Pain, Inflammation and Anti-Inflammatory Flashcards
Inflammation
Inflammation is a process that begins following sub-lethal injury to tissue and ends with \_\_\_\_\_\_\_\_ destruction of tissue or with complete healing after removal of the injurious stimulus. It is characterized by five cardinal signs: rubor (redness) calor (increased heat) tumor (swelling) dolor (pain) -\_\_\_\_\_\_\_\_
permanent functio laesa (loss of function
Inflammation
-Elicits a series of events
-Humoral and Cellular (?)
These events bring about:
-Localization of injury
-Removal of noxious agent(s)
-Repair of_____ damage
________ of function in the injured tissue
Excessive/ Chronic inflammation is not beneficial :Rheumatoid arthritis, tuberculosis, psoriasis, mastitis etc.
physical
restitution
Inflammatory Mediators
-Generated at the _____ site
-Usually exist as precursors or sequestered in cells
-Cell damage results in release of _______ enzymes, -_________ and synthesis of various ________ ( Prostaglandins, Prostacyclines, Leukotreines, Thromboxanes)
-_________ have effects on blood vessels, nerve endings and blood cells
Two fundamental features of inflammation:
1. Increase permeability of the _______
2. Activation of ________
injury lysosomal arachidonic acid eicosanoids prostaglandins microvasculature leukocytes
Therapeutic Strategies
2 Goals of treatment:
-Relief of symptoms and maintenance of function
-Slowing of tissue damage
Drugs:
______: Relief of pain and Inflammation
_________: Long term control
_______: Decrease symptoms, slow bone damage in Arthritis and Decrease inflammation
NSAIDs
Corticosteroids
DMARDs
Anti-Inflammatory Agents
-Non-steroidal Anti-inflammatory Agents (NSAIDs):
Aspirin, Ibuprofen, Diclofenac, Piroxicam,
Celecoxib, Naproxen
-Steroidal Anti-inflammatory Agents:
Hydrocortisone, Betamethasone, Prednisolone
Triamcinolone, Fludrocortisone, Dexamethasone
-DMARDs (Disease Modifying Antirheumatic Drugs): Abatacept, Azathioprine, Cyclophosphamide, Methotrexate, Rituximab
idk
NSAIDs
NSAIDS: attenuate the inflammatory pain response
-Reduce biosynthesis of mediators of inflammation (______, ________)
-Cyclooxygenase (COX)-2 selective drugs: ______
Inhibition of _______ synthesis through selective inhibition of COX-2 isoenzyme
-COX -1 and Non-selective COX inhibitors: _____ GI complications. dyspepsia, ulceration, and upper GI ____ resulting in hematemesis
-Lower GI complications: small bowel, colon, and rectum leading to ulceration, overt or occult bleeding
-Cardiovascular effects of COX-2 inhibitors (MI/ Stroke)
prostaglandins, leukotrienes Celecoxib prostaglandin upper bleed
Cycloxygenase Enzyme
COX-1
Physiologic effects:
Platelets : production of ______
Kidney: regulate renal ______ in response to changes in blood volume and fluid & electrolyte transport
Gastric mucosa - maintain mucosal integrity
Regulate _______ tone
TXA2
blood flow
vasomotor
Cycloxygenase
COX-2
Physiologic
-_______ tract
Inducible (Pathologic)
-_______ and Pain by inflammatory mediators
Brain (_____): discovered in 2002
-found to be selectively inhibited by ________ andphenacetin and some ______
-Acetaminophen is a mild analgesic and antipyretic
-Suitable for mild to moderate pain.
-Its site of action has recently been identified as a COX-3 isoenzyme, a variant of the _____ enzyme
reproductive inflammation COX-3 acetaminophen NSAIDs COX-1
- __________ is a chronic, progressive, degenerative joint disease
Symptoms: Pain in DIP/ Morning stiffness/ Discomfort/ No systemic symptoms
-Diminished QOL
-Pain relieved by ____
-Radiographic findings: Narrowed ________
-Prevalence of OA is expected to increase primarily due to the world’s aging population and the increasing prevalence of
osteoarthritis
rest
joint space
Osteoarthritis
- Most common form of joint disease
- 90% population has radiographic features of OA in weight bearing joints by age ___!!
- Arthropathy includes degeneration of _____ and ______ of bone at articular margins
- Hereditary and mechanical factors involved
- _____ is felt in joint (Initially small, then large joints)
- No laboratory finding
- Radiology: Lipping of marginal bone, narrowing of joint space, thickened subchondral bone
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cartilage, hypertrophy
crepitus
Osteoarthritis
-Several guidelines for the management of OA pain
-Continues to be ____ treated!!!
-Inadequate pain therapy commonly reduces quality of life.
-Lack of understanding of the principles of pain therapy
-Misconceptions in regard to pain medications
-Unwarranted fears of treatment side effects.
Patient-related factors:
-Inadequate patient education
-Reluctance to report pain/ take pain medications.
under
Pain of Osteoarthritis
Pain is classified as:
________: adaptive (protective) because it prevents further injury and/or promotes ______
________ pain: maladaptive (pathologic) with no protective function/ results from tissue damage
_______ pain: Direct injury or dysfunction of the nervous system (post-herpetic neuralgia, diabetic neuropathy)
_________ pain is associated with abnormal neural processing in the absence of neurologic deficit or peripheral abnormalities
nociceptive healing inflammatory pain neuropathic pain functional
Pain of Osteoarthritis
- OA pain mechanisms are unknown
- Peripheral inflammatory in origin caused by damage occurring around the ____ (capsule, ligaments, menisci, periosteum, subchondral bone)
- Severe OA pain associated with high expression of inflammatory _____ and ________ in the joint tissues.
- Involve both _______ and ______ sensitization of pain.
- Recent data suggests that there might be a neuropathic component
joint
cytokines, neuropeptides
peripheral, central
Management of Osteoarthritis
- _______ and ______ pain syndromes are generally responsive to analgesics, such as acetaminophen, NSAIDs, COX-2 selective inhibitors and opioids
- ______ and _____ pain syndromes often require the use of adjuvant analgesics such as ______ (Gabapentin and Pregabalin) and antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors
- _____ therapy may require combining different drug therapies
nociceptive, inflammatory
neuropathic, functional
anti-convulsants
optimal
Acetaminophen
-Acetaminophen: _____ and ______ drug
-It lacks potent _________ activity
-Recent reports suggest that acetaminophen acts as a _____ (endogenous cannabinomimetic substance)
-It activates the ________CB1 receptors in the central nervous system (FDA, 2009)
COX-3 inhibitor
-Recommended oral dose: 325 mg every 4-6 hours, as needed, to a maximum daily dose of 3250 gm
-Combined with ______( and COX-2 Inhibitors)
-Opioids (Codeine, hydrocodone)
analgesic, antipyretic anti-inflammatory prodrug cannabinoid NSAIDS
FDA advisory
- Acetaminophen toxicity is a leading cause of Acute ____ failure, resulting in an estimated 400 deaths in the US each year.
- Many of these events are happening because patients are unknowingly taking too much of the drug.
liver
Acetaminophen: March 2017
- FDA announced that it is limiting the maximum amount of Acetaminophen in products to _____ mg per tablet, capsule or other dosage unit.
- FDA : ‘This will reduce the risk of severe liver injury from acetaminophen overdosing, an adverse event that can lead to liver failure, increased need for liver transplant and death.’
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