Opioids
Examples
"Opiates" is the term used to define chemicals which are derived directly from the opium poppy, whilst the term "opioids" is reserved for drugs which have been made synthetically as an opiate substitute. It is important to remember that opioids may have slightly different actions than opiates.
Weak Opioids:
- Codeine
- Dihydrocodeine
- Tramadol
Strong Opioids:
- Morphine
- Diamorphine
- Fentanyl
- Pethidine
- Methadone
Indications
Analgesia: opioids are used to relieve pain, particularly moderate to severe pain. See the
WHO Analgesic Ladder.
Contraindications
Contraindications
- Acute Respiratory Depression
- Risk of Paralytic Ileus (as a side-effect of opioids is decreased peristalsis)
- Raised intra-cranial pressure (as opioids can interfere with pupil responses that are vital to monitoring neurological status)
Caution
- Impaired respiratory function (e.g. Asthma, COPD)
- Hypotension
- Shock
- Obstructive or inflammatory bowel disorders
Care should be taken when prescribing for the elderly (who are more prone to side effects) and in pregnancy.
Care should be used when prescribing opioids in patients with hepatic impairment as it may precipitate comae. It is recommended that opioids are avoided or doses reduced in these patients.
Likewise some opioids like morphine and to a lesser extent oxycodone are excreted renally. Therefore in patients with impaired renal function consideration should be given to reducing the doses of these opioids or switching to a type of opioid which is not affected by poor renal function such as Alfentanil
Mechanism
The analgesic effects of opioids are due to decreased perception of pain, decreased reaction to pain and increased pain tolerance.
When a patient is experiencing pain, primary sensory neurones release substance P and glutamate at the dorsal horn of the spinal cord. Then, nociceptive information is transmitted to the brain via the ascending spinothalamic tract. This information activates descending pathways from the mid-brain and the thalamus, which attempt to relieve the pain by inhibiting the dorsal horn of the spinal cord.
Opioid receptors are present in many parts of the nervous system, including primary afferent neurones, the spinal cord, the mid-brain and the thalamus. In simple terms, opioids help to relieve pain by:
- Inhibiting neurotransmitter release from the afferent neurones in the spinal cord (thus preventing painful stimuli from reaching the brain)
- Activation of inhibitory pathways which begin in the midbrain (helping to inhibit painful stimuli)
The inhibition of neurotransmitter release through opioid use is achieved by closing calcium channels and opening potassium channels in the neurone's cell membrane, which prevents an action potential (a necessity for neurotransmitter release).
Opioids act on 3 subtypes of Opioid Receptor - m receptors, d receptors and k receptors. It is not necessary to know which drugs act on which opioid receptor subtypes or which cause adverse effects, however it is helpful to appreciate that different drugs affect receptors differently which may be used to the patient's advantage. Morphine acts primarily on m receptors.
Administration
Opioids are highly versatile and can be administered through a variety of routes. Oral and IV are the most common, but intra-nasal, sub-cutaneous and trans-dermal preparations may be useful in some instances. They may also be used in epidural or intra-thecal procedures.
In most cases, oral or IV doses are used initially and then switched to other preparations. It should be noted that parenteral doses of opioids are usually half the equivalent oral dose e.g 10mg oral morphine is equivalent to 5mg of IV morphine.
N.B. Conversions between opioids are complex and should not be undertaken lightly. However the BNF does offer some guidance on doing this in its ‘Prescribing in palliative care’ section.
Adverse Reactions
The most important documented side-effect of opioids is respiratory depression. This can lead to hypoxaemia and respiratory acidosis if left untreated. Whilst it is not known definitively what causes this respiratory depression, evidence suggests that it is through opioids blocking specialised respiratory neurones in the brainstem. It is opioid-naive patients who are receiving parenteral administration that are at highest risk.
Constipation and urinary retention are also common side-effects of opioid analgesia and are caused by sphincter contraction and decreased peristalsis. Opioids should always be given along with a laxative.
Other important side effects of opioids include:
- Nausea and vomiting
- Bradycardia / Tachycardia
- Palpitations
- Muscular rigidity
- Confusion
- Mood changes
One very important thing to look out for when prescribing opioids is
toxicity. Opioid toxicity can be subtle and is very often missed. It often presents as agitation, confusion or myoclonic jerks. In some cases it presents as subtle hallucinations in the peripheral vision. It is very important that symptoms such as agitation or confusion are not simply dismissed as uncontrolled pain and "cured" by giving more opioids, as this will obviously only cause increased toxicity!
If toxicity is suspected, the mainstay of treatment is dose reduction of the opioid, and proper hydration. It is
essential that the opioid is not stopped completely.
Interactions
Alcohol should be avoided when taking morphine, as both cause CNS depression, and the combination could be fatal.
Concomitant therapeutic use of tramadol and serotonergic drugs such as SSRIs and MAO inhibitors can result in serotonin syndrome.
Macrolides can in theory increase the exposure to opioids such as fentanyl and oxycodone
Education
Patients should be warned of the possibility of dependence and tolerance of opioids - see "Pharmacokinetics." Moreover, it is the responsibility of the prescriber to avoid this as much as possible.
In addition to this, patients should be aware of the fact that opioids can cause confusion and sleep disturbance, and consider this before operating heavy machinery.
Finally, the dangers of taking alcohol and morphine together should be stressed to patients.
Pharmacokinetics
The long term use of morphine can lead to both tolerance and dependence.
Remember, tolerance = "reduced responsiveness to a drug caused by previous administration".
Dependence is, "dependence on a drug for health or survival". There are both physical and psychological components of dependence. Psychological components are produced by stimulation of reward pathways within the brain by the use of a drug.
Due to tolerance and dependence, patients are prone to Withdrawal Syndrome when they stop taking opioids. For this reason they should be advised not to stop taking opioids suddenly, before speaking to a doctor. Withdrawal syndrome occurs because the body becomes tolerant to opioids when they are taken for an extended period of time. This simply means that greater quantity of the drug is needed to achieve the same level of analgesia. This tolerance comes about because of complex physiological adaptations that are basically designed to maintain homeostasis. The problem is that when opioids are stopped suddenly, this homeostasis is disrupted, and this causes a wide range of symptoms, including strong cravings, nausea and vomiting, cramps, sweating, muscle aches, shakes, insomnia, and agitation.
Many opioids are renally excreted and toxicity can occur if renal function is impaired.
