Pain management

Acts within CNS to increase pain threshold by inhibiting central COX enzymes

Indications: mild-moderate pain, pyrexia

Cautions: reduce dose in liver failure/low body weight, 6hrly intervals in severe renal impairment

Adverse effects: S/E rare, may include flushing and hypotension

Inhibit COX enzymes to block prostaglandin synthesis

Indications: mild-moderate pain, pyrexia, inflammation

Contraindications: hypersensitivity (e.g. asthma), PUD, renal/liver impairment, pregnancy (3rd trimester), coagulopathy

Adverse effects: GI ulceration (COX1), AKI, hepatotoxicity, increased risk of MI/stroke (COX2)

COX1: routine physiological functions

COX2: induced by pain and inflammation

Mechanism of action:

• binds to opioid receptor
• stimulates G protein: GTP -> GDP
• inhibits intracellular cAMP production
• blocks calcium efflux, increases potassium influx
• ion imbalance: decreased neurotransmitter release and decreased transmission of pain

Contraindications:

• respiratory depression
• comatose patients
• head injury/raised intracranial pressure (interferes with neuro assessment- pupil responses)
• risk of paralytic ileus
• some specifics for each opioid

Side effects:

• constipation (coprescribe senna +/- docusate)
• N+V: usually settles in a few days, PRN haloperidol
• sedation: decrease dose
• dry mouth: oral hygiene, artificial saliva
• respiratory depression
• bradycardia, hypotension and arrhythmias
• pruritus
• tolerance + withdrawal
• addiction- rare in severe pain

Opioid toxicity:

• features: myoclonic jerks, pinpoint pupils, hallucinations, confusion, respiratory depression
• mgmt: changing the opioid (reduce dose by 30-50%, contact specialist, consider alternative e.g. oxycodone), naloxone (if difficult to rouse/resp depression- RR<8/SaO2<90%, slow titration if opioid used for pain)

Metabolised via CYP450 enzymes to produce morphine, acts on opioid receptors

Used for mild-moderate pain

Mainly acts through its metabolite (opioid receptor agonist). Also inhibits noradrenaline and serotonin uptake

Indications: moderate-severe pain

May interact with SSRI/SNRI to cause serotonin syndrome

1st line for use (PO + SC)

Breakthrough doses should be 1/10 to 1/6 of regular daily dose

If breakthrough dose is >60mg this will be painful SC

Prescribing:

• Add together regular and breakthrough doses used in 24hrs to find total 24hr needs
• Divide by 2 to get dose each 12hrs
• Do not increase regular dose by more than 30-50%
• Convert PO to SC (e.g. for a syringe driver) when no longer able to use oral route e.g. end of life, poor swallow, drowsiness
• Convert to oxycodone if concerns about opioid toxicity
• Convert to alfentanil if concerns about renal failure

Alternative to morphine in toxicity/intolerance

Beware dosage conversions

Naming differences: Oxynorm (PO, immediate release), Oxycontin (PO, modified release)

Better in renal failure (but use alfentanil if GFR <30)

Highly potent- don't use IV/SC

Practical choice for transdermal/transmucosal route in end-stage renal disease:

• transmucosal: rapid onset, short duration
• transdermal: slow onset

Don't stop patches for patients during their last few days

Highly potent

Short acting

If eGFR <30: SC opioid of choice

Seek specialist advice when prescribing this

Options:

• nerve block
• epidural
• PCA pump
• neurolytic block therapy
• spinal stimulator

• Corticosteroids: raised intracranial pressure, nerve compression, liver capsule pain, soft tissue pain
• Antidepressants/anticonvulsants (e.g. amitriptyline, gabapentin, pregabalin): neuropathic pain
• Muscle relaxants (e.g. baclofen, diazepam): muscle spasm
• Bisphosphonates (e.g. pamidronate, zolendronic acid): bone pain
• Antispasmodics (e.g. hyoscine butylbromide, hyoscine hydrobromide): bowel colic, bladder spasm- butylbromide in renal failure

Examples: amitriptyline

Used for neuropathic pain

Central and peripheral action on histamine, muscarinic, and serotonergic receptors

Need 2wks before full effects

Can be poorly tolerated. S/E: dry mouth, dizziness, blurred vision, confusion, constipation

Used for neuropathic pain

Less effective than TCAs

Decreased reuptake of serotonin/noradrenaline

Need 2-4wks of treatment before full effect.

S/E: GI upset, weight gain

Duloxetine is best tolerated and is licensed for diabetic neuropathic pain

Used for neuropathic pain

Acts on calcium channels

Benign S/E profile

Needs initial dose titration- 7 days for full effects

Used for neuropathic pain

Benign S/E profile

Quicker onset of action than gabapentin

Now a class C controlled drug