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  About Pain       Medication Types      
 
 
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This page provides simple, concise online information about commonly used pain relieving medications and drugs, many of them available over the counter. These analgesic drugs are commonly used to treat acute and chronic pain conditions like low back pain, neck pain, sciatica, arthritis and joint pain, nerve pain, headaches, and menstrual cramps. For more information about emergency pain medicines, please look at the Analgesic Flow Chart.

2010 - Managing your pain effectively using "Over The Counter" (OTC) Medicines

Think about trying the Pain Gone Pen - a simple low-cost non-drug self-help pain device for home use.

Looking for that perfect pain killer (Do not open if easily offended.)

Numbers Needed To Treat
  • Numbers Needed To Treat (NNT) is a system that has been developed to allow the effectiveness of different pain killers to be compared.
  • It gives an indication of how many patients a pain killer has to be given to before one patients perceives 50% pain relief lasting 4 hours. So if a drug had a NNT of 5.0, only 1 in 5 patients it was given to would get 50% pain relief lasting 4 hours.
  • The lower the number the more effective the pain killer and vice versa.
  • It's a tool that's used frequently in clinical trials - the full equation takes in to account the placebo effect as shown below:-
       
1
NNT   =  
________________________________________________
       

(Proportion of those with 50% relief lasting 4 hours with  an active pain killer)

_

 

(Proportion of those with 50% relief lasting 4 hours with the placebo)

  • Clinical Trial Example
    • 40 out of 50 patients (80%) given an active pain killer had 50% relief lasting 4 hours.
    • 15 out of 50 patients (30%) given a placebo pain killer had 50% relief lasting 4 hours.
    • NNT = 1 / (0.8 - 0.3) = 1 / 0.5 = 2.0
    • Therefore, 1 in every 2 patients (50%) given the active pain killer would get 50% pain relief lasting 4 hours.
  • The NNT's of a wide range of pain killers have been calculated allowing different pain killing drugs and doses to be compared.
  • Numbers Need To Harm - a similar system exists allowing the risk of a harmful side effect to be assessed using the same equation above, only substituting the word Harm for the word Relief.
  • If a drug had an NNH of 50, then 1 in 50 patients given the active drug would develop a harmful side effect.
Paracetamol
  • Use - as an analgesic (pain killer) and an anti-pyretic (temperature lowering) - used alone for mild pain, or in combination with NSAIDs and Opioids for moderate and severe musculo-skeletal pain.
  • Mode of action is not completely understood, but is thought to act in the brain. It has very weak effects on the COX-1 and COX-2 systems (see NSAIDs below), and therefore it has minimal peripheral anti-inflammatory actions, and does not cause gastric ulceration. Recent research suggests that it may work through a newly discovered COX-3 enzyme system.
  • Dose - the maximum oral dose in adults is 1 gram (2 x 500 mg) 4 times per day. Intravenous paracetamol (Perfalgan ) is also available in hospital when the oral route is no longer available - the maximum dose is 60mg/kg/day given as a maximum of 4 doses per day. See local hospital guidelines for those under 50kg and those with liver and kidney impairment.
  • Side effects - Fatal liver failure is very common after overdose. Available as:-
    • Paracetamol 500 mg oral tablets  
    • Paracetamol 60 mg, 125 mg, 250 mg suppositories
    • Paracetamol 500 mg, 1000 mg intravenous vials (Perfalgan)
    • Paracetamol eMC Medicine Guide
NSAIDs (Non Steroidal Anti-Inflammatory Drugs)
  • Use - as an analgesic, anti-inflammatory and anti-pyretic - may be used alone or in combination with paracetamol and/or weak/strong Opioids.
  • Mode of action - NSAIDs produce a range of effects in the body by inhibiting the enzyme cyclo-oxygenase (COX). COX is the main enzyme which converts arachidonic acid to prostaglandins, thromboxane and prostacyclins. It is found in many central and peripheral tissues in the body, and this explains why NSAIDs have such a wide range of effects. The known effects of these drugs are:-
    • analgesia - acting on peripheral tissues, the dorsal horn of the spinal cord, and the brain
    • anti-inflammatory - via the prostaglandin effect
    • anti-pyretic - temperature control in the brain
    • gastric ulceration - impaired gastric lining protection
    • anti-platelet - anti-thromboxane effect prevents platelets sticking together with increased bleeding tendency
    • renal impairment - altered kidney blood flow control worse with dehydration
    • increased wheezing in susceptible asthmatics increasing the muscle tone in the bronchi of the lungs
  • There are two forms of the COX enzyme - COX-1 and COX-2. Older NSAIDs inhibit both enzyme types, whereas modern NSAIDs have high specificity for the COX-2 enzyme. COX-2 specific NSAIDs produce comparable analgesia and anti-inflammatory effects, whilst helping to reduce gastric ulceration and anti-platelet effects. 
  • Below is a list of commonly used NSAIDs and the ratio of their COX-2 : COX-1 selectiveness:-
NSAID
COX 2:1 Ratio
Classification
Etoricoxib (Arcoxia)
106 : 1 **

Selective for

COX-2 

Rofecoxib (Vioxx) *
35 : 1 **
Valdecoxib (Bextra) *
30 : 1 **
Celecoxib (Celebrex)
7.6 : 1 **
Diclofenac (Voltarol)
3.0 : 1 **
Etodolac (Lodine)
2.4 : 1 **
Meloxicam (Mobic) *
2.0 : 1 **
Indomethacin (Indocid)
0.4 : 1 **

Selective for

COX-1

Naproxen (Naprosyn)
0.3 : 1     
Ibuprofen (Nurofen)
0.2 : 1 **
Piroxicam (Feldene)
0.08 : 1 **
* No longer available, ** Whole Blood Assay - from "Etoricoxib (MK-0663): Preclinical Profile and Comparison with Other Agents That Selectively Inhibit Cyclooxygenase-2."  JPET, 296: 558-566, 2001"
  • Dose - Ibuprofen can be bought over the counter, where the usual dose is 200 - 400 mg four times a day. For other NSAIDs please consult the product literature or your doctor for further advice.
  • Side effects - include gastric ulceration and bleeding, kidney impairment in the susceptible and elderly, increased bleeding risk due to an anti-platelet effect, poor asthma control in susceptible asthmatics, and potential drug interactions with other drugs. The risk of developing gastric ulceration is lowest for the COX-2 specific NSAIDs (rofecoxib, etodolac, meloxicam and celecoxib), whilst the older non-specific NSAIDs can be ranked in the following order (this is not an exhaustive list):-
NSAID Gastric Bleed Risk
IBuprofen (Nurofen)
Low
Diclofenac (Voltarol)
Moderate
Ketoprofen (Orudis)
Indomethacin (Indocid)
Naproxen (Naprosyn )
Piroxicam (Feldene)
Azapropazone *
High
* no longer available
  • Contra-indications
    • If you are asthmatic and aspirin causes your asthma control to deteriorate - you should not take NSAIDs because of the risk of developing severe life threatening wheeze. Consult your doctor for further advice.
    • Previous history of gastric bleeding / ulceration
    • Renal impairment - more common over 65 years of age
    • Severe liver disease
    • There are many drug interactions between NSAIDs and medication used for anti-coagulation (warfarin), hypertension, heart failure, diabetes, and epilepsy - see your doctor for advice about co-administration in these circumstances.
  • Interesting Articles
    • Drugs and Therapeutics Bulletin - January 2005
    • GP Notebook Article
    • Ibuprofen eMC Medicine Guide
Weak Opioids

Weak Opioids are often used for musculo-skeletal and visceral pain, usually in combination with paracetamol and/or NSAIDs. See Analgesic Flow Chart.

  • Codeine is a weak opioid (morphine like effect) which has no analgesic effect of its own. It is a pro-drug with 10% of the oral dose is converted to morphine by the liver. About 7% of the population do not have the necessary enzyme to convert it, and therefore codeine is ineffective in these people. Studies suggest that it most effective when taken with paracetamol. Side effects include drowsiness, sickness, constipation, and tolerance over time. May cause codeine-induced headaches requiring slow withdrawal. Total daily dose is limited by the maximum paracetamol dose. Taking codeine alone is not recommended. Possible addiction potential. Available as:-
    • Codeine 30 mg and 60 mg
    • Cocodamol 8 / 500
    • Cocodamol 30 / 500 (Tylex)
    • Paracetamol + Codeine eMC Medicine Guide
  • Dextropropoxyphene is a weak opioid which has mixed activity at morphine receptors. At low doses it is active at the receptors producing analgesia. At higher doses it inhibits these receptors producing a ceiling effect on analgesia. Dextropropoxyphene is therefore a mixed agonist-antagonist. When used with other morphine-like drugs, mixed agonist-antagonist drugs reduce the overall analgesia rather than producing an additive effect.  It has the same side effects as codeine as well as addiction potential. Available as coproxamol (paracetamol 325 mg plus 32.5 mg dextropropoxyphene). Total daily dose is limited by the maximum paracetamol dose. Please note: This drug is now only available from your GP on a named patient basis. If you need to change to a similar strength drug, please choose one of the other weak opioids in this section.
  • Dihydrocodeine is a weak opioid but slightly stronger than codeine. Still needs to be converted to morphine in the liver, Same side effects as codeine. Total daily dose is limited by the maximum paracetamol dose. Available as:-
    • Codydramol 10 / 500
    • Remedeine 20 / 500 and Remedeine Forte 30 / 500
    • Normal release Dihydrocodeine 30 - 60 mg 4 times a day
    • Slow release Dihydrocodeine 60 / 90 / 120 mg twice a day
    • Dihyddrocodeine eMC Medicine Guide
  • Tramadol is a weak opioid which is also converted to another active compound by the liver. It has two modes of action 1) a weak morphine like effect 2) stimulation of the descending nerves from the brain which inhibit the dorsal horn of the spinal cord, by preventing reuptake of noradrenaline (MAdr)and serotonin (5HT). Tramadol 50 mg = Morphine 10 mg. May cause dizziness and sickness. It may be used with paracetamol and/or NSAIDs. Caution: A serotonergic syndrome can be caused by using tramadol with other drugs that also prevent reuptake of NAdr and 5-HT e.g. anti-depressants like duloxitene (Cymbalta), tricyclics, SSRI's, SSRNI's and MAOI type drugs.Available as:-
    • Tramacet 37.5 / 325 1 - 2 tablets 4 times a day
    • Normal release Tramadol 50 - 100 mg four times a day
    • Slow release Tramadol 100 - 200 mg twice a day
    • Tramadol eMC Medicine Guide
  • Tapentadol (Palexia) is a drug simillar to Tramadol for treating acute and chronic moderate to severe pain. It's available in normal release and slow release formats.The starting dose is 50mg 4 times a day NR, converting to the twice daily SR preparation if necessary. The maximum recommended daily dose is 600 mg. Like tramadol it is active at morphine (mu), noradrenaline (NAdr)and serotonin (5HT) receptors. Tapentaadol is less active at 5HT receprtors but more active at NAdr receptors than tramadol. In terms of mu receptor activity, it is some where between tramaol and morphine (tapentadol 100mg = 5 - 10 mg morphine - figures vary between sources). It is not recommended in the prescence of kidney and liver disease. It should not be stopped suddenly, and should be tapered down slowly.
    • Tapentadol (Palexia) 50 mg NR every 4-6 hours
    • Tapentadol (Palexia) 100 mg SR twice daily
  • Partial agonists of morphine - these drugs are like dextropropoxyphene in that they have mixed actions at morphine receptors, and have a ceiling effect in higher dosage. Examples are pentazocine , butorphanol, and nalbuphine. They are weak in their analgesic action, but unlike morphine do not cause respiratory depression. Side effects like dysphoria and nausea are common. Pentazocine has an addiction potential and is slowly being withdraw from clinical use. Nalbuphine is used by paramedics prior to transfer to hospital.
  • Opioid Physical Dependence - Any drug that has activity at mu (morphine receptors) carries the risk of physical dependence if taken at a high enough dose and for sufficiently long enough (surprisingly short in some people).
  • If the need to take opioid drugs has passed (your pain has improved or lessened), but you find yourself physically dependent on the drug, you may find the following advice usdeful:-
    • Discuss the problem with your GP / Pain Specialist first, in case you need help in a hurry.
    • Work out your total daily mu drug dose. If you're taking multiple mu-like drugs, you may need to convert them all to a single morphine equivalent dose first - see table below.
    • Reduce the total daily mu dose by 10% and stay on that dose for 1 - 2 weeks (longer in some cases especially if psychological dependece is a factor as well).
    • You may need to change to normal release preparations of the drug if the slow release tablet size doesn't fit e.g. tramadol SR to tramadol NR
    • Carry on reducing the total daily dose by 10% every 1 - 2 weeks until you're off it or, you can change ovver to a paracetamol / NSAID mix instead (if you have residual pain that needs treating).
    • Get as much support as possible from friends, famlly, practice nurses, GP, Pain Team - this will improve your chances of success.

Strong Opioids

Strong Opioids are used for severe pain and their potency for different types of pain is ranked in the following order:- visceral pain > musculo-skeletal pain > nerve pain > sympathetic pain. They can be usefully combined with paracetamol and/or NSAIDs. Nerve and sympathetic pain may be partially sensitive to strong Opioids, but these drugs should not be used alone for this type of pain.

The following publications are available from the British Pain Society:-

File
Year
Article
2004
Recommendations for the Appropriate Use of Opioids for Persistent Non-cancer Pain
2004
Opioid Medicines for Persistent Pain: Information for patients
2005
The Use of Drugs Beyond their Licence in Palliative Care and Pain Management
2005
The Use of Drugs Beyond their Licence: Information for Patients
2007
Pain and Substance Misuse: Improving the Patient Experience
2007
Pain and Problem Drug Use: Information for Patients
  • Morphine is the "gold standard" strong opioid against which all other drugs are compared. It is a potent stimulator of morphine receptors, blocking pain impulses at several sites:-
    1. in inflamed peripheral tissues (e.g. knee osteoarthritis),
    2. in the dorsal horn of the spinal cord,
    3. centrally in the brain.

Morphine by mouth has a wide range of effects in different individuals because of its variable 20 - 50% bioavailability (the proportion of drug taken up from the bowel after oral administration). This means that by mouth there can be a 2.5 times difference in the dose required to achieve comfort between individuals. These differences are less obvious after intravenous, intramuscular, or subcutaneous administration as the bowel is bypassed producing 100% bioavailability.

The other problem with morphine is that it is converted in the liver to two metabolites (breakdown products). One product is called M-6-G and is much more potent than the parent drug, and accumulates in kidney failure causing drowsiness. The other is called M-3-G which acts as an antagonist of morphine and M-6-G, and produces anti-analgesia. Analgesia is often the result of the balance between how much M-3-G and M-6-G is produced by the liver, where there are separate enzymes controlling the amount of each metabolite produced. Some individuals produce too much M-6-G and are therefore very sensitive to small amounts of morphine. Other individuals produce too much M-3-G causing morphine resistance.

Morphine commonly produces side effects of drowsiness, nausea, vomiting, constipation, depressed breathing rate, and detachment from reality. Many of these effects disappear after acclimatization. Tolerance can occur during chronic administration. Available as:-
  • Normal release Sevredol tablets
  • Normal release Oramorph liquid
  • Slow release MST every 12 hours
  • Slow release MXL every 24 hours
  • In hospital it can also be given intramuscularly, intravenously, subcutaneously, epidurally, and intrathecally.
  • Morphine eMC Medicine Guide

The starting oral dose for morphine "virgins" is 10 mg normal release every four hours, allowing calculation of the 24 hour dose requirement, and conversion to a slow release preparation if necessary.

All patients on strong Opioids will develop constipation. The current laxative regime of choice is senna combined with lactulose. Senna reverses the bowel slowing effect of morphine, whilst lactulose assists lubrication.

  • Diamorphine (Heroin) is a strong opioid which is twice as potent as morphine. Morphine 10 mg is equivalent to diamorphine 5 mg. It is a pro-drug needing to be converted to morphine in the liver before it is active. It has no advantages over morphine by mouth, having the same side effects. Commonly used in the epidural space with local anaesthetics to give potent post-operative pain relief. Not available as a tablet by mouth, but can be used in hospital intravenously, subcutaneously and intramuscularly. It comes as a white powder and is very soluble in solution, making it useful for use in the hospice situation by subcutaneous driver in terminal illness.
  • Diamorphine eMC Medicine Guide
  • Hydromorphone is a strong opioid which is 7.5 times more potent than morphine by mouth. Morphine 10 mg is equivalent to hydromorphone 1.3 mg. Unlike morphine it has no active breakdown products, but has similar side effects. Available as:-
    • Normal release Palladone 1.3 - 2.6 mg 4 hourly
    • Slow release Palladone 4, 8, 16, 32 mg 12 hourly
    • Hydromorphone eMC Medicine Guide
  • Oxycodone is a strong opioid which is twice as potent as morphine by mouth. Morphine 10 mg is equivalent to oxycodone 5 mg. It has a basic morphine chemical structure except for an additional side chain. When taken by mouth, 60 - 80% of oxycodone is absorbed into the circulation, compared to only 20 - 50% of an oral morphine dose.  When oxycodone is given intravenously, these advantages are lost. Better bioavailability gives faster and more reliable onset. It is said to have fewer side effects when compared to morphine. Caution: Mixing oxycodone with pregabalin can cause excessive drowsiness requiring a dose reduction. Available as:-
    • Normal release OxyNorm 4 hourly
    • Slow release OxyContin 12 hourly
    • Oxycodone eMC Medicine Guide
  • Targinact is a combination of oxycodone SR plus naloxone SR (morphine antagonist) which helps to reduce constipation associated with strong opioids. Naloxone has greater affinity for morphine (mu) receptors than oxycodone, and blocks the mu receptors in the bowel wall before oxycodone gets there, thereby preventing constipation. Oxycodone is then absorbed in the normal way. Excessive amounts of naloxone are prevented from getting into the systemic circulation by first pass metabolism in the liver. This reduces the risk of "cold turkey" opioid withdrawal reactions. Caution advised in short bowel syndromes and liver impairment, where excessive amounts of naloxone could reach the systemic circulation. Available as:-
    • Oxycodone 5 mg SR + naloxone 2.5 mg SR
    • Oxycodone 10 mg SR + naloxone 5 mg SR
    • Oxycodone 20 mg SR + naloxone 10 mg SR
    • Oxycodone 40 mg SR + naloxone 20 mg SR
    • Oxycodone eMC Medicine Guide
  • Fentanyl is a strong opioid which is 100 times as potent as morphine. Morphine 10 mg is equivalent to fentanyl 100 micrograms. It is commonly used during operations by anaesthetists in the intravenous form. It has no active breakdown products and is relatively short acting. Fentanyl is commonly used in post-operative epidurals to complement the action of local anaesthetics, giving excellent pain relief. It is also used to treat malignant and non-malignant pain, and is available as a continuous delivery transdermal 3-day patch, and a normal release lollipop. Matrix patches may be cut in half but this is not recommended by the manufacturer. Resevior patches should not be cut. Only 50% of each lollipop dose is absorbed into the circulation, and the effects of the drug last for only 2 hours. There is uptake of the drug partly from the lining of the mouth, and partly from absorption in the stomach. Available as:-
    • Durogesic DTrans 3-day matrix patch 12 / 25 / 50 / 75 / 100 ug/hr
    • Normal release Actiq lollipops 200 / 400 ug
    • IonSys iontophoretic transdermal system, delivering 40 ug per push - for acute pain management in hospital only
  • Buprenorphine is a strong opioid which is now coming back into favour. It was once thought that it was a partial agonist of morphine, but recent studies have suggested that it is a full agonist in the normal clinical range. It is about 30 times more potent than morphine. Morphine 10 mg is equivalent to buprenorphine 0.3 mg (or 300 ug). It stimulates morphine receptors to produce potent pain relief, and has many of the side effects of morphine. Available as:--
    • Normal release Buprenorphine 200 - 400 ug sublingually every 4 - 6 hours
    • BuTrans transdermal 7-day patch 5 / 10 / 20 ug/hr
    • Transtec transdermal 3-day patch 35 / 52.5 / 70 ug/hr
    • Subutex tablets for opioid dependance weaning 0.4 / 2 / 8 mg
  • Pethidine is a strong opioid which is 1/10th as potent as morphine. Morphine 10 mg is equivalent to pethidine 100 mg. It has an active breakdown product called norpethidine which can accumulate after taking high doses or in kidney failure, producing epileptic seizures. In hospital it can be used intramuscularly, intravenously, and epidurally. It is very short acting which ever way it is administered, and is a poor choice orally for continuous pain as it only gives relief for 1.5 hours. Once thought to be good for renal and biliary colic because of its smooth muscle relaxing effect. This has been discounted recently with other strong Opioids being just as efficacious when compared to pethidine. Available as
    • Normal release Pethidine 50 - 100 mg tablets
    • Slow release - none available
  • Methadone is a strong opioid which is equipotent with morphine. Morphine 10 mg is equivalent to methadone 10 mg orally. Methadone has a very long and variable length of action (20 - 45 hours), and can be taken once a day. It is readily absorbed from the bowel into the circulation (high bioavailability), but can take many days before equilibrium is reached. Commonly used for maintenance therapy for heroin addicts, but can also be used to treat moderate to sever pain. Warning - recent evidence suggests Methadone can cause a dose dependant prolongation of the cardiac QT interval, increasing the risk of "torsade de pointes", a type of ventricular arrhythmia which can cause sudden death. This risk may also be increased by long term methadone treatment, high methadone doses, pre-existing ischaemic heart disease (angina / coronary heart disease), low potassium levels in the blood, and certain medical drugs that also increase the QT interval e.g. antibiotics (erythromycin, clarithromycin), antipsychotic drugs (chlorpromazine, haloperidol, pimozide), and gastrointestinal drugs (cisapride, domperidone). Available as:-
    • Methadone oral solution 1 mg / ml
    • Methadone oral solution 10 mg / ml
    • Methadone oral solution 20 mg / ml
  • Morphine Equivalents - below is a table showing how potent different Opioids are when compared to the gold standard of morphine 10mg IV:-
Drug
Dose
Route / Duration
Morphine
10 mg
IV - 2 hr
IM - 3 hr
-
Morphine
20 mg
NR - 3 hr
SR - 12 hr
-
Pethidine
100 mg
NR - 1.5 hr
IM - 1.5 hr
IV - 1.5 hr
Tramadol
50 mg
NR - 4 hr
SR - 12 hr
-
Fentanyl
100 ug
IV - 15 min
Patch - 72 hr
-
Oxycodone
5 mg
NR - 3 hr
SR - 12 hr
-
Diamorphine
5 mg
IV - 3 hr
SC - 3 hr
-
Buprenorphine
300 ug
SL - 4 hr
Patch - 72 hr
-
Hydromorphone
1.3 mg
NR - 3 hr
SR - 12 hr
-
Methadone
10 mg
NR - 12 to 24 hr
-
-
Codeine
100 mg
NR - 3 hr
IM - 3 hr
-
NR = oral normal release, SR = oral slow release, IM = intramuscular injection, IV = intravenous injection, Patch = transdermal patch, SC = subcutaneous injection, ug = micrograms, mg = milligrams.
  • Please be aware that a 100 ug fentanyl patch delivers 100 ug of fentanyl every hour (similar for buprenorphine 35 ug / 52.5 ug / 70 ug patches), and that this needs to be taken into consideration when converting from one drug or preparation to another.
  • Warning
  • Do not suddenly stop strong opioid medications as this can cause a serious withdrawal reaction caused by physical dependence on the drug.
    • Mild withdrawal can present with restlessness, mydriasis (dilated pupils), lacrimation (tears in the eyes), rhinorrhea (runny nose), sneezing, piloerection (hairs standing up on end), yawning, perspiration, restless sleep and aggressive behavior.
    • Severe withdrawal can present with muscle spasms, back aches, abdominal cramps, hot and cold flashes, insomnia, nausea, vomiting, diarrhoea, tachypnoea (rapid breathing), hypertension (high blood pressure), hypotension (low blood pressure), tachycardia (high heart rate), bradycardia (low heart rate) and cardiac dysrhythmias (abnormal heart rhythms). Seizures may be observed in neonates (only).
    • Should you wish to reduce or stop these types of drugs, please discuss it with your doctor first - also see advice below
  • Do not mix strong Opioids with other sedatives such as alcohol and sleeping tablets - this can cause severe sedation, life threatening respiratory depression, and increased risk of aspiration of stomach contents into your lungs.
  • Strong Opioids should be used with caution in those with a psychiatric history or in those taking psychotropic medications.
  • Opioid Physical Dependence - Any drug that has activity at mu (morphine receptors) carries the risk of physical dependence if taken at a high enough dose and for sufficiently long enough (surprisingly short in some people).
  • If the need to take opioid drugs has passed (your pain has improved or lessened), but you find yourself physically dependent on the drug, you may find the following advice usdeful:-
    • Discuss the problem with your GP / Pain Specialist first, in case you need help in a hurry.
    • Work out your total daily mu drug dose. If you're taking multiple mu-like drugs, you may need to convert them all to a single morphine equivalent dose first - see table below.
    • Reduce the total daily mu dose by 10% and stay on that dose for 1 - 2 weeks (longer in some cases especially if psychological dependece is a factor as well).
    • You may need to change to normal release preparations of the drug if the slow release tablet size doesn't fit e.g. tramadol SR to tramadol NR
    • Carry on reducing the total daily dose by 10% every 1 - 2 weeks until you're off it or, you can change ovver to a paracetamol / NSAID mix instead (if you have residual pain that needs treating).
    • Get as much support as possible from friends, famlly, practice nurses, GP, Pain Team - this will improve your chnaces of success.

Muscle Relaxants

  • Diazepam is from the benzodiazepine group of drugs. It is used as a muscle relaxant and for the control of anxiety (anxiolysis). It can be used for a maximum period of one week to aid muscle relaxation in acute severe back pain. It is not recommended for the control of chronic low back pain. It works by stimulating GABA receptors in the brain, enhancing descending inhibition of the spinal cord dorsal horn mechanism. The usual dose is 2 - 5 mg two to three times a day. All benzodiazepine drugs cause sedation and can aid sleep. However, they cause an increase in the number of hours spent in REM sleep (rapid eye movement sleep = dream sleep), reducing the time spent in restful deep sleep. Patients often awake unrefreshed, feeling as if they had never been to sleep at all, because of the disturbed REM sleep / deep sleep ratio. When benzodiazepine drugs are withdrawn, they cause rebound sleeplessness for up to six weeks afterwards. Hence they can be highly addictive, because patients have to resort to re-starting them again just to get some sleep, even though the quality of sleep is poor. Diazepam may be withdrawn in the next few months because of its poor track record in relation to addiction. Spinal manipulation is an alternative to taking muscle relaxants for acute low back pain.
  • Methacarbamol (Robaxin) is used in the treatment of acute muscle spasm in spinal pain and other musculo-skeletal disorders. It is not recommended for the control of chronic low back pain. Dose requirements vary between 750 mg three times a day to 1500 mg four times a day. The dose should be halved in the elderly. Extreme caution is urged in those with liver and kidney insufficiency due to drug accumulation. There may be an interaction with all other drugs which cause drowsiness or central nervous system depression. Driving or the operation of machinery is not advised when drowsiness occurs. Spinal manipulation is an alternative to taking muscle relaxants for acute low back pain.
  • Baclofen (Lioresal) is another drug which works through the GABA system. It is commonly used to help reduce spasticity associated with brain and spinal cord injuries, and is less commonly used for painful back spasms. The usual dose is between 30 - 80 mg per day in three divided doses, and comes in 10 mg tablets. Side effects are often dose related and include sedation, confusion, dizziness, insomnia, global muscle weakness and poor coordination. May be administered via an implanted intrathecal pump system for the long term relief of spasticity.
Anti-depressants
  • Amitriptyline is an older tricyclic anti-depressant. It is converted in the liver to the active metabolite nortriptyline. It has several uses in the pain clinic (some of which are unlicensed) :- 
    • for the control of nerve pain either alone or with an anti-convulsant
    • normalising disturbed REM sleep / deep sleep patterns in fibromyalgia-type syndromes
    • elevation of mood in depression
  • For nerve pain, the main mode of action is to increase descending inhibition of the spinal cord dorsal horn by affecting levels of noradrenaline and 5-HT. For depression it affects the balance of inhibitory and excitatory chemicals in the brain. 
  • The usual starting dose is between 10 - 25 mg at night. Most pain clinics do not use more than 50 mg per day due to side effects.
  • Common side effects include dryness of the mouth (inhibits saliva production) and sedation. When given at night, the sedation can be useful for sleep. Mouth dryness often declines after the first two weeks with low dose amitriptyline. High doses can produce cardiac rhythm disturbances in the people with ischaemic heart disease. Contra-indicated in glaucoma - seek medical advice. May worsen bladder function due to anticholinergic effects (uncommon).
  • Alternatives to amitriptyline include the following:-
    • Duloxetine (Cymbalta)
    • Prothiaden (Dosulepin)
    • Nortriptyline (Allegron)
    • Lofepramine (Lomont)
    • Desipramine
    • Clomipramine (Anafranil)
    • Imipramine (Surmontil)
Anti-convulsants

Anti-convulsants are used to treat nerve and sympathetic pain. Their mode of action is stabilisation of irritable nerve membranes by blocking certain ion channels. They are commonly co-prescribed with tricyclic anti-depressants like amitriptyline.

  • Gabapentin (Neurontin) is licensed for use in nerve pain and epilepsy. It is also used to treat anxiety states. It is a nerve calcium channel blocker with a fairly short duration of action.  It has become popular in recent years because of its lower side effect potential. Even so, common side effects encountered are sedation, dizziness, and headaches. Some people have also described weight gain, fluid retention, upper stomach pain and nausea. It is administered three times a day and needs to be gradually titrated upwards over several days and weeks. The upper licensed dose in the UK is 1800 mg per day, whereas in the USA doses of between 2400 mg and 3600 mg per day are frequently used. It accumulates in renal impairment, and therefore lower doses and more careful monitoring are required in this situation. There is non-linear absorption from the gut, reducing the amount of drug absorbed into the circulation.
Normal Kidney Function
Time
Breakfast
Lunch
Supper 
Step 1
-
-
300 mg
Step 2
300 mg
-
300 mg
Step 3
300 mg
300 mg
300 mg
Step 4
300 mg
300 mg
600 mg
Step 5
600 mg
300 mg
600 mg
Step 6
600 mg
600 mg
600 mg
  • Each step may be 3 or 7 days depending on side effects.
  • In young adults with normal renal function and acute nerve pain (e.g. Trigeminal Neuralgia), I would suggest each step should be 1 - 3 days
Impaired Kidney Function
Time
Breakfast
Lunch
Supper 
Step 1
-
-
100 mg
Step 2
100 mg
-
100 mg
Step 3
100 mg
100 mg
100 mg
Step 4
100 mg
100 mg
200 mg
Step 5
200 mg
100 mg
200 mg
Step 6
200 mg
200 mg
200 mg
  • Renal Impairment Doses are suggestions only - doses may need to be lower or higher according to patient response and side effects
  • Pregabalin (Lyrica) is a new drug in the UK, licensed for use in nerve pain and epilepsy. It may have some effect in anxiety states but further work is ongoing to investigate this. It works at specific types of nerve calcium channels. It has more potent activity at these calcium channels than gabapentin. It has predictable (linear) absorption from the gut, with a rapid onset of action, and shows less inter-patient variability in terms of dose requirements. It has been shown to help nerve pain even at the initial starting dose of 150 mg per day. If required, higher doses may be used on day 3 - 4, and the maximum dose may be used if necessary after a further 7 days(see table below). There are very few interactions with other drugs, the exceptions being potentiation with alcohol and oxycodone (excessive drowsiness). 98% of pregabalin is excreted in the urine, and therefore dose adjustments are required where there is poor renal function (elderly, renal failure). Positive effects on sleep interference have been found, and further research into the mechanism behind this is ongoing. The positive effects on sleep seem to out perform low dose amitriptyline. Side effects are similar to gabapentin and include dizziness, drowsiness, and fluid retention. It is usually prescribed twice a day.
Normal Kidney Function
Time
Breakfast
Supper
Step 1
75 mg
75 mg
Step 2
150 mg
150 mg
Step 3
300 mg
300 mg
  • Step 1 is the starting point.
  • If necessary on day 3 - 4 you can go to Step 2.
  • If necessary on day 7 you can go to Step 3.
Impaired Kidney Function
Time
Breakfast
Supper
Step 1
25 mg
25 mg
Step 2
50 mg
50 mg
Step 3
75 mg
75 mg
  • Renal Impairment Doses are suggestions only - doses may need to be lower or higher according to patient response and side effects
  • Converting from Gabapentin to Pregabalin
    • Below are some suggested conversion regimes. Each step could be 3 - 7 days. Doses may need to be adjusted according to patient response and side effects. If excessive drowsiness occurs, reduce the Gabapentin dose faster than instructed
Convert From Gabapentin 2400 mg / day To Pregabalin 600 mg / day
Time
Breakfast
Lunch
Supper
Drug
Gaba
Pregab
Gaba
Pregab
Gaba
Pregab
Step 0
900 mg
-
600 mg
-
900 mg
-
Step 1
600 mg
75 mg
600 mg
-
600 mg
75 mg
Step 2
300 mg
150 mg
300 mg
-
300 mg
150 mg
Step 3
-
300 mg
-
-
-
300 mg

 

Convert From Gabapentin 1800 mg / day To Pregabalin 600 mg / day
Time
Breakfast
Lunch
Supper
Drug Gaba Pregab Gaba Pregab Gaba Pregab
Step 0 600 mg - 600 mg - 600 mg -
Step 1
300 mg 100 mg 300 mg - 600 mg 100 mg
Step 2 300 mg 200 mg - - 300 mg 200 mg
Step 3 - 300 mg - - - 300 mg

 

Convert From Gabapentin 900 mg / day To Pregabalin 300 mg / day
Time
Breakfast
Lunch
Supper
Drug Gaba Pregab Gaba Pregab Gaba Pregab
Step 0 300 mg - 300 mg - 300 mg -
Step 1
300 mg 50 mg - - 300 mg 50 mg
Step 2
- 100 mg - - 300 mg 100 mg
Step 3
- 150 mg - - - 150 mg
  • Carbamazepine (Tegretol) is licensed for use in nerve pain. It has useful membrane stabilising properties, but is more likely to cause side effects than gabapentin. Dose titration is necessary from 100 mg per day upwards. The usual adult dose is 200 mg three times a day. Dose reduction is necessary in the elderly, with the usual dose being 100 mg twice a day. Doses above 600 mg per day are likely to cause drowsiness and ataxia (unsteadiness).
  • Oxcarbazepine (Trileptal) is the 10-ketoanalogue of carbamazepine with similar mode of action. Its principal advantage over carbamazepine is that the former causes little if any, induction of hepatic enzyme with consequent lack of autoinduction and fewer pharmacokinetics interactions. In view of its longer half life, this drug can be administered in twice daily dosages.
  • Phenytoin (Epanutin) is licensed for use in trigeminal neuralgia. It is highly bound to proteins in the blood, and can therefore affect blood levels (and therefore drug effects) of other drugs which are also highly protein bound. It is a more difficult drug to use and needs to have levels in the blood stream checked regularly. More frequent side effects means that phenytoin is rarely used for nerve pain today.
  • Sodium Valproate (Epilim) is used for nerve pain, but has no license for it. May cause abnormal liver enzymes and low blood platelets, and therefore needs careful monitoring of liver function tests and full blood count.
  • Lamotrigine (Lamictal) is used for nerve pain, but has no license for it. Rarely used today because of side effects.
Anti-arrhythmics
  • Lignocaine (Lidocaine) is a local anaesthetic which acts by blocking sodium channels in nerves. In the pain clinic it is used by intravenous infusion in hospital under full vital signs monitoring. Short infusion periods over 30 minutes can be used to help classify the type of pain in question (usually 300 mg over 30 minutes). Long infusion periods over days and weeks have been described to treat nerve pain in the longer term. Some clinics use a short diagnostic test in order to assess suitability for a trial of mexiletine. (See  also Lignocaine 5% patch).
  • Mexiletine (Mexitil) is a older drug used to treat heart rhythm disturbances. It is chemically related to lignocaine and can be taken by mouth. It has a license for nerve pain up to 50 mg three times a day. Clinically doses as high as 600 mg per day may be needed, but is often associated with a high rate of side effects such as indigestion, nausea, dizziness and palpitations. Others in the same group include flecainide and tocainide but are rarely used due to side effects.
Topical Agents
  • Capsaicin is the active ingredient in chilli peppers. It is licensed for use in post-herpetic neuralgia after shingles, and also in osteoarthritis. The cream is absorbed through the skin to reduce substance P (a neuro-transmitter) levels in peripheral C-fibre nerves, and in the dorsal horn of the spinal cord. Substance P in the periphery is often associated with inflammatory processes like osteoarthritis, whilst in the dorsal horn it is involved in the gate control of pain. Capsaicin produces depletion of stored substance P in nerve endings, and therefore causes initial heat and redness in the skin. With regular use (4 times a day), nerve ending levels of substance P are kept very low, meaning that the heat and redness do not recur. It is important to use only a small amount of the cream to avoid excessive redness and heat. Hands must be washed in soap and water afterwards to avoid contact with sensitive mucous membranes. Available as:-
    • Zacin 0.025%
    • Axsain 0.075%
  • Capsaicin 179 mg 8% (Qutenza) applied topically every 3 three months has been found to be useful in refractory Post Herpetic Neuralgia and Diabetic Neuropathy. HIgh dose capsaiciin is thought to act by at TRP V1 receptors (vanilloid 1 receptors).
    • Qutenza 179 mg (8%) cutaneous patch
  • Lignocaine 5% Medicated Plaster (Versatis) was launched in the UK in January 2007. It's main use is for post herpetic neuralgia following shingles, but may have important off-license uses in the management of peripheral neuropathic pain states. Each patch contains 700 mg of lignocaine (50 mg per gram), and measures 10 cm x 14 cm. Up to 3 three patches can be worn at any one time for up to maximum of 12 hours in any 24 hour period. The patch can be trimmed with a pair of scissors to exactly match the area affected by the neuralgia. It provides topical analgesia to the affected skin, and should not be used on areas where the skin is broken due to the risk of overdose. The patch has a low side effect potential, but it should not be used with mexiletine, tocainide or other local anaesthetics.
  • - Manufacturer's Information Leaflet.
NMDA Antagonists
  • Ketamine (Ketalar) is an intravenous induction agent used in anaesthesia, and is also an NMDA (N-methyl-D-aspartate) receptor antagonist. It has been suggested that NMDA receptor activation in the dorsal horn helps contribute to dorsal horn sensitisation. Ketamine has NMDA blocking effects and therefore can reduce the degree of dorsal horn sensitisation and overall pain relief. Ketamine has been used orally and by intravenous infusion in patients with severe neuropathic pain states. The intravenous infusion rate is between 5 - 10 mg per hour used 48 hours prior to, and 5-7 days after limb amputation. The suggested oral ketamine dose for neuralgia is 10 - 20 mg three times per day. Oral Ketamine tastes foul and therefore needs to be mixed 50 / 50 with Ribena. It's oral bioavailability is only 17%.
  • Dextromethorphan (Robitussin Dry Cough) is an over the counter cough suppressant which has the same but weaker effect as ketamine at NMDA receptors.
Intrathecal Drugs
  • A small number of drugs may be injected directly into the spinal fluid (intrathecally), usually via an external or implanted infusion pump.
  • Intrathecal drugs may be used singly or in combination. Drug combinbations may vary from country to country dependant on local practice, and the presence of preservatives, which preclude their use (e.g. midazolam in France is preservative free, but is not in the UK)
  • A list of intrathecal drugs (not exhaustive) used in implanted intrathecal pumps is as follows :-
    • Preservative free morphine
    • Bupivacaine (Marcain)
    • Levo-bupivacaine (Chirocaine)
    • Baclofen (Lioresal)
    • Clonidine (Catapres)
    • Midazolam (Hypnovel)
    • Ziconotide (Prialt)
      • A relatively new drug, a toxin derived from the marine snail Conus Magus, and which acts by blocking spinal calcium channels in a similar way to gabapentin and pregabalin.
      • Given by intrathecal infusion at doses between 2.4 - 21.9 ug / 24 hours (average 9.6 ug / 24 hours), either in isolation or together with IT morphine.
      • May be used to treat chronic and cancer pain.
  • Please note - drug choices and combinations may vary in the palliative care situation.
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