Overview Therapeutic strategies for treating asthma include: decreasing inflammation increasing sympathetic tone There are 7 families of drugs that are commonly used: corticosteroids β-agonists muscarinic antagonists methylxanthines cromolyn antileukotrienes omalizumab Corticosteroids Inhaled corticosteroids are first line therapy for chronic asthma Examples mometasone fluticasone budesonide beclomethasone triamcinolone flunisolide Mechanism inhibiting the synthesis of virtually all cytokines inactivating NF-κB NF-κB is the transcription factor that induces the production of TNF-α and other inflammatory agents Toxicity oral candidiasis use spacers or post-inhalation mouth rinse to prevent β2-agonists Drugs short acting -- used for breakthrough symptoms and during acute exacerbation albuterol known internationally as salbutamol levalbuterol Others used much less commonly terbutaline metaproterenol (β2, minor β1) isoproterenol (nonselective) tachycardia may lead to cardiac death long acting -- used for maintenance in combination with inhaled corticosteroid (never without) salmeterol tremors, arrhythmia formoterol Mechanism β2 receptors are activated on bronchial smooth muscle to achieve bronchodilation stimulation of adenylate cyclase leading to closing of calcium channels and ultimately the relaxation of smooth muscles Methylxanthines Drugs theophylline (rarely used) Mechanism inhibition of phosphodiesterase leading to decreased cAMP hydrolysis causes bronchodilation metabolized by P-450 blocks actions of adenosine Toxicity seizures narrow therapeutic index nausea/vomiting arrhythmia Muscarinic antagonists Drugs ipratropium tiotropium Mechanism competitive inhibition of muscarinic receptors prevents bronchoconstriction Also used for COPD Cromolyn Prophylaxis only! ineffective during an acute asthma attack Mechanism prevents release of mediators from mast cells Toxicity rare Antileukotrienes Drugs zileuton 5-lipoxygenase pathway inhibitor blocks conversion of arachidonic acid to leukotrienes zafirlukast, montelukast blocks leukotriene receptors particularly effective in aspirin-induced asthma Omalizumab Clinical use severe uncontrolled asthma with elevated IgE symptoms and activity refractory to standard therapies and oral glucocorticoids Mechanism anti-IgE antibody inhibits action of IgE with inflammatory cells asthma can be caused by uncontrollably high IgE response
QUESTIONS 1 of 11 1 2 3 4 5 6 7 8 9 10 11 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.PL.33) In patients with chronic obstructive pulmonary disease, stimulation of muscarinic acetylcholine receptors results in an increase in mucus secretion, smooth muscle contraction and bronchoconstriction. The end result is an increase in airway resistance. Which of the following pharmacologic agents interferes directly with this pathway? Review Topic QID: 100836 1 Epinephrine 0% (0/3) 2 Theophylline 0% (0/3) 3 Ipratropium 100% (3/3) 4 Albuterol 0% (0/3) 5 Metoprolol 0% (0/3) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.PL.126) A new drug is designed to treat asthma by inhibiting bronchoconstriction. Experimental assays show that treated animals had markedly reduced acetylcholine binding to muscarinic receptors relative to untreated controls. The drug is most similar to which of the following: Review Topic QID: 100929 1 Theophylline 6% (1/16) 2 Cromolyn 0% (0/16) 3 Zafirlukast 19% (3/16) 4 Prednisone 0% (0/16) 5 Ipratropium 75% (12/16) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.PL.106) An 8-year-old female is given omalizumab for the treatment of bronchial asthma. Omalizumab treats asthma through which mechanism? Review Topic QID: 100909 1 Inhibition of IgE binding to mast cells 55% (6/11) 2 Binding to nuclear receptors 0% (0/11) 3 Inhibition of leukotriene binding to receptor 36% (4/11) 4 Inhibition of phosphodiesterase breakdown of cAMP 9% (1/11) 5 Mediating type IV hypersensitivity reaction 0% (0/11) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.PL.91) A 12-year-old female presents to her pediatrician with an asthma exacerbation. Upon physical examination, the physician notes the finding shown in Figure A. This presentation is a common side effect of which of the following pharmacologic agents used in the treatment of asthma? Review Topic QID: 100894 FIGURES: A 1 Salmeterol 6% (1/16) 2 Albuterol 0% (0/16) 3 Inhaled beclomethasone 81% (13/16) 4 Ipratropium 6% (1/16) 5 Theophylline 6% (1/16) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.PL.41) A 7-year-old boy is brought to your office with complaints of wheezing and dyspnea. Laboratory work reveals eosinophilia and positive skin tests for allergens. Which of the following types of drugs would be an effective treatment in this patient? Review Topic QID: 100844 1 Beta-2 antagonist 19% (17/89) 2 Histone deacetylase inhibitor 4% (4/89) 3 VEGF inhibitor 4% (4/89) 4 Muscarinic antagonist 71% (63/89) 5 Anticoagulant 0% (0/89) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK