Page 54 - Demo

CONTINUING PROFESSIONAL DEVELOPMENT
MEDICATION MYSTERIES
You discuss Anna’s medicines with her, including
prescribed, over-the-counter (OTC) and complementary medicines; and changes in medicine dose or frequency. You also ask about her use of alcohol and lifestyle drugs such as cannabis. In Anna’s case, the addition of the tramadol 50 mg appears to be the trigger for the change in her equilibrium.4–6 Anna tells you that her pain has been so severe she has been taking both tramadol 50 mg and oxycodone 5 mg every 6 hours. She is also taking citalopram 40 mg each day. She mentions that she has actually taken two tramadol capsules a few times, as she says she just cannot cope with the pain levels and nothing is helping. The tramadol does ease the pain, but she feels very euphoric and delusional after taking it.
Serotonin syndrome
An accumulation of serotonin in the central and peripheral nervous systems can cause serotonin syndrome.5–7 This syndrome is potentially lethal.6
Serotonin syndrome can develop via several mechanisms, which may occur either alone or conjointly6:
• increased serotonin synthesis
• decreased serotonin metabolism
• increased serotonin release
• inhibition of serotonin re-uptake (e.g. SSRIs, tramadol)
• direct agonism of serotonin receptors.
Serotonin is involved in the regulation of attention, behaviour, body temperature, digestion, blood flow and breathing.3
Symptoms of serotonin syndrome include4–6:
• agitation or restlessness
• confusion or hypomania
• diarrhoea
• tachycardia
• hypertension and fluctuations in blood pressure
• hallucinations
• loss of coordination
• elevated core body temperature leading to fever
and heavy sweating
• nausea and vomiting
• neuromuscular hyperactivity including muscle
spasm, hyperreflexia, rigidity, shivering and tremor
• uncoordinated movements (ataxia).
Serotonin syndrome can be caused by antidepressants or tramadol alone, or in combination with other serotonergic medicines.5,6 It is more common to encounter serotonin syndrome when tramadol is combined with other serotonergic agents (see Table 1).5–7
Tramadol has analgesic activity with a partial agonist effect on the mu opioid receptor sites.5,6 The active metabolite, O-desmethyl-tramadol, has a 200-fold higher affinity for mu opioid receptor sites than the parent compound.6 Tramadol inhibits serotonin and norepinephrine (noradrenaline) in the peripheral nervous system, which may explain some of the adverse effects that it exhibits.6
Recommendations
The combination of citalopram 40 mg and tramadol would be the most likely
cause of Anna’s symptoms.5-7 Anna is concerned that, as she is in a lot of pain, she does not know how she will cope with the pain if tramadol is ceased. You recommend that she continue Panadol Osteo at a dose of two tablets every 6 hours (maximum of six tablets in 24 hours), and she continue to take oxycodone as needed. You also recommend that Anna return to see her GP.
You provide a written referral to the GP recounting your discussion with Anna. You provide the GP with a copy of the pain assessment checklist that you have completed with Anna in the pharmacy.7 You also recommend that a Home Medicines Review be conducted as soon as possible so you can follow up on your recommendations with Anna.
You recommend to Anna and the GP that the following options be considered:
• Cease tramadol.
• Use a short-term non-steroidal anti-inflammatory drug (NSAID) to reduce the pain
exacerbation.
• Use heat, massage and support to manage pain flare-ups in particular areas.
• Refer to the rehabilitation pain clinic at the local hospital that offers an exercise
program for managing arthritis pain using occupational therapy, land-based
exercises, and water-based exercises in the warm-water pool.
• Refer to a podiatrist to determine if Anna’s fall was caused by her feet/gait, and if
orthotics could be beneficial in relieving her back and knee pain.
• Add high-dose magnesium tablets to her regimen, as there is evidence that
magnesium can be opioid-sparing and of benefit in pain management.9
• Consider the use of duloxetine instead of citalopram if pain is difficult to manage
and if there is any neuropathic component.10,11
• Trial a low dose of amitriptyline at bedtime if night time pain is causing loss of
sleep; it may reduce pain and assist Anna to have better sleep.10,11
• Trial an anti-inflammatory dose of fish oil. Although most studies have been in
patients with rheumatoid arthritis, there is some evidence for beneficial effects of fish oil in osteoarthritis. Fish oil supplements at doses of ≥2.2 g omega-3 fatty acids daily have been shown to have anti-inflammatory and NSAID-sparing effects in patients with rheumatoid arthritis.8 Anna could trial a dose equivalent to at least 2.2 g omega-3 fatty acids daily to determine whether fish oil is of value for her.
• Trial turmeric if Anna chooses, as she is not taking any medicines that would be affected by it.8 Recommend that the other changes are implemented first as it will be difficult to determine which change provided benefit if they are all implemented at once. Recommend regular monitoring (every 6 months) if Anna is taking turmeric and fish oil, as both these complementary and alternative medicines (CAMs) can affect liver function tests (increase alkaline phosphatase [ALP] and alanine aminotransferase [ALT] respectively), and turmeric can increase lactate dehydrogenase (LDH).8
• Enrol in relaxation therapy programs that may assist in managing Anna’s pain, anxiety and depression.7
• Enrol in a pain management program involving a multidisciplinary approach to flexibility, strength and pain management.7 These programs also
involve a psychologist who can assist in managing Anna’s pain and anxiety/depression, and potentially enable her to lower the dose
of citalopram.
52 Australian Pharmacist January 2017 I ©Pharmaceutical Society of Australia Ltd.
Find more information in APF23
Further information about drug interactions, including serotonin syndrome (page 113), can be found in the Drug interactions chapter (page 105) of the 23rd edition of the Australian Pharmaceutical Formulary and Handbook (APF23).