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49 Cards in this Set
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- Back
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(I hate to do this, but it was indicated as a question) What characterizes inflammation?
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Redness (rubor) - Vasodilation
Heat (calor) - Vasodilation Pain (dolor) - hyperalgesia Swelling (Tumor) - increased vascular permeability Loss of function (functio laesa) |
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What are the three distinct phases of the inflammatory response?
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Acute Transient Phase - Local vasodilation and increased capillary permeability
Delayed Subacute Phase - infiltration of leukocytes and phagocytic cells (continued itching and swelling due to slowly migrating leukocytes) Chronic Proliferative Phase - tissue degeneration and fibrosis |
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What are the various classes of inflammatory mediators (you probably can't name all of them because you are dumb... hehe J/K... It'd be too difficult... just name a few)
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Vasoactive amines
Platelet Activating Factors Complement system Kinin System Fibrinolytic Pathways Cytokines Nitric Oxide Adhesion Molecules Arachadonic Acid |
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With regards to vasoactive amines histamine and serotonin what are their functions and locations?
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Histamine - abundant in granules of mast cells and function to regulate local immune responses as a potent vasodilator, gastric acid secretion, WBC chemotaxis, and decreases neutransmitter release
Serotonin - released by platelets after platelet aggregation or under the influence of PAF. Important inflammatory factor and neutransmitter similar actions to histamine |
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What is the function of Platelet Activating Factor (PAF)?
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Released by mast cells and basophils to cause platelet degranulation
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What is the active components of the complement system that affect inflammation?
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C3a and C5a both degranulate mast cells and basophils.
C5a is also chemotactic |
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What are the inflammatory mediators of the kinin system?
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Hageman factor (factor XIIa) - conversts prekallikrein to kallikrein a chemotactic factor which causes production of bradykinin. Factor XIIa also causes coagulation
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What are the inflammatory cytokines?
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IL-1, IL-2, TNF, and GMCSF
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What are the effects of Nitric Oxide in the realm of an inflammatory mediator?
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Relaxation of smooth muscle, inhibition of platelet aggregation, induction of cytokines (TNF-alpha and IFN-gamma), potent vasodilator, and pathogenesis of septic shock
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What are the inflammatory mediators of Arachidonic Acid Metabolites?
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Cyclooxygenase products - PGs and TXA2
Lipoxygenase products - HETEs and Leukotrienes |
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What are the three types of cyclooxygenases and what do they do?
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COX-1: Produces Prostaglandins that mediate homeostatic functions (constitutively expressed) - role in gastric mucosa, kidney, platelets, and vascular endothelium
COX-2: produces prostaglandins that mediate inflammation, pain and fever - induced mainly in sites of inflammation but constitutively expressed in brain and kidney COX-3: a splicing variant of COX-1 |
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Describe the production of prostaglandins.
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Phospholipase A2 cleaves membrane lipids into Arachadonic Acid which is cleaved by either COX or LIPOX to Prostaglandins and Thromboxanes or Leukotrienes through 5-HETE respectively
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What are the products of COX-1?
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PGE2, PGI2 - GI Protection
PGI2, TXA1 - Platelet function and Blood Flow Regulation PGI2 - Kideny function |
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What are the role of the Prostaglandins?
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Pain, Inflammation, Fever, and incrase in Mucus production or decrease in acid production
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What are some various types of NSAIDS?
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Salicylates
Propionic Acid Derivatives Enolic Acids (Oxicams) Arylacetic acid derivatives Selective COX-2 Inhibitors |
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Inhibiting what enzyme that is a inflammatory mediator may reduce colon cancer by up to 50%?
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COX-2
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What is the protype drug for the salicylates and how does it function?
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Acetylsalicylic acid (Aspirin) most widely used and prescribed analgesic-antipyretic-anti-inflammatory drug.
Covalently and irreversibly modifies both COX-1 and COX-2 by acetlyating Serine-530 in the active site. Not a complete block of COX-2. |
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How does Aspirin affect platelets?
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Aspirin inactivates COX-1 (the only one detected in platelets) leading to a decrease in production of TXA2 leading to a loss of platelet aggregation.
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How many days are platelets inhibited by Aspirin?
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Their entire lifespan of 8-10 days.
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How is Aspirin eliminated from the body?
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It is metabolized by glucouronidation
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What does the Salicylate Salicymide do?
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Analgesic action but lacks anti-inflammatory actions
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What does the Salicylate Diflunisol (dolobid) do?
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prolonged analgesic effect (2x longer than aspirin)
More potent anti-inflammatory than asirin but equal GI toxicity Can be used for Rheumatoid and osteoarthritis |
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What does the Salicylate Fendosal do?
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greater analgesic and anti-inflammatory activity than aspirin with less GI toxicity
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How is Salicylates normally transported in the blood?
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Mostly bound to the plasma protein albumin
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What are the major side effects associated with salicylate intoxication?
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Hyperventilation
Hyperthermia (due to inhibition and uncoupling of oxidative phosphorylation) Gastric Irritation due to decrease in PGE2 and PGI2 which protects gastric mucosa Microbleeding |
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What is Reye's syndrome and what are the symptoms?
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Aspirin given for fevers caused by viral infections (I forgot the mechanism of effects)
Acute onset of encephalopathy, liver dysfunction, and fatty infiltration fo the liver and other viscera |
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What are the proprionic Acid derivatives?
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Ibuprofen
Naproxen Ketoprofen Oxaprozin |
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What is the utility of Ibuprofen?
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Proprionic Acid Derivative:
Prescribed for Rheumatoid Arthritis and Osteoarthritis 99% bound to plasma proteins Side Effects: Not recommended for pregnaant women, blurred visiona nd skin rashes, and GI effects |
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What is the utility of Naproxen?
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Proprionic Acid Derivative:
20 times more potent than aspirin 99% bound to plasma proteins Side Effects: GI discomfort, drowsiness and headache, Not recommended for pregnant or breast feeding women |
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What is the utility of Ketoprofen?
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Proprionic Acid Derivative:
Orudis - effective in humans and animals |
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What is the utility of Oxaprozin?
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Proprionic Acid Derivative:
Daypro - can be administered once daily |
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What are the arylacetic acid derivatives?
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Indomethacin (Indocin)
Sulindac (Clinoril) Ketorolac (Toradol) Diclofenac (Voltaren) Bromfenac (Duract) Etodolac Nabumetone (relafen) |
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What is the utility of Indomethacin?
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Arylacetic Acid Derivative:
Stinky, Prescribed for Rheumatoid Arthritis and other arthritis |
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What is the utility of Sulindac?
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Arylacetic Acid Derivatives:
8 times more effective than aspirin but less potent than indomethacin |
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What is the utility of Ketorolac?
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Arylacetic Acid Derivative:
Potent Analgesic but only moderate anti-inflammatory Greater analgesia only when used IM |
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What is the utility of Etodolac?
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Arylacetic Acid Derivatives:
Shown to be selective for COX-2 Postoperative Analgesia for 6-8 hours |
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What is unique about Nabumetone?
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Arylacetic Acid Derivative:
Prodrug - converted to active drug (6-methoxy-2-napthylacetic acid) in the liver. |
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What are the Enolic Acids (Oxicams)?
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Piroxicam (Feldene)
Meloxicam (Mobic) |
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What is the utility of Piroxicam?
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Enolic Acid:
Better tolerated than asprin or indomethacin Once a day Additive anti-inflammatory effect: inhibits migration of neutrophils |
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What is the ultility of Meloxicam?
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Enolic Acid:
Osteoarthritis and Rheumatoid Arthritis More selective COX-2 Inhibitor |
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How is that most if not all NSAIDS have the ability to increase the affects of Warfarin?
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By competitively binding for plasma proteins the NSAIDS displace Warfarin allowing more to float freely in the blood increasing its effects.
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How do NSAIDS affect Thiazides?
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THey decrease the effectiveness of Thiazides by competing for excretion space in the proximal tubule
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How do NSAIDS affect methotrexate?
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May increase its toxicity by competing for tubular secretion
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What effects do NSAIDS have on Lithium?
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Causes increased toxic doses by competing with lithium for renal elimination
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What are some up and coming COX-2 specific inhibitor drugs and what is so great about them?
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Celecoxib (celebrix)
Refecoxib (VioXX) Valdecoxib (Bextra) Not better at treating symptoms but do not cause GI or renal side effects There effectiveness is identified by their IC50 Cox2 to IC50 Cox1 ratio. (IC50 - Inhibitory COncentration 50%) Want low Cox2 IC50 and High Cox1 IC50 |
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What are the benefits of Acetaminophens and what are they?
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provide analgesic and antipyretic activity possibly inhibiting COX-3 in the CNS and maybe weakly inhibiting other COX enzymes
Tylenol Paracetamol Acetyl-para-aminophenol |
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What are the side effects of Acetaminophen compared to NSAIDS?
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Little to no anti-inflammatory reaction
No gastric irritation or ulceration No platelt function interference Does not inhibit neutrophil activation No effect on cardiovascular or respiratory systems |
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What is some general info on acetaminophen?
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20-50% bound to plasma proteins
90-100% recovery in urine as hepatic conjugates from glucuronidation or sulfation after first day of therapeutic dose Converted into N-acetylimidoquinone (NAPQI) - a toxic metabolite Contraindicated with alcohol intoxication due to depletion of glutathione levels |
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What is an antidote for tylenol overdose?
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N-acetyl-cysteine (mucomyst, mucosil) IV because it replenishes Glutathione
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