chondroprotectives and bisphosphonates

Question 1

what is the function of chondroprotectives?

Answer 1

= agents that retard the degradation of articular cartilage and promote chondrocyte metabolism

Question 2

what are chondroprotectives generally used for?

Answer 2

osteoarthritis

Question 3

name 2 groups of drugs and any subgroups that are used as chondroprotectives?

Answer 3

GAGs - hyaluronic acid, chondroitin sulphate, glucosamine (precursor)
pentosan polysulphate

Question 4

describe the nature of chondroprotectives

Answer 4

nutraceuticals, no official evidence for efficacy, unlicensed and content not standardised

injectable products are marketed as drugs so must be standardised

Question 5

what is osteoarthritis?

Answer 5

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

Question 6

what is the mode of action of chondroprotectives?

Answer 6

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

Question 7

describe properties of glucosamine?

Answer 7

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

Question 8

describe the properties of chondroitin

Answer 8

predominant component of joint cartilage and constituent of other tissues. made from animal cartilage

Question 9

why are the 2 types of drug often given in combination?

Answer 9

may be together/ with other substances. may have synergistic effects

Question 10

describe the use of polysulphated GAGs

Answer 10

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

Question 11

describe the use of pentosan phosphate

Answer 11

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

Question 12

describe the use of hyaluronan (hyaluronic acid)

Answer 12

= component of synovial fluid and articular cartilage. improves lubrication. can give intra-articular.
inhibits PG synthesis (inflammatory)

Question 13

what evidence is there for the use of chondroprotectives?

Answer 13

Moreau et al -ground reaction forses with NSAID, placebo and chodroprotective supplement. no change with chondroprotective

Question 14

what are bisphosphonates?

Answer 14

drugs which reduce bone absorption by inhibiting osteoclasts.

Question 15

when are B’s used?

Answer 15

in dogs with bone tumours to reduce pain and inhibit metastases
and in DC with hypercalcaemia

Question 16

what are the 2 main types of B’s?

Answer 16

amino and non-amino

Question 17

what is the mechanism of action of b’s?

Answer 17

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

Question 18

give examples of B’s and their routes of admin

Answer 18

non-amino - clodronate PO

amino - pamidronate IV, alendronate PO

Question 19

list actions of b’s

Answer 19

inhibit osteoclasts, inhibit neoplastic cell proliferation (metastases), induce apoptosis, inhibit angiogenesis, inhibit phagocytic cells etc

Question 20

what conditions are b’s used in?

Answer 20

osteosarcoma, hypercalcaemia, malignant histiocytosis, immune mediated haemolytic anaemia

Question 21

describe the use in hypercalcaemia

Answer 21

caused by renal failure, toxicity, idiopathic.

reduce bone resorption, which reduces Ca uptake into the circulation

Question 22

use in malignant histiocytosis

Answer 22

combo with therapeutic agents. causes cell death and regression of tumour

Question 23

use in immune mediated haemolytic anaemia

Answer 23

stops macrophages engulfing RBC’s

Question 24

how are b’s administrated?

Answer 24

poor absorption orally and can cause oesophagitis
IV
goes to bone
long half life.

Question 25

what are the SE of b’s?

Answer 25

oesophagitis, delayed bone healing, increases fragility of bone, allergy, nephrotoxic