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 arrhythmogenic (VF) properties |
| CNS | ↓ Seizure threshold |
| Renal | Natriuresis and hypokalaemia |
| Toxic Effects | Low therapeutic index, with toxicity manifested as tachyarrhythmias including VF, tremor, insomnia and seizures |
References
- Lexicomp. Theophylline: Drug Information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.