anti inflammatory Flashcards
Prostaglandins and leukotrienes
Platelet activating factor (PAF)
Histamine
5-hydroxytryptamine
Neuropeptides
Nitric oxide
Bradykinin
Adenosine and purines
Complement
Cytokines
are all examples of — which are secreted by — cells by which the are responsible for the symptoms of —- as: —
- pain occurs when iflammation occurs near a — fiber
local mediators
immune cells
inflammation as vasodilation
nerve fibre
Rheumatoid arthritis
Atherosclerosis & heart disease
Chronic obstructive pulmonary disease (COPD)
Crohn’s disease
Asthma
Lupus
Psoriasis
Cancer
Type II diabetes
are all examples of —
by which a trigger occurs and then it triggers active inflammation n response leafs to tissue damage n tissue repair is by fibrosis for example
chronic inflammation ( inflammation itself is the problem )
in acute inflammtion: ( acute is when inflammation is usually a coalition to an insult as infection/damage)
- bacteria triggers Mac prophages to release — and —
- vascular response as :
- cellular response as when inflammatory cells migrate into tissue releasing —- that cause pain
- —- they key immune cells in acute inflammation
- cytokines n chemokine
- vasodilatation n permeability causes heat redness n swelling
- inflammatory mediators
- neutrophils
( check slide 5)
-Anti-inflammatory drugs provide — relief as reducing — and —
- ideally used as — measure util underlying disease is brought under control
- acute iflammation can be treated w —– but it doesnt always need a treatment
- Chronic inflammation can be treated with combinations of —- to target individual cytokines or immune cells
- The longer any anti-inflammatory agent is used (e.g. during chronic inflammatoryconditions like rheumatoid arthritis or gout), the higher the risk of developing —
- symptomatic relief as reducing pain n fever
- temporary
- anti inflammatory drugs NSAIDS or steriods
- NSAIDs, steroids, biologic
agents - side effects
—- are immunosuppressive
—– anti-inflammatory
- cortisol (endogenous), cortisone, prednisone, prednisolone,
dexamethasone are all examples of —
- indicated in patients w —-
- contra-indicated in patient w —
steroids
nsaids
steroids
lupus, asthma, COPD, inflammatory bowel disease,chronic inflammatory conditions
active infection, depression or alcohol
dependence, high blood pressure, diabetes, heart failur
Corticosteroids and the HPA axis:
the pathway started off from —- –> —- > and then —-
1- hypothalamus CRH ( CRF)
2- pitiurtry ( ACTH )
3- adrenal glands ( cortisol )
(info: Glucocorticoid receptors in multiple downstream cells and tissues
Eg. immune cells, bone, liver, fat tissue)
Glucocorticoid signalling via GC receptors:
Prednisone, prednisolone etc are —
Cortisol is —-
- — the transaction of pro inflammatory genes
- —- the transcpriton of anti inflammatoy genes
synthetic
endogenous
decrease
increase
glucorticoid effects on immune cells :
1- inhibits —- which increases —- production
2- reduces the production of ——
3- decreases —
4- increases —
5- Circulating lymphocyte number is — ( T > B , CD4 > CD8)
6- adverse effects on —-
- phospholipase A₂
- Annexin A1 (aka lipocortin-1)
- IL-1, IL-2, interferon, prostaglandins, leukotrienes
- basophils, eosinophils and monocytes
- neutrophils
- reduced
- carbs metabolism
( glucorotidode needs to be used in caution as during disease flare ups in chronic inflammatory states bc we have wide selection of receptors)
CHECK SLIDE 15 PLSSS
COX enzyme ( prootagladin H synthesis ) produces —- which is constitutively expressed aka housekeeping and — which is inducible as for: shear stress, growth factors, tumour promoters, cytokines
cox 1
cox 2
—– Used for temporary, symptomatic relief of inflammation
act by inhibititing — which reduces —- production
are —–
examples :
NSAIDS ( non steroidal anti iflammatory drugs)
COX enzyme
reduces prostaglandin production
anti inflammatory analgesic anti pyretic
aspirin ( irreversible) ibuprofen, indomethacin, diclofenac
mechanism of COX inhibition by NSAIDS:
cox enzyme are —
inhibition of one site makes the dimer —
asprin — modifies —
- cox can be protected by co-
administration of a —
- homodimers
- inactive
- covalently
- cox
- reversible inhibitor
aspirin side effects:
1- — due to the reduced platelet function
2- —– due to an increase acid production
3- acetylation of liver proteins causes —- in children
* important info:
Aspirin is the only NSAID with — &— antiplatelet effects - other NSAIDs are —
excessive bleeding
Gastrointestinal (GI) haemorrhage
Reye’s syndrome in children
potent and specific
reversible
( check slide 20)
-Coxibs selectively inhibits the inducible form of —
-developed to protect against —-
-Have similar efficacies to that of the —– , but much—- side effects
- examples: —
- Significant increase in —
- Rofecoxib (trade name, Vioxx) was taken off the market in 2004
- cox 2
- gastric ulceration
-non selective inhibitor - fewer GI
- celecoxib n rofecoxib
-myocardial infarction (MI), stroke and death from a vascular event
- Selective COX-2 inhibition reduces —- production by — which causes —- and tendency for —-
- Little or no inhibition of potentially —- production this leads to exaggeration effects in patine treated chronically w coxibs
- prostaglandin I₂ (PGI₂ / prostacyclin)
- vascular endothelium
- reduced vasodilation
- platelet aggregation
- pro-thrombotic platelet thromboxane A₂ (TxA₂) production
- All NSAIDs increase —- risk but Naproxene the least
- The increased risk is —-
- Avoid —- use in patients at high risk of cardiovascular event
- When using , use — dose for—- period
cardiovascular risk
dose dependent
nsaidssssss
lowest dose n shortest period
What about the other side of the arachidonic acid pathway?
1-NSAIDs block conversion of —- to —
2- Excess arachidonic acid is diverted to —- which can either be:
— for pro resolution mediators
—- Bronchoconstriction,
inflammation(esp. in asthma)
acrahcnodic acid to prostagaldon
- lipoxugenase
- LOX aka lipoxins
- leokitrines 5-LO
paracetamol info:
- Not an NSAID…used for fever (anti-pyretic) and pain (analgesic) but is not an anti-inflammatory
- Mechanism of action is unclear : only a very weak inhibitor of COX-1 and COX-2, yet inhibits
downstream prostaglandin production - Multiple theories (COX-3??)
- Still shows CV, GI and renal risks
Antagonising cytokines to reduce inflammation:
* Monoclonal antibody therapies to target either — or —-
* A frequent goal is to inhibit signalling from —-
- CK receptors or CK itself
- pro inflammatoy cytokines ( pro inflammatory cytokines as IL-1, IL-6, and TNF-α.)
example of targeting a cytokine receptor:
1-Basiliximab– Simulect (Novartis)
Mob acts as an —-
used in —- to prevent rejection of the new organ
Antagonises the function of — in driving T cell proliferation
Protects the transplanted organ (“non-self”) from being targeted by the —
2- Remicade (Infliximab) - Janssen:
- mab acrs aș —
- indicated in —
- anti-IL-2 receptor antibody
- organ transplant
- IL-2
- recipient’s T cells
- anti tnf alpha reagent
- mutable inflammation condition of chronic nature
info
( don’t focus much on drugs in this lecture )
Other miscellaneous drugs to treat inflammation
* Metformin for patients with Type II diabetes…reduces circulating levels of pro-
inflammatory cytokines and C-reactive protein
* Statins can be both anti-inflammatory and anti-oxidant…inhibit pro-inflammatory cytokine
production from activated T cells, and inhibit Th1 cells
* Disease-Modifying Anti-Rheumatic Drugs
* Block inflammation
* Multiple drugs, multiple individual mechanisms of action
Examples: Methotrexate (interferes with DNA synthesis and repair reduces cellular replication)
Sulfasalazine (broadly anti-inflammatory, no single agreed mechanism of action)
Leflunomide (activates P53, halts lymphocyte proliferation)
