New series; #theophylline was extracted from green/black tea leaves in 19thC; a natural derivative of the purine ‘xanthine’ & structurally similar to caffeine. Used 1902 as diuretic & since 1930s for asthma. Oral prep as m.r formulation/given i.v as aminophylline (more soluble)

Day 2 #theophylline; indications include adult & children >5 (UK step 3+) for chronic asthma (specialist use <5). Adults only severe acute asthma /COPD. Asthma 2-11yrs 9mg/kg every 12 hrs, can incr 10-16mg/kg; 12-17 yrs 200-400 every 12 hrs; COPD 200-400mg twice daily

Day 3 kinetics; #theophylline thought 100% bioavailable orally! Metabolised in liver- this process determines blood levels. ~10% renally excreted unchanged.Prolonged release tablets t½ 7 hrs. Caution hepatic impairment, heart failure & viral infection. Can use in pregnancy.

Day 3 (cont); #theophylline clearance altered by age, weight, diet, smoking, some disease e.g cardiorespiratory & hepatic. #theophylline is a drug with a narrow therapeutic index – monitor at the start & with each dose adjustment or change to clearance e.g altered smoking habit

Day 4 MOA: Unknown for #theophylline. Thought to inhibit phosphodiesterase & antagonise adenosine, thus regulating Ca flow > relaxing bronchial smooth muscle. Also stimulates CNS & cardiac muscle, induces diuresis & increases gastric acid secretion

Day 5 ADRs: freq unknown for #theophylline as pre-dates licensing regs. Arrhythmias, anxiety, nausea /vomiting, rash, abdominal discomfort, tremor, sleep disorders, convulsions. Risk of severe hypokal when used with beta2 agonists(not exhaustive) p.r prep can > delayed toxicity

Day 6: DDIs for #theophylline incl numerous ‘severe’ interactions from either hypokalaemia e.g citalopram, clarithromycin, as well as asthma meds e.g salbutamol; OR via enzyme induction e.g St John’s wort, or drugs which can worsen respiratory function e.g beta blockers

Day 7:Interesting fact; At lower concentrations #theophylline is believed to exert an anti-inflammatory effect in lungs; reduced no. of eosinophils & IL-8. Theories incl inhibition prostaglandin levels, T cell apoptosis, antagonism TNF-alpha while increasing IL-10 (anti-inflamm)