Antihistamines and Bronchodilators PDF

Antihistamines & Bronchodilators Peter Abel, Ph.D. Professor and Chair Department of Pharmacology & Neuroscience Creighton University School of Medicine – Omaha Email: [email protected] Histamine Release Histamine is rele...

Antihistamines & Bronchodilators Peter Abel, Ph.D. Professor and Chair Department of Pharmacology & Neuroscience Creighton University School of Medicine – Omaha Email: [email protected] Histamine Release Histamine is released from: Mast Cells Basophils Histamine is released by: Pollen Dust Mechanical Injury Venoms Toxins Radiation 2 Seasonal Allergies 3 Effects of Histamine Mediated by H1, [H2, H3, and H4] histamine receptors Organ or System Effects of Histamine Affected Respiratory tract Nasal congestion, increased secretions, bronchoconstriction (H 1) Arteriolar dilation causes heat and redness. Contraction of Blood vessels endothelial cells causes local edema and swelling. If widespread, blood pressure falls. (mainly H1) Heart Increased rate, force of contraction (H2) GI tract Increased gastric acid secretion (H2) Peripheral nerves Stimulation of sensory nerves causes itching and pain (mainly H 1) 4 Effects of Antihistamines Antihistamine drugs only block the effects of H1- receptors Some Organ or antihistamines System also Effects block muscarinic of Antihistamine (H blockers) 1 cholinergic Affected receptors Decreased swelling and edema, decreased but thickened Respiratory tract secretions (partly anti-muscarinic action), relieves symptoms of seasonal allergy. Antagonism of arteriolar dilation reduces heat, flushing and Blood vessels edema GI tract - Secretions None (only H2 receptors involved here) Usually drowsiness, sedation (partly an anti-muscarinic action) at CNS therapeutic doses. Peripheral nerves Block itching and pain 5 Antihistamines 6 Diphenhydramine (Benadryl) 7 Clinical use of Antihistamines Treatment of seasonal allergy, OTC- Chlorpheniramine, Loratadine (Claritin), Cetirizine (Zyrtec), Fexofenadine (Allegra), etc. Treatment of motion sickness, OTC– Dimenhydrinate (Dramamine) Treatment of nausea and vomiting – Promethazine (Phenergan) Treatment of itching – Hydroxyzine Sedation, OTC – Diphenhydramine (Benadryl), Doxylamine (NyQuil) 8 Adverse Effects First generation drugs* > Second generation drugs Sedation* Anti-muscarinic effects*: Dry mouth, blurred vision, urinary retention, decreased GI motility GI : nausea, diarrhea, constipation In children an overdose may cause CNS stimulation: insomnia, nervousness, tremors In the elderly may cause dizziness, confusion, incoordination, fatigue 9 Histamine Release Histamine is released from: Mast Cells Basophils Histamine is released by: Pollen Dust Mechanical Injury Venoms Toxins Radiation 10 Steroid Nasal Sprays, OTC Decrease synthesis and release of inflammatory mediators Decrease infiltration and activity of inflammatory cells 11 Bronchodilator Drugs 12 Asthma Pathology Constriction Wall Thickening 13 β2-Adrenergic Receptor Agonists Acute – Reliever, Rescue Short Acting Beta Agonists (SABAs) Albuterol (Proventil®, ProAir®, others) Long Acting Beta Agonists (LABAs) Salmeterol (Serevent®) Chronic – Controller, Prevention + Fluticasone (Advair®) Formoterol (Foradil®) + Budesonide (Symbicort®) Both SABAs and LABAs activate β2- Adrenergic receptors Drugs have different half-lives 14 Uses, Adverse Effects, Precautions Used by inhalation for asthma and for other conditions (COPD). Acute attacks – Reliever (SABAs: Albuterol etc., Albuterol + Budesonide [Airsupra®]. Budesonide is an inhaled corticosteroid [ICS]). Prophylaxis - Controller (LABAs: Formoterol [Foradil®], Formoterol + Budesonide [Symbicort®]). Fewer adverse effects when given by inhalation compared to oral administration. Patient education on inhaler use. Use carefully in patients with cardiovascular disease and the elderly These drugs can worsen or cause tachycardia, palpitations, angina, hypertension (β1 effect). CNS stimulation, anxiety, irritability, insomnia. Muscle tremor (β2 effect). 15 Bronchodilation Caffeine Theophylline (Bronkodyl®) Albuterol Theophylline Caffeine Variable blood levels X which contribute to adverse effects and limits therapeutic use. 16 Tiotropium (Spiriva®) 17 Tiotropium (Spiriva®) LAMA’s can Long-Acting Muscarinic Antagonists remove (LAMAs) Elephants Blocks muscarinic cholinergic ! receptors, prevents acetylcholine induced bronchoconstriction. Used for maintenance therapy as a prophylactic for asthma and COPD. Inhaled, acts locally, poor absorption which limits adverse effects. Adverse effects - dry mouth, airway irritation, GI upset. 18 Histamine Release Histamine is released from: Mast Cells Basophils 19 Inhaled Corticosteroids (ICS) Used by inhalation for asthma and COPD. Anti-inflammatory agents that are effective and safer by inhalation. Prophylaxis – Controller, Beclomethasone (Qvar RediHaler), Budesonide (Pulmicort®) Fluticasone (Flovent®) etc. Acute attacks – Reliever, Albuterol + Budesonide (Airsupra®), Formoterol + Budesonide (Symbicort®) Suppress inflammation by: Decreased inflammatory mediators, histamine, leukotrienes, prostaglandins, cytokines (Interleukins), etc. Decrease infiltration and activity of inflammatory eosinophils, etc. Fewer adverse effects when given by inhalation compared to oral administration. Most often cause oropharyngeal candidiasis and dysphonia – rinse mouth with water. Little: slowed growth, bone loss, adrenal suppression. 20 Leukotriene receptor antagonists (LTRA) Montelukast (Singulair®) and Zafirlukast (Accolate®) block leukotriene receptors. These drugs reduce leukotriene effects to cause both bronchodilation and reduced inflammation in the airways. Taken orally to prevent asthma. Not first choice drugs. Montelukast is approved to be used in children as young as 12 months old Montelukast is given once-daily compared to twice-daily for zafirlukast Adverse effects and precautions Headache, GI upset Joint and muscle pain, soreness Warning: Insomnia, irritability, agitation, depression, suicidal thoughts 21 Monoclonal Antibodies Omalizumab – lowers IgE antibodies Limits the ability of allergens to trigger the release of inflammatory mediators For use in severe allergy-related asthma that cannot be controlled by ICS Administered SubQ every 2-4 weeks Reslizumab and Mepolizumab – target interleukin-5 (IL-5) For patients with eosinophilic asthma, a subtype of asthma IL-5 is a key cytokine in the recruitment of eosinophils Adverse Effects Injection-site reactions, respiratory tract infections, headache, severe allergic reactions. Small increased risks of cancer? 24 22 Treatme nt of Asthma + LAMA or other or other biologics biologics SABA prn may be used ± ± acutely to relieve an ICS ICS asthmatic attack in all stages. 23