Simple analgesics Paracetamol regularly Codeine phosphate NSAIDS Diclofenac

Simple analgesics • Paracetamol regularly • • Codeine phosphate NSAIDS - Diclofenac and naproxen – common examples - Not well tolerated in the older person so must be used with caution

Morphine • Mu-opioid receptor agonist • Active metabolites • Renally excreted – therefore, not for use in renal impairment • Subcutaneous morphine - approximately twice as potent as oral morphine - i. e. 20 mg oral = 10 mg subcut • Codeine 60 mg = 5 -8 mg morphine i. e. 60 mg codeine QID = approx. 5 mg Q 4 H

Methods of morphine administration • Normal Release - Morphine elixir 4 strengths available – be careful to check before administration - Sevredol™ (10 mg & 20 mg tablets only) • Controlled release morphine - Note: NOT to be crushed - m-Eslon™ (10 mg, 30 mg, 60 mg, 100 mg) can be sprinkled - Arrow-Morphine LA tablets (10 mg, 30 mg, 60 mg, 100 mg) • Intraspinal – Step 4 on WHO Ladder

Oxycodone • Mu- and kappa- opioid receptor agonist (semi-synthetic) • • Renally excreted - 19% unchanged, 50% oxymorphone Onset action: 20 -30 min orally • ? Less active metabolites than morphine

Oxy. Norm. TM and Oxycodone CR • In palliative care, Oxy. Norm. TM is generally considered to be twice as potent as morphine when taken orally • Subcutaneous oxycodone • approximately twice as potent as oral oxycodone • i. e. 20 mg oral = 10 mg subcut • All preparations are funded - cost not excessive - useful alternative to morphine when morphine not tolerated or in presence of mild to moderate renal impairment

Oxy. Norm. TM and Oxycodone CR contd Normal release: • Oxy. Norm. TM capsules (5 mg, 10 mg, 20 mg) • Oxy. Norm. TM oral liquid (5 mg/5 m. L) • Can be used for titration and breakthrough pain (1/5 th – 1/10 th of the 24 hr dose) Controlled release: • Oxycodone CR tablets (5 mg, 10 mg, 20 mg, 40 mg, 80 mg) have a biphasic response - therefore, no need to give immediate release at the same time as slow release dose

Methadone • Indications: - Morphine toxicity / unacceptable side effects - Inadequate pain relief with other opioids - Renal failure - Neuropathic pain - Previous narcotic dependence – on maintenance methadone • Routes: oral or subcut • 5 mg tablet • 3 strengths of elixir available – 2 mg, 5 mg and 10 mg per m. L - check carefully before administration

Methadone contd • Less nausea, constipation and drowsiness than morphine • t ½ or half life – 8 -75 hrs • Difficult medication to use – needs medical specialist input

Transdermal Fentanyl • Indications - When the oral route is unavailable e. g. dysphagia or severe nausea and/or vomiting - Renal failure - Social (convenience) - Morphine “phobia” - Side effect profile, e. g. less constipation and sedation • Pain unresponsive to morphine is unlikely to be responsive to fentanyl, due to also being a mu-opioid receptor agonist • Need to titrate with short acting morphine or oxycodone before starting patch - see example on next slide

Transdermal Fentanyl contd Example of dose comparison when titrating: A 12. 5 microgram/hour patch is (approx. ) equivalent to 30 mg morphine in a 24 hr period

Transdermal Fentanyl contd • t ½ or half life - 13 -22 hrs • Steady state plasma concentrations after 36 -48 hrs • Onset of action 12 hrs • Duration of action 72 hrs • Contraindication – uncontrolled pain requiring rapid dose titration • Patches are 12. 5, 25, 50, 75 and 100 mcg/hour – not daily • The depot of drug in skin will continue to provide some analgesia for approx. 17 hrs after a patch is removed

Co-analgesics • Antidepressants e. g. nortriptyline • Anticonvulsants e. g. sodium valproate, gabapentin, clonazepam • Non steroidal anti-inflammatories e. g. diclofenac, naproxen • Steroids e. g. dexamethasone • Anti-spasmodics e. g hyoscine butylbromide (Buscopan)

Antiemetics • Metoclopramide - Dopamine receptor antagonist - Increases peristalsis in upper gut - Contraindicated in complete bowel obstruction and those with Parkinson’s disease - Watch for agitation and akathisia in higher doses, with chronic use, and with presence of renal disease - Oral or subcut • Domperidone - Similar to metoclopramide but less extrapyramidal effects - Drug of choice in older person - Oral route

Antiemetics Haloperidol • Dopamine receptor antagonist, hence not for use in Parkinson’s disease • Potent centrally acting antiemetic – very useful for opioid induced nausea, hypercalcaemia and renal failure • Can be given subcutaneously

Antiemetics Cyclizine • Oral and subcut routes available - although subcut can be painful • Antihistamine, antimuscarinic • Indicated for motion sickness, mechanical bowel obstruction, raised intracranial pressure • Drowsiness can be profound • Can cause confusion in elderly so best to dose reduce

Antiemetics Dexamethasone • Centrally acting antiemetic • Especially useful in liver metastases, raised intracranial pressure, and to reduce vomiting in bowel obstruction • Added to first line antiemetics in palliative care • Watch for signs of confusion in the older person • Can cause insomnia – given in the morning to reduce this effect • Can be given subcut - need to watch for volume if given as bolus dose – may need to be divided

Antiemetics Levomepromazine • Low potency anti-psychotic, blocks a number of differing receptors including dopamine, histamine, adrenergic and serotonin • Offers analgesic, antipsychotic, hypnotic and anti-emetic properties in palliative care • Most commonly used for intractable nausea and vomiting and severe agitation or delirium in last days of life • Side effect – akathisia and significant sedation

Midazolam • Commonly used for agitation and anxiety associated with dyspnoea • Short acting benzodiazepine • It is more quickly eliminated from the body compared with clonazepam. • Preferred routes in palliative care subcut, intranasal and buccal

Laxatives • Start laxatives when starting opioids • Laxsol™ - daily or twice daily - up to 3 tablets TDS sometimes necessary - docusate softens and senna stimulates • If not effective, add in Lax-Sachets™ as an osmotic – needs to be introduced early (note: requires special authority funding) • Kiwi crush will not normally control opioid induced constipation

Suppositories and enemas These will not often be required if a good bowel regime has been started - use glycerine suppositories to soften and bisacodyl suppository to stimulate - or use sodium citrate/sodium lauryl sulfoacetate/glycerol (Microlax. TM enema) – use with caution - or if these are not effective, try an oil retention enema - or use a Fleet™ enema with care

Precautions • Stimulants are contraindicated for people with complete bowel obstruction • Bulking agents and high fibre diets are poorly tolerated in the palliative person • Lactulose is an osmotic laxative which is poorly tolerated in people who are unable to maintain a high fluid intake

Remember to ask • Why are you using the medication? • What is the most appropriate route? • Can we reduce the burden of taking lots of tablets? • Are there any contraindications? • Have you considered non-pharmacological interventions? Reassess, reassess

Useful resources and references • New Zealand Palliative Care Handbook. (8 th Edition). (2016) - http: //www. hospice. org. nz/resources/palliative-care -handbook • New Zealand Formulary - http: //nzformulary. org/ • Palliative Care Drugs - http: //nzformulary. org/ • Medsafe - http: //www. medsafe. govt. nz/ • The local hospice or community pharmacist • Local DHB prescribing guidelines e. g. local hospice or specialist hospital team