arthritis drugs Flashcards
what is arthritis?
joint inflammation. it causes pain, and affects mobility. currently affects 10% of the worlds population.
action of type 1 collagen?
located in the bone. involved with osteoblast differentiation from bone marrow.
location and function of type 2 collagen?
located in cartilage - it maintains integrity of cartilage.
where is aggrecan located?
synovial membrane
location of matrix metalloproteinases?
synovial tissue. it degrades ECM proteins to enable growth.
describe osteoarthritis
disease affecting the synovial joints. it is characterized by loss of cartilage and bone from articulating surfaces.
why is cartilage degraded?
due to the upregulation of cytokines.
risk factors for osteoarthritis?
obesity, age >40, collagen gene mutations, metabolic disorders, previous joint injury/disease, gender (common in women due to decrease in oestrogen after menopause).
what is arachidonic acid?
a constituent of the cell membrane, derived from linoleic acid in the diet
where is PGI2 synthesised?
vascular endothelial cells
what causes a reduction in prostaglandins E2 and I2?
blocking COX enzyme
describe COX-1 enzyme?
a constitutive enzyme (expressed all the time). It regulates blood flow/ clotting and renal function, and protects the GI mucosa.
function of COX-2?
inducible and produced when needed. it produces inflammatory cells, and is also involved in ovulation and uterine contractions during labour.
examples of NSAIDs?
aspirin, ibuprofen, diclofenac, meloxicam, indomethacin, celecoxib
actions of NSAIDs?
antipyretic - inhibits PG action on hypothalamus, analgesic - reduces sensitivity of neurons to bradykinin
anti-inflammatory - reduces vasodilation and decreases permeability of venules.
where is aspirin absorbed?
stomach and small intestine
problems with NSAIDs?
gastric ulcers, impairs coagulation, risk of GI bleeding, risk of CV events in patients with CV disease/hypertension, may induce asthma attack, angioedema, urticarial or rhinitis
how are NSAIDs administered?
tablets, suspensions, gels, injection
examples of COX-2 inhibitors?
celecoxib, etoricoxib, etodolac.
side effects of COX-2 inhibitors?
headache, dizziness, skin rash, peripheral odema
what is misoprostol?
a synthetic prostaglandin given alongside NSAIDs, that preserves mucous lining of GI tract and inhibits gastric acid secretion that stimulates increased mucus production and protects against ulceration.
side effects of misoprostol?
diarrhoea and vaginal bleeding
mechanisms of paracetamol?
analgesic and antipyretic. supresses PG production and stimulates serotenergic pathways involved in the inhibition of pain sensation.
problems with too much paracetamol ?
chronic use of large doses can lead to kidney damage and toxic doses can lead to fatal liver damages
