1. Review pharmacologic
management
in palliative care
Patama Gomutbutra MD.
Revised 23 March 2012

2. Comprehensive palliative care
Pain, N/V etc.
Symptom
control
Goal of care
clarification
Ethic and law
ie. consider
Disease Psychosocial Depression
withhold or withdraw
management spiritual Grief and
life-prolongating support
intervention Bereavent

3. Common symptom in terminal
illness
• Fatigue >90%
• Pain 35-90%
• Delirium 80% esp the last wk of life
• Dyspnea 75%
• Nausea 70%
• Depression 25-75%
• Insomnia 19-36%
Harrison’s 17th ed. P 70-75

4. Medication used in Palliative care
• Often “Off label” : Experience based -
less rigorous evidence based support
• Dose calculation formula/ conversion
table is only guide
• Global assessment and titration is the
key

5. Opioid
Common misperception
• Apnea
Pain act as physiological antagonist
• Addiction
Drug seeking behavior is unlikely”
• Alteration of conscious
Drowsiness – self limited
Delirium – finding precipitating cause

6. Holistic assessment
-> Effective & Safe

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

8. 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 guide
( keep in mind: It’s source is acute pain
healthy volunteer)
3. Individualize the dosage *
* Use information from PQRSTU

9. 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
relieved by other method)
2. Dehydration
3. Disease status change (ie wrosening
Liver/Renal function,wt loss, infection )
4. Drug interaction

10. Opioid prescription
• Weak opioid for mild-mod pain
• Strong opioid for mod- severe pain
• Tramadol for severe pain is not adequate

11. Weak opioid
• Ceiling effect -> higher maximum dose not gain
benefit only increase SE
Tramadol 400 mg/day
Codeine 240 mg/day
• Generally prefer Tramadol
• Codeine metabolite by cytP2D6 which cause
drug interact with Haloperidol and AMT and
2% of Asian no response because are poor
metabolizer
• Pethidine is NOT proper for chronic pain

12. Strong opioid
1. Morphine
1.1 Immediat release (IR)
Half life 2-4 hrs -> Fast reach steady state
Peak 15 min -> Fast titration
1.2 Modified release (MR)
- MST 12 hrs
- Kapanol 24 hrs
2. Fentanyl 72 hrs
3. Methadone, Ketamine : Consult expert

13. Breakthrough dose :
When baseline pain was controled
pain crisis: rapid
titration dose
Finding
maintanance dose
to cover background
pain

14. Pain crisis
• Pain that need immediate intervention
“severe pain”
• Rapid titration by IV form ( SC as
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 minutes
Moderate -> 50 % increase eg. 5-> 7 mg
Severe -> 100 % increase eg. 5-> 10 mg

15. Finding maintance dose
Two concepts
1. Start with IR “steady state” concept
switch to MST later
-> Prefer for opioid naïve
2. Start with MST
-> Who ever use weak opioid

16. 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

17. 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
• Frail elder/poor renal function use 25-50%
of standard dose
• PRN 1/6 of Around the clock dose
eg. MO oral 5 mg q 4 hrs
MO oral 5 mg prn

18. Titration (Thai guideline 2005)
• Previous 24 hrs “ Total” dose
= Around the clock + PRN used
• “Controled” pain
Pain severity <3 and PRN used <3
• If patient uncontroled
step us by recalculate Around the clock
and PRN
New Around the clock
= previous “Total” dose

19. พิจารณาว่าจําเป็ นต้องให้ Strong opioid
Morphine IR 5 mg Morphine MST 15 mg
oral q 4hrs oral q 12 hrs
+ Morphine IR 5 mg + Morphine IR 5 mg
oral prn q 1 hr oral prn q 1 hr

20. Example
• Yesterday, Mr.A start Morphine IR 5mg q 4 hrs
and received PRN Morphine IR 5 mg X5 times
Today, He reveal that his pain still be 5/10
What should we do?
• Total dose = (5X6) + ( 5X5) = 55
New around the clock = 55/6
choose lower end because not so severe
= 8 mg q 4 hrs
New PRN = 8 mg prn q 1 hrs

21. • Don’t forget bowel regimen
eg. 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

22. Method 1: Conservation table
Oral 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

23. Method 2: Brietbart, et al
2000
• 2 “mg/day” morphine
1 “mcg/hr” transdermal fentany
rounded to the nearest patch size.
Eg. 60 mg/day MO oral
= 30 mcg/hr trans fentanyl
round to available size = 25 mcg/hr

24. Symptomatic drug
Non-drug
treatment treatment
Correct correctabl causes
“Terminal”
Breathless on Breathless at risk or
exertion Breathlessness
Minimal activity
Adapted from Robert Twycross

25. Pharmacologic Mx for
dyspnea
• For “Terminal dyspnea”
Opioid is the best evidence
Even COPD with CO2 retention opioid therapy
still be justifiable
Starting dose lower than using in pain
20 mg MO oral/day
Who already on Opioid for pain
Increase dose about 25%

26. • Benzodiazepine
May consider as adjuvant
esp. Dyspnea prominent agitation
• Lorazepam oral 0.5-1 mg is drug of choice
Midazolam 2.5 mg IV also have evidence
• This dose + morphine is safe

27. Antiemetic
• Combination of antiemetics with different
receptor can act additive
• However, start from single druge
Need awareness of side effect

28. Drugs Used In Vomiting
VESTIBULAR
Hyoscine hydrBr
CORTEX Cyclizine
Dexamethasone
Cinnarizine
Reduce intracranial Benzodiazepine
pressure? Anticipatory NV H1, ACh(m)
Vomiting centre
D2,Ach(m), H1,
Abdominal CTZ
organs µ-opioid, 5HT3
Haloperidol
Metoclopramide Metoclopamide
Domperidone (not cross BBB) Ondansetron
NOREEN CHAN Prochlorperazine
DOVER PARK
HOSPICE
D2 SINGAPORE 5HT3

29. Last slide
• Medication is not the only answer for
symptom control
• However, when it necessary don’t let
patient suffer from our myths

30. Recommended resource