Phosphodiesterase Inhibitors / Methylxanthines

Methylxanthines non-selectively inhibit phosphodiesterase, which results in reduced levels of cAMP hydrolysis and therefore increased intracellular cAMP, and subsequent smooth muscle relaxation. This effect is synergistic with β2 agonists, which also increase cAMP by increasing production.

Property Theophylline
Class Methylxanthine/Non-selective phosphodiesterase inhibitor
Uses Asthma and COAD
Route of Administration IV or PO
Dosing 4-6mg.kg-1 IV load, then at 0.4mg.kg-1.hr-1 targeting serum concentration of 10mcg.ml-1
Absorption High oral bioavailability
Distribution VD 0.5L.kg-1, 40% protein binding.
Metabolism Hepatic via CYP450 to active metabolites (caffeine and 3-methylxanthine), low hepatic extraction ratio
Elimination Highly variable elimination affected by age, renal disease, hepatic disease
Resp Bronchodilation, ↑ Diaphragmatic contractility
CVS ↑ Inotropy, ↑ chronotropy. Narrow therapeutic range due to arrythmogenic (VF) properties
CNS ↓ Seizure threshold
Renal Natriuresis and hypokalaemia
Toxic Effects Low therapeutic index, with toxicity manifested as tachyarrythmias including VF, tremor, insomnia and seizures

References

  1. Lexicomp. Theophylline: Drug Information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  2. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  3. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
Last updated 2017-09-22

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