Presentation on theme: "Pharmacology of drugs used in bronchial asthma & COPD"— Presentation transcript:
1 Pharmacology of drugs used in bronchial asthma & COPD ByProfs. Abdulqader Hanan Hagar1435 H
2 Main disorders of the respiratory system are : Disorders of Respiratory FunctionMain disorders of the respiratory system are :1. Bronchial asthma2. Cough3. Allergic rhinitis4. Chronic obstructive pulmonary disease(COPD, also called emphysema)
3 Asthma Asthma is a chronic inflammatory disorder of bronchial airways that result in airwayobstruction in response to external stimuli(as pollen grains, cold air and tobacco smoke).
4 Characters of airways in asthmatic patients : Airway hyper-reactivity: abnormal sensitivity ofthe airways to wide range of external stimuli.InflammationSwellingThick mucus production.Bronchospasm (constriction of the bronchial muscles).
6 Symptoms of asthma Asthma produces recurrent episodic attack of Acute bronchoconstrictionShortness of breathChest tightnessWheezingRapid respirationCoughSymptoms can happen each time the airwaysare irritated by inhaled irritants or allergens.
11 Aims of anti asthmatic drugs: To relieve acute episodic attacks of asthma (bronchodilators, quick relief medications).To reduce the frequency of attacks, andnocturnal awakenings (anti-inflammatory drugs, prophylactic or control therapy ).
12 Anti-inflammatory Agents (control medications or prophylactic therapy) Anti asthmatic drugsBronchodilators(Quick relief medications)treat acute episodic attack of asthmaShort acting 2-agonistsAntimuscarinicsXanthine preparationsAnti-inflammatory Agents(control medications or prophylactic therapy)reduce the frequency of attacksCorticosteroidsMast cell stabilizersLeukotrienes antagonistsAnti-IgE monoclonal antibodyLong acting ß2-agonists
13 Anti asthmatic drugs Bronchodilators : (Quick relief medications) are used to relieve acute attack ofbronchoconstriction1. 2 - adrenoreceptor agonists2. Antimuscarinics3. Xanthine preparations
14 - adrenoceptor agonists Sympathomimetics- adrenoceptor agonistsMechanism of Actiondirect 2 stimulation stimulate adenyl cyclase Increase cAMP bronchodilationInhibit mediators release from mast cells.Increase mucus clearance by (increasingciliary activity).
16 Classification of agonists Non selective agonists:Epinephrine – Isoprenaline (Obselete)Selective 2 –agonists (Preferable).A. Short ActingSalbutamol (Albuterol)TerbutalineB. Long ActingSalmeterolFormeterol
17 Non selective -agonists. EpinephrinePotent bronchodilatorRapid action (maximum effect within 15 min).S.C. or by inhalation (aerosol or nebulizer).Has short duration of action (60-90 min)Drug of choice for acute anaphylaxis (hypersensitivity reactions).Note: Epinephrine good for both the hypotension and Bronchoconstriction.
18 CVS patients, diabetic patients DisadvantagesNot effective orally.HyperglycemiaCVS side effects:tachycardia, arrhythmia, hypertensionSkeletal muscle tremorNot suitable for asthmatic patients with hypertension or heart failure.Contraindication:CVS patients, diabetic patients
19 Selective 2 –agonists Drugs of choice for acute attack of asthma Are mainly given by inhalation (metered dose inhaler or nebulizer).Can be given orally, parenterally.Short acting ß2 agonistse.g. Salbutamol (VentolineR), TerbutalineLong acting ß2 agonistse.g. Salmeterol, Formeterol
21 Long acting selective ß2 agonists Salmeterol & formoterol:Long acting bronchodilators (12 hours)have high lipid solubility (creates depot effect)are given by inhalationare not used to relieve acute episodes of asthmaused for nocturnal asthma (long acting relievers).combined with inhaled corticosteroids to control asthma (decreases the number and severity of asthma attacks).
22 Minimal CVS side effects Advantages of ß2 agonistsMinimal CVS side effectssuitable for asthmatic patients with hypertension or heart failure.Disadvantages of ß2 agonistsSkeletal muscle tremors.NervousnessTolerance (ß -receptors down regulation).Tachycardia over dose (ß1-stimulation).
23 Short acting ß2 agonists Salbutamol, inhalation, orally, i.v.Terbutaline, inhalation, orally, s.c.Have rapid onset of action (15-30 min).Short duration of action (4-6 hr)Used for symptomatic treatment of acuteepisodic attack of asthma.
24 Muscarinic antagonists Ipratropium – Tiotropium Act by blocking muscarinic receptors.Given by aerosol inhalationQuaternary derivatives of atropine therefore,Does not diffuse into the blood anddo not enter CNS, minimal systemic side effects.Delayed onset of actionIpratropium has short duration of action 3-5 hrTiotropium has longer duration of action (24 h).
27 Pharmacodynamics Uses Inhibit bronchoconstriction and mucus secretion Less effective than β2-agonists.No anti-inflammatory actionUsesMain choice in chronic obstructive pulmonary diseases (COPD). Why?In acute severe asthma combined with β2-agonists & steroids.
28 MethylxanthinesTheophylline – Aminophylline (theophyline with ethylenediamine in 2:1 ratio).Mechanism of Actionare phosphodiestrase inhibitors cAMP bronchodilationUniversal Adenosine receptors antagonists (A1)Increase diaphragmatic contractionStabilization of mast cell membrane
32 Pharmacokinetics metabolized by Cyt P450 enzymes in liver T ½= 8 hours has many drug interactionsEnzyme inducers: as phenobarbitone-rifampicin → ↑metabolism of theophylline → ↓ T ½.Enzyme inhibitors: as erythromycin→↓ metabolism of theophylline → ↑T ½.
33 UsesSecond line drug in asthma (theophylline)For status asthmatics (aminophylline, is given as slow infusion). Why not theophylline?)Side EffectsLow therapeutic index narrow safety marginmonitoring of theophylline blood level is necessary.CVS effects: hypotension, arrhythmia.GIT effects: nausea & vomitingCNS side effects: tremors, nervousness, insomnia, convulsion
34 2. Anti-inflammatory Drugs: Since airway hypersensitivity is related the degree of inflammation; anti-inflammatory drugs are considered one of the most effective drugs in the treatment of chronic and acute types of asthma?
35 Anti - inflammatory Agents: (control medications / prophylactic therapy) reduce the number of inflammatory cells in the airways and prevent blood vessels from leaking fluid into the airway tissues. By reducing inflammation, they reduce the spasm of airways & bronchial hyper-reactivity.
37 Glucocorticoids Mechanism of action Inhibition of phospholipase A2 therefore,↓ prostaglandin and leukotrienes↓ Number of inflammatory cells in airways.Mast cell stabilization →↓ histamine release.↓ capillary permeability and mucosal edema.Inhibition of antigen-antibody reaction.Upregulate β2 receptors (have additive effect to β2 agonists).
39 Pharmacological actions of glucocorticoids Anti-inflammatory actions (useful effects)Immunosuppressant effects (useful effects)Metabolic effects (Side Effects)Hyperglycemia↑ protein catabolism, ↓ protein anabolismStimulation of lipolysis - fat redistributionMineralocorticoid effects (Aldosterone)Sodium/fluid retention (hypertension)Increase potassium excretion (hypokalemia)Increase blood volume (hypertension)
40 Behavioral changes: depression Bone loss (osteoporosis) due toInhibit bone formation↓ calcium absorption.
41 Routes of administration Inhalation:e.g. Budesonide & Fluticasone, BeclometasoneGiven by inhalation, given by metered-dose inhaler0Best choice in asthma, less side effectsOrally: Prednisone, methyl prednisoloneInjection: Hydrocortisone, dexamethasone(Note :Both have first pass metabolism)
42 Glucocorticoids in asthma Are not bronchodilatorsReduce bronchial inflammationReduce bronchial hyper-reactivity to stimuliHave delayed onset of action (effect usually attained after 2-4 weeks).Maximum action at 9-12 months.Given as prophylactic medications, used alone or combined with beta-agonists.Effective in allergic, exercise, antigen and irritant-induced asthma,
43 Systemic corticosteroids are reserved for: Status asthmaticus (i.v.).Inhaled steroids should be considered for adults,children with any of the following featuresusing inhaled β2 agonists three times/weeksymptomatic three times/ week or more;or waking one night/week.
44 Clinical Uses of glucocorticoids Treatment of inflammatory disorders (asthma, rheumatoid arthritis).Treatment of autoimmune disorders (ulcerative colitis, psoriasis) and after organ or bone marrow transplantation.Antiemetics in cancer chemotherapy44
45 Side effects due to systemic corticosteroids Adrenal suppressionGrowth retardation in childrenOsteoporosisFluid retention, weight gain, hypertensionHyperglycemiaSusceptibility to infectionsGlaucomaCataractFat distribution, wasting of the musclesPsychosis
46 Inhalation has very less side effects: Oropharyngeal candidiasis (thrush).Dysphonia (voice hoarseness)WithdrawalAbrupt stop of oral corticosteroids should be avoided and dose should be tapered (adrenal insufficiency syndrome).
47 Mast cell stabilizers act by stabilization of mast cell membrane. e.g. Cromolyn (cromoglycate) - Nedocromilact by stabilization of mast cell membrane.given by inhalation (aerosol, microfine powder,nebulizer).Have poor oral absorption (10%)
48 are Not bronchodilators Pharmacodynamicsare Not bronchodilatorsNot effective in acute attack of asthma.Prophylactic anti-inflammatory drugReduce bronchial hyper-reactivity.Effective in exercise, antigen and irritant-inducedasthma.Children respond better than adults
49 UsesProphylactic therapy in asthma especially in children.Allergic rhinitis.Conjunctivitis.Side effectsBitter tasteMinor upper respiratory tract irritation (burning sensation, nasal congestion)
50 Leukotrienes antagonists produced by the action of 5-lipoxygenase onarachidonic acid.Synthesized by inflammatory cells found in theairways (eosinophils, macrophages, mast cells).Leukotriene B4: chemotaxis of neutrophilsCysteinyl leukotrienes C4, D4 & E4:bronchoconstriction increase bronchial hyper-reactivitymucosal edema, mucus hyper-secretion
54 Uses of leukotriene receptor antagonists Are not effective to relieve acute attack of asthma.Prophylaxis of mild to moderate asthma. Like:- Aspirin-induced asthma- Antigen and exercise-induced asthmaCan be combined with glucocorticoids (additive effects, low dose of glucocorticoids can be used).Side effects:Elevation of liver enzymes, headache, dyspepsia
55 Omalizumab is a monoclonal antibody directed against human IgE. prevents IgE binding with its receptors on mast cells & basophiles.↓ release of allergic mediators.used for treatment of allergic asthma.Expensive-not first line therapy.
56 Anti-immunoglobulin E (e.g. Omalizumab) MOA: Selective anti-IgE monoclonal antibody that binds to IgE and prevents its association with IgE receptors, thus preventing allergen from activating mast cells or basophilesDecreases serum IgEDue to the above effects, omalizumab decreases the numbers of eosinophils, T and B lymphocytesUses: for resistance type of asthma and allergic rhinitis.Side effects and Limitations:Infusion side effects and very expensive.
58 Drugs used in COPDCOPD is a chronic irreversible airflow obstruction, lung damage and inflammation of the air sacs (alveoli).Smoking is a high risk factorTreatment:Inhaled bronchodilatorsInhaled glucocorticoidsOxygen therapy
59 Antibiotics specifically macrolides such as azithromycin to reduce the number of exacerbations. Lung transplantation
60 Treatment of COPD Inhaled bronchodilators Inhaled antimuscarinics (are superior to β2 agonists in COPD)β2 agoniststhese drugs can be used either alone orcombinedsalbutamol + ipratropiumsalmeterol + Tiotropium (long acting-less dose frequency).
61 Does treatment of COPD differs from bronchial Asthma? Antimuscarenic drugs like Ipratropium is preferred for COPD Why?Short acting b2-adrenergic agonist is used like for Asthma.However, oral or inhaled corticosteriods are only used for severe form of COPD. Why?Mucolytics like Acetylcysteine may be used.Routine administration of Oxygen may be included for advanced cases.