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New Treatments for Cancer Pain

With drugs thereís only three things we can do to treat pain: we can modify mechanisms at the source of the pain - and thatís what we do when we use Tylenol, NSAIDís - we can alter transmission to the central nervous system with a local nerve block, a local anesthetic. In the case of neuropathic pain, thatís what we do with we give antidepressants or anticonvulsants, or we can alter central perception. Thatís what opiates do. They donít block pain, they alter it. I learned that years ago talking to a cancer patient who Iíd gotten very close to. She told me that she still felt something where she used to feel pain but it just wasnít pain anymore. It wasnít that there was no sensation but it just isnít pain anymore. In complex pain states we can do all three. A polypharmacy for the treatment of complex pain is good if you do it intelligently. Having a patient on amitriptyline, Motrin and morphine is very sensible. Having a patient on Tylenol with codeine, Tylenol with Vicodin, fentanyl patch and MS Contin is kind of silly. It indicates to the whole world that you donít have a clue what you are doing and the patient should 

We have a couple of guidelines that are really interesting. These guidelines are health policy statements developed by Health and Human Services but unlike most things that the Federal Government does, these were developed by clinicians. These were developed by clinicians, most of them physicians and the acute pain guidelines and the chronic pain guidelines have some interesting similarities. The acute pain guidelines say that NSAIDís should be used around the clock for all moderate pain unless itís contraindicated. Now I know, unless you are really unusual, you 

Because thatís how you write them. But think about that for a minute. When you are treating an acute painful condition and the patient comes to you and you make the decision to use an NSAID, that process is as bad as itís likely to get right then. These drugs work by slowing down a biochemical cascade and it doesnít make a lot of sense to slow that cascade down every now and then. Especially since most of your patients are afraid of medicine. They really are. They arenít hot drug takers. They are scared to death of medicine. So what you should do is tell them to take it around the clock - every four hours, every six hours, every 12 hours depending on what youíre taking - for x number of days. And you determine what x is. Thatís the time when you think this condition should start resolving. When you do that theyíll get the benefit of the analgesia and the antiinflammatory effect of that drug and theyíll do much better. Then, after x number of days have passed, they can start taking it p.r.n. The acute guideline said that strong opiates such as morphine is what we should use for severe pain. Not Vicodin. Morphine or other strong opiates. They said that Dilaudid is the best morphine alternative. They may not say that now. I think that OxyContin would have replaced that now. But meperidine use is to be 

The cancer pain guidelines are very similar. Now the chronic pain guidelines are being developed and in many aspects the chronic non-malignant pain guidelines are going to be little different from the cancer pain guidelines. In the pharmacologic use of the drugs thereís practically no differences. But look at the similarities. All mild to moderate pain therapies should include an NSAID or Tylenol unless itís contraindicated. Use these as chronic pain guidelines. You add an opioid if pain persists or increases. If the patient is already on an opioid change from a weak one to a strong one, or change from a strong one to more of a strong one. And I never cease to never to just totally not understand the tremendous fear that we seem to have towards opiates. One of my colleagues on the faculty came to me two weeks ago. His wife had developed shingles. Fortunately they are in their 30ís because if they are in their 50ís this would be a horrible problem. She developed ocular shingles and at first they thought the problem she was having was related to her history of Bellís palsy. But it turns out to be shingles. The shingles were resolved but now she has incredible pain. And this is severe pain. She went to a physician who gave her an NSAID. And NSAIDís donít work for severe pain. Shingles pain is severe pain. Went back to the physician. The physician gave her Lortab 10. Thatís hydrocodone and acetaminophen, 10 milligrams of hydrocodone. And after a week she said it took the edge off a little bit so the physician prescribed her Lortab 5, take two at a time, which is basically the same thing. I told him what the contemporary therapy of shingles is. Itís strong opiate, antidepressant because itís a neuropathic pain. The physician gave them OxyContin 

Chronic pain guidelines say that opioid tolerance and physical dependence do not equate with addiction. They are expected. But they are very easily dealt with in 95% of the people, and why should we brutalize the 95% because of our fear of the 5%?

Pain is really deadly. Pain can cause a number of horrible problems for our patients. Poor wound healing, muscle weakness, tissue breakdown. In acute painful conditions patients wonít do deep breathing exercises. They wonít move around in bed so they are going to be at increased risk of thromboembolic events.

We donít really understand the patients. You know, they donít choose to be in pain. It rips apart every fabric of their life. By the time they seek medical attention - and itís the most common reason a patient walks into your office, itís the most common reason a patient walks into a drugstore and asks the question.

Now, you also tell them, "Iím not going to permit any illegal activity in regard to drugs and in order to do that Iím going to occasionally do urine drug screens." They agree that you have their permission in regards to medication use and the law to report any illegal acts to the police. So when you get one of these patients in whoís been using a lot of Vicodin and their urine drug screen says thereís nothing in there, you must notify the police that you have a probable seller. Because thatís what you have.

The concept of co-analgesia is one that we often forget. Tylenol is a pretty mild analgesic. Codeine is even milder. Codeine is less analgesia than Tylenol. But when we combine the two of them together we get a pretty good analgesic. Think how much better it is to add Motrin to morphine. When I get consulted by physicians or others for pain management questions, with severe pain, the thing I do most often is not increase the opiate dose - because the kind of people who are calling me up have 

Darvon itself has a 13-hour half life and what you get from a single dose study of Darvocet is Tylenolís activity. You have to take Darvocet for a couple of days in order for the propoxyphene component to reach steady state and be a reasonable analgesic. And it is. Itís a reasonably good analgesic for those patients who understand that Darvonís metabolism is saturable, which most of your patients have figured that out. And if you take twice as much as the doctor orders it works a hell of a lot better. Thatís why most of your patients who get prescriptions say Darvocet in 100, one tablet every four to

We have an injectable non-steroidal now. It is really potent, the injectable. The oral product isnít nearly as potent but it is so potent there are a number of caveats. If you give this drug to patients with a history of GI bleeding, they will bleed just as sure and night follows day. This drug has killed a lot of people who had a history of GI bleed, who got the drug. We had one patient die in our institution. They were given a 60 mg - it was a 70-year-old patient with a history of GI bleed - was given a single dose

Remember, the oral is only a 10 mg tablet and the reason it is only a 10 mg tablet is because we know that although even not all that is absorbed, is the side effects are so great they couldnít market more than a 10 mg tablet. I donít suggest you use it. Now there are some patients with migraines who respond very well to this, so the question I get asked very often by primary care

The risk for NSAID-induced bleeding is related to their risk for peptic ulcer disease. So your patients who smoke, your patients who drink to excess have a much higher incidence of getting NSAID-induced renal dysfunction or gastrointestinal dysfunction than others.

A word about Tylenol. In a two year period 300 patients were see in 13 major transplant centers who presented with acute liver failure. Now not everyone with acute liver failure makes it into a transplant center. The patients who most often died were patients who were taking Tylenol therapeutically. Not suicide attempts. The most common cause of that renal failure was Tylenol and those who most often died were the patients taking too much, trying to eliminate pain. Did you know that Nyquil has a gram of Tylenol in it? Most of your patients donít. So they take some Nyquil, they take some aspirin-free Excedrin, they take some Tylenol PM for leg cramps and you give them Vicodin, and since you gave them Vicodin for severe pain they are

Ultram is an interesting drug. Itís one drug, two mechanisms which is really unique. One of them is an opiate-like mechanism. The primary mechanism is a serotonin re-uptake inhibition. And itís an analgesic. Now the serotonin re-uptake inhibiting antidepressants, Prozac and Zoloft and whatever, are not analgesic and cannot be used for the treatment of neuropathic pain. But this drug works slightly differently. Nobody understands it yet - or if they do, I havenít read it - but this is an analgesic. The

The antidepressants, these antidepressants, work very well for neuropathic pain which is described as stinging or burning. The anticonvulsants work for the pain that really involves nerve invasion. Most often seen in cancer pain but sometimes seen in acute accidents. This pain the patients describe as "Stabbing" and itís often accompanies by mild clonic jerks. You have to use therapeutic doses of the anticonvulsants, you have to use significant doses of the antidepressants. Twenty-five mg of Elavil for example, rarely works. Seventy-five works much better.

And we are really afraid of opiates. Your neighbors are afraid of opiates. The people you go to church with are afraid of opiates. We canít change their irrational fears but there is something that I want to suggest to you that will really increase the compliance of your patients in taking the medications you prescribe. Patients are afraid of narcotics. Cocaine - Iíd like you think of it this

We have other strong opiates. We have short-acting strong opiates, Dilaudid, Demerol, morphine and OxyContin we have long-acting strong opiates, topical Fentanyl, Levo-Dromoran, methadone, sustained release morphine and sustained release OxyContin.

I need to explain to you about opiate potencies because I know, if you have been paying attention at all to what the drug company salesman has been saying, itís confusing. Because they all have a different story. The FDA, when they assess opiate potencies, they do it very differently than any other drug. They take the super, the little 5% sample. That says the drug is super-potent and they use it. First of all, they donít want to get screamed at by some senator running for election next year, they want to do no harm and they are absolutely convinced that if itís not enough you are going to change the dose tomorrow anyway. They donít know that the patients donít tell you itís not working, they increase it on their own or whatever. And the drug companies love this because they do their pricing based upon the cost of the other guys therapy. My proof? When Nalbuphine was introduced, it says Nalbuphine is milligram for milligram as potent as morphine. Well, it is as a sedative, but as an analgesic it takes 1 Ĺ to 2 times as much. Same thing with Butorphanol. They said 2 mg equals 10. Doesnít. Takes 3 to 4. When meperidine was introduced it says 50 mg of Demerol equals the analgesic potency of 10 mg of morphine. Wrong. Takes 100. Fentanyl patches are twice as good as Jansen says they are. And Purdue-Frederick is now saying that OxyContin is twice 

Hydrocodone: youíve heard me take a couple of shots at Vicodin. Now Vicodin is an excellent drug, it really is. Vicodin now is combined with ibuprofen and Vicoprofen. These are real good analgesics. If was going to take something like that I would much prefer to take Vicodin than Tylenol with codeine because I think itís a much better analgesic. The problem is that physicians as a group - Iím not talking about you individually - are afraid to write schedule II prescriptions. You are. You will go through all kinds of mental gymnastics to convince yourself that you can write a schedule III or that the patient doesnít need a schedule II. With severe herpes pain, you canít treat it with a moderate analgesic. So what happens is you write Vicodin when the patient needed morphine or oxycodone. The patient takes the Vicodin, it 

Methadone is a great analgesic. Tricky to use. We used to use it a lot for cancer pain before we had the controlled release forms of morphine available. We seldom use it now, in fact, most teaching hospitals avoid it like the plague because itís so tricky to use

This is the problem with meperidine. At therapeutic doses itís toxic. The therapeutic dose of meperidine, the amount designed to relive severe acute pain, in 2/3 of the instances is 100 mg every three hours. The drug only works for three hours. I know - unless you are really unusual - if you write meperidine you write 50 to 75 mg every four to six hours p.r.n. pain. If the patient

Levo-Dromoran is a good drug. We donít use it that much anymore because we have sustained release products. Oxycodone, the opiate in Tylox and Percocet, Percodan, is really good. Again, if you are using those products use enough peripheral analgesic. Thereís only 300 mg acetaminophen in a Percocet. Thereís only 225 aspirin in a Percodan. We have a controlled

Morphine is the gold standard. This is what we measure everything else against. The sustained release products are called the most effective and