Inflammation (Chapter 6) Flashcards
what is inflammation ?
localized heat, swelling, redness and pain in response to a trigger
what can be a trigger for inflammation ?
extreme heat/cold, radiation, UV light, chemicals, anything that damages the skin, allergy infection, cancer
inflammation is propagated by chemical factors. where do they come from (3 places)
plasma
injured cell
immune system
is inflammation good or bad ?
it’s good, meant to remove infections and to promote clotting and tissue repair, however side effects are uncomfortable
inflammation is good, but there are bad side effects. what are 5 examples of chronic and debilitating inflammatory diseases that arise from inflammation ?
rheumatoid arthritis gout arthritis tonsillitis asthma multiple sclerosis
if something is inflamed, is it infected ?
no, but something may become inflamed with infection
eg psychosomatic inflammation
explain the main goal of the arachidonic acid pathway
metabolites produced inside an injured cell
COX enzymes activated, producing prostaglandins, thromboxane, leukotriene
how does the arachidonic acid pathway result in inflammation and clotting ?
when a cell is injured:
phospholipase A2 removed arachidonic acid from diacylglycerol/phospholipid membrane
then cox-1, cox-2, peroxidase turns it into prostaglandin, prostacyclin, thromboxane
lipooxygenase turns arachidonic acid into leukotrienes
what enzymes is the prostaglandin pathway promoted by
PGH2 synthase
cox-1, cox-2, peroxidase
what pathway would a drug acting against lipooxygenase target ?
it would target the leukotriene pathway and therefore would not help against inflammation
what enzymes do leukotrienes require ?
no enzymes.
what is the main purpose of leukotrienes ?
attract immune cells
what is the role of thromboxane ?
forming platelet aggregation (blood clots) and reducing blood flow to the site of a clot.
what happens in healthy vs injured endothelial cells ?
healthy: produce prostacyclins and nitric oxide that prevent clotting
injured: cells stop producing prostacyclin, meaning clotting can begin. therefore collagen sticks on platelets to create clotting.
what is a prostacyclin ?
a vasodilator that opposes the clotting pathway
how are leukotrienes involved in asthma ?
they trigger contractions in the smooth muscles lining the bronchioles
what is the role of bradykinin ?
causes vasodilation and pain response
what do chemotactic factors do ?
attract other cells to the injury
what do platelet-activating factors do ?
stimulate platelets to help form a clot
what does NSAID stand for ?
Non-steroidal anti-inflammatory drug
what pathway do NSAIDs target ?
arachidonic acid
name 3 examples of NSAIDs
aspirin, ibuprofen, naproxen (aleve)
what are the 4 purposes of NSAIDs
anti-pyretic (reduce fever)
analgesic (reduce pain)
anti-inflammatory (reduce inflammation)
anti-coagulant (thin blood)
how do NSAIDs act on the arachidonic pathway ?
inhibit COX enzymes, preventing prostaglandin production
what are the advantages of NSAIDs?
prostaglandins can be suppressed by NSAIDs, which prevents the pain caused by vascular permeability and edema
what are the bad sides of NSAIDs?
prostaglandins are also important to protect stomach lining from acid, so inhibiting prostaglandins means more acid damage, ulcer, GI tract issues. NSAIDs therefore cause stomach problems sometimes
what are the risks of NSAIDs?
modulating COX enzymes affects balance of blood clotting vs thinning, increasing risk of stroke or hemorrhage bleeding
what is COX1? what does it produce ? when it is expressed ?
expressed all the time in most cells of the body
produces thromboxane, which promotes blood clotting
what happens if you inhibit COX-1?
it thins the blood (anti-clotting)
what is COX-2? what does it produce ? when it is expressed ?
expressed only when there is inflammation in the cells that are injured
produces prostacyclin, which causes pain, and inhibits blood clotting
what happens if you inhibit COX-2?
it promotes clotting (clotting effect)
how does aspirin act on the arachidonic acid pathway ?
it is a very strong COX-1 inhibitor.
this inhibits blood clotting, therefore is a blood thinner
what does aspirin do to the GI system ?
causes disturbance
which NSAID inhibits COX-2?
ibuprofen (advil, aleve) a little
specific inhibitors: celebrex, vioxx, and vextra
which COX does ibuprofen inhibit ?
COX-2 and COX-1
inhibits COX-2 a lot more
inhibits COX-1
therefore only a slight anti-coagulant effect, with strong anti-inflammatory effect
why is it not good to use ibuprofen right after an injury?
it inhibits the clotting.
also increases swelling, edema, and pain.
what are three cox-2 specific inhibitors ? which ones are still on the market ?
celebrex, vioxx, vextra
only celebrex is still being used
what is the action of celebrex, a cox-2 specific inhibitor ?
this causes cox-1 to be more active, enhances clotting. this acts as a coagulant, can be dangerous
what are the risks of taking a cox-2 specific inhibitor ?
promotes clotting, therefore increases manifold the risk of myocardial infarction or stroke
what are the benefits of taking a cox-2 specific inhibitor ?
relieves GI symptoms
what is the best medication to take 24-48 hours after an injury for pain relief ?
tylenol which is not an NSAID.
how does tylenol work ?
doesn’t have the anti-coagulant effect, but works only in the brain to prevent pain so the injury heals faster
which tissues are affected by tylenol?
the brain
why doesn’t tylenol have all the blood and GI side effects NSAIDs do ?
because it only affects the brain
what are the clinical guidelines for NSAIDs?
there aren’t many, so a lot of people die and are hospitalized from the side effects
what are the recommendations for using aspirin for children ?
avoid it, risk of Reyes syndrome in children 17 or younger.
what is Reye’s syndrome?
causes swelling in liver and brain following a viral infection
what is the right dose to take for aspirin ?
it depends on what it is being used for:
analgesic, anti-inflammatory, blood thinner
what are the food intake recommendations for aspirin ?
always take with a meal, or at least with milk. this is because prostaglandins protect the GI tract, so prostaglandin inhibitors will be less harsh with food
food and milk helps neutralizes acid in stomach
why is it not a good idea to use NSAIDs on musculoskeletal injuries ?
NSAIDs are anti-inflammatory, but inflammation is a necessary component in the healing process.
why is it not a good idea to use NSAIDs on tendon injuries ?
a lot of tendon injuries are actually degenerative and not inflammatory conditions, therefore NSAIDs won’t help.
what is the major concern with concussion in the early phases
cerebral hemorrhage
what is a concussion ?
a traumatic brain injury that changes the way your brain functions
brain shifts and hits against the skull
in the brain, what can a concussion lead to ?
bruising and swelling of the brain, tearing of blood vessels, injury to nerves
what are the symptoms of a subdermal or epidermal hematoma ?
increased headache with worsening symptoms
what medication to give to a concussed person ?
none, it will mask the symptoms
don’t give anti-coagulants
when can you rule out an epidural hematoma ?
after a few days
if you really need to recommend a medication for a concussion, what would it be
tylenol
what are the base of corticosteroids ?
cortisol
what are the effects of cortisol ?
- glucogenic effects
- reduces inflammation
- increases healing
what are the three steps in an injury?
1) injury
2) inflammation
3) resolution and healing
at what stages of the injury does cortisol play a role ?
it blocks inflammation early on and then accelerates later stages of healing
what is hydrocortisone ?
a steroidal anti-inflammatory drug
what are the abilities of hydrocortisone?
cause anti-inflammation and mineral retention
what is dexamethasone ?
a steroidal anti-inflammatory drug
what are the abilities of dexamethasone ?
more potent anti-inflammatory as compared to mineral retention
what do the effects of corticosteroids reflect ?
natural glucocorticoid response
what are the effects of corticosteroids (5)
gluconeogenesis in liver
protein breakdown for amino acids
triglyceride hydrolysis to supply glycerol
increased excretion of calcium from kidney
diminished immune and inflammation response
how do corticosteroids decrease swelling and pain ?
by decreasing prostaglandins and leukotrienes
how exactly do corticosteroids inhibit inflammation
inhibit infiltration of phagocytes and lymphocytes at the site of inflammation
what diseases are corticosteroids used in ?
autoimmune, bronchial asthma, inflammatory bowel disease, tendonitis, bursitis, allergies, dermatitis, cancers, organ rejection, adrenocortical insufficiency
what is the dose-response relationship between concentration of cytokine IL-17A (symbolizing immune T-Cell response) and a corticosteroid like dexamethasone ?
in an environment with activated immune cells, the more dexamethasone, the less of a response in t-cells will happen.
what should be the dosing of corticosteroids ?
lowest amount for the shortest time, with exception of cancers or chronic diseases.
how should corticosteroids be administered ?
depends on the location of desired effect. can be oral, intramuscular injection, inhalation, topical
what are the adverse effects of corticosteroids ?
nausea, anorexia, headache, lethargy, fever
what can happen to adrenal glands with corticosteroid use ?
adrenal suppression through negative feedback
prolonged use of corticosteroids can lead to what syndrome?
Cushing’s, which is due to hypercortisolism
what is glucosamine ?
dietary supplement
what is glucosamine used for ?
treating osteoarthritis
how does glucosamine affect the arachidonic pathway ?
it doesn’t
it’s not an analgesic and not an anti-inflammatory agent
what is the chemical structure of glucosamine ?
aminomonosaccharide
what is the use of glucosamine based on ?
it stimulates the production of cartilage to replace damaged cartilage
is used to make glysoaminoglycans which are used to make cartilage
what have clinical studies shown for the use of glucosamine in treating osteoarthritis short term ?
it reduces its symptoms, compared with placebo
studies have shown that glucosamine can be effective in treating osteoarthritis combined with a medication. which one ?
ibuprofen
what is the difference between treating osteoarthritis with glucosamine or ibuprofen
ibuprofen- takes 1 week to be effective
glucosamine- takes 2 weeks
just as effective or more effective with glucosamine and ibuprofen
how is glucosamine consumed ? what does this imply ?
oral route
therefore first pass effect reduces bioavailability to about 1/4 oral dose
are there any benefits to using glucosamine with chrondroitin to treat osteoarthritis ?
in a controlled study, it was found that there was no difference between that group and the placebo group
however, in the subset with severe disease, there was a significant benefit
adverse effects of glucosamine ?
minimal
mostly GI distress
what are topical anti-inflammatory products?
treat topical inflammatory conditions
what is salicylate?
a counterirritant NSAID
where is salicylate usually applied ?
on strains, sprains, muscle soreness
how do salicylates work ?
by penetration directly to the tissue rather than absorption into the systemic circulation
greater rate of absorption on abdomen than on foot
are salicylates transdermal medication ?
no since the amount absorbed is too low to be for systemic therapeutic purposes
used for local response only
are salicylates less risky to use than oral NSAIDs?
no
to be used with caution if risk factors like renal disease, liver disease, GI bleeding, alcohol use
what is the form of salicylate usually used ?
methyl salicylate or trolamine salicylate
what happens if you apply methyl salicylate and then use an occlusive bandage or heating pad ?
increased irritation, tissue damage
what kind of skin are counterirritants applied on ?
intact skin, never wounds
what are the benefits of capsicum ?
relieving pain associated with osteoarthritis and rheumatoid arthritis
how does capsicum work ?
inhibits substance P, a NT involved in pain at peripheral sites
also has anti-inflammatory properties
what medications are used to relieve itching ? what kind of med are they ?
camphor and menthol
local analgesics
what is the word for a med that relieves itching ?
antipruritic
what is good in a combination with camphor and/or menthol for the antipruritic response ?
local anesthetics
what is the only corticosteroid available without prescription ?
hydrocortisone
what about eucalyptus oil, wormwood, Echinacea ? are they effective as anti-inflammatory / anti-irritants ?
we dont know for sure
how many NSAIDs should be used at a time
1
what should NSAIDs be taken with ?
food/ milk
what NSAID should you not prescribe to a teen with a viral infection ?
aspirin
athlete takes NSAID, gets dark black stools. what could it be ?
GI bleeding
