07- NSAIDS Flashcards
analgesic
is any member of the group of drugs used to achieve analgesia, or relief from pain (painkiller)
-accomplished by NSAIDs through reduction of PGE2 and PGI2 induced hyperalgesia and general reduced inflammation (not effective against non-inflammatory pain
anti-platelet
drugs that decrease platelet aggregation and inhibit thrombus formation
-NSAIDs inhibit platelet COX-1 (no COX-2)
antipyretic
are substances that reduce fever
-antipyretics cause the hypothalamus to override an PGE2-induced increase in temperature
gastric effects
histamine activation of H2 receptors in mucosal lining of stomach leads to increased acid production, pepsin, and intrinsic factor
-leads to mucosal erosion and ulceration
arachidonic acid
the substrate for production of lipid mediators of inflammation (prostaglandins produced by cyclooxygenase, or leukotrienes produced by lipoxygenase)
- cyclooxygenase inhibited by NSAIDS
- lipoxygenase inhibited by Zileuton (Zyflo)
cyclooxygenase (COX)
produces prostaglandins which are lipid mediators of inflammation
-inhibited by NSAIDS
dyspepsia
indigestion, upper abdominal pain, bloating, nausea
-common symptom of chronic NSAID use
eicosanoids
prostanoid and leukotriene derivatives of C-20 fatty acids
Fc Domain
area of an antibody protein that does not change
-this area does not bind to antigen (variable region is specific for and binds antigens)
humanized antibody
also know as chimeric antibody
- graft ligand binding domain from animals onto backbone of fully human antibody
- has same function as a fully human antibody with out resistance produced from animal antibodies
leukocytes
cell that circulates in the blood and body fluids and is involved in counteracting foreign substances and disease; a white (blood) cell
-several types including lymphocytes, granulocytes, monocytes, and macrophage
mast cells
a cell filled with basophil granules, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions
-most dense in tissue with higher chance of injury such as mouth, nose, hands/feet, blood vessels, GI mucosa
motion sickness
triggered by histamine activation of H1 receptors in the emetic center of the CNS
phospholipase A2 (PLA2)
hydrolyzes phosphatidylcholine in plasma membrane to release free arachidonic acid (AA)
- eventually leads to production of lipid mediators by AA
- activity inhibited by annexins (aka lipocortins) (annexin expression increased by glucocorticosteroids)
phospholipase C (PLC)
activates signaling pathways that increase Ca+2 mobilization and promote fusion of cytoplasmic vesicles with the plasma membrane and extracellular release of their contents (degranulation)
- stored mediators (e.g., histamine) are released in response to PLC activation
- inhibited by agents such as cromolyn (Intal) and nedocromil (Tilade)
prostaglandin
lipid compounds that play a major role in initiation and mediation of inflammatory response
-formed by cyclooxygenase and can be inhibited by NSAIDs and glucocorticosteroids
prostanoid
synthesized by cyclooxygenase
- short half-lives and lack of stored products make activity synthesis dependent
- membrane permeable and passively released from other cells
- have autocrine and paracrine activity
- can effect blood vessels, smooth muscles, platelet aggregation, pain response, and body temperature
Reye’s syndrome
associated with the use of ASA and other salicylates in children who have viral illness
- acute encephalopathy, fatty liver degeneration
- also associated with viral vaccines
salicylism
hypersensitivity to ASA
-symptoms include: hyperventilation, tinnitus, vertigo, emesis, sweating
triple response
response seen in the skin caused by histamine release
- WHEAL = edema (and reddening from dilation of small vessels)
- FLARE = axon reflex: histamine stimulation of sensory nerve terminals cause release of vasodilators at other branches
- ITCHING
urticaria
hives which caused raised, itchy, and red skin
-triggered by histamine activation of H1 receptors on sensory nerves
Anti-Inflammatory action of NSAIDs
block production of all prostanoids by inhibition of cyclooxygenase
-COX-2 primarily responsible for prostanoid production during inflammation
Infliximab
anti- TNF alpha, human antibody
- Rheumatoid arthritis
- Crohn’s disease
complications: increased frequency of infection (respiratory and urinary)
Adalimumab
anti-TNF alpha, human antibody
- Rheumatoid Arthritis
- Crohn’s disease
complications: increased frequency of infection
Etanercept
anti-TNF alpha, fusion protein
- Rheumatoid Arthritis
- Crohn’s disease
complications: increased frequency of infections
Anakinra
competitive IL-1 receptor antagonist
- Rheumatoid Arthritis
short half-life, daily injections
complications: increased susceptibility to infections
Tofacitinib
Jak Inhibitor
-Rheumatoid Arthritis (for those who fail methotrexate)
-inhibits activities for many inflammatory cytokines
small dose (5mg)
adverse effects: anemia, neutropenia, myelosuppression
increased risk of infection (herpes zoster)
Prednisone
GLUCOCORTICOSTEROID
-inhibits PLA2
-inhibits production of chemotactic factors
decreased production of prostaglandsin, leukotrienes
-induces annexins (inhibits PLA2)
Cyclizine
H1 Receptor Antagonist (1st generation)
Uses: allergic rhinitis and urticaria, motions sickness/emesis
adverse effects: sedation, anticholinergic effects (dry mouth, urinary retention, tachycardia)
dimenhydrinate
H1 receptor antagonist (1st generation)
uses: motion sickness/ emesis
adverse effects: sedation,
anticholinergic effects (dry mouth, urinary retention, tachycardia)
diphenhydramine
H1 receptor antagonist (1st generation)
uses: allergic rhinitis and urticaria, motion sickness/emesis
adverse effects: sedation, anticholinergic effects (dry mouth, urinary retention, tachycardia) blocks Na channels
promethazine
H1 receptor antagonist (1st generation)
uses: antiemetic
adverse effects: sedation, anticholinergic effects (dry mouth, urinary retention, tachycardia) blocks Na channels
loratadine
H1 receptor antagonist (2nd generation)
Uses:
poor CNS penetration
few anticholinergic effects
cetirizine
H1 receptor antagonist (2nd generation)
uses:
poor CNS penetration
few anticholinergic effects
fexofendadine
H1 receptor antagonist (2nd generation)
uses:
poor CNS penetration
few anticholinergic effects
aspirin
mixed COX-1 and COX-2 inhibitor
rapidly converted to salicylic acid (reversible inhibitor)
(ASA irreversible inhibitor)
all metabolites excreted in urine
elimination saturates beyound 600 mg and 1/2 life increases to 12-16 hours
uses: fever, analgesia, muscle pain, tendonitis, bursitis (inflammation)
rheumatoid and osteoarthritis
Cardiovascular prophylaxis– reduced platelet aggregation (75-80 mg/daily)
ketorolac
mixed COX-1 and COX-2 inhibitor
uses: post-surgical analgesic
indomethacin
mixed COX-1 and COX-2 inhibitor
uses: Rx- arthritis/anti-inflammatory
high frequency of intolerance
naproxen
mixed COX-1 and COX-2 inhibitor
Rx- anti-inflammatory
ibuprofen
mixed COX-1 and COX-2 inhibitor
OTC: analgesic/antipyretic
diclofenac
mixed COX-1 and COX-2 inhibitor
Rx- arthritis/anti-inflammatory
acetaminophen
non-selective COX inhibitor
uses: analgesic and antipyretic
hepatotoxicity with overdose
celecoxib
selective COX-2 inhibitor (10-20 times more selective for COX-2 than COX-1)
anti-inflammatory effects, antipyretic, analgesic effects, renal toxicity
mainly used for osteoarthritis and rheumatoid arthritis
expensive
