inflammation

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Author:
bshin
ID:
88779
Filename:
inflammation
Updated:
2011-06-16 02:59:08
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inflammation
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inflammation
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  1. LTB4
    neutrophil chemoattractant
  2. LTC4, LTD4, LTE4
    • bronchoconstrict
    • vasoconstrict
    • contract smooth muscle
    • increase vascular permeability

    -Leukotrienes come from Hydroperoxides (HPETEs)--LOX path-->
  3. PGI2 (Prostacyclin)
    • inhibit platelet aggregation
    • vasodilate
  4. PGE2
    • decrease vascular tone
    • increase pain
    • increase uterine tone
    • increase temp!
  5. TXA2
    • increase platelet aggregation
    • vasoconstrict
  6. Corticosteroids inhibit
    • phopholipase A2
    • COX-2
  7. In motion sickness, M1, H1 pathways are stimulated--> nausea, vomiting.
    1st gen Antihistamines are effective in preventing these sympotms but are sedating! -so use Scopolamine.
    What are the SE?
    dry mouth, blurry vision, palpitations, urinary retention, constipation
  8. 1st generation H1 blockers
    • Diphenhydramine
    • Dimenhydrinate
    • Chlorpheniramine
  9. Diphenhydramine
    Dimenhydrinate
    Chlorpheniramine
    • 1st gen H1 blockers
    • reversible

    USE- allergy, motion sickness, sleep aid

    SE- sedation, anti-muscarinic (blurry vision, dry mmouth, urinary retention), anti- adrenergic (postural dizziness), anti-serotonergic (appetite suppressant)
  10. 2nd generation antihistamines
    • Loratadine
    • Fexofenadine
    • Desloratadine
    • Cetirizine
  11. Loratadine
    Fexofenadine
    Desloratadine
    Cetirizine
    2nd gen antihistamines

    USE- allergy

    Much less sedation than 1st gen. because less crossing of BBB--> less CNS effects!
  12. Isoproterenol
    • Astha drug
    • nonspecific beta agonist
    • -relax bronchial smooth muscle (beta2)

    USE- asthma

    SE- tachycardia (beta-1)
  13. Of the numerous inflammatory mediators postulated to play role in pathogenesis of allergic asthma, only Leukotrienes (LTC3, LTD4, LTE4), Ach produce bronchospasm that is relieved by pharmacologic antagonists!
    Histamine bronchoconstricts too, but antihistamines do NOT cause bronchodilation!
  14. Albuterol
    • beta-2 agonist
    • relax bronchial smooth muscle
    • bronchodilate

    USE- acute exacerbation of asthma

    SE- tremor, arrythmia
  15. Salmeterol
    • beta-2 agonist
    • long acting

    USE- prophylaxis of asthma

    SE- tremor, arrhythmia
  16. Theophylline
    • methylxanthine
    • inhibit PDE--> decr cAMP breakdown--> incrs cAMP
    • narrow TI
    • -metabolized by CYP
    • -block action of Adenosine!

    USE- asthma (limited use)

    SE- cardiotoxicity, neurotoxicity, block action of Adenosine!
  17. Ipratropium
    • Muscarinic blocker
    • competative block M--> prevent bronchoconstrict

    USE- Asthma, COPD
  18. Cromolyn
    • Astha drug
    • -block release of mediators from Mast cells

    • USE- only Prophylaxis of asthma
    • -useless for actue asthmatic attack
  19. Beclomethasone
    • Corticosteroid
    • -inhibit synthesis of all cytokines!
    • -inactivate NF-kB (block TX of TNF-aphla)

    USE- Ist line for Chronic asthma
  20. Prednisone
    • Corticosteroid
    • -inhibit synthesis of all cytokines!
    • -inactivate NF-kB (block TX of TNF-alpha)
    • -rapid symptom relief, most potent antimflammatory, but SE..

    USE- 1st line for Chronic asthma

    SE- increase neutrophil count (demargination- fever, chills, severe fatigue), decrease bone density (pathologic fractures)- inhibit Collagen synthesis, Inhibit GnRH--> hypogonadism
  21. Zileuton
    • anti-Leukotriene
    • -block 5-LOX pathway inhibitor
    • -block AA--> leukotriens

    USE- asthma
  22. Zafirlukast
    • anti-leukotriene
    • -block leukotriene receptors

    USE- good for Aspirin-induced asthma
  23. Montelukast
    • anti-leukotriene
    • -block leukotriene receptors

    USE- good for Aspirin-induced asthma
  24. Inhaeld glucocorticoids re the most effectivew aniti-nflammatory agents from chronic preventative treatment of bronchial ashtma.
    -No role in acute episodes
    -inhibit cytokine synthesis, induce apoptosis of inflammaotry cells, decrease mucus
    No direct bronchodilatory but reduce airway hyperresponsiveness.
  25. Asthma path
    Exposure to antigen--> antigen+ IgE on Mast cells--> mediator release (leukotriene, histamine)--> early response : bronchoconstrict, late response: inflammation (bronchial hyperreactivity)!

    Beta-agonist, theophylline, M-antagonists inhibit early response!

    Steroids inhibit late response!
  26. AC--> cAMP in asthma
    cAMP--> bronchodilate

    Ach, Adenosine--> bronchoconstrict
  27. Guaifenesin
    • Expecorant
    • -remove excess sputum
    • -does NOT suppress cough reflex

    USE- Asthma
  28. N-acetylcystein
    Mucolytic

    • USE- loosen mucous plugs for CF patients
    • -antidote for Acetominophen overdose
  29. Bosentan
    • block Endothelin-1 receptors
    • -decrease pulm vascular resistance

    USE- Pulm HTN!
  30. Aspirin
    -low dose
    -medium dose
    -high dose
    irreversibly inhibit COX by covalent binding--> decrease both TXA, PGs

    • low dose- decrease platelet agg
    • medium dose- antipyretic, analgesic
    • high dose- anti-inflammatory

    • SE- GI bleed
    • Samter's triad: asthama, aspirin hypersensitivity (nasal, bronchospasm, pnasal polyposis-from Leukotrien increase)
    • Salicysm- vertigo, tinnitus, hearing loss
    • very high dose- metabolic acidosis + resp alkalosis
  31. NSAIDS
    Ketorolac, Ibuprofen, Naproxen, Indomethacin
    • reversibly inhibit COX-1, COX-2
    • block PG synthesis

    • USE- antipyretic, analgesic, anti-inflammatory
    • Indomethacin- close PDA!

    SE- renal damage, fluid retention, aplastic anemia, GI distress, ulcers
  32. Celecoxib
    • COX-2 inhibitor
    • reversibly inhibit COX-2 (inflammatory cells, vascular endothelium--> inflammation, pain)
    • -spare COX-1 (better for gastric mucosa)
    • -no GI ulcers

    USE- Rheumatoid, Osteoarthritise (pts w/ gastric ulcers)

    SE- Thrombosis, Sulfa-allergy
  33. Acetominophen
    • reversibly inhibit COX in CNS
    • inactivated peripherally

    • USE- antipyretic, analgesic, no anti-inflammatory properties!!
    • -used instead of Aspirin to prevent Reye's in kids

    SE- hepatic necrosis, deplete glutathione, FR-injury
  34. Etidronate
    Pamidronate
    Alendronate
    Risedronate
    Zoledronate (IV)
    • Bisphosphonate
    • -inhibit osteoclastic activity (Pyrophosphate analogs)
    • -reduce both bone formation, resorption of hydroxyapatite
    • -careful in renal failure cuz secreted unchanged!

    USE- malignancy assoc. hypercalcemia, Paget's disease, Postmenopausal osteoporosis

    SE- corrosive esophagitis (except Zoledronate), nausea, diarrhea, osteonecrosis of jaw, careful in renal patients!!
  35. Colchicine
    • -acute gout w/ NSAID (1st line)!
    • -bind stabilize tubulin--> block pol--> block leukocyte chemotaxis, degranulation
    • -if elderly w/ bad kidney, give Glucocorticoids for acute gout

    • SE- diarrhea, nausea
  36. Probenecid
    • Chronic gout
    • -inhibit reabsorption of Uric acid in PCT
    • -also inhibit penicillin secretion
  37. Allopurinol
    • Chronic gout
    • -inhibit xanthine oxidase
    • -decrease xanthine--> uric acid
    • -increase conc of azathioprine, 6-MP

    USE- chronic gout, prevent tumor lysis syndrome (urate nephropathy)

    -Febuxostat- new xanthine oxidase inhibitor (fewer SE)
  38. Diuretics and low dose Salicylates block secretion of Uric acid in PCT!
  39. How to treat Osteoporosis?
    Estrogen, SERMS, Bisphosphonates, Calcitonin, PTH
  40. TNF-alpha inhibitors?
    -name 3
    • Etanercept (decoy receptor)
    • Infliximab (anti-TNFa)
    • Adalimumab (anti-TNFa)
  41. Etanercept
    recombinant TNFa receptor

    USE- Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis

    SE- reactivation TB! do PPD skin test
  42. Infliximab
    anti-TNF alpha-antibody

    USE- Crohn's disease, Rheumatoid arthritis, ankylosing spondylitis

    SE- reactivation TB! do PPD skin test
  43. Adalimumab
    anti-TNF alpha-antibody

    USE- Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis

    SE-reactivation TB! do PPD skin test
  44. SE of Methotrexate?
    • Hepatotoxic
    • Apthous ulcers

    -takes weeks to work
  45. Hydroxychloroquine SE?
    Retinal damage
  46. Isotretinoin SE?
    hypertriglycerimia, Teratogenic!!

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