Pain expert Dr. Scott Fishman answers questions about cancer pain:

Q:  What are the chances of a large dose of morphine (opioids) resulting in accidental death?

A:  Patients, as well as doctors, worry about overdoses and the potential opioid side effect of decreased breathing. I answer concerns about overdosing and depressed breathing by explaining that when a medication gradually is increased with an eye on the patient's breathing rate, the body adjusts. Despite what many people believe, there is no ceiling or single maximum amount or dose of opioids that is automatically fatal.

It may help you understand how morphine works by knowing a little of its history. A German scientist extracted morphine, opium's most potent ingredient, from the plant in 1803. Since morphine was first extracted from opium, more than forty other alkaloids have been found in the plant, although fewer than half can be formed into active drugs.

Later alterations and modifications of opium stimulated a host of painkilling variations, including codeine (one-sixth as strong as morphine), meperidine (now known as Demerol and distilled in 1939 as the first synthetic opioid), methadone (developed by the Germans during World War II as a substitute for hard-to-get morphine), hydromorphone (now known as Dilaudid, which is ten times stronger than morphine), and fentanyl (at present the only opioid that is given in a patch form and absorbed through the skin).

An opioid works systemically and circulates through the body to latch onto specific receptors on the outside of cells in the brain and elsewhere. Think of a receptor as a lock on the door of a cell. Molecules, in the form of a naturally produced hormone or an opioid drug, act like a key that fits into that lock to open the door to the cell.

Once a cell door is open, there are infinite possibilities for what happens next, depending on the cell, the receptor, the timing, and other reactions in other cells or parts of the body. Morphine, once it has unlocked the receptor, may cause the nerve to fire more slowly or more quickly. This change in cell action produces pain relief as well as other sensations.

An important factor influencing the use of opioids is the fact that when they are inserted right into the spinal fluid, the amount needed for pain relief is much less than when they travel via the blood and through organs. Since the drugs bypass the gastrointestinal system in this case, they may stir up fewer side effects.

In my book, The War on Pain, I tell the story of Dr. Ira Byock, a hospice physician in Missoula, Montana and author of Dying Well. Dr. Byock had a dying patient able to absorb monumental doses of opioids. The woman had kidney cancer and treating her pain forced him to exhaust the entire supply of injectable Dilaudid (hydromorphone) in all of Missoula's pharmacies and both hospitals in the city.

At her worst, the patient needed nine grams of morphine per hour (one-tenth of a gram will knock out mostly healthy adults). Therefore, an effective dose depends on the individual and the pain. Sometimes the pain accelerates not only because of increasing tolerance but also because the disease has worsened.