Respiratory Pharmacology

Transcription

1 Allergy Targets of allergies Type I Histamine Leukotrienes Prostaglandins Bradykinin Hypersensitivity reactions Asthma Characterised by Triggered by Intrinsic Extrinsic (allergic) Mediators Result Early phase Late phase Bronchial smooth muscle innervation Altered reactivity of a host on re-exposure to a foreign substance. First exposure mast cell modified Second exposure modified mast cell degranulates Inappropriate activation of immune system. Skin, respiratory tract, GIT, blood, blood vessels Anaphylactic IgE Immediate hypersensitivity Allergen binds with specific antibody on mast cell degranulation of storage granules release mediators from granules Pain, oedema, vasodilation (warmth and redness), bronchoconstriction Inflammation, bronchoconstriction, mucous secretion Pain, inflammation, vasodilation Pain, vasodilation Opposes action of ang II Synergistic action mediates pain, not create pain. Asthma Urticaria Adverse drug reactions Chest tightness, wheezing, shortness of breath, coughing, recurrent reversible obstruction of airways. I: Exercise (cold air), pollen, pollution, aspirin (NSAIDS), emotional stress E: Dust mites, mould, animal fur/hair, food protein (eggs) Hyperresponsive airways Involves IgE antibodies mast cell degranulation histamine and leukotriene release. Histamine stimulates larger bronchi smooth muscle spasms, inflammation and oedema. Leukotrienes bronchoconstriction and mucus secretion Acetycholine (via vagal stimulation) vagal tone and bronchial secretions Spasms in smooth bronchial muscle, mucus secretions, swollen mucosa. Hyperinflation of alveoli loss of elasticity and collapsed alveoli. Immediate/acute phase. Bronchospasm mucus secretion. Chronic phase. Inflammation PNS bronchoconstriction via M 3 receptors. SNS (NA) bronchodilation via β 2 receptors. To bronchodilate, mimic SNS or block PNS. Allergen avoidance. Monitoring of severity peak expiratory flow (PEF) and forced expiratory volume in one second (FEV 1 ). Medication

2 Metered dose inhalers (MDIs) Spacers Dry powder inhalers Delivery of drugs Management Quick delivery of drugs in an inert propellant gas. Require good hand-breath coordination. Autohaler breath activated MDI. Throat/mouth rinsing after steroids. ~10% of drug reaches lung. Used in conjunction with MDI. Require less hand-breath coordination. With MDI, ~15% of drug reaches lung. Deliver drugs in powder form. Accuhaler, turbuhaler. Devices designed to deposit drug in lung. Highly vascular pulmonary capillary system aids absorption. Absorption also dependent on particle/droplet size. Most deposited on upper airways. Some deposited in small airways. Some reach alveoli. Some drugs swallowed variable systemic effects. Spirometry for diagnosis and ongoing assessment by doctor. PEF Peak flow meter for home use. FEV 1 Self-management plan. strategy 1 & 2 Minimum dose of short acting β 2 agonist for occasional use as required. Regular prophylactic medication (low dose inhaled corticosteroid) in patients with more frequent symptoms. 3 If asthma remains inadequately controlled. Use high dose inhaled corticosteroid with spacer. 4 Symptoms continue. Introduction of long-acting β 2 agonist.

3 Relievers Symptom controllers Short acting β agonists Long acting β agonists (LABA) Drug Mechanism Usage Adverse effects Orciprenaline Initially non-selective β 2 agonist Tachycardia Terbutaline heart rate Salbutamol Skeletal muscle (Ventolin) New drugs relatively β 1 selective tremor Salmeterol Eformoterol Act on adenylate cyclase camp Ca 2+ available for contraction bronchodilation, inhibition of mast cell release Removes symptoms but inflammation still present Others Ipratropium Antimuscarinic Block vagal tone (ACh) bronchodilation Theophylline Methylxanthine (caffeine is xanthine group) Relax smooth muscle bronchodilation Onset: 5-15min Duration: 3-6 hours not useful at night. 1 st line treatment for acute asthma. As needed basis not regular Protection against exercise induced asthma Move on to preventers if using more than 3-4 times a week. Duration: >12hours Alternative to increased dosage of inhaled steroids. Should not use in isolation. Protection against exercise induced or nocturnal asthma. Used less frequently Adjunct treatment for severe persistent asthma Variable pharmacokinetics Contraindication β antagonists (antihypertensives) Narrow therapeutic index

4 Preventers LT receptor antagonists 5- lipoxygenase inhibitors Other preventers Corticosteroids Hydrocortisone Cortisone Prednisolone Dexamethasone Betamethasone Budesonide Beclomethasone Fluticasone Mast cell stabilisers Montelukast Zefirlukast Zileuton Cromoglycate Nedocromil Act on PLA 2 prevents formation of arachidonic acid from membrane phospholipid LTs Anti-inflammatory Immunosuppressant Reduce early and late phases of asthma (bronchial hyperactivity and muscosal inflammation) activation of eosinophils production of cytokines generation of prostaglandins /leukotrienes histamine release production of IgE production of mast cells Prevent formation of LT from arachidonic acid Prevent release of mediators Inhaled minimal absorption from site of action (mucus membranes) Oral for short term use longer use requires tapering and introduction of inhaled. Penetration increased by β agonists secretions and swelling Do not relieve muscle spasm Delayed action Prophylaxis Tablets Less effective than inhaled corticosteroids. Used for maintenance treatment. Inhaled prophylactic Growth suppression / osteoporosis

5 Seasonal Perennial Allergens act on nasal mucosa Hayfever Dust mites, animal hair/fur etc. Allergen avoidance Antihistamines (H 1 antagonists) Steroids COPD Symptoms Syndrome with similar clinical features to asthma Airflow limitation due to decreased bronchial lumen diameter. Not fully reversible. Slow progression. Abnormal inflammatory response of lungs to noxious particles. Excessive phlegm and cough. Latter stages. Chronic bronchitis Emphysema Risk Normally associated with heavy smokers. Assess severity (FEV 1 ) Identify/avoid risk factors. Smoking cessation. Bronchodilators (LABA) Long term domiciliary oxygen therapy reduced mortality Antibiotics for infection. Anaphylaxis Anaphylactic Anaphylactoid Characteristics Common causes Immunological allergen/antigen specific IgE. Non-immunological. Similar mediators. Liberated by non-antibody mediated mechanisms. Rapid onset laryngeal oedema Bronchospasm Respiratory arrest Cardiovascular collapse (hypotension, arrhythmias, shock, coma) Insect stings, antibiotics, food. Antihistamines Steroids Relievers Adrenaline (Epipen) intramuscular.