Drugs for Asthma by medicalnotes


									Drugs for Asthma
 Sympathomimetics (β2 receptor agonists)                 Methylxanthines                              Anticholinergics                                 Corticosteroids                          Mast cell stabilizers                   Leukotriene pathway inhibitors
   Non selective             Selective            Oral                    IV             Ipratropium bromide                          Require regular bronchodilator                 Sodium Cromoglycate                         Leukotriene pathway inhibitors
  Adrenaline          Short acting           Theophylline      Aminophylline             Tiotropium                                   (prevent acute attack)                         Nedocromil                                          Receptor            Synthesis
                      Salbutamol                               (Theophylline +                                                        High potency inhaled drugs (budesonide)                                                           antagonist           Inhibitors
                      Terbutaline                              ethylenediamine)          Synthetic analogue of atropine               AEBA – may require oral/IV corticosteroids     Aerosol (not significantly absorbed after     Monteleukast         Zileuton
                      Fenoterol             Most selective for smooth muscle             Use as adjunct to β2 agonist                 (↓ inflammation & prevent relapse)             oral administration)                          Zafirlukast
                      Long acting                                                        Given by Aerosol, Nebuliser                  Rescue course of prednisolone                                                              Orally (b.d. or daily)
                      Salmeterol                                                                                                      (if clinical condition is deteriorating)                                                   Fairly safe drugs
                      Fomoterol                                                                                                       Tapering of dose needed                                                                    Not used in acute asthma
MOA                                         MOA                                          MOA                                          MOA                                            MOA                                         MOA
Act at β2 receptor (bronchial smooth ms.)   Block adenosine receptor                     Competitively inhibit Ach                    Anti-inflammatory                              Inhibit mast cell degranulation             Bronchodilators
(β2 receptor agonist) (via cAMP)            Inhibit phosphodiesterase enzyme             (at muscarinic receptors)                     Inhibit production of inflammatory           (release of mediators in lungs)             Anti-inflammatory
Smooth ms. relaxation (Bronchodilatation)   (involved in metabolism of cAMP)                  Responses have individual variation      mediators (cytokines, chemokines)
Other effects                               ↑ cAMP & cGMP                                     ↑ effective in COPD (than asthma)        (phospholipase A2)
Prevent mediator release from Mast cells    Relax bronchial smooth ms.                        Used in patients who cannot tolerate    Inhibit lymphocytic, eosinophilic mucosal
Prevent leakage from microvasculature       Prevent mediator release from Mast cells           β2 agonist                               inflammation of asthmatic airways
(↓ edema)                                   ↑ Mucociliary clearance                      Bronchodilatation                              ↓ bronchial reactivity
                                            Prevent microvascular leakiness                                                             ↓ frequency of asthma (if taken regular)
                                            Stimulate diaphragm                                                                        Contraction of engorged vessel in
                                                                                                                                        bronchial mucosa
                                                                                                                                        (relieve some airway obstruction)
Bronchodilatation                           Bronchodilatation                            Bronchodilatation                            ↓ Inflammation                                 ↓ Inflammation                              ↓ Inflammation
Indications                                 Uses                                         Combination with β2 agonist                  Mode of administration                         Prophylactic only                           Uses
Relief acute attack of asthma               Improve long term control of asthma          Better efficacy                                      Systemic                Inhaled             No effect on bronchial tone           Effective in – allergic rhinitis
Prophylactic (before exercise)               When taken as maintenance treatment        Prolonged bronchodilatation                    Hydrocortisone(IV)      Beclomethasone            Ineffective in reversing asthmatic    ↓ Steroid dosage
Nocturnal cough (asthmatic)                  Added to inhaled corticosteroids           Recommended in acute exacerbation              Prednisolone(Oral)      Budesonide                 bronchospasms
COPD                                        Narrow therapeutic window                    (of bronchial asthma)                                                  Fluticasone
Prevent premature labour                     Monitor blood level                                                                                               Triamcinolone
Methods of delivery                         Newer Generations (↓ Toxicity)                                                              No improvement          Avoid adverse        Uses
Oral                                        Roflumilast                                                                                 despite                 systemic effects     Prevent bronchoconstriction
Nebuliser                                   Cilomilast                                                                                  maintenance             (minimal                  Before exercise
Aerosol inhaler                             Tofimilast                                                                                  therapy                 systemic absorp.)         Before unavoidable exposure to
Dry powder inhalation                                                                                                                   1 week – 10 days        Oropharyngeal              allergen
Subcutaneous                                                                                                                                                    candidiasis          Regular use 2-4X daily
Intravenous                                                                                                                                                     (gargle after use)        ↓ severity
Adverse effects                                                                                                                                                 Switching from            ↓ need for bronchodilator
Fine tremor                                                                                                                                                     oral – use higher    Children (more commonly used)
Headache                                                                                                                                                        dose for patient
Peripheral vasodilatation                                                                                                                                       requiring
Palpitation                                                                                                                                                     continued use of
Tachycardia                                                                                                                                                     oral prednisolone
Hypokalaemia – K+ uptake to cells
                                            Sites of action                                                                           Advantages                                     Adverse effects
                                            CNS                                                                                       ↑ Lung function                                (safe drug – few)
                                                  Cortical arousal                                                                   ↓ Bronchial hyperresponsiveness                Hypersensitivity reactions (mainly)
                                                  Convulsions (toxicity)                                                             ↓ Asthmatic symptoms
                                            Cardiovascular                                                                            ↑ Health-related quality of life
                                                  +ve inotropic action                                                               ↓ Asthmatic exacerbations
                                                  +ve chronotropic action                                                            ↓ Risk of death/ near-death from asthma
                                                  Relax vascular smooth ms.                                                          Adverse effects
                                            GIT                                                                                       Impairs CHO metabolism – diabetogenic
                                                  Stimulate secretions                                                               ↓ Protein anabolism
                                            Renal                                                                                     Abnormal fat deposition
                                                  Weak diuretic                                                                      ↓ Growth in children
                                            Bronchioles                                                                               Suppress immune response
                                                  Dilates smooth ms.                                                                 Suppress hypothal/pit/adrenal system
                                                  Inhibits antigen-induced release of                                                Psychiatric illness
                                                   smooth ms. contracting substances                                                  Peptic ulcer
                                                   from mast cells                                                                    Cataract
Drugs for Asthma (cont.)
 Sympathomimetics (β2 receptor agonists)                    Methylxanthines                Anticholinergics   Corticosteroids              Mast cell stabilizers                     Leukotriene pathway inhibitors
Short Acting (β2 receptor agonists)          Theophylline (Oral)                                                                                                               Leukotriene Receptor Antagonists
(Inhalers, Nebulizers)                       Rapid & completely absorbed by GIT                                                                                                Montelukast, Zafirlukast
Acute treatment of bronchospasm (inhale)     Metabolized by Liver (90%)                                                                                                        Actions
Most effective                               (liver disease lead to toxic concentration)                                                                                             ↓ Bronchoconstriction
      Relax airway smooth ms.               Side effects                                                                                                                            ↓ Inflammatory cell infiltration
      Reverse bronchoconstriction                5 – 20mg/L              > 40mg/L                                                                                             Effects
Symptomatic treatment                           Nausea              Hypotension                                                                                                      ↓ Hypersensitivity
      Asthma                                   Diarrhoea           Hypokalaemia                                                                                                     ↓ Mucus
      COPD                                     Tachycardia         Seizures                                                                                                         ↓ Inflammation
Prophylaxis before exercise                                         Cardiac dysrhythmias                                                                                       Route – Oral (1-2h after meals)
Nocturnal cough                              Uses                                                                                                                              Use
Onset – seconds → 5 mins                            Acute severe asthma (IV)                                                                                                        Moderate asthma
Duration of action – 2–6h                           Chronic asthma (Oral)                                                                                                           Maintenance
Long Acting (β2 receptor agonists)                  COAD (Oral)                                                                                                                     Prophylaxis
(Inhalers)                                   Inexpensive (can be taken orally)                                                                                                 Favourable response in 50%
Highly selective for β2 subtype              (slow release available – neulin SR)                                                                                              Affects – early & late stages
Duration of action > 12h                                                                                                                                                       Adverse effects (mostly mild)
High lipid solubility                                                                                                                                                                GI upset
(persist longer, slowly dissociate from                                                                                                                                              Headache
receptor environment, ↑duration of action)                                                                                                                                     Interactions
Chronic treatment                                                                                                                                                                    Inhibit cytochrome P450 isoenzymes
      ↑ lung function                                                                                                                                                               ↑ Warfarin levels
      ↓ asthma symptoms                                                                                                                                                       Leukotriene Synthesis Inhibitors
      ↓ use of short acting β2 agonists                                                                                                                                       Zileuton
      ↓ nocturnal asthma                                                                                                                                                      Actions
Added to patient with chronic asthma                                                                                                                                                 Inhibit 5-lipooxygenase reversibly
(not controlled by inhaled glucocorticoid)                                                                                                                                     Effects
Not for acute asthma (delayed onset)                                                                                                                                                 ↓ Hypersensitivity
Not recommended as sole therapy                                                                                                                                                      ↓ Mucus
Oral (β2 receptor agonists)                                                                                                                                                          ↓ Inflammation
Onset of action – 30mins                                                                                                                                                       Route – Oral
      Salbutamol                                                                                                                                                              Use
      Terbutaline (IV/ SC)                                                                                                                                                          Maintenance
       (status asthmaticus)                                                                                                                                                          Prophylaxis
Clinical use                                                                                                                                                                   Adverse effects
      Children – cannot use inhaler                                                                                                                                                 Dyspepsia
       (occasional wheezing with URTI)                                                                                                                                               Liver toxicity
      Severe acute asthma exacerbations                                                                                                                                       Interactions
       (MDI/ nebulizer can be irritating)                                                                                                                                            Inhibits cytochrome P450 isoenzymes
       Worsening of cough, bronchospasm
      Prevent premature labour

                                                                                                                                Other Drugs for Asthma
                                                                                                                                                                Anti-IgE monoclonal antibodies
                                                                                                                                Inhibit IgE binding to mast cell & other inflammatory cells
                                                                                                                                Inhibit IgE synthesis
                                                                                                                                Subcutaneous injection (2 – 4 weekly)
Drug Delivery by Inhaled Aerosol                                 Asthmatic Control

                                                                 Asthmatic Drugs

Anti-IgE drugs

                                                                 Inhaled Drugs
                                                                 Factors affecting
                                                                      Particle size
                                                                      Technique
                                                                             o     Coordination
                                                                             o     Breath holding, rate of breath
                                                                             o     Use of spacer
                                                                 Aerosol delivery
                                                                      Metered dose (MDI)
                                                                      Nebulizer
                                                                 Alternative – dry powder form
                                                                      Lactose or glucose to carry drug
                                                                      Need high airflow
                                                                      May irritate bronchi

Better efficacy (in combination form of drugs)
    Ipratropium + Salbutamol
    Salmeterol + Fluticasone
    ↓ Reversible portion of bronchoconstriction/ inflammation
     (not fully reversible)
       Advantages                            Disadvantages
Use less dose              Need coordination
Local action               Technique need to be checked regularly
↓ Systemic side effects    Different method for different capability of patient
Fast actions               Expensive

Types of Inhalers
                    Aerosols (MDI)                                                Powder                                  Liquid form (Nebulizer)

2 Components                                            Fine powder                                          Liquid form
       Active Drug                Propellant            Consists of                                          Machine serve as jet to form aerosol
  Salbutamol                Chlorofluorocarbon               Active drug                                    Do not need coordination
  Beclomethasone                                             Lactose (patient know that inhalation occur)

Technique of Inhaler Use
Open the cap
Shake well
Breathe in & out a few times, then breathe out completely
Put inhaler in mouth, press inhaler & inhale deeply through mouth
Hold breath for 10 seconds
Breathe out & repeat as necessary
(If >2 doses, wait for 1 min before next one)



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