Pain management

Preeyaphan Arunakul MD FRCAT

Department of Anesthesia

Faculty of Medicine, Thammasat University

“An unpleasant sensory and emotional

experience associated with actual or

potential tissue damage, or described in

terms of such damage.”

Definition

• Acute pain

- Pain less than 12 weeks

• Chronic pain

- Pain longer than 12 weeks

Classification of pain by time

Nociceptive Nonnociceptive

Somatic Visceral Neuropathic Psychogenic

sharp, dull

achingPoorly localized,

deep squeezing,

crampy

Burning, electrical

(lancinating),

numbing,

allodynia,

hyperalgesia

-Rarely pure

-No nociceptive or

neuropathic mechanism

can be identified

-With sufficient

psychogenic symptoms

-Myofascial

-Metastatic

bone pain

-Postsurgical

-Arthritis

-Small bowel

obstruction

-Carcinomatosis

peritonii

-Trigeminal neuralgia

-Postherpetic neuralgia

-Painful peripheral

neuropathy

-CRPS I,II

-Phantom limb pain

Antidepressants

Psychological therapy

Anticonvulsants

Antidepressants

Interventions

Multimodalities

TCA/SSRI

Gabapentin

Opioids

Interventions

Psychotherapy

NSAIDs

Opioids

Muscle relaxants

Aniline deriv.

Multimodalities

Acute Postoperative Pain

ผู้ ป่วยมีอาการปวดเฉียบพลนั

มีสาเหตทุี่ท าให้เกิดอาการปวด

ประเมินระดบัความปวด

อาการปวดต้องการการรักษาหรือไม่

รักษาโดยใช้ยารักษาโดยไม่ใช้ยารักษาแบบผสมผสาน

รักษาสาเหตุ

เคร่ืองมือท่ีใช้ประเมินความปวด- VAS/VRS/NRS- FACE/FLACCs- CHEOPS

ไม่ต้องการ

ต้องการ (PS ≥ 4 หรือปวดปานกลางขึน้ไป)

ประเมินซ า้และบนัทกึ

การรักษาได้ผลดีหรือไม่

เกิดภาวะแทรกซ้อนจากการรักษาหรือไม่

ประเมินซ า้และบนัทกึ

รักษาภาวะแทรกซ้อน

ไม่ได้ผล ปรึกษาผู้ เชี่ยวชาญ

เกิดได้ผลดี

ไม่เกิด

“5th Vital sign”

Postoperative pain

• Acute pain

• Choices:

- iv bolus/iv PCA/oral opioids

- neuraxial opioids (spinal & epidural)

- peripheral nerve blocks with LAs

- NSAIDs and other medications

• Effects of pain on systems

CNS & Neuroendocrine

1. Secretes enkephalins, endorphins

2. Reflex escape response “Fight or Flight”

- stimulated sympathetic nervous system

- increased E and NE

- inhibit peristalsis and secretion of digestive enzymes

3. Increasing CRH, ACTH, Cortisol from hypothalamus

4. Increasing glucagon and reduce insulin level

CNS & Neuroendocrine

5. Increasing E & NE from adrenal medulla

6. Decreasing ADH = Na & water retention

7. Increasing renin & AT II secretion from adrenal gland

8. Increasing protein breakdown = reduce wound healing

9. Increasing IL-1 level = increase inflammatory effect

Cardiovascular system

Increasing sympathetic activity

Hypertension increase myocardial

Tachycardia O2 consumption

Myocardial ischemia

GI and Immune system

• Depress immune system

• Impaired GI function

- delayed gastric emptying

- reduce bowel motility, potential paralytic ileus

- nausea & vomiting (also from CTZ)

Limiting movement of thoracic & abdominal muscles

Respiratory dysfunction

Retained sputum and secretion

(reluctant to cough)

Reduction in vital capacity

Hypoxia

Cardiac complication, disorientation,

confusion, and delayed wound healing

Respiratory system

Increasing CAs, aldosterone, ADH, cortisol, AT-II, and PGs

(regulate urinary output, fluid & electrolyte balance, blood volume, and BP)

Na & water retention

Increase K+ excretion

Fluid overloadIncrease cardiac workload

Hypertension

KUB system

Reflex muscle spasm, impaired muscle function

Muscle fatigue

Immobility

Venous stasis

Increase coagulability

Increase risk of developing DVT

Musculoskeletal system

Acute stress-induced hormonal changes

1. Anxiety interrupt sleep pattern (insomnia)

Depression interfere daily activity

2. Distressing cognitive impairment

- disorientation

- mental confusion

- reduce ability to concentrate

3. Poorly-controlled acute pain --> chronic pain

Psychological & Cognitive function

Neuropathic pain

Definition

• “Pain caused by a lesion

or disease of the somato-

sensory nervous system”

• Clinical description

(not a diagnosis) ; requires

demonstrable lesion or disease

that satisfies established neurological diagnostic criteria

• Central and peripheral neuropathic pain

• Pharmacotherapy

• Physical and Psychotherapy

• Interventions

• Surgery

• Lifestyle modifications

• Alternatives

• Neurostimulation (SCS)

Management

Pharmacotherapy

• Gabapentin/Pregabalin (Neurontin®/Lyrica®)

• Amitriptyline/Nortriptyline

• Carbamazepine/Oxcarbazepine (Tegretol®/Trileptal®)

• Duloxetine/Venlafaxine (Cymbalta®/Effexor®)

• Tramadol (for acute exacerbation only)

Cancer pain

Medications

• Opioids

• Gabapentin and pregabalin

• NSAIDs (for bone metastasis)

• Antidepressants/antianxiety

ยาNociceptive

painNeuropathic cancer pain

Cancer-induced

bone pain

Tumor-induced

headache

Visceral pain MBO*

Opioids ดีมาก ปานกลาง ดีมาก ดีดีมากส าหรับอาการปวดตลอดเวลา

NSAIDs ดีมาก ไม่ดี ดีมาก ดี ไม่แนะน าAntidepressants TCAsและSNRIs

นอ้ย ดีมาก ปานกลาง ไม่แนะน า ไม่แนะน า

Gabapentinoids นอ้ย ดีมาก ดี ไม่แนะน าดีส าหรับ visceral

hyperalgesia

Carbamazepine ไม่ดีดีส าหรับ paroxysmalsharp shooting pain

นอ้ยนอ้ย ยกเวน้ใชเ้ป็นยา

กนัชกัไม่ดี

Bisphosphonates ไม่ดี ไม่ดี ดีเม่ือใหร้ะยะยาว ไม่ดี ไม่ดี

Corticosteroids ไม่แนะน าดีมากส าหรับ

nerve/cord compression

ปานกลาง ดีมากดีส าหรับ liver capsule

distension

Strong opioids

• Morphine (Morphine, MST, Kapanol)

• Meperidine (Pethidine)

• Fentanyl (Fentanyl, Duragesic, Durogesic)

• Methadone

• Oxycodone

Visceral Pain

Visceral pain

Clinical features :

• Diffuse localization, deep, squeezing, crampy

• Unreliable association with pathology

• Referred sensation to cutaneous structures

• Cutaneous or deep tissue hyperalgesia

• Strong autonomic and emotional response may be

evoked with minimal sensation

Referred pain

• Pain referred from a deep somatic or visceral structure to

a distant region within the same segment

• With/without hyperalgesia and hyperesthesia, deep

tenderness, muscle spasm, and autonomic disturbances.

• No changes in reflexes, no weakness or atrophy

• Segments involved are identified (all somatic and visceral

structures innervated are carefully examined for a

pathologic process)

• Ex: Shoulder pain in subphrenic abscess

Visceral pain etiologies

• Inflammation (acute and chronic), including inflammation

caused by mechanical irritants (kidney stone)

• Infection

• Disruption of normal mechanical process (GI dysmotility)

• Neoplasms (benign or malignant)

• Alterations in nerves carrying sensations from the viscera

• Ischemia

• Opioid for cancer in origin

• Antidepressants

• Gabapentin/pregabalin

• Sympathetic plexus block/neurolysis

Medications & Interventions

Musculoskeletal pain

Pharmacotherapy

NSAIDs

Muscle relaxants

Medications

Oral medications

- Acetaminophen (paracetamol)

- NSAIDs

- opioids = tramadol, codeine

- tramadol + paracetamol (Ultracet®)

- antidepressants/anticonvulsants

IV medications

- Opioids = morphine, pethidine, tramadol, fentanyl

- NSAIDs = Parecoxib (Dynastat®), Ketorolac

WHO step ladder

modified by TASP

Patient-controlled analgesia (PCA)

Patient-controlled epidural analgesia (PCEA)

1. Improved pain control

2. Receive immediate

delivery of pain med.

3. Patient control

4. Frequent but smaller

dose, less side effects

PCA variables

• Bolus dose or PCA dose or demand dose

(self-administered intermittently)

• Lock out interval (time between dose)

• Loading dose

• Background infusion

• Dose limit in 1 or 4 hour

Using PCA

- Patient education

- Monitor O2 saturation (in high risk patient)

1. Pain scores at rest/movement

2. Side effects

Sedation, N/V, pruritus, respiratory depression,

urinary retention

3. Total amount of opioids delivered

Neuraxial Opioids

Spinal/epidural morphine

- duration 18-24 hours/it depends

- no sedatives or sleeping pills (except for order

from anesthesiologist)

- side effects :

respiratory depression

nausea and vomiting

pruritus

urinary retention

Local anesthetic for epidural

0.0625% - 0.15% Bupivacaine/Levobupivacaine

1-2% Lidocaine with or without adrenaline

Opioids

• Morphine 1-5 mg bolus or epidural infusion at

0.005-0.02 mg/ml

• Fentanyl 1-2 mcg/ml epidural infusion

- Local anesthetics only

- Single shot or catheter

- US-guided and/or peripheral

nerve stimulator

- 18-24 hours

- Side effects :

motor weakness

catheter migration

Peripheral nerve blocks

Acetaminophen

Acetaminophen (paracetamol)

• tablet 500 mg 1 tab oral prn/every 4-6 hrs

• tablet 650 mg 1 tab oral prn/every 8 hrs

• FDA Liver warning:

Severe liver damage may occur if you take

- more than 4,000 mg of acetaminophen in 24 hours

- with other drugs containing acetaminophen

- 3 or more alcoholic drinks everyday while using this

product

• FDA reminds health care professionals to stop dispensing

prescription combination drug products with more than 325

mg of acetaminophen (4/28/2014)

• Acetaminophen in both OTC and prescription products

and the risk of attention deficit hyperactivity disorder

(ADHD) in children born to women who took this

medicine at any time during pregnancy.

Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during

pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr

2014;168:313-20.

NSAIDs

Role of NSAIDs

• Acute postoperative pain

• Chronic musculoskeletal pain

• Cancer-induced bone pain

Evidence-based practice

• Prevent and treat postoperative pain in ambulatory surgery

• Decrease: opioid consumption

early return of bowel function

early recovery of physical activity

increase patient satisfaction

• No difference if given before or after surgery

Drug mg FrequencyMaximum

dose/day

Parecoxib (dynastat®) 40 IV q 12 h 80

Ketorolac 15, 30 IV q 8 h 90

Ibuprofen 200,400,600 q 4-6 h 2400

Diclofenac25,50 q 8 h

150SR75,100 q 12-24 h

Indomethacin 25 q 8-12 h 200

Naproxen 250 q 12 h 1000

Piroxicam 10,20 q 24 h 20

Meloxicam 7.5 q 12-24 h 15

Celecoxib 200,400 q 12 or 24 h 400

Etoricoxib 30,60,90,120q 24 h

120120 mg < 8 days

Compounds appearing above the line are COX-1-selective, those

below the line COX-2-selective.

Warner TD, Mitchell JA. FASEB J 2004; 18: 790-804

“NSAIDs cause an increased risk of serious

gastrointestinal adverse events including inflammation,

bleeding, ulceration, and perforation of the stomach or

intestines, which can be fatal. These events can occur

at anytime during use and without warning symptoms.

Elderly patients are at greater risk for serious

gastrointestinal events.”

FDA Black box warnings

GI toxicity

Relative Risk in developing

NSAIDs-induced Gastropathy

• History of complicated ulcer 13.5

• Multiple NSAIDs (including ASA) 9.0

• High dose of NSAIDs 7.0

• Use of anticoagulant 6.4

• Age > 70 5.6

• Use of corticosteroids 2.2

Tannenbaum, et al. J Rheum 2006

NSAID-induced small bowel injury

• Rebamipide (Mucosta®)

• Gastroprotective effect by modulate gene expression of protein

-increases growth factors thus accelerates healing

-reduces inflammatory cytokines

-acts as free radical scavengers

-increases PGs production

• Peak serum concentration at 2.4 hrs

• Distribute mostly to GI mucosa

• Does not require CYP450, less drug interaction

J Gastroenterl 2009; 44:879-88

Role of COX-2 inhibitors

• Developed to reduce GI complications

• CLASS trial1

- Symptomatic ulcer and ulcer complications

2.1% in Celecoxib group

3.5% in conventional NSAIDs group (p=0.02)

- Presence of aspirin negated GI benefit

- After 1 year, no difference in GI events2

1.Silverstein FE, et al. JAMA 2000; 284: 1247-55

2. Wright JM, et al. JAMA 2001; 286:2398-400

What if patients also taking aspirin

• Risk of GI complications

ASA + coxib = nonselective NSAID alone

• Risk of hospitalization for adverse GI event

ASA + coxib = 0.86 (hazard ratio)

ASA + NSAIDs = 1.61 (hazard ratio)

FDA Black box warning

Cardiovascular risk

“NSAIDs and COX-2 inhibitors may cause an increase

risk of serious cardiovascular thrombotic events,

myocardial infarction, and stroke, which can be fatal.

Patients with cardiovascular disease or risk factors for

cardiovascular disease may be at greater risk.”

Fosbol. Clinical Pharm Ther 2009; 85(2):190-7

Cox proportional hazard ratios for the composite end point of death and

myocardial infarction associated with exposure to NSAIDs in a study population

of 1,028,437 individuals characterized by no prior concomitant pharmacotherapy

and no comorbidity.

2.01

0.97

1.01

1.63

2.13

Healthy Individuals

NSAID alone NSAID +

PPI/Misoprostol/Rebamipide or

Coxib +

PPI/Misoprostol/Rebamipide

Naproxen (if no ASA) Avoid NSAIDs if possible

Naproxen +

PPI/Misoprostol

(if ASA)

Naproxen +

PPI/Misoprostol/Rebamipide

(regardless of ASA use)

AVG

CV risk

High

CV risk

AVG GI risk High GI risk

Chan Am J Gastroenterol 2008; 103: 2908-2918

What’s happening to kidney?

Serious side effects

• Myocardial ischemia/infarction

• Hypertension, stroke

• Heart failure (fluid retention)

• Renal insufficiency

• Bleeding & ulcers

• Life-threatening skin & allergic reactions

• Liver failure

• Induce asthmatic attacks in asthmatic patients

Contraindications for NSAIDs

• Cardiovascular thromboembolic events

• CrCl < 30 ml/min

• Active GI bleeding

• Thrombocytopenia from chemotherapy

• Active liver disease (enzymes rising > 3 times)

• Allergic to Sulfonamides

• Pseudo-allergic reactions from NSAIDs

Prolonged use of NSAIDs

• Baseline

- Serum Cr

- Hepatic function

- K+

- CBC

- BP, pulse, BW

• 2 weeks after starting

- Serum Cr

- K+

• Periodically

- Serum Cr

- K+

- BP, pulse, BW

- Hepatic function

Other drug interactions

• Celecoxib metabolized by CYP2D6, 2C9

- Celecoxib + warfarin = increase INR

- Conventional NSAIDs + warfarin/clopidogrel

= increase risk of bleeding

• SSRIs itself increase risk of GI complications

- SSRI + NSAIDs even more risk

Do NSAIDs interact with aspirin??

• Other NSAIDs (naproxen) also have been

considered to attenuate the effect of aspirin.

Ibuprofen Aspirin30 mins

8 hrs

Risk Reduction

• Avoid NSAIDs in pts with existing renal dysfunction,

CHF, resistant hypertension

• Monitor BP and serum Cr in high risk patients

Elderly, cirrhosis, HT, DM, hypovolemia

“Lowest effective dose with shortest duration”

Eperisone (Myonal)

Tolperisone (Biocalm, Mydocalm)

Orphenadrine (Pormus)

Baclofen

Tizanidine (Sirdalud, Zanaflex, Tizan)

Cyclobenzaprine (Flexeril)

Benzodiazepines (Diazepam)

Contraindications: Myasthenia gravis

Muscle relaxants

Eperisone (Myonal)

• Centrally-acting skeletal muscle relaxant used to improve

myotonic symptoms

• Should be taken with food. Take after meals

• Weakness, dizziness, insomnia, drowsiness, hepatic and

renal dysfunction

• Avoid concomitant use with Tolperisone

• Muscle spasm

• Adult: 50 mg 3 times/day

Tolperisone (Biocalm)

• Centrally-acting muscle relaxant

• Adult: PO 50-150 mg 3 times/day with food

• Well absorbed from GI tract.

• Bioavailability: 20%

• Extensively metabolized by liver and kidney

• Excreted mainly via urine as metabolites

• Side effects: muscular weakness, headache, hypotension, N/V,

sedation, drowsiness, ataxia, dizziness, confusion

• Concomittant use with levodopa in Parkinson pts may result in

confusion, agitation, hallucinations

• Orphenadrine 35 mg + Paracetamol 500 mg

• Dosage: PO BID, Duration: 4-6 h

• Indications: Adjunctive treatment for acute, painful

musculoskeletal conditions.

• Contraindications:

Glaucoma, pyloric/duodenal obstruction, PU,

prostatic hypertrophy, obstruction of bladder neck, and

esophageal achalasia.

Pormus

Norgesic

Orphenadrine 35 mg + Paracetamol 450 mg

Multilayer: Orphenadrine 25 mg + Aspirin 385 mg +

caffeine 30 mg

Orphenadrine citrate

• Derivative of diphenhydramine, acts on brainstem

• Pharmacology:, antihistamine and anticholinergic

• Onset 1 hr, duration 4-6 hrs

• Maximum 100 mg divided into BID

• Pharmacokinetics: good GI absorption, T max is 2 hrs

• Side effects: tachycardia, lightheaded, N/V, dry mouth

• Caution in renal and liver impairment

Baclofen

• GABA derivative binds to GABAB, antispastic

• Inhibits Glu and SP release at both monosynaptic and

polysynaptic reflexes at spinal level

• Onset 3-4 days, variable duration

• 5 mg PO TID (40-80 mg/day)

• Side effects: drowsiness, slurred speech, hypotension,

constipation, urinary retention, short-term memory loss

Tizanidine (Sirdalud, Tizan)

• α2-adrenergic receptor agonist

• Decrease spinal excitatory amino acid release

• FDA-approved for mx of increased muscle tone

• Onset 2 wks, 2-8 mg PO TID-QID

• Clearance is reduced >50% in pt with CrCl<25 mL/min

• Side effects: bradycardia, dose-related hypotension,

dizziness, lightheadedness but rarely syncope

Diazepam

• GABA agonist

• Onset 30 min, variable duration

• 2-10 mg PO TID

• Side effects:

Sedation, fatigue, hypotension, ataxia,

respiratory depression

• Must be slowly tapered after long-term use to

avoid withdrawal symptoms

Opioids

Alters perception of pain

Mesolimbic dopamine system = reinforcing and

rewarding properties (euphoria)

Modulates nociceptive pathways, enhancing

effects of endogenous opioids

Opioid Pharmacodynamics

How does opioid inhibit pain transmission??

Opioids

Opioid receptors (mu, kappa, delta)

Inhibits voltage-gated Ca2+ channels

Opens K+ channels causing hyperpolarization

Decreases synaptic transmission of pain signals

in the spinal cord dorsal horn

Weak opioids

“Never combined with Strong Opioids”

Tramadol

Dosage: 0.5-1 mg/kg iv (prn) q 4-6 H

50-100 mg oral (prn) q 4-6 H

max 400 mg/day

Forms : - Tramol 1-2 caps oral (prn) q 6 H

- Ultracet 1-2 caps oral (prn) q 6-24 H

(37.5 mg of Tramadol + 325 mg of paracetamol)

Side effects: dizziness, N/V, constipation

Cautions: Epilepsy, Serotonin syndrome (SSRI/SNRI),

liver or renal insufficiency

- mental status change

- autonomic instability (labile BP, tachycardia,

dizziness, diaphoresis, flushing, hyperthermia)

- neuromuscular changes (tremor, rigidity, myoclonus,

hyperreflexia, incoordination)

- seizure, use BZD

- GI symptoms (N/V/D)

Rx: Cyproheptadine in severe case

Serotonin syndrome

Codeine

• Tylenol with codeine (TWC)

• Codeine 15-60 mg + Tylenol 300 mg

• Q 4-6 H, max 240-360 mg of codeine/day

• metabolized by CYP2D6 to morphine (10%)

• extra careful in ultra-rapid or rapid metabolizer

• Analgesic effect is reduced when combined with

CYP2D6 inhibitor (fluoxetine, paroxetine)

• Side effects: drowsiness, N/V, constipation (>mo)

• Renal excretion

Strong opioids

• Morphine (Morphine, MST, Kapanol)

• Meperidine (Pethidine)

• Fentanyl (Fentanyl, Duragesic®)

• Methadone

• Oxycodone

* Commonly used in acute pain

Intravenous dosage

Morphine

• binds to mu receptor

• Hepatic metabolism to M3G, M6G (active metabolite)

• consider other opioids in stage 4-5 CKD, dialysis pt

• respiratory depression in high risk pts :

1. respiratory problems

2. severe cardiovascular problems

3. renal dysfunction

(+ benzodiazepine)

Meperidine (pethidine)

• binds to mu and kappa receptor

• Short term use only!!!! ( < 72 hrs)

• prolonged use may lead to addiction and seizure

(toxic metabolites = Normeperidine)

• Delirium, myoclonus

• Reversal with naloxone can exacerbate convulsant

effect of normeperidine

Fentanyl

• potent mu agonist

• immediate onset, duration 30-60 min

• can also be used in epidural/spinal analgesia

Central effects of opioids

- Analgesia - Mood effect

- Sedation - N/V

- Respiratory depression - CNS excitation

- Pupil constriction - Tolerance

- Antitussive effect - Dependence

- Hypothalamic effects - Addiction

Peripheral Effects of Opioids

• Constipation

• Itching/pruritus

How to deal with complications

from opioids?

Constipation

Colon contains large population of mu opioid receptor

Inhibit peristalsis

Rx : Drink lots of water

Exercise

Stimulating laxatives/stool softener

Senokot 1-4 tabs oral hs

MOM 15-30 ml oral hs

Itching

Release of histamine from mast cells

Rx : Antihistamines

CPM 10 mg iv

Ondansetron 0.1 mg/kg IV prn q 6 h

Opioid Rotation

Nausea and vomiting

- stimulate CTZ in area postrema of medulla

- alter vestibular sensitivity

Rx - 5HT3 antagonist : Ondansetron

- Gastric prokinetic : Metoclopramide

Respiratory depression

- acts on brainstem and “dose-related”

- depress all phases of respiratory activity

(Rate, MV, TV)

- high risk pt: - impaired respiratory function

- opioid-naïve pt

- OSA

Rx - Naloxone (mu antagonist) (0.1 mg/ml iv titration)

titrated carefully (excessive saliva, bronchial spasm)

(in meperidine overdose : seizures)

Is your patient overdosed?

3 Pathognomonic signs :

1. Miosis (pinpoint pupil)

2. Respiratory depression (RR≤10/min)

3. Loss of consciousness

(sedation score ≥ 2)

Rx 1. Intubation

2. respiratory support

3. iv Naloxone

Opioids in Chronic pain

Chronic pain divided into 2 groups

1. Chronic non-cancer pain

1.1 Chronic neuropathic pain

antidepressant/anticonvulsant

gabapentin/pregabalin

1.2 Chronic musculoskeletal pain

muscle relaxant, α2-agonist

NSAIDs

interventions

2. Cancer pain – depend on causes of pain

Opioid for

chronic non-cancer pain

Evidence of opioid efficacy

* A limitation of these trials was that the duration of opioid

therapy was a maximum of 3 months.

Evidence of opioid efficacy• Nociceptive pain of musculoskeletal origin

Only small-moderate benefits in improving

function and relieving pain

• Neuropathic pain

Only small-moderate benefits

• Migraine, tension headache, functional GI problems

Not indicated

• Widespread soft tissue pain

Only small benefit with weak opioid

Opioids for Cancer Pain

MST

• MST 10, 30, 60 mg tablets oral q 8 or 12 h (not TID/BID)

• peak onset 2-4 h, duration 8-12 h

• no crushing/chewing

• IV 24-hr dose x 3 = oral maintenance dose per day

• then divide maintenance dose into q 8 or 12 h

Kapanol

• Sustained-release capsule of morphine sulfate

• 20, 50, 100 mg capsules with pellets

• peak onset 2-4 h, duration 24 h

• pellets can be dispersed in water, juice, yogurt,

custard, ice cream, and drink within 30 min without

crushing or chewing on pellets

Morphine for breakthrough pain

Syrup 10 mg/5 ml

• peak onset 30 min, duration 3-4 h

• always use exact measurement (syringe)

Immediate release tablet 10 mg

• Onset 15-30 min, duration 4-6 h (t1/2 2-4 h)

Fentanyl transdermal patch

• Release 12, 25, 50 microgram/hour topical patch

• Onset 8 h, duration 72 h

• NOT used in acute pain/ opioid-naive patient

• chest, back, flank, upper arm (no shaving)

• Need subcutaneous fat for absorption

• No sauna, hot bath, tanning, electric heating pad, or exercise

that may increase body temperature

• caution in MRI

Methadone

• tablet 5, 10 mg or syrup 1, 5 mg/ml

• binds to mu receptor, NMDA receptor antagonist,

inhibits serotonin reuptake transporter

• Not recommended as 1st line medication

• oral bioavailability 36-100%, half-life 8-59 h

• peak plasma concentration at 1-7.5 h

• Not dialyzed, inactive metabolites

Oxycodone

• moderate-severe pain if morphine is not tolerable

• Morphine : Oxycodone = 2:1

• binds to mu and kappa receptor

• controlled release (Oxycontin)

• metabolized by CYP3A4/CYP2D6 to

• noroxycodone : weak analgesic

• oxymorphone : strong analgesic (14 times potency)

Key principles of care

• pain reduction

• adverse effects

• daily activities and participation (such as ability to

work and drive)

• mood (depression and/or anxiety)

• quality of sleep

• overall improvement as reported by the person

Take home message

Pain

? Type or characters of pain

? Causes

? Medications (benefits vs risks)

? Patients’ conditions

Start a possibly effective smallest dose of

appropriate drugs

If not sure, consult!!

Dose titration/adjustment according to pain

score and side effects