ANTI-INFLAMMATORY DRUGS (s) Flashcards
these secrete cytokines, tumor necrosis factor (TNF), interleukin (IL-1) into synovial cavity
monocytes and macrophages;
will cause:
o increased cellular infiltrations into endothelium due to the
release of histamines, kinins, and prostaglandins leading to
vasodilation
cytokines
increased production of C-reactive protein by hepatocytes
(marker of inflammation)
cytokines
increased production and release of proteolytic enzymes
(collagenases, metalloproteinases) by chondrocytes leading to degradation of cartilage and joint space narrowing
cytokines
o increased osteoclast activity and bone demineralization around joints
o systemic manifestations (heart, lungs, and liver are adversely affected)
cytokines
PHARMACOTHERAPY IN MANAGEMENT OF RHEUMATOID ARTHRITIS (RA
→ anti-inflammatory drugs
→ immunosuppressive agents
GOALS OF TREATMENT
→ modulate/reduce inflammatory process
→ halting or slowing progression of disease
→ reduce pain
Aspirin
Diflunisal
Diclofenac
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Etodolac
Fenamates
Flurbiprofen
Ibuprofen
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Indomethacin
Tolmetin
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Ketorolac
Meloxicam
Methyl salicylate
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Nabumetone
Naproxen
Oxaprozin
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Piroxicam
Sulindac
Non-Steroidal Anti-Inflammatory Drugs (NSAID)
Celecoxib
COX-2 Inhibitors
Acetaminophen
Other Analgesics
Abatacept
Adalimumab
Drugs for Arthritis
Anakinra
Chloroquine
Etanercept
Drugs for Arthritis
Etanercept
Gold Salts
Infliximab
Drugs for Arthritis
Methotrexate
D-Penicillamine
Drugs for Arthritis
Allopurinol
Colchicine
Drugs for Gout
Probenecid
Sulfinpyrazone
Drugs for Gout
→ inhibits the synthesis of prostaglandins
NSAIDs
primarily inhibits cyclooxygenase enzymes (catalyzes first step
prostanoid biosynthesis); leads to decreased prostaglandin
synthesis
NSAIDs
contraindicated in:
o perioperative pain like in coronary bypass graft surgery
o patients at risk for gastrointestinal adverse effects such as
bleeding, ulcer, or perforation of the stomach or intestine
NSAIDs
unsaturated fatty acid derivatives (eicosanoids)
PROSTAGLANDINS
its precursor, Arachidonic acid, a 20-carbon fatty acid causes an increase of intracellular calcium and is a component of the
phospholipid of the cell membrane
PROSTAGLANDINS
from the Arachidonic acid there are two pathways
o cyclooxygenase pathway
o lipoxygenase pathway
described as the housekeeping enzyme that regulate the normal cellular processes such as vascular homeostasis, gastric cytoprotection, kidney function, and platelet aggregation
COX-1
causes the increased production of prostanoids in the disease sites and inflammation
COX-2
enzymes produce the leukotrienes depending on the tissue
LIPOXYGENASE PATHWAY
antileukotriene drugs such as Montelukast and Ziluton are useful in the treatment of moderate to severe asthma (allergic type)
LIPOXYGENASE PATHWAY
is a prototype of traditional NSAIDs; most commonly used
Aspirin
- blocks prostaglandin synthesis at thermo-regulatory centers in hypothalamus and peripheral target sites (antipyretic)
- prevents sensitization of pain receptors (mechanical and chemical stimuli)
salicylates
may be given in prevention of cardiovascular events rather than for pain control
ASPIRIN
ANALGESIC ACTION
used for low to moderate pain for musculoskeletal disorders than those pain from the viscera
→ pain caused by malignancy is treated with NSAID and opioids
salicylates
is 3-4x more potent than Aspirin as analgesic and anti-inflammatory but not antipyretic
Diflunisal
ANTIPYRETIC ACTION
lowers body temperature in patients with fever by impeding PGE2 synthesis and release
Salicylates
ANTIPYRETIC ACTION
resets “thermostat” to normal and rapidly lowers body temperature by heat dissipation as a result of peripheral VD and sweating; has no effect on normal body temperature
Aspirin
ANTIPYRETIC ACTION
does not reduce fever because does not cross BBB
Diflunisal
GI EFFECTS
with aspirin, prostanoids are not formed so there is:
o ↑_____ gastric acid secretion
o ↓ decreased mucus protection
increased
agents to prevent gastric and duodenal ulcers are misoprostol &
PPIs
Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole
GI EFFECTS
H2 blockers relieves dyspepsia due to NSAID but mask serious GI complaints and are not as effective
as PPIs in healing and preventing ulcers
Cimetidine, Ranitidine)
for long term, high dose of ____ treatment, both renal and hepatic functions should be monitored and avoid if creatinine clearance is less than 10 ml/min
aspirin
CONTRAINDICATIONS
→ pedia group (less than 15 years old) with varicella or influenza to prevent Reye’s syndrome
ASPIRIN & OTHER SALICYLIC ACID DERIVATIVES
should be taken with food and large amounts of fluid to diminish dyspepsia
aspirin
should not be taken at least 1 week prior to surgery
aspirin
Reye’s Syndrome
fatal, fulminating hepatitis and cerebral edema seen in children given _______during viral infection (flu & varicella)
o an option for fever would be acetaminophen or ibuprofen
aspirin/salicylates
patients taking_____ or _____ must avoid prolonged aspirin because it can cause increased renal UA excretion
probenecid, sulfinpyrazone
aspirin + ____ is contraindicated because there is increased risk of GI bleeding
ketorolac
alters platelet function and prolong bleeding time
Propionic acid derivatives
(Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin)
→ acute gouty arthritis
→ ankylosing spondylitis
→ OA of hip
Indomethacin
closely related to indomethacin but less potent
Sulindac
ACETIC ACID DERIVATIVES
Indomethacin, Sulindac, Etodolac
Piroxicam, Meloxicam
OXICAM DERIVATIVES
Mefenamic acid, Meclofenamate
o no advantages as anti-inflammatory over NSAIDs
FENAMATES
adverse effect:
o diarrhea (inflammation of bowel)
o haemolytic anemia
FENAMATES
Diclofenac, Tolmetin Ketorolac
HETEROARYL ACETIC ACIDS
mode of action:
o selective inhibitor COX2 (time-dependent and reversible)
o does not inhibit platelet aggregation and does not increase
bleeding time
CELECOXIB
contraindicated in patients allergic to sulfonamides
CELECOXIB
increases serum celecoxib
Fluconazole, Fluvastatin, Zafirlukast
increases beta blockers, antidepressants, antipsychotics
Celecoxib
antipyretic and analgesic but weak anti-inflammatory
ACETAMINOPHEN
→ alternative antipyretic or analgesic for patients with gastric complaints or with prolonged bleeding time
ACETAMINOPHEN
drug of choice in pedia patients with viral infection
ACETAMINOPHEN
→ does not antagonize uricosuric drugs (probenecid,
sulfinpyrazone)
o can be used in gout under these meds
ACETAMINOPHEN
→ mainstay treatment of RA and psoriatic arthritis
→ slows erosion of involved joints
METHOTREXATE
→ an immunosuppressant
→ much lower dose required than in cancer chemotherapy
METHOTREXATE
→ also used to treat malaria
→ used for early, mild RA
HYDROXYCHLOROQUINE
→ metabolic disorder with high UA in blood (hyperuricemia)
→ hyperuricemia leads to deposition of sodium urate crystals in
tissues (joints and kidneys)
GOUT
is an overproduction of uric acid than the patient
is able to excrete
hyperuricemia
to decrease movement of granulocytes into affected area
Indomethacin
ACUTE GOUT
to decrease pain and inflammation; initial dose is doubled within first 24-48 hours then reduced in next days
NSAIDs
→ a plant alkaloid; used in treatment of acute gouty attacks and chronic gout
COLCHICINE
neither uricosuric nor analgesic but relieves pain in acute attacks
COLCHICINE
→ a purine analog
→ reduces UA production
ALLOPURINOL
ADVERSE EFFECTS
alopecia (chronic use)
COLCHICINE
weak organic acid; irreversibly acetylates COX
ASPIRIN & OTHER SALICYLIC ACID DERIVATIVES
mode of action:
o reversible inhibitors of cyclooxygenases and inhibits synthesis of prostaglandins but not leukotrienes
Propionic acid derivatives
(Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin)
mode of action:
o inhibits COX1 and COX2
OXICAM DERIVATIVES
THERAPEUTIC USES
→ treatment of primary hyperuricemia of gout
→ treatment of hyperuricemia secondary to malignancies and
renal disease
ALLOPURINOL
