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29 Cards in this Set
- Front
- Back
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Bradykinin
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Causes the synthesis and release of prostaglandin
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Prostaglandin
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Sensitizes nociceptors and increases the likelihood that other inflammatory agents will come to the site
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Prostaglandin Synthesis
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Bradykinin activates Phospholipase A2
Phospholipase A2 cleaves phospholipids into Arachodonic Acid Arachodonic Acid can then be converted to prostaglandin |
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Inhibition of Prostaglandin Synthesis
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Glucocorticoids
Nonsteroidal Anti-Inflammatory Agents (NSAIDs) |
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Glucocorticoids
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-Inhibit Phospholipase A2
-Inhibit COX pathway, preventing synethesis of prosta's from Arachidonic Acid **Glucocorticoids are potent anti-inflammatory agents and not typically used as analgesics b/c there are so many glucocorticoid receptors throughout the body. |
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Nonsteroidal Anti-Inflammatory Agents (NSAIDs)
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Inhibit cyclooxygenase which prevents prostaglandin synthesis
-Blockage of prosta pathway may also increase leukotriene synthesis |
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Normal Physiological Functions of Prostaglandins
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Smooth muscle contraction/relaxation
Renal electrolyte and water transport CNS activity Bone Absorption Inflammation Vascular Permeability GI Secretion Hormone Release Platelet Aggregation Nociception |
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COX 1
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Constitutive (Always around)
Smooth Muscle Contraction/Relaxation Renal Electrolyte and Water tranport CNS Activity Bone Absorption Hormone Release GI Secretion Platlet Aggregation |
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COX 2
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Inducible
Some preceding event produces COX 2 Inflammation Renal Functions CV Function |
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Aspirin
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Covalently modifies COX 1&2 resulting in irreversible inhibition of cyclooxygenase activity-->duration depends on rate of cyclooxygenase turnover (body size)
-More selective for COX 1 |
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Therapeutic Uses for Salicylates
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Analgesia
Antipyresis Anti-Inflammatory Agents Prophylaxis of Coronary Artery Disease |
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Salicylates Analgesic Effects
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Relieve mild-moderate nociceptive pain
*Advantages -Can be used to treat neurogenic pain -Lack the unwanted effects of opiods (tolerance, dependence, abuse potential) |
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Salicylates Antipyretic Effects
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NSAIDs promote return of set point to normal
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Salicylates as Anti-Inflammatory Agents
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Inhibit prostaglandin synthesis
Tx of musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis *Anti-Inflammatory effects can take days to appear and must use high doses |
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Salicylates & Prophylaxis of Coronary Artery Disease
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Inhibit platelet aggregation
low doses are used (<325mg/day) |
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Hemostatis
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Vascular Injury
-Exposes subendothelial matrix providing a substrate for platelet adhesion/aggregation Platelet Aggregation -Thromboxane A2 (COX1) aggregate nearby platelets forming a hemostatic plug ASPIRIN BLOCKS FORMATION OF THIS PLUG BY INHIBITING COX 1 Inhibition of Platelet Aggregation Prostacyclin (COX2) are released and inhibit platelet aggregation and vasoconstriction ASPIRIN IS LESS LIKELY TO AFFECT THIS B/C IT IS MORE SELECTIVE FOR COX1 |
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Shared Side Effects of Salicylates
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--Gastric Ulceration and Intolerance
--Impaired renal function --Hypersensitivity Reactions --Toxicity |
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GI Effects from Salicylates
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-->prostaglandins normally have a protective effect on gastric mucosa so inhibition of prosta synthesis can be bad
--GI Effects can also be due to inhibition of COX2 which increases luekotriene synthesis |
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Renal Impairment from Salicylates
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Prosta's normally reduce water and sodium reabsorbtoin-->NSAIDs can lead to increased retention-->increased BP, renal artery vasoconstriction
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Hypersensitivity Reactions associated with Salicylates
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Cross reaction occurs to all NSAIDs
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Salicylates: Contraindications
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Ulcer, Gout, Diabetes, Influenza/Chickenpox, Hypocoagulation states
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Propionic Acid
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Aspirin alternatives
less likely to produce GI side effects than aspirin less effective in reducing platelet aggregation EX. Ibuprofen & Ketoprofen |
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COX 2 Inhibitors
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Bextra, Celebrex, Vioxx (Rofecoxib)
--50-60% decrease in serious GI complications |
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Mechanism of Action Acetominophen
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Effective antipyretic due to inhibition of COX in the brain
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Clinical Uses of Acetominophen
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Analgesia & Antipyretic
DOES NOT inhibit inflammation DOES NOT inhibit platelet aggregation |
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Adverse Effects of Acetominophen
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Largely confined to acute overdose
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Acetominophen Overdose
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Overdose depletes glutathione levels which leads to a dangerous increase in NAPQI levels. NAPQI is a toxic metabolite which can be fatal to cells
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Chronic Alcohol and Acetominophen
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Chronic booze results in increase in CYP2D1 which leads to depletion of glutathione
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Combo Therapy: Opiods and NSAIDs
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Periphereal analgesics act to reduce inflammatory reponse
Opioids alter reaction to pain -->Can increase analgesia wile decreasing dose of opioiods |
