ANALGESICS

(see Agonist/Antagonist Analgesics, Brompton’s Cocktail, Heroin, Meperidine, Methadone, Morphine, Subcutaneous Infusions)

«  Continuous pain needs continuous pain relief. The cardinal rule is to give regular analgesia to keep pain away. Never prescribe PRN. (In hospice medicine, PRN means “Pain Relief Negligible”.)

Regular analgesia should ideally be oral, easy to take, and with few side effects, so that the patient can live as normal a life as possible once pain is controlled.

There are three basic analgesics:

•  Acetaminophen (non-opioid)

•  Codeine (weak opioid)

•  Morphine (strong opioid)

Other analgesics are alternatives to these.

Mild pains need mild analgesics. Acetaminophen (1g every 4 hours) is an effective analgesic for mild pains. 

Moderate pains respond to weak opioid drugs such as codeine. If oral codeine 60mg every 4 hours does not abolish pain, the patient should be started on oral morphine. If weak opioids reduced the pain, it usually means that the pain is opioid-responsive, and will be well controlled on the correct dose of oral morphine.

It is illogical and ineffective to try several drugs from the same group (morphine with another opioid drug).

When weaker opioids prove ineffective, start oral morphine. The principle is to start with a low dose, and to titrate, increasing promptly in steps until the pain is controlled. The usual starting dose for 4-hourly oral morphine is 5mg. The dose may be increased every 4 hours in steps: 5mg, 10mg, 20mg, 30mg, 45mg, 60mg (or more as needed). Once the patient’s pain is well controlled on 4-hourly oral morphine, it is possible to stop the 4-hourly morphine and change to an equivalent dose of MS-Contin (morphine sulfate controlled-release) every 12 hours. (Do not use 4 hourly oral morphine and MS-Contin together. It is unnecessary and tends to confuse both patient and carers.) If the patient is pain-free and drowsy, reduce the dose of morphine. The aim is to have a pain-free and alert patient. (see Morphine, Prescribing)

Never prescribe opioid agonist/antagonists (buprenorphine, nalbuphine, pentazocine) with opioid agonists (codeine, morphine). (see Agonist/Antagonist Analgesics)

Always start a laxative and  anti-emetic at the same time as morphine or any of the opioids, weak or strong. (see Constipation, Laxatives, Nausea & Vomiting)

Polypharmacy in hospice and palliative care is unavoidable and necessary. However, fixed mixtures of drugs which have not been individually titrated should be avoided. (see Brompton’s Cocktail, Prescribing)

«  There is no place in terminal care for patient-controlled analgesia. The aim is to achieve total pain control with as simple a regime as possible, releasing the patient to think about more important things than pain.

If the patient is unable to swallow (for example, due to dysphagia or vomiting), change to one of the following:

•  Morphine suppositories

•  Morphine by IM injection (for the short term only)

•  Morphine by continuous subcutaneous infusion

Many analgesics are not suitable for management of chronic pain, and include:

•  Dihydrocodeine (constipating)

•  Pentazocine (dysphoriant effect)

•  Meperidine (too short-acting)

•  Methadone (too long-acting)

«  There is no known opioid superior to morphine. Pain that does not respond to carefully titrated doses of morphine will not respond to other opioid analgesics. Other opioid analgesics should generally be avoided. (see Morphine)

The table below is a guide to equi-analgesic oral doses. It is useful when changing a patient from regular oral analgesia with one of the other opioids to regular oral analgesia with morphine, in order to avoid prescribing too much morphine (drowsiness) or too little (pain breakthrough) at time of changeover. The table does not apply to single doses.

Opioid is a term meaning any compound (natural or synthetic) which has morphine-like activity and which is antagonized by naloxone. No known opioid analgesic is superior to morphine, but since the elucidation of the structure of morphine in 1925, much effort has gone into producing new chemical entities with equal analgesic effect but without the side-effects.

Opioids act at receptors in the brain (especially the midbrain) and at the spinal cord to inhibit the transmission of pain. There are several different types of receptors.

Most opioid drugs in clinical use (like morphine, codeine, methadone, and meperidine) act at the mu-receptors. They are selective mu-receptor agonists (causing strong analgesia but also other side effects). The structure of all these drugs (and the naloxone molecule) is similar, with a phenyl-N-methyl piperidine backbone which “fits” the mu-receptor.  Some analgesics (pentazocine, for example) also stimulate sigma-receptors, causing dysphoria.

If an opioid selective to kappa-receptor agonists could be developed there is some evidence that the result would be strong analgesia with fewer side-effects.

Clinical differences between opioids concern:

•  Analgesic ceiling

•  Oral efficacy

•  Speed of onset

•  Duration of action

•  Side-effects

•  Potential for abuse

The potency of the drug (the amount in milligrams needed to achieve a given analgesic effect) is not as relevant as the analgesic ceiling (the highest strength of the drug which can be given in order to achieve the needed analgesic effect). Morphine has a high ceiling, so increasing the dose can increase the analgesic effect even at high doses. Agonist/antagonist drugs have a low ceiling. (see AgonistlAntagonist Analgesics)

Oral efficacy depends on lipid solubility (rate of absorption) and susceptibility to first-pass metabolism in the liver. Methadone is well absorbed and slowly metabolized and therefore has a long half-life. More lipid-soluble drugs have a more rapid onset of action (crossing the blood-brain barrier more easily), but also leave the CNS more readily (and thus have a shorter duration of action).

Duration of action also depends on receptor affinity. The duration of pain relief varies from about 1 to 2 hours (meperidine) to 4 hours (morphine) to 8 hours (buprenorphine, methadone).

Side-effects depend not only on the receptor profile of the drug, but also on the receptor profile of the patient, which explains, for example, why some patients develop severe nausea with buprenorphine or constipation with dihydrocodeine, and others do not. (If a patient cannot tolerate one opioid analgesic it is still worth trying another.)

Physical dependence can occur with most opioids after 3 to 4 weeks in a person without pain, but does not occur in a patient with pain.

The author and publisher have taken precautions to ensure that the information in this book is error-free. However, readers must be guided by their own personal and professional standards of good practice in evaluating and applying recommendations made herein. The contents of this book represent the views and experience of the author, and not necessarily those of the publisher.