Caffeine metabolism theophylline inhibition

Some dmg interactions have been reported. An older example is that of low activity towards phenacetin favoring a potentially toxic secondary pathway, deacetylation followed by quinonei-mine formation and methemoglobinemia [96]. Furafylline was a drag candidate but was never developed because of its strong P450 1A2 inhibition and interference with caffeine metabolism [330]. High levels of P450 1A2 activity have also been associated with ineffectiveness of theophylline therapy (for asthma) [331,332]. 

Omeprazole can inhibit the metabolism of drugs metabolised mainly by the cytochrome P-450 enzyme subfamily 2C (diazepam, phenytoin), but not of those metabolished by subfamilies lA (caffeine, theophylline), 2D (metoprolol, propranolol), and 3A (ciclosporin, lidocaine (lignocaine), quinidine). Since relatively few drugs are metabolised mainly by 2C compared with 2D and 3A, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited, but the half lives of diazepam and phenytoin are prolonged as much as by cimetidine. 

The clearances of both theophylline and caffeine are reduced in oral contraceptive users and half-lives are increased, probably because of inhibition of hepatic metabolism by cytochrome P450 (348). Caution in dosage is advisable. 

Many people drink coffee to reduce drowsiness. How does caffeine achieve this effect in the brain The answer begins with a consideration of the function of the acetylcholine neurons that control your ability to pay attention. Adenosine negatively controls the activity of these neurons, meaning that when adenosine binds to its receptor on acetylcholine neurons, their activity slows. The production and release of adenosine in your brain is linked to metabolic activity while you are awake. Therefore, the concentration of adenosine in the neighborhood of acetylcholine neurons increases constantly while your brain is active during the day. As the levels of adenosine increase, they steadily inhibit your acetylcholine neurons, your brain s activity gradually slows, and you begin to feel drowsy and ultimately fall asleep. Caffeine comes to the rescue because it, like theophylline... 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

Drug interactions The effect of antacids and cations on the absorption of these agents was considered above. Ciprofloxacin, ofloxacin and enoxacin can increase the serum levels of theophylline by inhibiting its metabolism. They also may raise levels of warfarin, caffeine and cyclosporine. Cimetidine interferes with the... 

This is due, probably, to the fact that both theophylline and fluvoxamine are metabolized (at least to some extent) by hepatic CYP1A2. As theophylline toxicity is a serious, sometimes fatal, condition, fluvoxamine should be avoided in patients taking theophylline. Even at low daily doses (10-20 mg), fluvoxamine inhibits the metabolism of caffeine, another methylxanthine. ... 

Fluoroquinolone antibiotic bactericidal inhibitor of topoisomerases active against E coli, H influenzae, Campylobacter, enterobacter, pseudomonas, shigeUa. Tox CNS dysfunction, GI distress, superinfection, collagen dysfunction (avoid in children and pregnant women). Interactions inhibits metabolism of caffeine, theophylline, warfarin. 

Use cimetidine with caution in >50 year olds w/kidney or liver failure Little plasma protein binding, little metabolism. Cimetidine T levels of many drugs (see notes ) by inhibiting liver P450 enzymes. Oral anticoagulants, theophylline, caffeine, phenytoin, phenobarbital, benzodiazepines, propranolol. 

It is likely that, as with theophylline (see Theophylline + Mexiletine or Tocainide, p.ll88), mexiletine inhibits the hepatic metabolism of caffeine by the cytochrome P450 isoenzyme CYP1A2. 

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