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.

• 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.

Morphine is used to treat moderate to severe pain. It works by dulling the pain perception center in the brain. Short-acting formulations are taken as needed for pain. Extended-release formulations are used when around-the-clock pain relief is needed.

Morphine is not for treating pain just after surgery unless you were already taking it before the surgery.

Morphine may also be used for purposes other than those listed in this medication guide.

 

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. 

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

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 

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 10 mg SR + naloxone 5 mg SR  
• Oxycodone 20 mg SR + naloxone 10 mg SR  

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:-