Arthritis Drugs Flashcards
What is osteoarthritis?
Inflammation of the bone, caused by wear and tear, ageing, trauma, disease. Affects synovial joints and involves loss of cartilage and bone.
What is rheumatoid arthritis?
An auto-immune disorder, inflammation flowing in a stream, affects other tissues.
Where is the site of action for NSAIDs?
COX
What is the difference between COX 1 and COX 2?
COX 1 = responsible for the protection of GI mucosa and production of PGs for platelet aggregation.
COX2 = PGE2 causes vasodilation and inflammatory effects
List the actions of NSAIDs
Inhibits actions of prostaglandins
Analgesic = reduce sensitivity of neurone
Anti-inflammatory = reduce vasodilation and reduce tissue damage
What are the actions of aspirin?
Inhibits NFkB expression - reduces transcription of genes for inflammatory mediators
Pain relief is immediate
Rapidly absorbed in stomach
Displaces warfarin bound to plasma proteins
Increased plasma warfarin = risk of bleeding
How many patients respond to aspirin?
60%
What are the side effects of aspirin?
Gastric Ulcers Impaired coagulation GI bleeds in the elderly Risk of CV events May induce asthma attacks
Why does aspirin produce side effects?
May inhibit COX1 as well as COX2, COX1 is responsible for the protection of GI mucosa and PGs inhibit platelet aggregation
Name the COX2 selectivity drugs:
Meloxicam, Rofecoxib, Celecoxib, Etoricoxib
What is an alternative strategy to using aspirin?
Misoprostol: synthetic PG. Used alongside NSAIDs, preserves mucous lining of GI tract, protects against ulceration. Side effects = diarrhoea, vaginal bleeding, precautions in women of child bearing age!!
Paracetamol…
Not an NSAID!!!
Analgesic and Antipyretic effects
Suppresses PG production
May involve COX1
Side effects of paracetamol
Few side effects
Chronic use = kidney damage
Toxic doses = liver damage
What type of drugs are use to control Osetoarthritis?
Paracetamol - regular dosing and NSAID Topical NSAID or Capsaicin Opioid Analgesic Corticosteroid injection Joint replacement surgery
What is Strontium Ranetate?
Drug used to treat osteoarthritis, promotes osteoblast differentiation, reduces pain.
Side effects: increased risk of MI and thrombotic events.
What is Glucosamine Sulphate?
Drug used to treat osteoarthritis. Constituent of ECM. Present in cartilage and synovial fluid.
What type of drugs are used to treat Rheumatoid arthritis (RA)?
NSAIDS/Opioid Analgesics Glucocorticoids Immunosuppresants DMARDs Anticytokines
What are the main actions of glucocorticoids?
Metabolic effects
Anti-inflammatory
Immunosuppressive
What are the actions of mineralocorticoids?
Water and electrolyte balance
Hydrocortisone/Corticosterone…
Show both MC and GC activities
short acting - 1-12 hours
twice daily cream or IM injection
Aldosterone
MC only
Prednisolone
GC and MC activity
GC activity only…
Dexamethasone, betamethasone, beclomethasone, budesonide
Which steroid is intermediate acting (12-36 hours)?
Prednisolone, daily oral or IM injection
Which steroid is long-acting? (36-55 hours)
Dexamethasone - Injection every 3-21 days
What are the actions of glucocorticoids in RA?
decrease transcription of pro-inflammatory cytokines
decrease circulating lymphocytes
increase synthesis of anti-inflamm. proteins
Side effects of oral corticosteroids?
buffalo hump, moon face, hypertension, increased abdo fat, thinning of skin, muscle wasting, poor wound healing, osteoporosis
What are Disease Modifying Antirheumatoid Drugs? (DMARDs)
Drugs with unrelated structures and diff. mechanisms of action
Therapy only started upon definite diagnosis of RA
What is the common 1st choice of DMARD in the UK?
Sulfasalazine.
How does Sulfasalazine work?
Thought to act by scavenging free radicals produced by neutrophils.
Causes remission in active RA.
Given as enteric-coated tablets
What are the side effects of Sulfasalazine?
GI upset, headache, skin reactions, leukopenia.
What is Penicillamine?
Type of DMARD. 75% of patients respond but effects take weeks. Decreases IL-1 and fibroblast proliferation which decreases the immune response. Given orally.
Side effects of Penicillamine?
rashes, stomatitis, anorexia, taste disturbance, feve, N and V
What are Gold Compounds and give the names of 2?
Type of DMARD. Sodium aurothiomalate and Auranofin
What does Auranofin do given orally?
Inhibits induction of IL-1 and TNF so reduced pain and joint swelling.
Side effects of gold compounds?
skin rashes, flu-like symptoms, mouth ulcers, blood disorders
Types of Anti-Malarials?
Chloroquine/Hydroxychloroquine
What do anti-malarials do?
increase PH of intracellular vacuoles - interferes with antigen-presenting.
Side effects of anti-malarials?
N&V, dizziness, blurring of vision
What are Anticytokine drugs?
Treat RA. Engineered recombinant antibodies. Given S/c or IV
Types of anticytokine drugs?
Etenercept, infliximab, rituximab, abatacept
Side effects of anticytokine drugs?
TB , Hep B, Herpes, opportunistic infection, nausea, ab pain, worsening heart failure, hypersensitivity
Ciclosporin…
An immunosuppresant. Inhibits IL-2 gene transcription. Poorly absorbed orally.
Side effects of Ciclosporin?
Nephrotoxicity, Hepatotoxicity, Hypertension, N&V, GI problems
Azathioprine…
Immunosuppresant. Interferes with purine metabolism. Depresses immune reactions. Suppression of bone marrow.
Methotrexate…
Immunosuppresant. Folic acid antagonist - inhibits DNA synthesis. Inhibits T cell activation.
Side effects of Methotrexate?
Blood dyscrasias, liver cirrhosis, folate deficiency.
Leflunomide…
Immunosuppresant. Inhibitor of activated T cells. Well absorbed orally.
Side effects of Leflunomide?
Diarrhoea, alopecia, increased liver enzymes.
What is cyclophosphamide?
Immunosuppressant. Prodrug.
