OPIOID MEDICATION

OPIOID MEDICATION

OPIOID MEDICATION

Dr. S. A. Andreae-Jones MB BS

DEFINITION:

The term opioid refers to any drug , natural, semi-synthetic or synthetic compounds which act on opiate receptors in a similar way to opium. Opiates are natural or semi-synthetic drugs. They may also be known as narcotic drugs.

HOW DO THEY WORK?

The body has its own opiates which are called endorphins. These act on opiate receptors predominantly affecting the central nervous system and the smooth muscles of the gut.

Opiate receptors responsible for pain are divided into µ1, µ2(mu 1 and 2) , d (delta)and k (kappa) types. Genes encoding for these receptors have been cloned. More recently other types have been found (sigma and epsilon).

Opioids can be classified as agonists, antagonists, partial agonists or mixed agonists/antagonists:

Agonists -- are agents that can combine with receptors and initiate events.

Antagonists -- are agents that combine with receptors and inhibit the effect of agonists

Partial agonists -- have characteristics of both agonists and antagonists -- at times appearing to cause actions and other times to decrease the effect of agonists with greater intrinsic activity

1. Full Opioid Agonists: Morphine, Heroin, Methadone, Meperidine, Fentanyl, Hydromorphone

2.Agonists of Lesser Potency: Codeine, Oxycodone and Propoxphene

3.Mixed Agonist/Antagonists and Partial Agonists: Pentazocine, Nalbuphine and Buphrenorphine

The third category are important to remember because if you are on one of the stronger agonists such as morphine, and then changed to buprenorphine, you may experience some withdrawal symptoms(including pain) because buprenorphine partly works against (antagonises) morphine.

Similarly, if you were to be given a drug called naloxone, you might be precipitated into withdrawal as this drug is a full antagonist which opposes the action of morphine and other opiates.

METABOLITES:

Morphine is broken down by the liver(“first pass metabolism”) into metabolites morphine-6-glucuronide(M-6-G) and morphine-3-glucuronide. M-6-G is considered to be the active metabolite ( i.e. the one that acts on the receptors) The metabolites are excreted from the body via the kidneys into the urine. It is possible that M-3-G may be implicated in hyperalgesia.

THE CONTENTIOUS ISSUES:

Using opioids in chronic non-malignant pain has been regarded in some medical quarters as highly contentious. However, in the past 5 years, this practice has started to become more widespread.

Authors such as Dr. Russell Portenoy have paved the way in encouraging a new approach to this problem.

In 1999, a study at the San Francisco Spine Institute by J. Schofferman([i]) looked at long-term opioid treatment for “severe, refractory lumbar spine pain” and concluded that this form of therapy was appropriate and useful for some patients, but noted that “this therapy is a serious commitment, probably for life.”

Schofferman also stated that “the major barriers that deter physicians from using long-term opioids for chronic non-malignant pain are the question of efficacy, and the perceived risks of tolerance, systemic toxicity, addiction, and sanctions. None of these perceived risks were a problem during this study.”

1. Addiction: refers to psychological dependence: a condition characterised by a pattern of compulsive behaviour and overwhelming involvement in acquiring a drug for non-medical purposes e.g. for psychic effects as opposed to pain relief. In other words, addiction involves a pattern of behaviour that includes compulsive use of opiates and a preoccupation with obtaining them, despite evidence that continued use results in physical, emotional, social or economic damage. Chronic pain patients may sometimes be labelled as addicts when they repeatedly seek opiates as a result of inadequately treated pain: they are in fact “pseudoaddicts” as their behaviour may be suggestive of addiction but is entirely motivated by a need for pain relief. In reality, there is plenty of evidence that pain patients very rarely develop addiction. Physical dependence is a term meaning that if the drug is discontinued or the dose reduced, then withdrawal symptoms will be experienced . It is due to the body becoming accustomed to the drug. Virtually all patients who take opioid analgesics will develop physical dependence to some degree and will experience withdrawal symptoms if the drug is suddenly discontinued.
2. Tolerance: this means the need for increasing doses to achieve the same effect: a common feature if opiates are being used for recreational purposes. In pain patients, tolerance to adverse effects such as sedation and nausea develops readily within a couple of weeks, but it appears that tolerance to the pain relief does not. A need for escalating doses of opiate is therefore more likely to be related to the condition that is causing the pain. When tolerance does occur, the patient tends to notice that the duration of pain relief becomes shorter and they experience an increase in pain.
3. Respiratory depression and other side-effects: Respiratory depression is the most serious adverse effect of opioids as it can be immediately life-threatening. However, it is now recognised that it only tends to be a short-lived problem in patients who have never had opioids before (are “opioid naïve”) and that pain itself antagonises it.(pain is a respiratory stimulant). Side-effects such as sedation and nausea tend to subside within a couple of weeks. Constipation is the most common long-term side-effect but can often be managed fairly simply. Long-term use does not carry risks such as those with Non-steroidal anti-inflammatory drugs (NSAIDs): these are known to cause liver, gut and kidney damage. Opiates do not cause this kind of “end-organ damage”.
4. Opioid responsiveness: neuropathic pain has been regarded as “opioid resistant” but it has now been found that it can respond provided that high enough doses are used. Patients may be labelled as “unresponsive to opioids” unless there has been an adequate trial of opioids with properly titrated doses as well as adequate time for tolerance to adverse effects to develop.
5. Chronic pain of unknown origin: clinicians have tended to label patients whose diagnosis is unclear as suffering from psychological problems. This can lead to patients who are experiencing understandable distress and possibly depression as a result of being in chronic pain, being reluctant to admit this to their doctor. Pain specialists generally acknowledge that depressive symptoms accompanying chronic pain are likely to be a secondary effect of the pain itself rather than the reverse, and true primary psychological pain disorders are very rare.

SUMMARY OF IMPORTANT POINTS:

1. Physical dependence is not the same as addiction (substance dependence syndrome)

2. Tolerance and physical dependence are both part of the body’s adjustment to the presence of drug.

3. `Addiction’ rarely results from misuse of prescribed medication.

4. It is rare for physical pain to be due to a psychological problem.

CAUTIONS:

Situations where great caution should be used as regards opioid use:

i. Respiratory problems: asthma, emphysema

ii. Decreased blood volume (hypotension)

iii. Biliary colic

iv. Liver disease

v. Impaired kidney function

vi. Opioids may aggravate pre-existing convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels (because of tolerance) convulsions may occur in patients who have no previous history

DRUG INTERACTIONS:

1. Cross-tolerance with other opioids: this means that if one drug, say, morphine, is changed to another, say oxycodone, then there will be some tolerance to effects such as nausea, sedation etc. but this is not a complete tolerance and the differing strengths of the drugs must also be borne in mind. Most doctors tend to start with one half the dose when switching to another opioid agonist. Switching to a partial agonist or a mixed agonist-antagonist may precipitate withdrawal in a patient who has previously been maintained on a full opiate agonist.

2. Central nervous system depressants : sedatives, hypnotics ,tranquillisers, tricyclic antidepressants (such as amitriptyline) and alcohol: these drugs can have a potentiating effect on the sedation and respiratory depression due to opiates.

3. Muscle relaxants: opioids may enhance the neuromuscular blocking action of skeletal relaxants and produce an increased degree of respiratory depression.

4. Monoamine oxidase inhibitors (MAOIs) : possible increase in confusion, anxiety, respiratory depression. Opioids are not recommended for use in patients taking MAOIs or within 14 days of stopping them.

5. Diuretics: opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone (Adh).

6. Food: the bioavailability of opioids is generally not affected by food intake EXCEPT grapefruit juice: this was investigated by Johns Hopkins University some years ago to see if it could be developed as a potentiator as it can dramatically increase the availability of opioids : however, it is highly unpredictable so not advisable to try at home!

7. Analgesic effect of opioids is enhanced by: chlorpromazine and methocarbamol.

ORAL MEDICATION:

Oral opioids can be very effective in treating pain. The World Health Organisation (WHO) states that analgesics should be administered by the oral route, whenever possible.

They should be given “by the clock” at regular dosing intervals and not on an “as required” basis, which tends to result in maximum side effects and minimum analgesia. Irregular intervals and insufficient dose are likely to lead to the pain returning repeatedly and the patient constantly seeking higher doses.

It must be remembered that only about 40% of the administered dose of some preparations will actually reach the plasma due to “first-pass metabolism.”

Commonly used opioids include morphine, hydromorphone, codeine, oxycodone, hydrocodone, methadone, levorphanol and fentanyl. These opioids are classified as full agonists (see above)

They do not have a ceiling to their analgesic efficacy and will not work against the effects of other opioids within the class when given simultaneously. The term ceiling effect refers to a dose that if increased will produce no change in effect. There is no maximum recommended dose for full opioid agonists (except in opioid-naïve patients) so the dose can continue to be titrated up according to pain level and side-effects to very high doses if necessary.

Short-acting opioids should not be given chronically on a daily basis in most cases as there is a higher incidence of side-effects and development of tolerance.

Moderate pain can also be treated with an opioid/ non-opioid combination. However, it may be better to treat with just the opioid so that it can be titrated without having to worry about exceeding maximum daily dosages of non-opioids, for example the maximum daily dose of paracetamol(acetaminophen) = 4000 mg daily.

Generally, when opioid therapy is commenced, the necessary dose is established by using short-acting preparations. However, the majority of patients on long-term opioids are maintained on long-acting preparations such as MS Contin. These allow a steadier plasma level of the drug to be maintained and also reduce the number of tablets that need to be taken.

As a rule, it is best to begin treatment with a low test dose, to avoid serious or intolerable side-effects. Should these arise, an alternative opioid may be tried. If the initial dose is ineffective, then a second dose 3-4 hours later, say 50-75% higher may be attempted. If the second dose is ineffective (but tolerated) a further increase of 50% 3-4 hours later is tried. With each dose, the pain level and side-effects should be recorded.

Once pain relief has been achieved, the relevant dose may be repeated at 4-6 hourly intervals. There may be some adjustment necessary depending on effectiveness and side-effects. In general, short-acting opioids reach a steady state (stable plasma level) after about 48 hours.

After becoming accustomed to short-acting opioids, it is possible to move onto longer-acting preparations. If methadone is being used, doses should only be increased every 3 days as it is very slowly metabolised and may otherwise accumulate to dangerous levels.

TROUBLESHOOTING:

“Opiate-induced neurotoxicity” is a syndrome of delirium, hallucinosis(hallucinations), myoclonus(muscle jerks)/seizures and hyperalgesia(increased pain) which may occur at higher doses.

Myoclonus (muscle jerks) may be seen with high dose opioid therapy. Myoclonic jerks are brief, involuntary jerks which may be severe enough to be painful. They are not the same as muscle spasms, which tend to be more sustained.

Paradoxical pain can occur at high doses; this means that there is an increase in pain which may be actually reduced by decreasing the opiate dose. I know of one man who had escalating pain levels that could not be controlled by increasing doses of opiates: but once the doses were significantly decreased, he actually improved considerably.

Opioid rotation/switching may be helpful to manage these problems. This is simply exchanging one opiate for a different one, when the side-effects of the original opiate have become intolerable for the patient.

Movement-related pain or “incident pain” is particularly difficult to treat, but recently a new innovation, the Fentanyl lollipop has been of some help with this. However, another type of incident pain, which is intermittent and unpredictable (being unrelated to exercise or nursing procedures etc.) is extremely problematic. Often it is necessary to tackle this kind of pain using other types of medication (such as anticonvulsants, which will be covered in a later article).

Breakthrough pain occurs when the medication doses are insufficient to control the pain and it “breaks through”. Usually the dose needs to be increased to provide adequate background pain control, but sometimes a short-acting opioid may be used in addition to the long-acting one. This may be termed a rescue dose, or supplemental or breakthrough dose. Breakthrough pain may come on suddenly or gradually and may be brief or prolonged. Some episodes are spontaneous and others are associated with an identifiable precipitant, such as stress or a change in the weather. Whenever possible, the rescue dose should be the same opioid and route as the around-the-clock(ATC) drug (e.g. use oral immediate-release morphine as rescue for controlled-release morphine). The formula for calculating the rescue dose range is one tenth to one sixth (10%-15%) of the total DAILY dose. For example, if taking 30 mg of MS Contin (oral morphine) twice daily, the calculation is : 30mg x 2=60 mg/day. 60 ¸ 10 (1/10)=6mg. 60mg ¸ 6 (1/6)=10mg. The rescue range is approximately 6 to 10 mg of immediate release morphine every 1 to 2 hours PRN (as required)for breakthrough pain.

WHICH OPIOID TO USE?

Morphine is the standard opioid. Other preparations that are believed to act faster, have longer duration or are better tolerated as regards adverse effects, may in fact have little real advantage to offer.

Speed of onset and duration can only be altered by changing the route of administration. Immediate-release oral preparations take about 1 hour to work, whereas sustained-release preparations take 2-4 hours.

There is little appreciable difference between different opiates in speed of onset and duration of effect. There may be slight differences in adverse effects, though constipation is a side-effect of all opioids,

NMDA-ENHANCED ANALGESIA:

Clinical trials have established that a combination of morphine and dextromethorphan (an NMDA antagonist available in the United States over the counter as a cough medicine) is more effective than morphine alone. Phase I/II safety studies showed that adding dextromethorphan does not seem to compromise the safety of morphine nor enhance the addictive potential. However, MS:DM has a rapid onset with peak blood levels at one hour (like morphine sulphate alone) and on average, studies have found that patients experience satisfactory pain relief with half the dose of morphine, when using MS:DM, which is known as Morphidex. Trials have also shown that there is no increased incidence of adverse effects.

CCK ANTAGONISTS:

Animal studies have suggested that the anti-opioid peptide cholecystokinin (CCK) is implicated in neuropathic pain and that neural damage raises plasma CCK. Administering a CCK antagonist such as proglumide may render neuropathic pain more responsive to opiate medication. In addition, it has been found that in chronic opiate use, CCK levels may be raised which can work against the analgesic effect of the opiates, contributing to the tolerance that may develop; using drugs like proglumide may help to reverse this aspect of tolerance. CCK antagonists may therefore be useful as adjuncts in opiate therapy for neuropathic pain.

TRANSDERMAL PREPARATIONS:

Fentanyl: this drug can be administered via a patch on the skin. It is simple, non-invasive and allows continuous release into the bloodstream. In passive (conventional) transdermal administration, the patch is available in 4 sizes and provides sustained release of fentanyl at rates of 25,50,75 and 100 micrograms/hour for periods of 48-72 hours. The patch is attached to the skin using a contact adhesive, adjacent to which is a microporous membrane that controls the rate at which fentanyl is transferred from the drug reservoir to the skin. The reservoir is a shallow compartment with a gel matrix and may contain up to 10mg of fentanyl, in order to provide a high concentration gradient to facilitate diffusion across the skin. It has a backing to prevent escape of fentanyl. The skin layers act as a secondary reservoir and thereby dampen any fluctuation in fentanyl level. This also means that after the patch has been removed, there is a prolonged residual effect. Other disadvantages include slow onset time and inability to adjust the dose during the period of application. Side-effects tend to be the same as for oral opiates, and there may be slight redness around the site of the patch.

There is also a new type called the iontophoretic(active) transdermal system which enhances drug delivery using a skin electrode, a skin current returning electrode and an electric power source. However, this has yet to be used clinically.

TRANSMUCOSAL PREPARATIONS:

Again, fentanyl : oral transmucosal fentanyl citrate (OTFC) : this has been recently marketed as Actiq®. This is a lozenge on a stick which allows rapid absorption of fentanyl and onset of analgesia within 5-10 minutes. It has a duration of action of 2-3 hours. It is useful to treat incident pain, as it allows delivery of sufficiently high doses to cover the transient increase in level of analgesia needed without necessitating a sustained level that may be too high once the incident pain has passed (which would increase the risks of side-effects and tolerance). A single 800microgram dose is roughly equivalent to a single intravenous bolus of 10mg morphine in terms of speed of onset, duration and quality of analgesia.

INTRANASAL PREPARATIONS:

A group of German researchers are studying the use of a nasal spray preparation of fentanyl. This may be of help for movement-related pain.

RECENT NEWS:

In June 2000, news from University of California San Francisco(UCSF) suggests that kappa-opioids such as nalbuphine combined with naloxone, an opioid antagonist, whilst previously thought to be ineffective painkillers, have recently been found to be highly effective analgesic for moderate to severe pain with minimal side-effects, providing a significant alternative to morphine.

INTRASPINAL NARCOTIC ANALGESIA: THE PUMP(INA)

A NOTE OF CAUTION… Angel et al ([ii]) contend that the use of the morphine pump is a “viable alternative in the management of failed back syndrome” but suggest that “its use in long-term therapy, however, is not without its limitations and should be a last choice option.”

It is important to bear in mind that any invasive treatment may carry a potential risk of causing or exacerbating arachnoiditis (indeed, Medtronic list it as a complication.)

The Arachnoiditis Trust do not endorse the use of the pump on the basis of lack of evidence of long-term safety. The pump was developed to treat severe intractable pain in terminally ill patients and therefore longer term use was not an issue, nor was there the clinical opportunity to assess the safety of prolonged use. Chronic non-malignant pain is a lifelong problem, and use of the pump a commitment without foreseeable termination; in some cases, we could be dealing with 10, 20 or even 30 years using the pump. There is no published data to establish a safety record for that length of use.

Hodgson et al ([iii]) have discussed the neurotoxicity of spinal drugs as a central safety issue. They cite animal studies which have failed to show any evidence of histologic or physiologic toxicity. There have been limited postmortem neurohistopathology studies in cancer patients who received long-term continuous intrathecal morphine infusion. These have not implicated the drug (with metabisulfite preservative) in any histopathological abnormalities. However, there is a dearth of animal studies in the use of spinal meperidine, hydromorphone and fentanyl. Indeed, the authors note “fentanyl is notably absent from animal safety testing data.” Moreover, “controlled human safety data are also minimal with spinal fentanyl.” They conclude that “overall, most spinal drugs in clinical use have been poorly studied for spinal cord and nerve root toxicity.” Clinical use suggests that spinal opioids are safe but they recommend further research “to follow a systematic approach to determine potential neurotoxicity.”

Morphine is the standard drug used in INA, but other drugs include: baclofen( for muscle spasm), clonidine (an adjuvant), ketamine( a dissociative anaesthetic used as analgesic) and local anaesthetics such as bupivicaine.

INA is addressed in more detail in a separate article, and the use of non-opioid medication is described in articles about the relevant drugs.

MANAGEMENT OF SIDE-EFFECTS OF OPIOIDS:

1. Constipation: this common side effect may cause nausea, vomiting and abdominal cramps and if extreme, may produce overflow diarrhoea. A useful definition of constipation is: a decrease in the frequency of bowel movements, passage of hard stools that may be difficult to pass. As well as delaying gastric emptying, and stool transit through the small bowel, opioids decrease propulsive peristalsis, dry out the stool and may also affect the urge to defaecate. Prevention strategies include: (a) increased dietary fibre(e.g. high fibre cereal, apple sauce, prune juice, rhubarb); (b) increased fluid intake (c) adequate exercise if possible (d) adequate time and privacy for toileting. Several options are available to treat constipation: (a) osmotic laxatives (disaccharides and saline cathartics) Disaccharides exert an osmotic effect as they are not absorbed by the bowel, thereby increasing bulk, but they may cause cramps, abdominal distension and flatulence. Milk of magnesia, a saline cathartic, uses osmotic forces to pull fluid into the bowel to increase the weight of the stool and soften it. (b) emollient or lubricant laxatives : e.g. docusate sodium, glycerin suppositories. (c) bulk cathartics: increase the mass and soften stool e.g psyllium (Metamucil) (d) stimulant cathartics: these promote intestinal motility and may be given orally or rectally: e.g. senokot. They may cause painful cramping, but this can be minimised by giving small doses with each meal and a slightly larger dose at bedtime. (e) naloxone: has been found to be useful in opiate-induced constipation.. but it causes withdrawal symptoms as it is an opiate antagonist, so is not recommended. (f) combination preparations : e.g senna-S which is docusate+senna, a useful combination in narcotic-induced constipation. (g) enemas: may be necessary: breaks up and washes out impacted faecal matter. Should only be used sparingly. (h) Mestinon 60mg half-1 tablet 3-4 times a day may help : this drug is usually used to treat a condition called Myasthenia gravis and may also relieve dry mouth.

2. Sedation: (a) eliminate contributory factors such as non-essential drugs and metabolic disturbance; (b) reduce opiate dose if possible (c) add in an adjuvant such as an antidepressant in order to be able to reduce the opiate dose required (d) switch to a different opioid (e) consider more invasive methods

3. Mental clouding: cognitive impairment may be managed in a similar way to sedation. Confusional state may require low dose haloperidol.

4. Nausea and vomiting: persistent nausea is uncommon. Transient problems can be relieved by using agents such as promethazine, prochlorperazine, metoclopramide or hydroxyzine. A typical prescription might be phenergan 25mg every 4-6 hours. Stemetil can be taken buccally which allows rapid absorption if vomiting precludes usual oral administration. Hydromorphone and levorphanol seem to cause less nausea than other opioids. Severe nausea and vomiting may require rehydration with intravenous fluids and other causes need to be excluded. Treatment of constipation as a contributory factor may be required.

5. Fluid retention: swelling in the feet and lower legs is quite common. It may be due to fluid retention or to vascular dilatation caused by opioids. A low salt diet, restriction of fluid intake and possibly administration of mild diuretics such as Lasix may assist. ( these may cause some loss of potassium which might slightly increase symptoms such as muscle weakness, but can be avoided by eating plenty of fruit and vegetables, especially bananas)

6. Headache: opioids taken regularly may cause a daily low-grade headache known as “rebound headache.” They are of a vascular type, generally throbbing in the back of the head or forehead and temple region. In susceptible patients, migraine headaches may be triggered. Simple headaches may respond to mild analgesics such as paracetamol (acetaminophen) or aspirin whilst migraines may be prevented or aborted by ritalin.

7. Insomnia: this is a paradoxical effect of opioids. Using an opioid that causes sedation may overcome this: a sustained-release formula can be used at night. Some patients have benefited from using melatonin, which is a hormone involved in induction of sleep. Failure of these strategies may be addressed by adding in an anti-depressant medication at night such as trazadone(50-100mg) or nortriptyline(25-50mg). Use of benzodiazepines such as oxazepam, temazepam or diazepam should be restricted to short-term use (up to 2 weeks) only due to the high risk of dependence and tolerance. Use of caffeine early in the day to boost energy and promote daytime activity may help to encourage sleepiness at night.

8. Myoclonus: it is not a common clinical problem and is benign, but may be distressing for the patient. Measures such as clonazepam or valproate may alleviate the symptoms. If myoclonus is persistent it may be worthwhile changing to a different opiate. Of course, myoclonus may be a part of the underlying condition.

9. Pruritus: (itching): this rarely persists chronically and can be relieved by diphenydramine if it occurs during the initial treatment phase. Itching associated with a rash suggests an allergic problem and may indicate the need to change to a different opioid preparation.

10. Urinary retention: this is rare as a chronic problem due to opioid therapy and may be treated using bethanecol. Underlying neurological or urological problems are more likely to be the cause of this symptom if it is persistent.

11. Decreased libido: men may experience decreased libido and potency that can be relieved by supplemental testosterone administered orally or by injection.

12. Respiratory depression: generally not a significant problem as pain itself antagonises the respiratory depressive effect of opiates; however, if the dose is too high, it may occur. The least possible efficacious dose of naloxone is given in order to preserve analgesia and avoid withdrawal.

Withdrawal syndrome: if the medication is abruptly discontinued, anyone who has been taking opioids regularly is likely to suffer from : increased pain (plus hypersensitivity), generalised aches, cold sweats, restlessness, tremor, involuntary movements, dizziness, nausea, vomiting, diarrhoea, sneezing and yawning. Heart rate and blood pressure may rise. These symptoms usually occur within 8-12 hours of the last dose and are likely to peak at 48-72 hours. If it is proposed to discontinue opiate medication, reducing the dose gradually by 10-20% every 3-6 days may reduce the severity of any withdrawal symptoms. Clonidine 0.1-0.3 mg (1-2 tablets) every 6-8 hours may alleviate the symptoms (or it can be administered as a patch). Tranquillisers such as diazepam (valium) 5-10mg every 6 hours may reduce agitation and tremors.

EXPERIENCES WITH OPIOIDS:

“I took MS Contin 15mg q 12 hours post-op x 3 weeks…….although the medication alleviated the pain effectively, I suffered from visual hallucinations( I thought a hair barrette was a giant spider etc.), severe nausea, poor appetite, weight loss and extreme fatigue-also constipation! More recently I have been on a regimen of oxycontin 20mg q 12 hours….it helps to reduce pain levels to a tolerable ‘3-4’, however I am experiencing nausea and appetite loss along with malaise. I am not suffering from constipation - I try to drink 8-10 large glasses of water daily and eat high fiber foods - unlike the MS contin - I have had no further hallucinations!!”

“Over the last 36 years it has been determined that Morphine or any derivative of that I am allergic to: It makes me horribly sick to my stomach and I cannot keep anything down and getting violently ill to my stomach and vomiting. So the only drug I have able to say on is Demerol: I have been on this since the early 70’s. It started with 50mg twice a day ……………

I now am still on Demerol but 100mg, 5 times a day, Valium with it 5 mg., five times a day. This has maintained the pain especially the valium ……. For spasms but nothing I take works on the nerve pain. It just keeps it at a level of tolerance…….The downside of the medications are:

1. Constipation
2. Depression at times
3. Memory loss (big time over 30 years)
4. Personality changes ( I say this because I am not the person I was when I was in my 20’s. When you are completely dependent on medication to keep you sanity, the medication changes your personality over 30 years)
5. What bothers me the most I think is that we need to take these drugs and then are called addicts. I know this is not true, because if I am having a good spell I can cut the meds out for one or two days at a time without any shakes or things like that. But when the pain is bad it is really horrible.”

“I take the fentanyl patch. It has been good. The only side affect for me is stomache(ache)s. And for break through pain I take Percodan. I have only been taking them for about a year. So far so good. They only had to be upped once.”

“I take codeine by the name HYDR/ADAP5/500 - one tablet every twelve hours. When pain increases I take one tablet every eight hours. ( The codeine takes me down to a manageable level of pain. It is mildly fatiguing. No other side effects.) For pain flares my doctor has prescribed morphine sulfate 15 mg. every 12 hours. (The side effect is constipation and I must supplement with something very strong or the combining of several things for normal bowel function. Such as warm prune juice, a stool softener, and a laxative.) I find this side effect troublesome and though my doctor feels I should be on morphine all the time, I try to avoid it as much as possible because of it. I am always in pain but the level is reduced considerably with the opioids.”

I take “Norco (10mg/325), Hydrocodone. I have been on this now for a year. . I take Darvon-N-100 for breakthrough. He gives me Demerol 50mg for flare ups. I also take Ativan 3 times a day for spasms. How do they make me feel? Well most of the time I can’t even tell that I took them except that the pain has been relieved somewhat. I very rarely feel “high” or anything from them. No one can ever tell if I took anything. I take 2 Norco every 4 hours and the Darvon maybe twice a day. Is that a lot? My doc seems to think so”

“Currently I’m on oxycodone…….Initially I started off taking 40mg. every 4 hours, then it was increased two weeks later to 60mgs, then approximately 6 months later it was upped to 90 mgs. I stayed there for a long time, about l6-18 months then I was started on l20mgs every 4 hours, which was just changed 2 months ago. Now, the pain is NEVER completely gone or taken away. This does keep the pain down to a level that is tolerated, but never below a 3.”

“I am presently on fentanyl 75mg patches and 4 percocets daily. The fentanyl patches last 72 hours and I have had no side effects from either the fentanyl or percocet. When I was taking percocet for pain only it was not controlling the pain and the doctor suggested I try 2 every 6 hours. That made me feel drugged and I still had pain, not quite as bad as when I was taking 1 every 4 hours but I didn’t like the drugged feeling and slight headache so I went back to 1 every 4 hours. Then they prescribed fentanyl 25 mg patches and that didn’t seem to help at all so the dosage was increased to 50 mg. I was still in a lot of pain so I was told I could take percocet with it. I still was in a lot of pain so I was increased to 75 mg patches. I still needed to take 6 percocets with this but after awhile I started cutting back on the percocet and got down to 4 percocets a day with the 75 mg patches. I tried to cut back to 50 mg patches for about a week. Then the severe pain returned and the doctor ordered another MRI. I went back to the 75 mg patches and 6 percocets per day and after about a month I was feeling better so I gradually started cutting back on the percocets. I am now taking 4 percocet daily and the 75 mg fentanyl patches……..I am able to walk 1 mile to 1-1/2 miles per day right now and the pain is only in the 3 to 4 range on a scale of 1 to 10.”

“I have been on Roxicodone 5 mg 1 every 4 hrs as needed and oxycontin 10 mg 1 2x a day. I have been on these drugs for nearly 2 years. I am experiencing the best pain management I have had in nearly 18 years! I feel very fortunate that I have not had any bad side affects from these medications that I am aware of. With the exception of the inevitable flare ups, I am most functional with the second dose of medications. On these medications there is a small window of opportunity to live my life more comfortably.”

“Until late 1997, she relied on some form of codeine as a pain med. Her condition was such, that in early 1997, her doctor put her on Oxycontin (morphine), 10mg time-release, every 12 hours, and Oxycontin, 5mg tablets, 1-2 per 24 hours as a break-through medication. She did receive significant benefit in relief of pain, level of energy, and could think more clearly. She had no negative side effects. However, after about 18 months, her pain level increased significantly in a short period of time. Her doctor then elected to have her evaluated for a pain pump. The testing protocol was extensive. The last test was a one week trial with an external pain pump. ____was 90 % pain free with some nausea as the one side effect. _____ had the pump implanted Sept, 1999. She was given morphine, 5mg/day plus Marcaine to start. She experienced nausea for about a week with about 60% pain relief. Since she was sensitive to medication, the doctor increased the dosage by 10% when she felt ready for a “bump up.”

Then it was time in Dec(ember) for her first refill (with a needle through the skin). The port on the pump that the needle was supposed to penetrate could not be found, it simply wasn’t there. This could only mean that the pump was backwards. The next day she was back in surgery. The doctor claims that pump flipped over the one time _____ vomited early in the process…….. ______is now receiving 7.5mg per day plus the marcaine and is 80 - 95% pain free. The variance is do to ____’s new found life, and she sometimes exceeds the endurance level of her back and/or leg muscles. She has no side effects since she only needs a small dosage of morphine that is delivered only to the site of her pain. Her new doctor believes that he will achieve greater efficiency in the near future by repositioning the location were the morphine enters _____’s spine.”

“Two months after implantation of the pump, I developed excruciating nerve pain, which started out of the blue, late one night, in a spot about 6 inches square in my left outer calf. Since that night over four years ago, the nerve pain has spread to my entire left leg, foot, ankle, butt, and hip…(later)

….cut it back from 30 mg to 15 mg per day right then. by nightfall I knew we were on to something. I had felt something like “pressure being reduced” in the leg. My normal afternoon routine was to come into the house and immediately rub ice cubes on the affected nerve. Not today, however, as I experienced much less nerve pain……..I want to stress that I am NERVE pain free, well almost. So I am convinced that four years of Hell, including surgeries done by a neurosurgeon, swelling of my leg until the skin burst open, no long trousers for more than four years, Allodynia so bad that I could not go outside in the wind, all of this was caused by a doctor pushing too much morphine through my pump. I can’t even begin to describe the pain I’ve gone through in these years. It makes the “other” pain, the Arachnoiditis pain, pale in comparison.”……… well, we are now three months into this change, and a few weeks ago I had my pump replaced due to dead battery. Other than another case of withdrawal due to an air bubble or something akin to it, while replacing the pump, I am fine. I now live on 3 mg per day only (down from 30), and have almost no A(rachnoiditis) pain. Well,. call it a “2” instead of a 10. I can now wear long trousers, socks, and whatever else I wish. I am crossing my fingers. Sometimes we truly can’t see the forest for the trees.”

APPENDIX:

Alfentanyl :Alfenta

Anileridine :Leritine®

Buprenorphine: Temgesic®

Butorphanol :Stadol®

Codeine: Codeine Phosphate (Abbott/ Technilab)

Dextromoramide: Palfium®

Dextropropoxyphene Diamorphine:

Dihydrocodeine: DF 118 Forte® DHC Continus®

Dipipanone: Diconal®

Fentanyl :Duragesic®, Oralet®, Sublimaze® Fentanyl Citrate (Abbott), Fentanyl Citrate Injection (Faulding), Innovar® Actiq® approx. 70 times more potent than morphine

Hydrocodone Vicodin® (with acetaminophen*) Lortab® Lorcet® similar to codeine. Onset approx. 30 mins peak approx. 1.5 hours dosage every 4-6 hours

Hydromorphone: Dilaudid® Hydromorphone HCl, Hydromorph Contin® 8 x more potent than morphine

Levorphanol :Levo-Dromoran®

Meperidine/Pethidine Demerol® Meperidine (Abbott) Pamergan P100® usually given by injection as very poorly absorbed by stomach ; short duration and has a toxic metabolite. Not generally used for chronic pain.

Meptazinol: Meptid®

Methadone Diskets®, Dolophine®, Methadose® long-acting opiate. Oral: Onset 30-60 mins., peak 1.5-2 hours, recent data suggests half-life may be from 72 hours up to as long as 150 hours, so drug levels may accumulate. Usually twice a day dosage. Can also be used intravenously, intramuscularly and epidurally. Oral dose is half as potent as injected.

Morphine Duramorph®, Infumorph®, Kadian®, MS Contin®, MSIR®, Oramorph™, Roxanol™

M-Eslon®, Morphine 50mg/ml and 1mg/ml, Morphine (Abbott), Morphine HP®, Morphitec®, M.O.S.™, M.O.S.-Sulphate, MS Contin®, MS-IR® Sevredol® Morcap® SR, MST Continus® (Napp) MXL® Zomorph® Min-I-jet® Morphine Sulphate Cyclimorph® Kapanol®

Morphine sulphate Immediate Release: onset 15-60 mins. Peak plasma concentrations 0.5-1 hour. Usual dosage 4 hourly. 25% bioavailability in oral preparations

Nalbuphine Nubain®

Nalmefene Revex™

Naloxone Narcan®

Naltrexone ReVia™

Oxycodone Roxicodone®, Endocet®, Endodan® Percocet®* Tylox®* Roxicet®* Percodan®*

Oxycontin® short-acting: onset 10-15 mins. Duration 3-6 hours

Pentazocine: Talwin® tends to increase rather than decrease blood pressure, effects are similar to morphine

Phenazocine: Narphen®

Propoxyphene Darvon® Darvocet® half to a third as potent as codeine; approx. same effect as 30-60 mg codeine or 600mg aspirin; onset 30-60 mins;

Sufentanil Sufenta®

Tramadol : Ultram® Zamadol® Zydol® Zamadol® SR Zydol SR® centrally acting, exact mode of action not understood; short-acting 4-6 hours or slow release form.

(* some preparations also contain either acetaminophen (paracetamol) or aspirin)

This is not an exhaustive list.

APPENDIX 2:

EQUIVALENCE TABLES: (q values refer to frequency of doses e.g. q 3-4 hr=every 3-4 hours)

ORAL PREPARATIONS

Drug name	Equianalgesic dose	Usual starting dose (moderate to severe pain - opiate naïve patient)	CF ratio versus morphine
Morphine (IR)	30mg q3-4 hr. (repeat around the clock dosing)	0.3mg/kg q3-4 hr.	1:1
Morphine - Controlled release	90-120mg q12hr.	N/A
Hydromorphone	7.5 mg q3-4 hr.	0.06mg/kg q 3-4 hr.	1:4
Levorphanol	4mg q 6-8 hr.	0.04 mg/kg q 6-8 hr.	1:15
Meperidine	300mg q 2-3hr.	Not recommended	1:0.066667
Methadone	20mg q 6-8 hr.	0.2 mg/kg q 6-8 hr.	1:3
Codeine	180-200mg q 3-4 hr.	0.5-1mg/kg q 6-8 hr.	1: 0.166667
Oxycodone	30mg q 3-4hr.	0.2 mg/kg q 3-4 hr.	1:1
Hydrocodone	30 mg q 3-4 hr.	0.2 mg/kg q 3-4 hr.	1:1

References:

[i] Schofferman J Clin J Pain 1999 15(2):136-140 Long-term opioid analgesic therapy for severe refractory lumbar spine pain

[ii] Angel IF, Gould HJ, Carey ME Surg Neurol 1998 Jan;49 (1):92-98 Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin

My thanks to those who contributed their stories about the experience of using opioid medication.

[iii] Hodgson PS , Neal JM , Pollock JE, Lui SS Anesth Analg 1999;88:797 The neurotoxicity of drugs given intrathecally (spinal)