anti-inflammatory drugs Flashcards
examples of inflammatory drugs
- NSAIDs
- SAIDs
- disease modifying anti-rheumatoid drugs (DMARD) but now biological response modifiers (BRMs)
what are the pathways for arachidonic acid?
- cyclo-oxygenase producing prostaglandins
- lipo-oxygenase producing leukotrienes
- CYP450 producing EET
what is eicosanoids?
antacids
what is COX 1?
- control homeostasis production of prostaglandins
- housekeeping genes
- expressed in most tissues
what is COX 2?
- increased production of prostaglandin in certain conditions eg: inflammation and cancer
what is COX 3?
predominantly found in CNS
where is PGE2 (prostanoids) located and its effect?
- in many cell types as inflammatory cells
- contraction and relaxation of smooth muscle
- immunosuppressive and anti-inflammatory
- fever
- gastric secretion and inhibition
- form cancer and promotes metastasize
- promotes angiogenesis
where is PGI2 (prostanoids) located and its effect?
- in vascular endothelium
- cause vasodilation
- inhibit platelets aggregation
where is PGD2 (prostanoids) located and its effect?
- in mast cells
- cause vasodilation
- inhibit platelets aggregation
where is TXA2 (prostanoids) located and its effect?
- in platelets
- cause vasoconstriction
- promotes platelets aggregation
what are the main aims for anti-inflammatory drugs?
- relieve pain
- arrest tissue damage
what are the 5 major actions in NSAIDs?
- anti-inflammatory action
- analgesic effect
- antipyretic effect
- anti-platelet effect
- anti- cancer effect
what NSAIDs do in anti-inflammatory action?
decrease in PGE2 and PGI2, reduce vasodilation
what NSAIDs do in analgesic action?
decrease PG production results in decrease sensitivity of nerves to inflammatory mediators
what NSAIDs do in antipyretic action?
largely inhibition of PG production in hypothalamus
what NSAIDs do in anti-platelets action?
- reduction in TXA2
- preventing platelets aggregation
- prolong bleeding time
what NSAIDs do in anti-cancer action?
- reduce PGE2 formation
- inhibition of tumour cell proliferation
- enhance tumour cell apoptosis
- inhibition of angiogenesis
side effects of NSAIDs in GI (most common)
- GI bleeding
- ulcer disease
- perforation in GI tract
- due to inhibition of PG that protect the mucosa from acidic
side effects of NSAIDs in renal
- cause renal insufficiently due to inhibition of PGE and PGI
- neuropathy if chronic use
side effects of NSAIDs in blood
- disturbance in platelets function
- increase bleeding time
side effects of NSAIDs in liver
failure to excrete drugs
side effects of NSAIDs (coxibs) in heart
- MI
- angina
- stroke
- TIA
examples of NSAIDs in cox 1 selective
- aspirin
- sulindac
- indomethacin
examples of NSAIDs in non-selective cox 1
- ibuprofen
- paracetamol
examples of NSAIDs in both selective and non cox 1
- flurbiprofen
- diclofenac
examples of NSAIDs in cox 2 selective
- celecoxib
- rofecoxib
aspirin?
- oldest NSAIDs
- irreversibly inhibit cox 1 and cox 2
side effects of aspirin
- gastric ulcer
- asthma
- diabetes
- gout
- hypocoagulation state
- reye’s syndrome in children
drugs interactions with aspirin
- increase warfarin
- heparin
- increase insulin
- increase phenytoin
- increase methotrexate
ibuprofen?
- competitive inhibitor of cox 1 and cox 2
- better tolerated than aspirin and indomethacin
- fewer GI problems
indomethacin and sulindac?
- not normally used as analgesic/ anti-pyretic
- potent anti-inflammatory agents
- indomethacin:
- less tolerated than aspirin and ibuprofen
- high GI problems - sulindac:
- better tolerated than indomethacin
- fewer GI reactions
paracetamol?
- suitable for children
- effective analgesic and anti-pyretic
- weak anti-inflammatory agents
- well tolerated
- overdose cause hepatotoxicity
- max daily dose 4 g
what are celecoxib and rofecoxib?
- cox 2 selective inhibitors
- competition inhibition of cox 1
- less serious GI reactions
side effects of cox 2 inhibitor
- small GI disturbances
- dizziness
- bronchitis
- coughing
- pharyngitis
- rhinitis
- somnolence
- insomnia
- cardiac problems
5-lipoxygenase inhibitors?
- blocks antigen and exercise induced asthma
- reduce underlying inflammation
- low potency, short half life
- eg: zileutin
cysteinyl leukotriene antagonists?
- competitive antagonist at LT receptor
- prevents aspirin-induced bronchoconstriction
- eg: zafirlukast, montelukast, pranlukast
dual cox 5-LO inhibitors?
- competitive inhibitor of 5LO and cox 2
- improved tolerability
- eg: licofelone
indirect inhibitor?
- still under development
examples of DMARD
- methotrexate (common use)
- leflunomide
- chloroquine (treatment of malaria)
- sulfasalazine
- azathioprine
DMARD?
- slow onset of action
- mechanism unclear
- variable efficacy
- many side effects
biological response modifiers (BRM)?
- quick onset of action
- target specific receptor
- fewer side effects
examples of TNF inhibitors (BRM)
- etanercept
- infliximab (mouse gene)
- adalimumab (100% human genes)
examples of anti-interleukin therapy (BRM)
- IL-1 anakinra
- IL-6 tocilizumab
examples of B-cell depleting theraphy (BRM)
rituximab
examples of blocking cell adhesion and migration
- teplizumab
- daclizumab
examples of blocking T cell coreceptors
abatacept
side effects of TNF inhibitor
- fungal infection
- reactivation of myco tuberculosis
- malignancy/lymphoma
- congestive heart failure
- demyelination
- autoantibodies
- congenital abnormalities
