0521 - Chronic inflammation and pain - EG Flashcards
Define chronic inflammation.
inflammation of prolonged duration in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously.
Provide some examples of conditions where chronic inflammation can arise.
Can be due to persistent infection, e.g. tuberculosis, chronic osteomyelitis; prolonged exposure to toxic agents either endogenous (e.g. lipids) or exogenous (e.g. silicosis); or autoimmune diseases (e.g. rheumatoid arthritis)
What are the three characteristic histological features of chronic inflammation?
(1) collection of chronic inflammatory cells (2) destruction of parenchyma (3) replacement by connective tissue (fibrosis)
Describe the origin of pain and suffering.
Pain can result from either nociception, psychological processes, or neuropathic mechanisms.The nociception of pain can be from either visceral or somatic stimulus. Psychological processes and pain lead to suffering.
Describe the various modes of action of anti-inflammatory drugs.
(1) decrease the number of cells producing cytokines, either by number of cells in immunosuppressants e.g azathioprine or by activity of cells e.g. prednisolone (2) decrease the production of inflammatory cytokines by non-steroirdal anti-inflammatories e.g. aspirin (3) decrease immunoglobulin synthesis e.g. penicillamine (4) antibodies to decrease response to cytokines e.g. the antiTNFalpa action of infliximab (4) decrease cellular response to cytokines by modification of nuclear responses.
What is the mechanism of action of NSAIDS?
decreases secretion of “prostanoids” which are some of the mediators of inflammatory response through the inhibition of cyclooxygenase (either specific to COX2 or non specific and to both COX1 and 2)
What is the function of COX?
To convert arachidonic acid (an essential FA) to prostanoids.
What type of inhibitor is aspirin to COX in comparison to other NSAIDs?
aspirin is a non-competitive, irreversible inhibitor of COX, thereby more COX needs to be synthesised to restore activity and effect of aspirin are therefore long lasting after drug is eliminated compared to other NSAIDs that are competitive, reversible inhibitors, their degree of inhibition is proportional to the drug concentration.
Which two prostaglandins work to potentiate pain?
PGE2 and PGD2; potentiate pain caused by bradykinin and serotonin.
Which prostaglandin affects temperature by acting as a pyretic in the hypothalamus?
PGE2 along with interleukin-1
Arachidonic acid has two fates, if the function of COX is inhibited, what becomes the fate of arachidonic acid? When is this a concern?
arachidonic acid is converted by lipoxygenase into leukotrienes, many of which are bronchoconstrictors, therefore NSAIDs should be given with caution to those with asthma.
Why do you think osteomyelitis can progress to become chronic?
the acute inflammation leads to an overactive immune response, impaired blood flow, and tissue necrosis, putting the tissue in simultaneous cycle of tissue destruction and repair.
What are three potential significant side effects associated with NSAID use?
bronchoconstriction (due to increased leukotrienes); gastrointestinal bleeding and/or ulceration (due to loss of protective prostaglandins); renal impairment (due to loss of prostanglandin dilation of afferent arterioles, worse with polypharmacy of ACE inhibitor and diuretic); pregnancy due to risk of premature closure of fetal ductus arteriosis.
Which anti-inflammatories are disease modifying and which are more symptom control?
Disease modifying: immunosuppressants, symptom control: NSAIDs, antibodies to cytokines.
