NSAIDs and Non-opioid Analgesics Flashcards
Exam 4
What are the 5 types of autocoids?
- Histamine
- Serotonin
- Bradykinin
- Prostaglandins
- Leukotrienes
What are the 2 pathways of arachidonic acid?
- Cyclooxygenase pathway - Arachidonic acid (AA) converted to prostaglandin by COX
- Lipoxygenase pathway - AA converted to leukotrienes by lipoxygenase
Differentiate between COX1 and COX2
COX1 - constitutive, wide distribution, homeostatic functions (platelets, GI, renal)
COX2 - expression is stimulus-dependent, facilitates inflammatory response
What are the 3 types of anti-inflammatory drugs?
- NSAIDs
- Glucocorticoids
- Slow-acting anti-rheumatic drugs (DMARDs)
What is the original NSAID?
Aspirin
Which NSAIDs are reversible vs irreversible?
Aspirin - Irreversible block of cyclooxygenase
Other NSAIDs - Reversible block
What is the toxicity of NSAIDs?
- All are gastric irritants
- All can cause nephrotoxicity and hepatotoxicity
Which NSAIDs inhibit COX and lipoxygenase?
Indomethacin and Diclofenac
Which NSAID inhibits COX1 > COX2?
Aspirin
Which 2 NSAIDs inhibit COX1 = COX2?
Ibuprofen and Ketorolac
Which 2 NSAIDs inhibit COX1 < COX2?
Celecoxib and Meloxicam
Acetaminophen is used when ___________ effect of NSAIDs isn’t required
anti-inflammatory
What are the 3 biologic DMARDs?
Abatacept
Rituximab
Adalimumab
What are the 5 mediators released during chronic inflammation?
- Interleukins
- GM-CSF
- TNF
- Interferons
- PDGF
All increase WBCs
Acute inflammation is mediated by ______
autocoids
Describe how aspirin is an irreversible inhibitor
Aspirin acetylates serine group, obstructing AA access → Irreversible block of cyclooxygenase → prevents platelet activation by TXA2
- lasts as long as platelets do (8-10 days)
What medication can cause Reye syndrome?
Aspirin - when given to kids after a viral illness
Aspirin can cause ________ poisoning
salicylate
Why should NSAIDs be avoided in pregnancy? What medication is the alternative?
- Fetal kidney development, decreased amniotic fluid
- Acetaminophen
What is the treatment for aspirin OD?
activated charcoal, IV fluids, dialysis
Patients with _______ allergies can’t take celecoxib
sulfonamide
NSAIDs that are COX-2 selective have fewer _______ effects
GI
What is the black box warning for celecoxib?
Increased risk of serious adverse CV events - Inhibition of prostacyclin (PGI2) production
What medication can be taken with diclofenac that can decrease adverse effects?
misoprostol
What are the indications for indomethacin?
- Rheumatism
- Gout
- Patent ductus arteriosus
What keeps a PDA open after birth?
prostaglandins
What NSAID can be used in conjunction with opioids to decrease pain?
Ketorolac
Why isn’t acetaminophen considered an NSAID?
No anti-inflammatory effect, just pain
Acetaminophen is COX-__ selective
2
Aspirin has a vaso_____ effect in peripheral tissues, but a vaso_____ effect in the CNS
dilation, constriction
Differentiate between acute and chronic effects of glucocorticoid use
acute - suppresses inflammation, salt and water retention, improved cognitive function, mobilizes energy stores
chronic - immunosuppression, diabetes, depression, HTN
Glucocorticoids inhibit immune response by blocking ______
transcription/translation
What are the 3 options for glucocorticoids?
- Hydrocortisone
- Prednisone
- Dexamethasone (longer acting)
What are the indications for glucocorticoid use?
- Suppression of inflammation
- Addison’s Disease
- Post-adrenalectomy (Cushing’s disease)
- Fetal lung maturation
DMARDs clinical uses
- Reduced Inflammation
- Joint disorders - decreased damage to bones and joints
Biologic DMARD that blocks T-cell activation
Abatacept
Biologic DMARD that depletes B-lymphocytes
Rituximab
Biologic DMARD that is anti-TNF-α
Adalimumab
Chronic exposure to inflammatory mediators leads to increased:
- Cell proliferation
- Mutatgenesis
- Oncogene activation
- Angiogenesis
Describe tumor-promoting inflammation
Initiation: Inflammatory response increases mutational rates
- Inflammatory cells emigrate to tumor cells
- ROS accumulation
Promotion: Cytokines activate transcription factors (NF-kB / STAT3) in premalignant cells
What are the 5 pharmacokinetic properties of NSAIDs?
- Weak acids
- Well absorbed
- Highly metabolized
- Renal and biliary excretion
- Highly protein-bound
Define the MOA for GI upset with all NSAIDs.
- Buffering may decrease (especially with COX1 inhibitors)
Cause: - Irritation of gastric mucosa
- Inhibition of GI protective prostaglandin
- Increase incidence of gastric ulcers
Define the MOA of glucocorticoids.
Glucocorticoids inhibit the conversion of phospholipids to AA by inhibiting phospholipase; this inhibits all of the AA products, decreasing inflammation and suppressing immune function
Explain the selection criteria for NSAIDs.
- Cost
- Toxicity
- Personal factors
Determine toxicity of aspirin from nomogram.
