Analgesia ChoicesHOW TO PLAN YOUR ANALGESIA FOR THE PATIENT

WHO Analgesic Ladder Analgesic framework proposed by WHO in 1986 For treatment of cancer pain Recommendations still relevant, & can be

extended to treatment of pain in general

Step 1- Non-OpioidsParacetamolNSAIDs/ COX-2+ Adjuvants

Step 2- Weak OpioidsCodeineTramadolBuprenorphine+ Adjuvants

Step 3- Strong OpioidsMorphineOxycodoneFentanylMethadone+ Adjuvants

Pain ↑ or persists

Pain ↑ or persists

WHO Analgesic Ladder 1. Oral route whenever possible 2. Administer at regular intervals 3. Prescribed according to pain intensity

If severe pain: additional analgesics made available as rescue analgesics (PRN on pt request)

4. Dosing should be individualised Age, renal/ hepatic function, side effect profile

5. Analgesic regime explained clearly to pt & staff Ask for PRN analgesics early rather than late Take xx mins prior to PT/OT

Analgesic Choices 1 1. PK considerations

Oral route is preferred Fast onset needed for severe acute pain (may need parenteral

route) Regular analgesia if pain expected to persist

Analgesic Choices 2 2. Side effect profile of patient

Simple analgesics eg. Paracetamol, have minimal side effects (within appropriate dosing), hence good as part of multimodal analgesia

Peptic ulcer disease: Coxibs slightly lower risk vs non-selective NSAIDs Risk of renal impairment/ existing renal impairment:

NSAIDs: Avoid Opioids: Dose adjustment needed for morphine

Hepatic impairment Paracetamol: Generally safe, consider ↓ dose or ↓ frequency if chronic use NSAIDs: Metabolised by liver, can use in mild liver disease. Avoid in cirrhosis Opioids: No dose adjustment needed for morphine or fentanyl

Opioid adverse effects Risk of opioid induced respiratory depression: elderly, renal impaired, OSA, obesity,

opioid-naive Tolerance to other opioid side effects: nausea, vomiting, giddiness, constipation

Analgesic Choices- Coxibs vs Non-selective NSAIDs Most side effects are dose-dependent Peptic ulcer disease

Generally lower in Coxibs: endoscopic & clinical outcomes (symptomatic ulcers/ ulcer complications)

May be similar in Coxibs + aspirin vs Non-selective NSAIDs Renal impairment

Coxibs & NSAIDs NOT recommended for at risk group: chronic renal insufficiency, DM nephropathy, volume depleted, CVS Dz/ CCF, concurrent use of meds that impair potassium excretion

Platelet function: Coxibs do not inhibit platelet function ↑ safety in anticoagulated patients eg. those on warfarin for PE

CVS disease Worsen CCF, ↑ BP: both Coxibs & Non-selective NSAIDs Ischaemic CVS events: May be ↑ in Coxibs as they do not inhibit platelet fx

Practical PK Non-opioidsPK Parameters Diclofenac Naproxen Celecoxib Etoricoxib KetorolacDose (max/d)

PO 50mg tds (100-150mg/d)PO SR 75-100mg bd (150-200mg/d)

PO 275/ 550mg bd (1100mg/d)

PO 100/ 200mg bd (400mg/d)

PO 60/90/120mg om (120mg/d)

IM 30/ 60mg (120mg/d)

Time to peak serum (mins)

IM 5 NA NA NA 30-60PO 15-30 60-120 180 60 45PO SR 120-300 240-360 NA NA NAPR < 60 NA NA NA NA

Protein bind (%) albumin, > 99 albumin, > 99 albumin, 97 92 99Metabolism

Hepatic HepaticHepatic, CYP2C9 Hepatic Hepatic

Active metabolites weak inactive inactive weak ?Bioavailability (%) 55 100 unknown 100 100Elimination T1/2 (mins)

IM 60-120 NA NA NA 300PO 120 720-1020 180-600 1200

Duration action (hrs) < 8 < 12 < 12 24 4-6

Source: UpToDate. May differ from other sources due to different parameters: eg different bolus doses, or time to serum peak vs time to peak effect

Analgesic Choices- Opioids

Most side effects are dose-dependent Consider dose-reduction if intolerable nausea, giddiness

Tolerance develops for most side effects except constipation Always monitor BO, prescribe laxatives

Desaturation is a late sign of respiratory depression, ↓ RR is an early sign O2 therapy, monitoring in at risk group

Needs renal dose adjustment

Practical PK OpioidsPK Parameters Morphine Oxycodone Pethidine Tramadol FentanylReceptor actions

mu, k, d mu, k, dmu, k, anti-muscarini, LA

mu, k, d, presynp 5HT release mu, k, d

Common Dosing PO 5mg 6H PRN,IV PCA PO 5mg 6H PRN IM/ IV 25-50mg

PO 50mg 8HIM/ IV 25-50mg SC or as IV PCA

Potency1

1 (IV)1.5 (PO) 0.1 0.1 100

Onset (min) PO IR 30 10-15 NA 60 NAIV 5-10 ? 5 ? 2-3

Time to peak serum (min)

PO IRNA

60-120 (cap)< 60 (liquid) NA 120 NA

PO SR 180-240 240-300 NA NA NASC 50-90 No data, but

should approximate morphine

60 NA No dataIM 30-60 60 45 NAIV 20 10 ? 3-4TD NA NA NA NA 18

Bioavailability (%) 17-33 60-87 20 75 50-70Duration (hrs) PO IR,

IM, IV 3-5 3-6 2-4 6 0.5-1PO SR 8-12 12 NA NA NA

Source: UpToDate. May differ from other sources due to different parameters: eg different bolus doses, or time to serum peak vs time to peak effect

How To Write Analgesic Prescriptions 1. Route = oral whenever possible

2. Drug Name 3. Dosage

Paediatric pt, liver/ renal impairment may need dose adjustment

4. Frequency Regular Intervals, if pain expected to persists. Eg x no of

times a day or x hourly Rescue Analgesics, if severe pain flares expected. Use

“PRN” (Pro Re Nata, Latin for as the circumstance arises) Examples:

PO Paracetamol 1g QDS PO Tramadol 50mg 8H PRN (for severe pain) PO Maxolon 10mg 8H PRN (for nausea, vomiting)

Frequency Abbrev.Every morning

OM

Every night ON1x a day OD2x a day BD3x a day TDS4x a day QDS8 hourly 8H

Analgesic Choices- Opioids as PCA

Responsibility of Acute Pain Service (Anaesthesia Department): patient/ programme selection

Most common PCA opioid = IV Morphine Advantages of Patient-Controlled Analgesia

↓ delay in analgesia delivery: do not need to request to nurse, wait for nurse to check & administer controlled drug

↓ respiratory depression: patient will not press when drowsy IV route more potent vs oral, faster onset Provides sense of control over pain to patient

IV PCA Morphine Common IV PCA Morphine Setting

Concentration: 1mg/ml Reservoir: 50ml or 100ml Bolus: 1mg Lockout: 5min Basal infusion: 0mg/hr Max: 6-10 doses/hr