Archive for the Cancer Treatment category.
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 can’t 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 – I’d like you think of it this way – from this day forward, marijuana is a narcotic, heroine is a narcotic, cocaine is a narcotic. All the things you prescribe for severe pain are opiates. Opiates are medicine. It works. I know it sounds hokey, but it really does work. Refer to them as opiates. Opiates are medicine. Taking medicine the way your physician prescribes it is called compliance, not drug abuse. And you need to tell them that too. “It’s really important that you follow my advice.”
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.
This is the hierarchy of effect when you give a patient a strong opiate. The only guarantee is constipation. You must have a reflex. You must never write for a strong opiate without writing for a stimulant laxative and a stool softener. Opiates cause constipation by three mechanisms, two of which we can affect with drug therapy. One of the mechanisms that we cannot effect is that it alters enzymatic action in the bowel. I increases the resorption of water from the bowel and it slows motility. So we have to give them a drug that increases water retention in the bowel and a drug that stimulates activity. Analgesia is the second most common event. If I, right this minute, gave each of you a 10 mg dose of opiate, a 10 mg dose of morphine, the most predictable outcome would probably be vomiting, but the most common event would be dysphoria. For patients without pain almost all of them find opiates unpleasant. They don’t make you feel good.
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, it’s 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 don’t 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 it’s not enough you are going to change the dose tomorrow anyway. They don’t know that the patients don’t tell you it’s 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 ½ to 2 times as much. Same thing with Butorphanol. They said 2 mg equals 10. Doesn’t. 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 as good as morphine. I don’t think so. I think it’s 1 ½ times.
What I suggest however, is that you use those conservative potencies but understand that on day two you need to get a report back from the patient on how they are doing and adjust the dose based upon t he patient response. Because about 10% or so will respond to those lower doses. About 80% will respond to a higher dose and 10% will need a much higher dose. Remember there’s a 10% over here that needs lower doses, there are people who are going to need higher just because it balances out the human response curve.
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 don’t. 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 taking about three times as much as you ordered because that’s the dose that works. So they are throwing down 15, 20 grams of Tylenol. Now the problem is, what the textbooks say about Tylenol toxicity is this, and these are two sentences one right after the other. It says, “Doses of Tylenol above 4 grams a day are implicated with liver toxicity. Reports of toxicity at daily doses below 10 grams are rare.” So the first dose says if you use more than 4 grams a day, you’re wrong. The second dose says, probably ain’t going to hurt. Guess which sentence the lawyer is going to bring out? I mean, if Tylenol were really so toxic that more than 4 grams a day would cause liver toxicity, I would guess that we would all have had a transplant by now.
Ultram is an interesting drug. It’s 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 it’s 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 haven’t read it – but this is an analgesic. The advantage is that is does not inhibit prostaglandin synthesis so you can add this into the therapy of your arthritis patients who are very uncomfortable and in whom you cannot increase their NSAID’s anymore. You can add it into the therapy of your fail-back patients, your chronic pelvic pain patients. You can add this into the therapy. Now this is not a great analgesic. As an analgesic it’s about as good as Tylenol with codeine. So you can’t take your patients on Tylox and switch them over to this drug because they are going to hate you. Because it just isn’t that good. It’s indicated for the long-term treatment or the intermediate treatment of moderate pain, or moderately severe pain. The reason it’s indicated for the intermediate or long-term treatment of pain is two-fold. One, it takes several days for it to start working effectively, but two, if you start people out – one tablet four times a day – about 40% of them are going to get distressing side effects. But if you titrate them up slowly – one tablet today, two tomorrow, three the day after and four on Monday – then they will respond much better. There is an indication in the literature that this drug can lower the seizure threshold so you should be cautious in using this drug with other drugs that lower the seizure threshold. Although it’s a tiny risk, I know a lot of people who are on this drug and are on amitriptyline or who are on Prozac who don’t have problems. This drug will not cause a psychological dependence. Absolutely, positively will not. But if the patient has a history or psychological dependence on opiates this drug will reactivate it. So this is not a drug you want to give to the patients who you know are recovering addicts or recovering alcoholics. If they are recovering and they know about this drug, they don’t want to take it.
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 it’s 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.
Darvon itself has a 13-hour half life and what you get from a single dose study of Darvocet is Tylenol’s 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. It’s a reasonably good analgesic for those patients who understand that Darvon’s 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. That’s why most of your patients who get prescriptions say Darvocet in 100, one tablet every four to six hours p.r.n. pain, number 50. Come back to the drugstore in five days asking for a refill. Because they figured out that 10 a day works really good for moderate pain. Of course that’s six grams of Tylenol, which means I get another consultation sometime down the line to talk about the likelihood of liver toxicity from 6 grams of Tylenol a day. So this is the activity.
We have an injectable non-steroidal now. It is really potent, the injectable. The oral product isn’t 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 in a surgical center, not associated with us. Came into the emergency room about 14 hours later and frank GI hemorrhage. Took him down to the operating room and he died. If you give this drug to patients with a history of renal dysfunction you will be absolutely amazed at how fast their creatinine rises. There are reported instances in 20-year-olds with moderate renal dysfunction, of the creatinine clearance going to 0 within a three or four day period following a single dose. But it’s a good dose for people who are younger and have healthy kidneys as long as you don’t use it for longer than five days. Because after more than five days therapy the incidence of renal dysfunction or GI bleeding starts rising dramatically. Almost logarithmically. The oral product says you may only use it after the patient has had a parenteral dose. What that means is, the reason for that, is there is a very high incidence of anaphylactic reaction to this dose. It’s a first-dose phenomena with this drug and they want to make sure that if the patient is allergic to the drug that they get that allergic reaction in your office, in your clinic or in the hospital, not in their living room. Now if the patient has had the drug before, no problem.
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 couldn’t market more than a 10 mg tablet. I don’t 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 practitioners is, “You mean, I have to tell this patient they can’t have this drug anymore?” I say, “No, I don’t think so.” Because the problem is with more than 5 days of consecutive use, you tell the patient take it when you have a migraine and then stop and you can’t take it again for 4 or 5 days, then they are going to be safe. Because pharmacologically they are starting over each time. And they should be relatively safe. Although I would make sure you do assessments of renal function and you occasionally make sure they are not having any indications of GI bleed. If you have migraine patients taking this drug all the time, and you’d better write those prescriptions indicating that that’s how they are to do it. If you write take as directed and I’m the pharmacist, I’m not going to fill it because I don’t want my neck on the chopping block either.
We notice that the elderly that don’t complain as much. They don’t appear to be as frustrated, they don’t appear to be as anxious, don’t appear to be as angry. They have different expectations. Most of the elderly patients we are dealing with now survived World War II, many of them have vivid memories – at least from their parents – of the depression. They think you are supposed to be in pain. That’s just the way life is, so they are not really frustrated by this. They don’t understand that we have the capability to relieve all that. And very often they are afraid. They are afraid of tests, they are afraid of the meaning of the pain. They think you are doing everything you can and they desperately want you to like them. Patients desperately want to be liked by their physician. So they are not going to do anything that makes you think that they think you are not really good. Unfortunately this is true. Sometimes they think that they will be punished for reporting the pain and that happens to a distressing frequency in some extended care facilities.
How many of you recall seeing, about two years ago, a report on 60 Minutes and they ran it twice, about a physician in Maryland who lost his license for prescribing Dilaudid for chronic non-malignant pain patients? Anybody remember seeing that? Right after that aired – and it was a wonderful story – they actually had interviews with two of his patients who had chronic non-malignant pain and one of them, between the time the segment was taped and the time it was aired, killed himself because this physician lost his DEA license. He could no longer prescribe opiates and these patients couldn’t find anybody else who would give them opiates for the chronic non-malignant pain, and one of them committed suicide. It was a very sympathetic portrayal.
If you have a physical exam in your chart, if you have a history that documents why you are doing what you are doing, you have progress notes that measure outcomes and measure pain – simply, how is the pain? “It’s a seven. It’s a five.” And measuring activity levels. “Have you increased your activity level any? Have you done anything else?” All that and an accurate record of the prescriptions you have written, makes you fireproof because you are practicing medicine.
Now, you also tell them, “I’m not going to permit any illegal activity in regard to drugs and in order to do that I’m 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 who’s been using a lot of Vicodin and their urine drug screen says there’s nothing in there, you must notify the police that you have a probable seller. Because that’s what you have. Now you have to insist that no other physician writes for controlled substances without your permission and knowledge. That all of their medications get filled by one pharmacy. You don’t care who, but you’ve got to know who. And the pharmacist is going to get a copy of the pain management plan. And trust me, they will let you know if someone calls in on a Saturday night with a refill, or a Thursday afternoon, and they will let you know if there are deviations from that plan.
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 heard me talk and are using plenty of opiates generally – what I usually do is add a co-analgesic and maybe change the intervals slightly. Co-analgesics. Now it doesn’t make any difference which NSAID you use. There is tremendous inter-patient variability and we have no idea which one is going to work. So what I suggest you do – I mean, we have to do sequential trials to figure it out, but where do you start? Well, where you start is ask the patient if they have ever had any NSAID’s that worked well for them as analgesics. If you get a positive response, use it. If you don’t, use the one that you are most comfortable with because you know it. If that doesn’t work, use your second choice. You ought to have three. If that doesn’t work, try your third choice. There is no structure activity relationship in the NSAID’s. They are just tremendous inter-patient variability. And intra-patient variability.
We don’t really understand the patients. You know, they don’t choose to be in pain. It rips apart every fabric of their life. By the time they seek medical attention – and it’s the most common reason a patient walks into your office, it’s the most common reason a patient walks into a drugstore and asks the question – but by the time they’ve seek professional advice they’ve already tried everything in their medicine cabinet, and in many cases everything in their neighbors and relatives medicine cabinets. They’ve tried everything they’ve ever seen advertised on television and increasingly they have tried everything some 19-year-old kid in the general nutrition store has told them is good for pain.
But more importantly, they’ve assigned a meaning to the pain. They’ve assigned a meaning to the pain. Now this meaning is a belief – and you have to understand that, because when you tell them what the pain means that doesn’t change the belief. You can’t change a belief by telling them once. So all their actions, all of what they do, all of their beliefs, all their behaviors are based upon the meaning they have assigned to the pain. This is what you see in your chronic non-malignant pain patients. All of their beliefs and these are beliefs. You can teach them that their beliefs are wrong but it’s just a little bit easier than teaching a teenager that wearing corduroys is cool when nobody else is wearing corduroys. It just isn’t that easy to change a belief. And this is what’s going on inside their mind. You know, terrible things are being done therefore worse are threatened. The outside forces are in control, the will is helpless. They cannot will this away. They can’t function. There’s all kinds of things that they can do. Since no one has been able to give them any time limit on when this is going to end – or they have no perception that it’s getting better – the only logical conclusion is, it’s going to go on forever. “Until I die.” And it will probably get worse and worse each day.
And the pain is meaningless, but more importantly, they focus all of their energies on things that make the pain less or they talk about the pain, or they avoid all behaviors that might exacerbate the pain. So they focus everything on themselves. And chronic pain patients are not likable. Even people who love them do not like them anymore. They really don’t. They are just not likable. And you thought you were being bad people because you can’t stand these patients. Nobody can stand them. They really can’t and it’s because the pain is their entire world. Now I know there is a percentage of patients for whom the pain has a lot of secondary gains and all that. I don’t have time to talk about all that psychosocial stuff. I’m just talking about those patients for whom we can do effective drug therapy.
And we don’t understand the elderly. You were probably taught that the elderly are less sensitive to pain. Now what that experiment was, was they used thermal probes and they had a group of patients, old and young and whatever, had their hand on a plate and have a thermal probe and very slowly they lower the thermal probe down. The patients are told, “Take your hand out when you can’t stand it anymore” and the elderly patients took their hand out much later than young people. You know what young people is? That’s people your age. I’m young. Inside I’m 34. But those probes were like at about 150 degrees. If you change the temperature of the probe to 400 degrees the age-related differences disappear. If the temperature of the insult becomes really dangerous there’s really no difference between the point at which a 90-year-old pulls his or her hand out and a 16-year-old pulls his or her hand out.
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 there’s practically no differences. But look at the similarities. All mild to moderate pain therapies(soma) should include an NSAID or Tylenol unless it’s 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 30’s because if they are in their 50’s 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 Bell’s 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 NSAID’s don’t work for severe pain. Shingles pain is severe pain. Went back to the physician. The physician gave her Lortab 10. That’s 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. It’s strong opiate, antidepressant because it’s a neuropathic pain. Went back to the physician. The physician gave them OxyContin which is what I suggested they talk to the physician about. Ten milligram tablets. It probably isn’t enough, but start at this. Ten milligram tablets once a day. They work for 12 hours. The pain is now successfully being treated. Now this is a patient who is never going to be addicted, she’s going to be physically dependent when she finishes the treatment for her herpes, or the secondary pain from the herpes infection that she had. But physical withdrawal from opiates is not a problem. It just is not. Even if we didn’t have Clonidine to block all the symptoms, most patients don’t want to be on opiates anyway.
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%? The oral route is preferred. It’s the most convenient. It’s the most cost effective. Rectal and transdermal should be reserved for patients who fail the oral route. This is an unbiased panel. And fail the oral route means that you’ve given them really adequate doses and they can’t absorb it or they can’t remember to take it often enough and it just doesn’t work.
Motrin
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 won’t do deep breathing exercises. They won’t move around in bed so they are going to be at increased risk of thromboembolic events. They won’t do deep breathing exercises, they splint, they breathe shallowly so they are at greater risk for atelectasis and pneumonia. A number of other physiologic events occur and there are immunological factors. It decreases NK killer cells activity, causes negative motions, anxiety, depression, sleep deprivation, and over time then pain, especially chronic pain, can lead to tremendous suffering. If you don’t think we should get actively involved in physician-assisted suicide, you are totally in control of that. Now I was a hospice pharmacist for 13 years. And I know that no one wants to live more than people who know that the end is approaching if we can make them comfortable. And you have the resources. Ninety to 95% of painful conditions can be treated by tools that you commonly employ and have available to you. I’m not talking about intrathecal therapy, I’m not talking about epidural therapy, I’m talking about oral drugs that you are capable of prescribing; 90% to 95% of painful conditions.