Anti-inflammatories (Respiratory)

Glucocorticoids (GCs) are the most effective anti-inflammatory agents for asthma. Their general actions include regulating gene expression to control carbohydrate, fat, and protein metabolism, and producing potent anti-inflammatory and immunosuppressive effects by preventing phospholipid release, decreasing eosinophil recruitment and action, and suppressing inflammatory cytokines and immune cells.

Molecular mechanism: GCs cross the cell membrane and bind to intracellular glucocorticoid receptors (GR). The GC-GR complex enters the nucleus and binds glucocorticoid response elements (GCREs) — specific DNA sequences — activating or repressing transcription. A key mediator is lipocortin-1 (annexin-1), whose transcription is upregulated. Lipocortin-1 downregulates pro-inflammatory mediators (IL-2, IL-3, IL-4, IL-5, TNF-alpha, GM-CSF, COX, phospholipase A2, iNOS) and upregulates anti-inflammatory mediators (IL-10, IL-12, IL-1 receptor antagonist).

In asthma, GCs reduce: mucosal oedema, mucus hypersecretion, airway smooth muscle hyperresponsiveness, eosinophil infiltration, subepithelial fibrosis, and angiogenesis. They do not directly cause acute bronchodilation.

Inhaled corticosteroids (ICS) — examples: fluticasone propionate, budesonide, beclomethasone dipropionate. Delivered via pressurised metered dose inhalers (pMDIs) or dry powder inhalers. Allows delivery at ~1/100 the concentration needed for equivalent systemic anti-inflammatory effect. Most inhaled drug is swallowed (inertial impaction on tongue/throat); the swallowed portion undergoes extensive first-pass GIT and hepatic metabolism (CYP3A enzymes), limiting systemic absorption. Sedimentation of smaller particles (1-10 µm) in lower airways constitutes the pharmacologically active fraction.

ICS ADRs at normal doses: oropharyngeal candidiasis (local immunosuppression → Candida albicans infection, especially with pMDI), dysphonia (hoarse voice from high-velocity crystal deposition on laryngeal soft tissue), osteoporosis (even at low doses), delayed growth in children, secondary adrenal insufficiency (only at high chronic doses). Prevention: rinse/gargle after use; use a spacer (reduces inertial impaction and velocity → less candidiasis and dysphonia); reduce dose frequency based on PEFR and symptom monitoring.

Oral corticosteroids — prednisone (prodrug; converted to prednisolone by hepatic metabolism). Indications: acute asthma exacerbations unresponsive to bronchodilators (SOS protocol: Salbutamol, Oxygen, Steroids). Short course high-dose (40-60 mg/day for ~5 days); use exceeding 7 days causes HPA axis suppression and requires dose tapering to allow HPA axis recovery. Gradual taper also needed when switching from chronic oral GC to ICS. Metabolic ADRs of chronic oral GC: decreased glucose uptake in skeletal muscle, increased gluconeogenesis → hyperglycaemia; increased protein catabolism → muscle wasting; fat redistribution → cushingoid features; bone resorption → osteoporosis.

COPD differs from asthma: COPD (GOLD definition) is a heterogeneous lung condition characterised by chronic respiratory symptoms due to abnormalities of airways and/or alveoli causing persistent airflow obstruction. Key distinction: in COPD, start with LABA and/or LAMA without ICS (ICS increases infection risk in COPD, which already predisposes to airway infection). ICS may be added in severe COPD with frequent exacerbations. High dose ICS should not be used in COPD. Patients with both asthma and COPD are at higher risk of death or hospitalisation if treated with LABA alone rather than ICS-LABA.