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

 

List:

·      Asthma pathophysiology

·      Medication table

 

Asthma pathophysiology:

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

 

Medications:

 

Mechanism of action

Side effects

Salbutamol nebulized 5mg/mL q4h

·  Short acting β2 agonist

·  Gs 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

·  Gq 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

 

 

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