Airways Pharmacology Notes

Lecture 14 & 15

Airways pharmacology

• ASTHMA

  • What is asthma? Characterised by:

    • Wheeze, cough, chest tightness, dyspnoea, airway hyper-responsiveness, inflammation of lungs, variable airflow obstruction

  • Asthma pathology

    • Causes

      • Genetic/ethnic

        • IgE levels genetically influenced

        • 50% higher prevalence in black vs. white children

      • Environmental

        • Higher in city than rural dwellers

        • Passive smoking

    • Triggered by…

      • Respiratory infections

      • Exercise, breathing in cold air

      • Exposure to allergens

        • Pollen/moulds; dust mites/cockroaches; pollution; pets; tobacco smoke

    • Pathological process

      • Initiation

        • Allergens stimulate T-cells

        • Generate B cell activating cytokines, leads to IgE production

        • Induces expression of IgE receptors (Fc receptor) mainly on mast cells & macrophages

      • Early/acute/immediate phase

        • Release mediators from macrophage/mast cells:

          • Histamine; leukotrienes; cytokines; neurokinins; platelet activating factor; prostaglandin

        • Promote bronchoconstriction (ACUTE ASTHMA ATTACK)

        • Mediators also attract T cells, neutrophils, platelets and monocytes releasing more spasmogens & inflammogens

        • Further exacerbates inflammation and triggers inflammation

      • Late phase

        • Progressive inflammation

        • Influx TH2 lymphocytes

        • Activation of Eosinophils releasing toxic proteins

        • PGE₂ from smooth muscle: permeable BVs= OEDEMA

        • Damage and loss of epithelium

        • Increased irritant receptor/C fibre accessibility=Bronchial hyperactivity

        • Subepithelial cell fibrosis

        • Hypertrophy and hyperplasia of smooth muscle cells

• COPD

  • Clinical features

    • Morning cough in winter, chronic cough

    • URI, bronchitis

    • Progressive dyspnoea

    • Pulmonary hypertension/heart failure

  • Pathogenesis

    • Small airway fibrosis/bronchitis

    • Destruction of alveoli/elastin fibres (emphysema)

    • Promoted by protease release due to inflammatory response

    • Impaired has transfer

    • Inflammatory mediators not as well defined as in asthma

  • Treatment options?

    • Stop smoking (slows progress)

    • Immunization against infections

    • Glucocorticoids largely infective

    • Long acting bronchodilators

    • Long-term oxygen therapy

  • Area of considerable research by pharmaceutical industry

    • Target inflammatory process/mediators

    • Chemokines receptor antagonists

    • Inflammatory (TNFa) inhibition

    • Inhibit cell signalling (p38 MAPkinase)

    • Anti oxidants (NO inhibitors/leukotriene antagonists)

• COUGH

  • Features

    • Protective reflex removing secretions/foreign material

    • Productive or dry

    • Very commonly seen with patients on ACE inhibitors

    • Triggered by inflammation

    • Only suppress if dry and painful, otherwise it’s protective

  • Clinically used anti-tussives

    • Opioids

      ...

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