41-ASTHMA GENERAL – Flashcards
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Acute inflammation is ------mediated |
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IgE mediated (aactivated by allergen) -Histamine -Eicosanoids -ROS(reactive oxygen species) -macrophage,mast cell activation |
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Chronic inflammation is ______mediated |
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-Epithelial cells -Eosinophils -Lymphocytes -mast cells, macrophages,neutrophils |
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Th1 lymphocytes are responsible for |
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cellular defense |
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Th2 lymphocytes are responsible for |
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allergic inflammation |
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chronic inflammation leads to |
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matrix fibrosis -inc smooth muscl bronchial hyperresponse inc mucus gland mass production -angiogenesis |
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Normal spirometry tests do not |
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RULE OUT ASTHMA |
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Used instrument for ASTHMA DIAGNOSIS |
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PEF-Peak Expiratory Flow meter(where spirometry not available) |
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Do not use PEF in |
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child <6 Yrs old |
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Chronic asthma FEV1/FVC ratio ADULT NORMAL CHILD NORMAL |
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ADULT NORMAL- >0.75-0.8 CHILD NORMAL- >0.9 |
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FEV1 is ____in asthma |
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reduced |
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Spirometry measures of CHRONIC ASTHMA ADULT CHILD |
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ADULT >12% and 200mL from baseline CHILD >12% predicted |
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Asthma exacerbation= O2 sat Lung Func Test |
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O2 sat= <90-92% Lung Func Test PEF or FEV1 <80% below baseline |
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Asthma exacerbation Sxs |
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Sx: wheeze,cough,SOB,Tight chest Physical: pale/cyanotic skin,accessory muscle use,wheeze,tachycardia |
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Allergic asthma |
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CHILDHOOD ONSET FAM HX OF ALLERGIC DISEASE (EOSINOPHILIC) |
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ALLERGIC ASTHMA RESPONDS WELL TO _______ -NON ALLERGIC ASTHMA DOSE NOT |
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INHALED CORTICOSTEROIDS |
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NON-ALLERGIC ASTHMA |
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ADULT ONSET NEUTROPHILIC/EOSINOPHILIC/FEW INFLAMMATORY CELLS |
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LATE-ONSET ASTHMA |
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ADULT ONSET (MOSTLY WOMEN) NON ALLERGIC -NEEDS HI DOSE ICS OR ICS MAY NOT WRK |
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iNHALED DRUGS ARE _____-____% DEPOSITED IN LUNGS THE REST IS ABSORBED ORALLY |
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10-40% LUNG DEPOSITION |
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THE DRUG CLASS USED IN BOTH COPD & ASTHMA |
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CORTICOSTEROIDS B-2 AGONISTS MUSCARINIC RECEPTOR ANTAGONISTS THEOPHYLLINE |
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GCs BIND TO GR TO INHIBIT HAT ACTIVITY BY_________ |
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RECRUITING HDAC2(REVERSES HISTONE ACETYLATION & DEC INFLAMMATORY GENE EXPRESSION) |
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CORTICOSTEROIDS CLEARANCE IS ______ ORAL BIOAVAILABILITY IS _____________ |
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CORTICOSTEROIDS CLEARANCE IS LOW ORAL BIOAVAILABILITY IS HIGH |
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CORTICOSTEROID SIDE EFFEX |
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-FLUID DISTRUBANCE/ELECTROLYTE -OSTEOPOROSIS/GROWTH RETARDATION -THINNING SKIN BRUISING/SLOW WOUND HEAL -MOOD/BEHAVIOR -CUSHHING SYNDROME(SUPRESSED HPA AXIS--CORTISOL SUPPRESSION) |
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SMALLEST RRA |
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HYDROCORTISONE |
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LARGEST RRA |
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MOMETASONE FUROATE (75%ORAL BIO) |
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LARGEST ORAL GC RRA |
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METHYLPREDNISOLONE (99% ORAL BIO) |
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RRA IS________ |
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RADIORECEPTOR ASSAY= DRUGS AFFINITY FOR GC RECEPTOR |
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CORTICOSTEROIDS ARE METABOLIZED THRU |
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CYP3A4 (KETOCAONAZOLE-->>POTENT INHIBITOR OF CYP3A4.INC PLASMA CONC OF ICS) |
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BETA-2 AGONIST EFFECTS |
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INCREASE IN -GLUCONEOGENESIS -HR -RELAXATION IN LUNGS/UTERUS -SKEL MUSC POTASSIUM UPTAKE/CONTRACTABILITY |
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SHORT ACTING BETA 2 ADRENERGIC RXs |
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EPINEPHRINE (SELECTIVITY low) ISOPROTERENOL (SELECTIVITY low) TERBUTALINE (SELECTIVITY high) ALBUTEROL |
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LONG ACTING BETA 2 AGONISTS |
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-SALMETEROL -FORMOTEROL -OLODATEROL -INDACATEROL -VILANTEROL |
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RESCUE INHALER MEDS |
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-ALBUTEROL -LEVALBUTEROL -TERBUTALINE |
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BETA 2 SIDE EFFECTS |
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TREMOR TACHYCARDIA HYPERGLYCEMIA HA,PAIN,DIZZINESS |
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beta 2 intrxn with |
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CYP3A4(KETOCONAZOLE/RITONAVIR) MOAs BETA BLOCKERS (PRODUCE SEVERE BRONCHOSPASM BY BLOCKING BETA AGONIST EFFECTS) DIGOXIN (MAY DEC DIGOXIN LEVELS) DIURETICS(POTENTIATES HYPOKALEMIA) |
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THEOPHYLLINE(METHYLXANTHINES) BRONCHODILATION DUE TO |
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-PDE INHIBTIOION |
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iNC CL OF THEOPHYLLINE BY |
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-SMOKING -INDUCING CYP1A2 -CHILDHOOD -HI PROTEIN,LOW CARB DIET -BARBECUED MEAT |
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DEC CL OF THEOPHYLLINE |
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CYP1A2 INHIBITON(CIMETIDINE,ERYTHROMYCIN,ALLOPUR, ZAFRILUKAST) |
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THEOPHYLLINE SIDE EFFECTS |
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NV HA DIURESIS CARDIAC ARRYTHMIAS BEHAVIOR DISTURBANCE/SEIZURES |
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PDE4 ROFLUMILAST |
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TX OF PT WITH SEVERE COPD AND HX OF EXACERBATION |
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PDE4 INHIBITION DOES |
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-INC cAMP -SMOOTH MUSCLE RELAX -DEC INFLAMM -DEC BRONCHOCONSTR -DEC NEUROPEPTIDE RELEASEIN PULM SENS NERVES |
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ROFLUMILAST SIDE EFFECTS & PK |
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ND HA WEIGHT LOSS PK:CYP1A2 & CYP3A4 CONTRA IN MOD-SEVERE HEPATIC IMPRMENT |
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LEUKOTRIENE MEDIATORS |
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ACT AT LTD2,LTE4,LTC4 TO HALT PROD OF BRONCHOCONSTRCT,MUCUS SECRET,PLASMA EXUD,EOSINOPHIL RECRUITMENT ZAFRILUKAST MONTELUKAST ZILEUTON |
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ANTI CHOLINERGICS(MUSCARINIC RECEPTOR ANTAGONISTS) |
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TIOTROPIUM,IPATROPIUM,ACLIDINIUM,GLYCOPYRROLATE (IPATROPIUM HAS A BAD TASTE) NEBULIZED CAUSES GLAUCOMA CAN CAUSE DRY MOUTH -URINARY RETENTION -BRONCHOCONSTRCTION WHEN USED WITH BENZALKONIUM |
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ANTI IgE ANTIBODIES |
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OMALIZUMAB,MEPOLIZUMAB,DUPILUMAB -DONT USE IN ASTHMA -DONT STOP CORTICOSTEROIDS ABRUPTLY -STOP IF FEVER,RASH,JOINT PAIN DEVELOPS |
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ADRB2 DEALS WITH |
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BETA AGONISTS |
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CRHR1 GENE DEALS WITH |
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INHALED CORTICOSTEROIDS |
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GLY16GLY GENE IN ADRB2 SHOWS |
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BETTER RESPONSE THAN ARG16ARG GENE TO SABA |
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ADRB2 DOES NOT SHOW DIF BETWEEN GLYGLY AND ARGARG FOR _________ |
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LABA RESPONSE |
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CRHR1 SHOWS BETTER LUNG FUNC IN ADULTS AND PEDS W/ HOMOZYGOUS |
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T/T & A/A (RS242941 & RS1876828) WITH INHALED CORTICOSTEROIDS |
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SNPs IN CRHR1 DECREAS ______________ |
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ENDOGENOUS CORTISOL AND IMPROVES PT SENSITIVITY TO ICS |
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GUIDELINES AND LABEL UPDATES FOUND WHERE???? |
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PHARMGKB CPIC DUTCH GUIDELINES FDA |
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TRANSLATE LAB GENOTYPE RESULTS |
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GENETIC TESTING REGISTRY PHARMGKB CLINVAR PUBMED |