2014A06 Outline the pharmacological management of bronchoconstriction in acute severe asthma.
Include mechanisms of action and potential adverse effects.

The triad

·   Bronchoconstriction, ↑airway reactivity

·   Swelling

·   Mucous hypersecretion

Physics of flow

·   ↓Radius -> ↑Resistance (Resistance ∝ 1/radius⁴)

·   Obstruction in expiration: earlier and exaggerated dynamic airway collapse

·   Inspiration less affected: ↑radial traction

Mechanism of action

Side effects

Salbutamol nebulized 5mg/mL q4h

·  Short acting β₂ agonist

·  G_s G-protein coupled receptor (GPCR)

·  ↑cAMP -> ↑PKA -> inhibit MLCK -> relaxation

·  Note tachyphylaxis

·  Tachycardia (β₁ cardiac)

·  Glycogenolysis, lactic acidosis (β₁ liver)

·  Tremor (β₂ skeletal muscle)

·  ↓K+ (β₂ -> ↑Na⁺K⁺ATPase activity)

Normal saline neb 5mL

·  Aids mucus removal

-

Ipratropium neb 500mcg QID

·  Non-selective mAChR antagonist

·  m₃AChR on ASM

·  G_q GPCR

·  ↓IP₃/Ca²⁺, ↓DAG

·  ↑HR (cardiac m₂AChR)

Hydrocortisone IV 50mg QID

·  Corticosteroid

·  ↓PLA₂ -> ↓leukotrienes

·  ↓Inflammation

·  ↓Mucous secretion

·  ↓ASM reactivity

·  Short term: insomnia, anxiety, depression, psychosis, ↑BSL if diabetic

·  Long term: T2DM, osteoporosis, immunodeficiency

Volatile anaesthetic INH

·  Inhibit L-Ca²⁺ -> relax ASM

·  Use: maintain sedation/anaesthesia

·  ↓SVR, ↓cardiac output, ↓mAP

·  Nausea

(R-)Ketamine

 e.g. IV 1mg/kg induction

·  Not clear

·  ↑SNS output, inhibit L-Ca²⁺

·  Use: induction/intubation in status asthmaticus

·  ↑Secretion

·  ↑SNS output -> ↑HR, ↑mAP

Magnesium IV 10mmol in 1 hour

·  Physiological antagonist at L-Ca²⁺

·  MoA for bronchodilation unclear

·  Sedation, hypotension (vascular L-Ca²⁺ antagonist)

Aminophylline

·  Non-selective PDE inhibitor
(and adenosine receptor antagonist)

·  PDE₃i? in ASM -> ↑cAMP -> ↑PKA -> inhibition of MLCK

·  Low therapeutic index

·  CVS: arrhythmia, hypotension

·  CNS: seizure