Arthritis drugs Flashcards
What is arthritis?
causes pain
affects mobility
unpredictable
Osteoarthritis definition
affects the bone
primary = wear and tear, ageing
secondary = trauma, disease or obesity
pain through INFLAMMATION
Rheumatoid arthritis definition
affects blood
systemic auto-immune disorder that can effect other tissues
pain through INFLAMMATION - release of cytokines
Osteoarthritis
disease affecting the synovial joints eg. knee, elbow, wrist
characterised by loss of cartilage and bone from articulating surfaces and alteration in cartilage structure (cartilage is needed to prevent bone friction)
Why is cartilage degraded?
? increase in cytokines which are inflammatory chemical causing inflammation
- IL-1B inhibits type 2 collagen synthesis of hyaline cartilage
- destroys environment surrounding cartilage cells = structure change
- increase in matrix metalloproteinase = breakdown of collagen = cartilage degradation
How is normal joint structure maintained?
Type 1 collagen = found in the bone, function is osteoblast differentiation from bone marrow
Type 2 collagen = found in cartilage, function is maintaining integrity of cartilage
Aggrecan = found in synovial membrane, function is maintaining integrity of cartilage
Matrix metalloproteinase = found in synovial tissue, function is degrading ECM proteins to enable growth
Risk factors of osteoarthritis
obesity, gender (females increased risk post-menopause due to decrease in oestrogen), previous joint injury/disease, metabolic disorders, age (<40) genetics eg collagen gene mutation
Prostaglandins
PGD2/PGI2 = vasodilation
PGE2 = vasodilation, pyogenic + anti-inflammatory effects
potentiate effects of histamine + bradykinin
- increased permeability of venules = oedema
- increased sensitivity of C fibres = PAIN
= enables WBC to reach site of injury/infection
COX enzyme
3 forms COX-1 - > produced all the time > expressed in most tissues > 'housekeeping' enzyme > protects GI mucosa, controls renal blood flow, initiation of labour COX-2 - > produced when needed > inflammatory cells induced by injury, infection, cytokines > produces inflammatory mediators > ovulation, uterine contractions COX-3 ALL catalyse arachidonic acid - PGs and thromboxane COX enzymes are a target for NSAIDs
NSAID examples
aspirin ibuprofen diclofenac meloxicam indomethacin available OTC different formulations
Actions of NSAIDs in osteoarthritis treatment
Antipyretic = inhibits actions of PGs on hypothalamus
Analgesic = reduce sensitivity of neurones to bradykinin, effective against pain of muscular/skeletal origin
Anti-inflammatory = reduce vasodilation and decrease permeability of venules
- may scavenge oxygen radicals = decrease tissue damage
pain relief almost immediate
Problems with NSAIDs
risk of gastric ulcers
impair coagulation
use with caution in elderly
risk of CV events in patients with cardiac disease/hypertension
may induce asthma attach, rhinitis, angioedema (rapid swelling of dermis, subcutaneous tissues), urticaria – skin rash
why problem ? many inhibit COX1 and COX2
- PGs produced in COX1 have many beneficial processes inc. production of GI mucus blocking increase risk of ulcers
Solving problems with NSAIDs
COX1 and COX2 differ in structure = should be possible to produce selective drugs
COX2 inhibits -
Celecoxib, eterocoxib used in patients with high risk of GI side effects
- common SE: headache, skin rash, peripheral oedema
Misoprostol
synthetic PG
given along side NSAIDs preserves mucous lining of GI tract and protects against ulceration
SE: vaginal bleeding, diarrhoea
Aspirin
rapidly absorbed in the stomach
displaces Warfarin bound to plasma proteins therefore it increases plasma Warfarin and potentiates Warfarin’s anticoagulant activity
Paracetomol
not an NSAID as has no anti-inflammatory effect
it is an analgesic and antipyretic
supresses PG production
chronic use of large doses = kidney damage
toxic doses (10-15g) = potentially fatal liver damage
can be given along NSAIDs (with proton-pump inhibitor)
Other Osteoarthritis treatment options
weight loss exercise to strengthen core muscles joint supports/braces suitable footwear thermotherapy intra-articular corticosteroid injection = temporary benefit joint replacement surgery bisphosphonates opioid analgesics eg. Oxycodone monoclonal antibodies eg Dunosomab
Strontium ranelate in treating osteoarthritis
promotes osteoblast differentiation/inhibits osteoclast activity
reduces pain
indicated to prevent fractures in severe osteoporosis
can increase risk of MI and thrombotic events
Glucosamine sulphate in treating osteoarthritis
major constituent of ECM
present in cartilage and synovial fluid
possible long term benefits, not reo=commended by NICE
Rheumatoid arthritis
causes joint inflammation
leads to proliferation of synovial membrane and erosion of cartilage/bone
autoimmune disorder
symptoms = swollen, stiff and painful joints
Treatment and management
NSAIDS/ opioid analgesics
glucocorticoids
immuno-suppressants
disease modifying anti-rheumatoid drugs (DMARDS)
anti-cytokines
managed by diet + complementary therapy, drugs and surgery
Glucocorticoids
roduced by the cortex
have metabolic, immunosuppressive and anti-inflammatory effects
> short acting (1-12hrs) eg. Cortisone, Hydrocortisone, twice daily cream/injection
> inter-mediate acting (12-36 hrs) eg Prednisolone, daily oral/injection
> long acting (36-55hrs) eg Dexamethasone, injection every 3-21 days
Actions of glucocorticoids
decrease transcription of pro-inflammatory cytokines
decrease circulating lymphocytes
inhibit phospholipase A2 causing a decrease in arachidonic acid
increase synthesis of anti-inflammatory proteins eg. Beclometasone, prednisolonw
Long term side effects of glucocorticoids
buffalo hump, hypertension, thinning of skin, increased risk of infection, poor wound healing, osteoporosis, muscle wasting
can reduce SE by not administering orally, or by lowering plasma concentrations
danger of stopping treatment immediately
