Transcript Non Steroidal Anti Inflammatory Drugs

Non Steroidal Anti
Inflammatory Drugs,
Nonopioid Analgesics
By S.Bohlooli, PhD
The immune reponse
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May lead to
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Cure
More injury
Eicosanoids
Kinins
Neuroptides
Histamine
Cytokines
Free radicals
Therapeutic strategies
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Relief of Pain
Slowing or arresting the tissue damaging
process
Drugs
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NSAIDs
Glucocoticoids
Slow acting antirheumatic drugs:
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Disease modifying antirheumatic drugs
Non steroidal anti
inflammatory drugs
Chemistry & Pharmacokinetics
Pharmacodynamics
Chemistry
Chemistry
Pharmacokinetics
Pharmacokinetics
Pharmacodynamics
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Inhibition of synthesis of prostaglandines
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Inhibition of cyclooxygenase isoforms
Inhibition of chemotaxis
Down regulation of interleukin-1
Decreased production of free radicals
Interface with calcium mediated intracellular
events
Pharmacodynamics
Aspirin
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Pharmcokinetics
Mechanism of action
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Anti-inflammatory effects
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Analgesic effect
Antipyretic effect
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Nonselective inhibitor of COX
Non-acetylated salicylate may work as oxygen
scavenger
Inhibition of COX in CNS
Inhibition of IL-1production
Antiplatelet effecys
Clinical use
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Mild to moderate pain
With opioids for cancer pain
High dose for:
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Decreased incidence of
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Rheumatic fever
Rheumatic arthritis and other joint conditions
Transient ischemic attacks
Coronary artery thrombosis
Colon cancer
May valuable in treating preeclampsia-eclampsia
Adverse effect
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Gastrointestinal upset
Gastric and duodenal ulcers
Hepatotoxicity
Bleeding
Asthma
Rashes
Renal toxicity
Upper gastrointestinal bleeding
Salicylism ( vomiting, tinnitus, vertigo)
Cox-2 selective inhibitors
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Developed in attempt to inhibit the synthesis
of PGs in the site of inflammation
Many of them are sulfonamide derivatives
Some evidence suggests higher
cardiovascular thrombotic event
Cox-2 is constitutively active within kidney so
renal toxicity is documented for this group of
drugs
Documented edema and hypertension
Cox-2 selective inhibitors
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Celecoxib
Etoricoxib: with highest ratio of selectivity
Meloxicam
Refecoxib
Valdecoxib
Non selective COX inhibitors
lipooxygenase
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Diclofenac
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Diflunisal
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Etodolac
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TNF-
Fenoprofen Nitric Oxide
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Flurbiprofen
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Ibuprofen
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indomethacin
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Tenoxicam
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Phosolipase A, C
Tiaprofen
Neutophil migration
T & B cell prolifration
tolmetin
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Ketoprofen
Ketorolac
Mefenamic acid
Nabumetone
Phospholipase A2
Naproxen
Oxaprozin
Phenylbutazone
Piroxicam
Sulindac
carpofen
Clinical Pharmacology of the NSAIDs
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Equally efficacious with few exceptions
Different on the basis of
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Toxicity
Cost-effectiveness
There is no best NSAIDs for all patients
Good Luck