Anti-inflammatory Drugs

D. CLASS M.A
Non-steroidal Anti-inflammatory Drugs (NSAIDs) aspirin -All mediated through inhibition of COX activity and PG production - prevent action of IL1 on PLA2

ACTION
-Anti-inflammatory -Analgesic -Antipyretic -Anti platelet effect (COX-1 effect)

SE
-GI disturbances: N+V, gastric erosions, ulceration, haemorrhage, perforation -Skin reactions: mild rashes, photosensitivity -Renal disease -Peripheral oedema/hypertension -asymptomatic Liver abnormalities usually, normalise when drug is stopped -Reyes syndrome (in children, with aspirin) -bone marrow toxicity -Bronchospasm in aspirin sensitive asthmatics -CNS effects : headaches, dizziness, confusion, seizures, drowsiness (NB indomethacin) -Salicycism: Tinnitus, dizziness, nausea, vomiting -Can be fatal in overdose -Drug interactions Warfarin - inhibition of warfarin catabolism - haemorrhage due anti-platelet effects and GI mucosal damage - aspirin also displaces warfarin from plasma proteins Betablockers, ACE inhibitors, diuretics loss of hypotensive +/- diuretic effect Increased levels of lithium, methotrexate and phenytoin increasing the risk of toxic effects Spironolactone, ACE inhibitors hyperkalaemia NB ibuprofen can interfere with the anti-platelet effect of aspirin (Binds to COX-1 instead of aspirin, but is reversible and shorter acting)

NOTE
- Aspirin= Largely superceded as an anti-inflammatory agent by other NSAIDs/coxibs

COX-2 specific inhibitors (-Celecoxib)

Selectively inhibit cox2

inflammation responce

-Oedema -hypertension -Cardiovascular Risk Myocardial infarction, stroke with prolonged usage even in patients without known vascular disease Inhibition of COX-2 derived PGI2, but ongoing production of TXA2 via COX-1 -Best avoided in patients with vascular dz

-Equivalent anti-inflammatory effects to non-selective NSAIDs BUT -Less risk of GI damage -Nimesulide COX-2 preferential LESS GI DAMAGE

D.CLASS
Paracetamol (acetaminophen)

M.A
-Binds to COX-3

ACTION
-analgesic and antipyretic effects = Equivalent to aspirin - low anti-inflammatory properties

SE
- allergic skin reactions - GI disturbance - analgesic nephropathy (long-term)

NOTE
-plasma half-life 1 to 4 hr -metabolised in the liver and excreted in the urine -In acute overdose, risk of dose-dependent, *hepatic necrosis Renal tubular necrosis, hypoglycemic coma and thrombocytopenia Due to Saturation of conjugating enzymesDepletion of glutathione Accumulation of toxic metabolite N-acetyl-pbenzoquinone Early symptoms: nausea, vomiting, diaphoresis and general malaise Treatment: -Gastric lavage/activated charcoal -N-acetylcysteine (increases liver glutathione formation), should be administered as early as possible, preferably within 16 hours

Licofelone

- AA analogue competitive dual inhibitor of COX and 5LO Inhibits production of PGs and LTs

-Symptomatic improvement in OA comparable with NSAIDs -possible role in preventing joint damage in OA

-May be safer than NSAIDs esp. from a GI viewpoint

04-05

J.A.M. Musallam

D. CLASS
Corticosteroids

M.A
-Is complex
Combine with cytosolic glucocorticoid receptor (GR entry to nucleus Binds transcription factors AP-1 and NF-kB. support tight structure of chromatin by inhibiting histone deacetylation. This prevents transcription factors from binding to and efffecting expression of their gene target. Inhibits transcription of COX 2 and inflammatory cytokines (interleukins and TNFa)+ -Reduced expression of adhesion molecules Induces Lipocortin-1 inhibits Phospholipase A2 Reduced synthesis of prostaglandins and leukotrienes

ACTION
Anti- inflammatory action generally -Reduced capillary permeability - migration/ activation of circulating leucocytes BUT IN NEUTROPHILS - basophils, eosinophils and monocytes but increase in neutrophils lymphocytes - (T>B; CD4+>CD8+) all \ neutrophil

USES
- inflammatory conditions :RA, gout, asthma, inflammatory bowel diseaseAct more rapidly and potent anti-inflammatory agents than NSAIDs -Maintenance therapy in many inflammatory conditions also e.g. RA - replacement therapy, e.g. malignancies

SE
Effective but side-effects limit long term use - Side-effects limit use as maintenance therapy -Cushingoid facies -truncal obesity, myopathy -Skin disorders, bruising -hirsuitism -dysphoria -hypertension -hyperglycaemia = Glucose intolerance, affect on carhydrates metabolism -acne .-Peptic ulcer disease prevented by Proton pump inhibitor -Cataract formation -Infection -Mental disturbance -HPA axis suppression - Irreversible osteoporosis, osteonecrosis

ADMI
-oral -IV -IM -intrasynovial

NOTE
Osteoporosis Prevention during steroid treatment -Weight-bearing exercise -Calcium, -Vitamin D (Calcichew -Bisphosphonates e.g. risedronate, alendronate 1/52

04-05

J.A.M. Musallam