what is the function of chondroprotectives?
= agents that retard the degradation of articular cartilage and promote chondrocyte metabolism
what are chondroprotectives generally used for?
osteoarthritis
name 2 groups of drugs and any subgroups that are used as chondroprotectives?
GAGs - hyaluronic acid, chondroitin sulphate, glucosamine (precursor)
pentosan polysulphate
describe the nature of chondroprotectives
nutraceuticals, no official evidence for efficacy, unlicensed and content not standardised
injectable products are marketed as drugs so must be standardised
what is osteoarthritis?
a slow, progressive, degenerative disease. rate of synthesis of cartilage reduced and cartilage degeneration increased. no cure.
management = NSAIDs, rest, weight loss, physiotherapy, hydrotherapy, chondroprotectives
what is the mode of action of chondroprotectives?
stimulate chondrocytes to secrete cartilage matrix, stimulate joint cells to produce hyaluronic acid, inhibit enzymes involved in cartilage degradation + release of inflammatory mediators, anti-inflammatory by inhibiting arachidonic acid metabolism
describe properties of glucosamine?
made from glucose and glutamine = building block of GAGs which make up ECM of joint cartilage. produced by hydrolysis of crustacean exoskeletons/ grain fermentation.
e.g. glucosamine sulphate
describe the properties of chondroitin
predominant component of joint cartilage and constituent of other tissues. made from animal cartilage
why are the 2 types of drug often given in combination?
may be together/ with other substances. may have synergistic effects
describe the use of polysulphated GAGs
injectible. made from bovine tracheal cartilage - primary is chondroitin sulphate. given IM in dogs and IM/ intra-articular in horses.
after IM admin, absorbed into system and incorporated into cartilage.
structurally similar to heparin so may inhibit coagulation on overdose
describe the use of pentosan phosphate
maintains joint health and preserves cartilage. stimulates chondrocytes to produce ECM and synoviocytes to produce hyaluronic acid, also anti-inflammatory properties. also increases joint perfusion so improves cartilage nutrition.
SC/ IM
describe the use of hyaluronan (hyaluronic acid)
= component of synovial fluid and articular cartilage. improves lubrication. can give intra-articular.
inhibits PG synthesis (inflammatory)
what evidence is there for the use of chondroprotectives?
Moreau et al -ground reaction forses with NSAID, placebo and chodroprotective supplement. no change with chondroprotective
what are bisphosphonates?
drugs which reduce bone absorption by inhibiting osteoclasts.
when are B’s used?
in dogs with bone tumours to reduce pain and inhibit metastases
and in DC with hypercalcaemia
what are the 2 main types of B’s?
amino and non-amino
what is the mechanism of action of b’s?
both disrupt metabolism of osteoclasts leading to apoptosis of the cells
amino are newer and more potent - disrupt intracellular signalling in osteoclast and cause cell death
give examples of B’s and their routes of admin
non-amino - clodronate PO
amino - pamidronate IV, alendronate PO
list actions of b’s
inhibit osteoclasts, inhibit neoplastic cell proliferation (metastases), induce apoptosis, inhibit angiogenesis, inhibit phagocytic cells etc
what conditions are b’s used in?
osteosarcoma, hypercalcaemia, malignant histiocytosis, immune mediated haemolytic anaemia
describe the use in hypercalcaemia
caused by renal failure, toxicity, idiopathic.
reduce bone resorption, which reduces Ca uptake into the circulation
use in malignant histiocytosis
combo with therapeutic agents. causes cell death and regression of tumour
use in immune mediated haemolytic anaemia
stops macrophages engulfing RBC’s
how are b’s administrated?
poor absorption orally and can cause oesophagitis
IV
goes to bone
long half life.
