Agents used for asthma:
- Uses – asthma, hyperkalaemia
- PD – selective B2 adrenocepter agonist –> bronchodilator.
- PK – 10-30% act directly on bronchial smooth muscle when inhaled, significant first pass metabolism and excreted renally
- B blockers antagonise effect
- Aminophylline enhances effect
- Boosts effect of concomittent B agonists
- Fine tremor
- Peripheral vasodilation–> hypotension
- Hypersensitivity reaction – anaphylaxis
- PD – anticholinergic
- inhibits vagally mediated reflexes by antagonizing acetylcholine action; prevents increase in intracellular calcium concentration that is caused by interaction of acetylcholine with muscarinic receptors on bronchial smooth muscle
- Decrease bronchial secretions
- Minimal systemic absorption, onset 15mins, peak plasma 1-3hrs, duration 3-4hrs, 0.9% protein bound, VD 340L, metabolised in liver, eliminated by kidneys (46%), T1/2 2hrs
- Used in acute life-threatening asthma
- Aminophylline is a 2:1 complex of theophylline and ethylenediamine. The activity is of theophylline alone.
- Hypersensitivity to either aminophylline or ethylenediamine.
- Active peptic ulcer disease
- Underlying seizure disorders (unless receiving appropriate anticonvulsant medications).
Sodium cromoglycate (basic).
- Mast cell stabiliser – inhibits release of histamine, leukotrienes, and slow-reacting substance of anaphylaxis from mast cell by inhibiting degranulation following exposure to reactive antigens
- PK – bio avail 0.5-2%, peak plasma time 15mins, T1/2 80-90mins, duration 6hrs, excretion 98% faeces(unabsorbed)
Theophylline (worth knowing in detail, particularly PK/PD/Overdose)
- Theophylline directly relaxes the smooth muscle of the bronchial airway and pulmonary blood vessels, thus acting mainly as a bronchodilator and smooth muscle relaxant. It has also been demonstrated that aminophylline has a potent effect on diaphragmatic contractility in normal persons and may then be capable of reducing fatigability and therapy improve contractility in patients with chronic obstructive airway disease. The exact mode of action remains unsettled.
- Used in neonatal apnoea too
- PK – almost 100% bioavailability, peak serum levels in 30-120mins, VD 0.5L/kg, 60% protein bound, 85-90% hepatic elimiantion, remainder by renal. T1/2 – 4-8hrs
- Levels over 20mcg/mL
- Inhibit PDE –> increase cAMP –> Excess catecholamines released –> cardiac arrhythmias(chronic OD), seizures(acute OD), death
- Hypokalaemia, hypoglycaemia, hypercalcaemia, hypophosphotaemia, acidosis
- Presentation – nausea, vomiting, abdo pain, tachycardia.