Transcript cGMP
ALLERGY IN ALABAMA SPRING - FLOWERING GRASSES, ORNAMENTAL FLOWERS, NOT PINE POLLEN FALL – RAGWEED NOT GOLDENROD YEAR ROUND-ANIMAL DANDER AND SALIVA SUMMER/HUMIDITY -MOLDS/ FUNGUS RAGWEED GOLDENROD Welcome to Alabama Timothy Grass Bermuda Grass HYPERSENSITIVITY REACTIONS TYPE I- ALLERGIC CONJUNCTIVITIS TYPE II- MYASTHENIA GRAVIS TYPE III-UVEITIS? SJOGRENS TYPE IV- CONTACT DERMATITIS & GPC Allergic conjunctivitis Myasthenia Gravis Sjogrens Phlyctenular Conjunctivitis ALLERGY CASCADE IGE BINDS ANTIGEN FORMS DIMER AT SURFACE OF MAST CELL MAST CELL DEGRANULATES HISTAMINE PROSTAGLANDINS THROMBOXANES LEUKOTRIENES VASOACTIVE AMINES EOSINOPHIL ATTRACTING FACTOR STAGES OF ALLERGIC DISEASE EARLY PHASE MAST CELLS AND PRODUCTS LATE PHASE LEUKOCYTES T -LYMPHOCYTES CHRONIC PHASE T CELLS FACTORS MAST CELLS DIFFERENT TYPES OF MAST CELLS CHYMASE POSITIVE TYPTASE POSITIVE (all mast cells, most common ocular surface, prevents clotting) CHYMASE AND TYPTASE (most common in non allergic) calcium Inside Mast Cells Increase synthesis of phosopholipase Aproduction of arachodonic acid Increase protein kinase productionnecessary for degranulation Increase in intracellular calcium levels 24-48 hours increase cytokine production CGMP INCREASES MAST CELL DEGRANULATION ALPHA AGONISTS INCREASE BY DECREASING CAMP CHOLINERGICS INCREASE CGMP CAMP DECREASES DEGRANULATION HISTAMINE INCREASES BETA ADRENERGIC DRUGS INCREASE ADENYL CYCLASE(PROSTAGLANDINS) cAMP cGMP Balance CAMP CGMP PROSTAGLANDIN D2 PRIMARY OCULAR PG IN HYPERSENSITIVITY CHEMOSIS REDNESS DISCHARGE EOSINOPHIL CHEMOTAXIS BIOLOGIC ACTIVITY OF PROSTAGLANDINS PGF2 & PGD2- BRONCHOSPASM PGI2- PULMONARY DILATION & < PLATELET AGGREGATION PGE2 BRONCHODILATOR PGE1 &PGE2 -> NERVE SENSITIVITY VASODILATION TXA2-VASOCONSTRICTION BIOLOGIC ACTIVITY OF LEUKOTRIENES LTB4 PMN ATTRACTANT EOSINOPHIL ATTRACTANT > VASCULAR PERMEABILITY >.EDEMA COFACTOR W/ PGE2 & PGD2 LTC4, LTD4, LTE4 BRONCHOCONSTRICTORS MYOCARDIAL DEPRESSANTS EOSINOPHILS-ACTIVATION EOSINOPHIL CHEMOTACTIC FACTOR(LTB4) HISTAMINASE DECREASES PHOSPHOLIPASE DECREASES ARYL SULFATASE DECREASES PLATELET ACTIVATING FACTOR STRONGLYATTRACTS EOSINOPHILS MAJOR BASIC PROTEIN (anti-parasite) HIGHLY TOXIC TO EPITHELIUM INCREASES MAST CELL DEGRANULATION EOSINOPHIL CATIONIC PROTEIN EOSINOPHIL PEROXIDASE HISTAMINE BRONCHOSPASM VASODILATOR INCREASES VASCULAR PERMEABILITY ACTIVATES NERVE TERMINALS PLATELET ACTIVATING FACTOR RELEASING CELLS BASOPHILS MAST CELLS EOSINOPHILS MONOCYTES/MACROPHAGES PMN’S T CELL MEDIATED FACTORS IL-3 INDUCES MAST CELL DEGRANULATION IL-4 FACILITATES IGE PRODUCTION BY B LYMPHOCYTES IL-5 STIMULATES EOSINOPHIL PROLIFERATION OCULAR RESPONSE IN ARACHADONIC ACID PATHWAY CYCLO-OXYGENASE PATHWAY LID SWELLING CHEMOSIS VASODILATION LIPO-OXYGENASE PATHWAY CHRONIC INFLAMMATION OCULAR SURFACE HISTAMINE RECEPTORS H1 RECEPTORS- NEURONAL PRODUCES ITCHING H2 RECEPTORS- VASCULAR PRODUCES REDNESS DIAGNOSIS OF ALLERGY RAST (RADIOALLERGOSORBANT ASSAY) PRICK TESTS INDERATION TESTS DIRECT CHALLENGE CONJUNCTIVAL CHALLENGE CONJUNCTIVAL CHALLENGE FDA REQUIREMENT FOR NEW DRUGS ALLERGEN APPLIED TO CONJ REDNESS,WATERING,CHEMOSIS GRADED RETEST WITH PRETREATMENT DRUG ACTIONS MAST CELL STABILIZERS STEROIDS ANTIHISTAMINES ASPIRIN NONSTEROIDALS VASOCONSTRICTORS THEOPHYLLINE STEROID ACTIONS DECREASE mRNA INHIBITS PHOSPHOLIPASE A POTENTIATES B ADRENERGICS CONSTRICTS BLOOD VESSELS DECREASES CHEMOTAXIS LYMPHOPENIA DECREASES MACROPHAGE FUNCTION GI, RENAL, PLATELET, MACROPHAGE DIFFERENTIATION STEROID EFFECTS DECREASE MESSENGER RNA INHIBITS PHOSPHOLIPASE A PRODUCTION INCREASES CAMP POTENTIATES B ADRENERGIC DRUGS CONSTRICTS BLOOD VESSELS DECREASES CHEMOTAXIS LYMPHOPENIA DECREASED MACROPHAGE FUNCTION DRUG ACTIONS STEROIDS-MULIPLE EFFECTS MAST CELL STABILIZERS-INHIBIT CALCIUM ENTRY INTO CELL ANTIHISTIMINES- EFFECT AFTER RELEASE ASPIRIN - INHIBITS CYCLOOXYGENASE PATHWAY NONSTEROIDALS- INHIBIT CYCLOOXYGENASE PATHWAY COX 1 AND COX 2 COX 1 PRESENT AT STEADY STATE LEVELS HOMEOSTATIC FUNCTIONS COX 2 ASSOCIATED WITH INFLAMMATION VIOXX, CELEBREX, BEXTRA PREFERENTIAL VS SPECIFIC DRUG EFFECTS VASOCONSTRICTORS -REVERSE VASODILATION THEOPHYLLINE- INCREASE CAMP FOOD ALLERGY VARIABLE EFFECT DUE TO ABSORBTION USUALLY LOCAL GI EFFECT CAN BE IDIOSYNCRATIC ALLERGIC SKIN REACTIONS ERYTHEMA-REDNESS FLARE-DIFFUSE REDNESS AROUND WHEAL WHEAL-LOCALIZED EDEMA,TYPICAL LID ANGIOEDEMA DRUG ALLERGY TOXICITY INTOLERANCE IDIOSYNCRATIC ALLERGIC IDIOSYNCRATIC REACTIONS DIRECT MEDIATOR RELEASE DIRECT ACTIVATION OF BIOLOGIC SYSTEM ENZYME DEFECT UNDERLYING DISEASE SIMILAR TO ANAPHYLAXIS? Anaphylaxis TREATMENT OF ALLERGY AVOIDANCE THERAPEUTIC AGENTS CHRONIC ACUTE IMMUNOTHERAPY Effects of Immune Therapy