About Theophylline, Part 1 Print E-mail



Scientific opinion now sees only marginal bronchodilating effects in COPD, in addition to the difficulty of maintaining effective levels in the blood without encountering potentially toxic side effects. Many physicians, however, still prescribe the various forms of this drug. Some focus on research suggesting possible benefit to the respiratory muscles, some physicians like the experience their patients tend to have on this drug, and for others, it's simply become a habit.

Theophylline is a drug chemically similar to caffeine. Caffeine, as we know, is found in coffee and tea, and is added to most cola beverages. Both theophylline and caffeine belong to the class of chemicals called methylated xanthines. They stimulate skeletal muscles, the central nervous system, and the heart. They relax smooth muscles, especially the airway muscles. Both theophylline and caffeine are an effective diuretic. But the relative emphasis of their effects in different.

Caffeine is primarily a stimulant for skeletal muscles and the central nervous system. Theophylline is most potent as both a heart stimulant and a relaxer of smooth muscle. More recently, theophylline's ability to strengthen the diaphragm and reduce its fatigue has come to be appreciated. It has also been recently learned that theophylline stimulates mucociliary clearance of the airways, inhibits the release of mediators causing anaphylaxis (a life-threatening allergic reaction involving all bodily systems), and suppresses the edema that often accompanies asthma.

So theophylline holds two benefits for COPD patients even when there is no asthma component. For one, it helps get rid of mucus. This is a daily need for some COPD patients, while others need it only during respiratory infections. Theophylline also strengthens the diaphragm; our main inspiratory muscle. The COPD patients normally hard-pushed respiratory muscles must labor far more intensively during an acute exacerbation. This can exhaust them, precipitating respiratory failure. But a strengthened diaphragm can resist this extreme, possibly life-threatening, fatigue.

For a long time, researchers thought they understood how theophylline works. They were confident that it simply maintained a high level of cAMP in the body by blocking the enzyme that would otherwise destroy it. This, in turn, would lower the amount of calcium available for smooth muscle cell contraction.

But more recent investigations have thrown serious doubt on this enzyme-blocking explanation, and also raised other possibilities. Some researchers believe theophylline may change the way in which calcium actually enters and leaves smooth muscle cells. Some think it may inhibit certain compoundscalled prostaglandinswhich are now tentatively implicated in some forms of asthma. Others suggestions have been raised as well. Now nothing is certain beyond acknowledging the complexity of the way in which theophylline produces bronchodilation.

The beta-2 bronchodilators are effective over a relatively broad range of concentrations in the blood. But for theophylline, the range between effective and toxic doses is extremely narrow. With a concentration of less than ten milligrams of the drug for each liter of blood plasma, most patients receive little or no therapeutic value even though some side effects may occur. (An occasional patient, though, may benefit from these low doses.) Above 20 milligrams per liter of plasma, the drug is toxic. It can become life-threatening if the blood concentration is allowed to rise high enough beyond this.

A drug's concentration in your blood depends on how much of it is taken, how fast it is absorbed, which organs it enters, and how fast it is then removed (metabolized) from your blood. Several factors can dramatically alter this removal rate. Smokersboth tobacco and marijuanaremove theophylline twice as fast, on the average, as nonsmokers do. So smokers need a higher standard dosage to compensate for this rapid elimination. What you eat is also important. A high-protein, low-carbohydrate diet means that theophylline will be eliminated 25% faster than otherwise. And a low-protein, high-carbohydrate diet slows its removal by 25%. Although we don't yet know why, eating a charcoal-broiled steak also speeds up theophylline's removal!

Viral illness and certain medications also affect the rate at which theophylline is removed. These circumstances all require an appropriate dosage change. Theophylline's removal rate is slowed by: fever from viral infections, drugs used for heart disease (such as Inderal), some antibiotics (for example, erythromycin) and drugs used for some digestive tract problems (for example, cimetidine Tagamet). This rate is slightly increased by: intravenous use of isoproterenol (during severe asthma attacks), and phenytoin (Dilantin) or high doses of phenobarbital (a barbiturate) for convulsions. A slight increase in removal rate only becomes important if the blood concentration is already at the low end of the effective range.

A precise technique for accurately determining theophylline's concentration in a patient's blood (called serum theophylline) minimizes the chances of ineffective or toxic doses. But this means thatif you are using a theophylline preparationthe level of the drug in your blood must be monitored periodically, and additionally whenever your symptoms of airway obstruction become unexplainedly worse or symptoms of toxicity appear. The only reliable information for warning your doctor of impending toxicity is the level of theophylline actually in your blood.

Side Effects

Theophylline can produce a wide range of negative effects on a variety of organ systems. When a patient first starts using this drug, central nervous system stimulation and slight nausea or queasiness are a common experience. These effects usually disappear, though, as tolerance for the drug develops. At the higher therapeutic doses (and beyond), a racing heartbeatcalled tachycardiaand heart palpitations are frequent.

Overdose

When the dose level goes beyond 40 milligrams of theophylline per liter of blood plasma, the heart can lose its normal rhythm or stop altogether. The initial central nervous system effects are restlessness, irritability, and increased nausea. They can progress to severe insomnia, agitation, and vomiting, and culminate in convulsions and coma. Intestinal pain and diarrhea occur, and the kidneys increase urine production.

Prompt emergency treatment is essential after overdosing with theophylline. First, syrup of ipecac is given to induce profuse vomiting. Then the patient is given at least 30 grams of charcoal (an absorptive poison antidote) and 10 grams of sodium sulfate (a laxative).

Even low effective doses of theophylline can have grave consequences if a COPD patient also suffers from heart failure or liver dysfunction. These conditions slow the rate of theophylline removal to such a degree that low doses automatically become high ones. Then the intense side effects also seriously exacerbate the other medical condition.


  No Comments.
Discuss this item on the forums. (0 posts)