Review pharmacologic Review pharmacologic management management

in palliative carein palliative carein palliative carein palliative care

Patama Gomutbutra MD. Revised 23 March 2012

Comprehensive palliative careComprehensive palliative care

Symptom

control

Pain, N/V etc.

Goal of care clarification

Disease

management

Ethic and law ie. consider withhold or withdraw life-prolongating intervention

Psychosocial spiritual support

DepressionGrief and Bereavent

clarification

Common symptom in terminal Common symptom in terminal illnessillness

• Fatigue >90% • Pain 35-90% • Delirium 80% esp the last wk of life• Dyspnea 75%• Dyspnea 75%• Nausea 70%• Depression 25-75%• Insomnia 19-36%

Harrison’s 17th ed. P 70-75

Medication used in Palliative careMedication used in Palliative care

• Often “Off label” : Experience based -less rigorous evidence based support

• Dose calculation formula/ conversion • Dose calculation formula/ conversion table is only guide

• Global assessment and titration is the key

Opioid

Common misperception• Apnea

Pain act as physiological antagonist• Addiction• Addiction

Drug seeking behavior is unlikely”• Alteration of conscious

Drowsiness – self limitedDelirium – finding precipitating cause

Holistic assessment-> Effective & Safe

PQRSTU

• Precipitating• Quality• Region and radiation• Severity• Severity• Timing• U YOU “ How pain affecting your life”

Steps approach opioid conversion

1. DDx. Worsening existing pain or new type of pain *

1. Total daily dose in MO oral ( Around the clock and Break through dose)

2. Use conversion table as a guide2. Use conversion table as a guide( keep in mind: It’s source is acute pain healthy volunteer)

3. Individualize the dosage *

* Use information from PQRSTU

Opioid side effect

Except constipation, opioid side effect usually self limited within 3-4 wks. If persist consider precipitating cause

1. Dose exess than requirement ( ie. Pain is 1. Dose exess than requirement ( ie. Pain is relieved by other method)

2. Dehydration3. Disease status change (ie wrosening

Liver/Renal function,wt loss, infection )4. Drug interaction

Opioid prescription

• Weak opioid for mild-mod pain• Strong opioid for mod- severe pain• Tramadol for severe pain is not adequate

Weak opioid

• Ceiling effect -> higher maximum dose not gain benefit only increase SETramadol 400 mg/dayCodeine 240 mg/day

• Generally prefer Tramadol • Generally prefer Tramadol • Codeine metabolite by cytP2D6 which cause

drug interact with Haloperidol and AMT and2% of Asian no response because are poor metabolizer

• Pethidine is NOT proper for chronic pain

Strong opioid

1. Morphine1.1 Immediat release (IR)Half life 2-4 hrs -> Fast reach steady statePeak 15 min -> Fast titration1.2 Modified release (MR) 1.2 Modified release (MR)

- MST 12 hrs- Kapanol 24 hrs

2. Fentanyl 72 hrs3. Methadone, Ketamine : Consult expert

Breakthrough dose : When baseline pain was controled

pain crisis: rapid titration dose

Finding maintanance doseto cover background

pain

Pain crisis

• Pain that need immediate intervention“severe pain”

• Rapid titration by IV form ( SC as alternative, Avoid IM-pain and slow)alternative, Avoid IM-pain and slow)- Opioid-naïve : 1-5 mg IV stat (or rescue dose convert to IV in previous opioid user)- Reassess q 15 minutesModerate -> 50 % increase eg. 5-> 7 mg Severe -> 100 % increase eg. 5-> 10 mg

Finding maintance dose

Two concepts1. Start with IR “steady state” concept

switch to MST later-> Prefer for opioid naïve-> Prefer for opioid naïve

2. Start with MST-> Who ever use weak opioid

Steady state

Steady state ( review pharmacology)If we give same dose 4-5 half life it will reach state that serum drug level “stedy” because IN = Out.

Opioid IR half life = 2 – 4 hrs ->reach steady state in 8-16 hrs -> adjust dose after 24 hrs

Starting dose

• Magic no. “MO oral 30 mg”• MO oral 30 mg/day Around the clock

MO - IR 5 mg q 4 hrs ( peak 15 min)MO – MST 15 mg q 12hrs MO – MST 15 mg q 12hrs

• Frail elder/poor renal function use 25-50% of standard dose

• PRN 1/6 of Around the clock doseeg. MO oral 5 mg q 4 hrs

MO oral 5 mg prn

Titration (Thai guideline 2005)

• Previous 24 hrs “ Total” dose= Around the clock + PRN used

• “Controled” painPain severity <3 and PRN used <3Pain severity <3 and PRN used <3

• If patient uncontroledstep us by recalculate Around the clock and PRNNew Around the clock = previous “Total” dose

พิจารณาวา่จาํเป็นตอ้งให ้Strong opioid

Morphine IR 5 mg oral q 4hrs+ Morphine IR 5 mg oral prn q 1 hr

Morphine MST 15 mg oral q 12 hrs+ Morphine IR 5 mgoral prn q 1 hr

Example• Yesterday, Mr.A start Morphine IR 5mg q 4 hrs

and received PRN Morphine IR 5 mg X5 timesToday, He reveal that his pain still be 5/10What should we do?

• Total dose = (5X6) + ( 5X5) = 55New around the clock = 55/6 choose lower end because not so severe

= 8 mg q 4 hrsNew PRN = 8 mg prn q 1 hrs

• Don’t forget bowel regimeneg. Senokot 2-4 tabs hs, MOM etc.

• Swithching Opioid -> Fentanyl• Stable pain with opioid tolerant

ie who recieveing > 60 mg MO equivalent more than 1 wk

• For refractory neuropathic pain : Methadone or Ketamin (NMDA antagonist) may be benefit but hard to titrate should consult pain specialist

Method 1: Conservation tableOral MO 24 mg/day Fentanyl

60-134 25

135-224 50

225-314 75

315-404 100

Note:Due to wide range: fentanyl is likely to be underdosing and unable convert Fentanyl back to MO oral with this table

Method 2: Brietbart, et al 2000

• 2 “mg/day” morphine1 “mcg/hr” transdermal fentany

rounded to the nearest patch size. Eg. 60 mg/day MO oralEg. 60 mg/day MO oral

= 30 mcg/hr trans fentanylround to available size = 25 mcg/hr

Non-drug

treatment

Symptomatic drug

treatment

Breathless on exertion

Breathless at risk or

Minimal activity

“Terminal”

Breathlessness

Adapted from Robert Twycross

Correct correctabl causes

Pharmacologic Mx for dyspnea

• For “Terminal dyspnea” Opioid is the best evidenceEven COPD with CO2 retention opioid therapy still be justifiable

Starting dose lower than using in pain20 mg MO oral/day

Who already on Opioid for painIncrease dose about 25%

• BenzodiazepineMay consider as adjuvantesp. Dyspnea prominent agitation

• Lorazepam oral 0.5-1 mg is drug of choice• Lorazepam oral 0.5-1 mg is drug of choiceMidazolam 2.5 mg IV also have evidence

• This dose + morphine is safe

Antiemetic

• Combination of antiemetics with different receptor can act additive

• However, start from single druge Need awareness of side effectNeed awareness of side effect

Drugs Used In Vomiting

Benzodiazepine

Anticipatory NV

Hyoscine hydrBr

Cyclizine

Cinnarizine

H1, ACh(m)

Dexamethasone

Reduce intracranial pressure?

CORTEX

VESTIBULAR

Vomiting centre

D2,Ach(m), H1,

µ-opioid, 5HT3

Metoclopramide

Domperidone (not cross BBB)

D2

Haloperidol

Metoclopamide

Ondansetron

Prochlorperazine

5HT3

CTZAbdominal Abdominal organsorgans

NOREEN CHAN

DOVER PARK

HOSPICE

SINGAPORE

Last slide

• Medication is not the only answer for symptom control

• However, when it necessary don’t let patient suffer from our mythspatient suffer from our myths

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