Respiratory Pharmacology

Reversible airflow obstruction increases in airway resistance involving bronchoconstriction + inflammation Decreases in FEV1 (forced expiration volume in first second) Value of < 70% means increased airway resistance If asthma, then reversed using Beta2-agonist

Airflow limitation that is not fully reversible Both chronic bronchitis + emphysema Loss of lung function 80-90% deaths related smoking Diseases of late onset in life (elderly) High energy demand + difficulty eating, e.g. use inhaler before meal, leading to weight loss

1) relief of symptoms (bronchodilators) - block early phase if asthma attack caused by bronchoconstriction 2) prevention of attack (anti-inflammatory agents) - prevents late phase caused by release of cytokines

Reverse bronchospasm + rapid relief Beta2 adrenoceptor agonists e.g. salbutamol • 1st choice • Increase FEV1 • Given by inhalation Longer acting agents (salmeterol) given for long-term prevention

On smooth muscle and mast cell Increase in cAMP prevents release of histamine Affects on mucus secretion

Caused by long-term use of Beta-adrenoceptor agonists which leads to tolerance/desensitisation Due to internalisation of the receptor Prevented by steroids

Salmetorol Formoterol Indacaterol Dont know why they are long acting Current theory = absorbed into lipid bilayer of cells - slowly released over time to activate

Tremor Palpitations Hypokalaemia Due to high doses of drugs e.g. nebulisers

Roflumilast (PDE4) inhibitor (DAXAS) For COPD Reduces inflammation Can enhance Beta-adrenoceptor effects

Block parasympathetic bronchoconstriction e.g. ipratropium (non-selective antagonist) Inhaled (fewer systemic effects) Inhibits mucous secretion Tiotropium = long-acting, due to slow dissociation from receptor Aclidinium = long-acting but newer

They are non-selective so they block muscarinic receptors all over body Dry mouth Nausea/headache Constipation Urinary retention Blurred vision Atrial fibrillation + Tachycardia + Palpitation

Bronchodilators (not as good as b2-adrenoceptor agonist) E.g. theophylline 2nd line use Orally inhaled (or IV aminophylline in emergencies)

Mix of theophylline + ethylenediamine (2:1 ratio) Improves solubility Measure plasma theophylline 4-6 hrs after infusion (iv) Monitor plasma levels - toxicity

Tremor Palpitations Nausea CNS stimulations Drug interactions: • inhibit of metabolism increases toxicity (cimetidine) • induce metabolism reduces plasma levels

Preventative - do not reverse an attack Target late phase of asthma response e.g. Corticosteroids

Act at intracellular or glucocorticoid receptor

Beclometasone Bidesonide Ciclesonide Fluticasone Mometasone

Prednisolone e.g. acute asthma attack

Hydrocortisone e.g. life threatening asthma

Annexin A1 Beta2-adrenoceptors IkB (Inhibitor of NF-kB) MKP1 (inhibits MAP kinase) Anti-inflammatory cytokines e.g. IL-10, 1L-12

Inflammatory cytokines - e.g. IL-2, IL-3, IL-6, TNFα Chemokines Inflammatory enzymes - e.g. iNOS, COX-2 Inflammatory peptides - e.g. endothelin-1

Involved in the up-regulation of anti-inflammatory genes Act through formyl peptide receptors (FPR) • inhibits histamine release from mast cells • inhibits cPLA2 - PGs