Drugs To Treat Inflammation Flashcards
What is acute inflammation?
- rapid onset following injury
- vascular: initial phase that leads to swelling and pain
- cellular: cellular changes involving blood flow
What role does cryotherapy have with acute inflammation?
Does not completely stop inflammation, just helps to keep it under control (similar to what medications do)
What are the cardinal signs of acute inflammation?
- swelling
- heat
- redness
- altered function
- pain
What are the signs of infection and not just inflammation?
- redness is more prevalent (large areas of redness)
- circle of redness or streaks of red going down the limb
- growing redness
- heat - excessively warm and red
What is chronic inflammation?
- continued exposure to an offending element
- activation of macrophages and lymphocytes
2 primary mediators of vasodilation:
- histamine
- bradykinin
Tissue damage activates ______ and causes release of ______ ______.
- nociceptors
- chemical mediators
Where is cyclooxygenase 1 (COX-1) found and what does it do?
- found in virtually all tissues, significant in GI system
- housekeeping functions
Where is cyclooxygenase 2 (COX-2) found and what does it do?
- produced in the brain, kidneys, blood vessel walls
- induced in inflammatory response
- involved in maintaining normal functions
3 chemical mediators in the cyclooxygenase (COX) pathway:
- thromboxane A2
- prostacyclin (PGI2)
- prostaglandins
What does thromboxane A2 do?
- increases platelet aggregation
- vasoconstriction
What does prostacyclin (PGI2) do?
- decreases platelet aggregation
- vasodilation
What does prostaglandins do during normal functions?
- protects gastric mucosa
- increases renal blood flow
What does prostaglandins do during the inflammatory response?
- increase blood flow
- produce erythema
- initiate chemotaxis
- mediate pain response
What are the 2 pathways created by arachidonic acid?
- COX (prostaglandins, prostacyclin, thromboxane)
- lipoxygenase (leukotrienes)
How does membrane-bound arachidonic acid turn into arachidonic acid?
With phospholipase A2
Anti-inflammatory drugs function to inhibit _____ ______ _______.
Arachidonic acid cascade
2 categories of anti-inflammatory drugs:
- non-steroidal anti-inflammatory drugs (NSAIDs)
- corticosteroids
Corticosteroids act at what point?
Phospholipase A2
NSAIDs inhibit at what point?
COX
4 types/potential actions of anti-inflammatory drugs:
- anti-inflammatory
- anti-pyretic
- analgesic
- anti-platelet
NSAIDs work to inhibit the _____ enzyme and decrease formation of ________ _______ metabolites. Decreased ______ production leads to anti-inflammatory effect.
- COX
- arachidonic acid
- prostaglandin
NSAIDs inhibit ______ and ______ synthesis.
- prostaglandin
- thromboxane
NSAIDs affect pain pathway in 3 ways:
- prostaglandin reduces activation at nociceptor neurons
- decrease recruitment of leukocytes
- NSAIDs in brain prevent prostaglandins, which cause pain
Primary therapeutic effect of NSAIDs:
- MSK pain/inflammation relief
- less effective than opioid but fewer ADEs
- coadministration of NSAID with opioid: reduce opioid dose needed
Non MSK examples of therapeutic effects from NSAIDs:
- menstrual pain is only hollow viscera pain treated successfully
- NSAID plus antiemetic to treat migraine headache
- Ketorolac can produce analgesia equivalent of morphine to treat diabetic neuralgia
Describe the pharmacokinetics of NSAIDs:
- absorption: reach plasma concentration in 2-3 hours (food/antacids may delay absorption - suggested due to gastric disruption)
- distribution: sufficient CNS concentration to be effective
- metabolism: first pass metabolism, reduced bioavailability
- excretion: primarily renal excretion
Indications for NSAIDs:
- mild and moderate pain
- fever
- headaches
- reduce swelling
- inflammatory conditions
- menstrual pain
- arthritis
- rheumatic conditions
4 routes of administration for NSAIDs:
- oral
- topical
- injection
- rectal
List some common NSAIDs:
- aspirin and other salicylates
- other non selective NSAIDs (ibuprofen, naproxen, diclofenac, ketorolac (Toradol))
- COX-2 selective inhibitors (celecoxib (celebrex), Vioxx)
Adverse effects of NSAIDs:
- gastrointestinal
- renal toxicity
- cardiovascular
- liver toxicity
Describe possible GI symptoms from NSAIDs:
- dark, tarry stools
- indigestion
- nausea, vomiting
- abdominal pain
How to minimize GI symptoms from NSAIDs:
- take with food or milk
- use of antacids, proton-pump inhibitors
- enteric-coated aspirin
- misoprostol: prostaglandin substitute
Describe potential renal adverse effects from taking NSAIDs.
- prostaglandins help regulate renal blood flow. Decreasing them can decrease renal blood flow, causing impaired kidney function
- use with caution in elderly and patients with conditions such as heart failure and kidney disease
Describe potential cardiovascular side effects of taking NSAIDs:
- increased bleeding time (aspirin and non-selective COX inhibitors)
- increased incidence of heart attack and stroke (selective COX-2 inhibitors)
_______ toxicity has lower incidence with NSAID use than ______ toxicity.
- liver
- renal
Drug interactions with NSAIDs:
- aspirin and non selective NSAIDs with NSAIDs decrease effects of anti-hypertensive agents
- ibuprofen interferes with the cardio protective effect of aspirin
- agents that increase the risk of GI side effects
Therapeutic guidelines for NSAIDs:
- use the lowest dose for the shortest duration of therapy
- selection of NSAID
- avoid concomitant use with alcohol, aspirin or other salicylates, other NSAIDs, corticosteroids, anticoagulants.
- take with food
What is the risk of giving NSAIDs to kids
- risk with kids getting Reye’s syndrome (can be fatal if not recognized) - reaction to aspirin in kids
- do not give aspirin to kids (last choice is baby/children’s aspirin)
Endogenous corticosteroids are produced by the _______ _____. An example of these are _________.
- adrenal cortex
- glucocorticoids
After approximately 7 days of taking systemic corticosteroids (oral), what do you need to do stop taking them?
Need to wean them off because your body has stopped producing it
What are the functions of exogenous corticosteroids?
- inhibit inflammatory response to injury
- suppress allergic disease by releasing histamine
- large doses inhibit ACTH release from pituitary gland
Mechanisms of action for corticosteroids:
- lower leukocytes migration
- reverse capillary permeability
- inhibit factors of inflammatory response
- decrease vasoactive factors; decrease fibroblast activity at site
- diminish secretion of lipolytic and proteolytic enzymes
- suppress vascular changes responsible for inflammation
Indications for short-term use of corticosteroids:
- pain
- reduce swelling
- inflammatory conditions
- arthritis
- rheumatic conditions
- skin conditions
- asthma
Routes of administration for corticosteroids:
- inhalation
- topical (to avoid systemic effects of oral medication)
- local injections
- oral
- intramuscular
With corticosteroids, the greatest risks come with what routes of administration?
- oral
- injections (tendon and joints)
Risk of multiple corticosteroid injections:
Can have degenerative impact on tissues, tendons, and joint surfaces
Adverse effects of corticosteroids:
- hypertension
- increased blood glucose (short term impact is important for diabetics)
- fat redistribution
- osteoporosis
- suppression of growth in children
- myopathy
- cataracts, glaucoma
- CNS adverse effects
- immunosuppressive
- peptic ulcer disease (only with oral version)
- agitation and irritability
- sleepiness
- weight gain
- avascular necrosis or osteoporosis (esp. of femoral head)
Therapeutic guidelines for corticosteroids:
- use the lowest dose possible for the shortest duration of time
- should be considered a bridge treatment
- generally used when other interventions have been unsuccessful
- do not abruptly discontinue corticosteroid
