Morphine

By Salahadin A.
 outline
• History of Morphine
• Morphine ,what is it?
• How to prescribe it
• Side effects
• Toxicity
• What are addiction , dependence, tolerance
• Regulations and restrictions of use
• exercises
God’s Own Flower -POPPY

“Morphine is God’s own medicine”

Emphasises the INDISPENSABLE
nature of opium alkaloid. Sir
William Osler(1849-1919)the most
influential physician in history
 History
• Evidence of using opium dates back to 4500
BC.
• Named after Morpheus, Greek God of
Dreams
• Widely used by ancient civilizations for
recreational, religious, medicinal and
cooking purposes.
 History

• Arab traders introduced it to China in 4th

Century AD
• The “Opium Wars” fought between China &
Britain (1839, 1856)
• In 1805 “morphium” was
isolated by German
pharmacist
• 1832-codein

• 1870s-Heroin
Morphine as indicator to
pain management
Access to morphine differs according to income
level

Maximum coverage rate for deaths in pain from HIV or cancer

based on national consumption of opioid analgesics:
• High-income countries: 100%
• Middle-income countries: 62%
• Low-income countries: 19%

People in lower income countries are

significantly less likely to get pain treatment
than people in higher-income countries
Treat the Pain: based on data from the International Narcotics Control Board and WHO Cause of Death data (2012) 8
Opioid analgesics for pain relief

• Analgesics are medicines that relieve pain

• Opioids are drugs that are derived from opium poppy plants
or synthetic formulations that act in the same way
– Weak opioids

• Codeine
• Tramadol
– Strong opioids

• Morphine
Beating Pain, 2nd Ed. APCA (2012) 9
World Health Organization

• Opioid analgesics, including morphine, are

considered essential medicines by the World
Health Organization
• Strong opioid analgesics are the only
treatment for moderate or severe pain
recommended in World Health Organization
guidelines
• No suitable alternatives have been found
Ensuring balance in national policies on controlled substances: guidance for availability and accessibility of controlled medicines.
World Health Organization (2011) 10
 Morphine

Pharmacology
Morphine…

1- Bio-availability due to first pass: 35% by Oral & 25% by Rectal.

2- Time to peak plasma concentration:
10 mt per IV
20min per IM/sc.
30-60 min per Oral.
1-6 h /rectal.
3- Plasma half-life: 1.5 h
4- Duration of action: 3-6 hrs. (four hours) for regular type
5-administered every 4 hours
6- starting dose 2.5 mg,5mg niave-10 mg in opiod experienced

12
Prescription ,narcotic prescription

• Morphine
• Route of administration
• interval
• Morphine preparation
• Total amount
• For how many days
• Break through dose

13
• Morphine 10mg every 4 hours orally for 10
days
• # 1 bottle of 150 ml Morphine with 5mg/ml
syrup,

(Total Amount required is 120ml,Extra 30mlis for break through

needs)

14
Morphine prescriptions….

• Extra /breakthrough dose may be required

(Next regular dose is not omitted).

• A laxative -routinely
(Unless there is a strong reason like-ileostomy)

• An anti-emetic should be included in the initial

days. Pro-kinetic or/and haloperidol 1.5 mgs.

• Patients should be informed (warned ),about the

possibility of initial drowsiness.
15
Morphine advantages

• Most effective treatment for severe pain

• Safe (if used according to guidelines)
• No ceiling effect
• Plentiful
• Inexpensive
• Easy-to-use , breakthrough pain /Rescue
• Morphine consumption is an indicator for
pain management
16
Most Effective analgesia

“ Opium Alkaloids have no rival for

relief of pain.”
The pharmacologic basis for Therapeutics, 1941
1st Edition of Goodman and Gilman’s Classic
Textbook.

17
Most effect analgesia

Early recognitions:
• “Among the most powerful remedies that God
bestowed to mankind in order to ease our suffering
none is as efficient or as universal as opium” Thomas
Sydenham, the famous 17th century English
Physician.
• “Morphine is God’s own medicine” Emphasises the
INDISPENSABLE nature of opium alkaloid. Sir William
Osler(1849-1919)the most influential physician in
history.
18
Safe: Opioids are the foundation of pain management

• No organ toxicity, even at high doses and

after prolonged use
• Step 1 drugs Renal ,liver, PUD when used in
long term,
• Side effects diminish over time
• Potential harmful side effects are avoidable
when opioids are used correctly

IASP: Treatment of pain in low-resource settings (2010) 19

 Safe
• Side effects: constipation, nausea, sedation
• No Toxicity to kidney and liver
• Neurotoxicity :accumulation, reversible or
preventable
No ceiling effect

-Pain is a natural, physiological antagonist to

the central depressant effects of opiates and
that overdose is unlikely as long as a patient
has pain

-If Titrated to pain and no neurotoxicity

-No side effect limitation to morphine use

21
Ethiomorph : inexpensive

22
Dispelling some myths

• Myth: Opioids are dangerous

According to the World Health Organization:
– “Opioid analgesics, if prescribed in accordance with
established dosage regimens, are known to be safe and
there is no need to fear accidental death or dependence.”
– “A systematic review of research papers concludes that
– only 0.43% of patients abused their medication and
– only 0.05% developed dependence syndrome.”

World Health Organization: Ensuring Balance in

National Policies on Controlled Substances: 2011
23
Dispelling some myths

• Myth: Pain relief is not affordable

– Locally produced oral morphine solution costs just 10 birr
per week in Ethiopia,70 birr per week in Uganda and 100
birr USD per week in Nigeria
– Tablets or injectable opioids may be more expensive

Treat the Pain Costing Data, 2014. 24

Dispelling some myths

• Myth: Morphine is only appropriate for patients at the end of

life
– Pain treatment should be determined by the level and
type of pain, not the stage of disease
– Many patients can live for a long time while taking
morphine, which allows them to live a more active life

25
Practical questions when starting morphine

• Is it better to start with morphine solution/ordinary

tablets or with slow-release tablets?
• How do I decide the initial dose of oral morphine?

• When pain free?

A good night’s sleep free of pain in 2-3 days.

comfort at rest, during the day in 3-5 days

Comfort when active in 3-7 days.

26
• What should be done if morphine does not
completely relieve the patient’s pain?

27
Poorly responsive

a. raised intracranial pressure

b. bone metastasis (and some soft tissue pains)

c. Neuropathic (i.e. nerve compression and nerve injury).

d. Under dosing (dose too small or given only as needed)

e. Ignoring psychological, social and spiritual factors.

28
Poor response

• Psychology-
• hepatic failure-metabolism
• Hypercalcaemia - absorption
• Hyponatraemia -absorption
• Septicaemia-distribution
• cardiac failure-distribution

29
Resistant to morphine

 migraine

 tension headache

 Muscle spasm (cramp).

 Bone pain

 Movement-related pain often does not respond well to

oral morphine.(musculoskeletal)

30
Persistent side effects

• renal failure- metabolism

• cerebral metastases-BBB

31
• By how much should the dose of morphine be
increased?

• Which of the morphine side effects are not self-

limiting?
• Do patients die of morphine-induced respiratory
depression?
• How should morphine be reduced?

32
Side effects
Step 3 analgesic: morphine

Constipation is a very common side effect of all opioids

and does not resolve spontaneously
• Laxatives should be prescribed as prophylaxis unless patient
has diarrhoea
• Treat with a bowel regimen: stimulant laxative and a stool
softener
– i.e. Bisacodyl 5mg at night, increasing to 15mg if needed

Beating Pain, 2nd Ed. APCA (2012) 34

Step 3 analgesic: morphine

Nausea and vomiting

• Usually mild and resolves within one week
• Anti-emetics (metoclopramide or haloperidol) can be given
for the first few days of treatment
– Metoclopromide 10mg every 8 hours or haloperidol 1.5mg
once a day

Beating Pain, 2nd Ed. APCA (2012) 35

Step 3 analgesic: morphine

Drowsiness
• Usually resolves within one week
• Advise patients not to perform dangerous tasks or operate
heavy machinery for 2 weeks while they adjust to the
medications
• Patients who have been unable to sleep well due to pain may
initially sleep for long periods once their pain has been
relieved
– These patients should be easily arousable
• If it does not improve, reduce the morphine dose

Beating Pain, 2nd Ed. APCA (2012) 36

Step 3 analgesic: morphine

Hepatic and renal impairment

• Not a contraindication for use
• Titrate slowly and carefully to avoid accumulation of
medication or active metabolites
– Consider increasing interval between doses to 6, 8, or even
12 hours
Elderly
• Older people respond well to lower doses
• Consider reducing the dose or increasing the dosing interval
to minimize side effects

Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010)
37
Itching
• Less common
• Treat with chlorpheniramine

38
Opioid neurotoxicity

• Toxic effects of opioids are rare when they are used

in appropriate doses
• Signs include
– Drowsiness that does not improve
– Confusion
– Hallucinations
– Myoclonus (abrupt spasms or muscle twitching)
– Respiratory depression (slow breathing)
– Pinpoint pupils

Beating Pain, 2nd Ed. APCA (2012) 39

Opioid toxicity

• If you are concerned that a patient is experiencing toxicity,

reduce the dose by 50% and consider giving parenteral fluids
to increase excretion
• In severe cases, stop the opioid and give Naloxone, an opioid
antagonist
• Haloperidol 1.5-5mg at night may help with any hallucinations
or confusion
– Be sure to rule out other causes (such as urinary tract
infection, hypoxia, or side effect of another medication)

Beating Pain, 2nd Ed. APCA (2012) 40

Respiratory failure

• In severe cases, stop the opioid and give Naloxone, an opioid antagonist.
Indications for Naloxon:
• 1. RR < 8/mt.
• 2. RR <12/mt, difficult to rouse, cyanosis
• 3. RR < 12/mt, difficult to rouse, SaO2 <90%

• 400microgram to 10ml with 0.9% saline. Give 0.5ml (20microgram)

IV every 2min

41
 Summary :Common opioid side-effects
and management
side effects management
nausea and vomiting Opioid reduction or rotation, anti-
histamines, dopamine antagonists, 5HT3
antagonists
constipation fluids, laxatives (bisacodyl, senna etc...)
pruritis moisturizer, oat-meal bath, anti-histamines,
TCA1
sedation opioid reduction or rotation
myoclonus and opioid rotation, benzodiazepines, adjuvants
hyperalgesia
respiratory depression opioid reduction or rotation, naloxone on
rare cases 42
 Side effect :
Opioid switching/rotation

interventional
analgesia-
blocks
 Equianalgesia
Drug IM/IV dose PO dose

Morphine 10mg 20mg

Codein 130mg 200mg

Tramadol 100mg 120mg

Hydromorph 1.5 7.5

Methadone 15mg 20mg

Fentanyl 100micg(0.1gm) 0.2mg 44

Summary Side Effects of Morphine
 Constipation -always
 Drowsiness – common /excessive doses
 Nausea & Vomiting over first few days,

 Twitching – rare/excessive doses

 Urinary retention-catheter in/out
 Respiratory Depression – pain is a physiological
antagonist to this/rare if ever
Tolerance ,dependance and
addiction
The spectrum of dependence
Abuse 0.43 addiction 0.05%

Addiction
Tolerance Dependence
Compulsion
Use despite harm
Loss of efficacy
Lying, stealing,
withdrawal
work /family problem
 Measuring tolerance
• Loss/reduction in effects
• Need to increase dose
• Reduction in physiological parameters
– Nausea/vomiting
– Respiration
– Pupils
– Saccadic eye movement velocity
• With opioids due to pharmacodynamic not kinetic
factors
Tolerance
• Decreasing response to a drug as a consequence of its
continued use

• An increased dose is required to achieve a similar effect

• Nausea ,vomiting, drowsiness are tolerated

• Euphoria is tolerated
• Constipation is not tolerated it continues
• analgesia is not tolerated

-Increases in opioid requirements are usually related to disease

progression

Oxford Textbook of Palliative Medicine (2010) 49

Dependence

• Dependence: The phenomenon of withdrawal when an

opioid is abruptly discontinued

– Physical dependence is a normal response to chronic

therapy
– Prevent withdrawal by titrating the opioid dose down
slowly
• Reduce daily dose by 25% each day

Oxford Textbook of Palliative Medicine (2010) 50

Withdrawal

Signs and symptoms of withdrawal

• Anxiety
• Nervousness
• Irritability
• Alternating chills and hot flushes
• Wetness: salivation, watery eyes, runny nose, sneezing, sweating, and
gooseflesh
• At peak intensity of withdrawal, patients may experience:
– Nausea and vomiting
– Abdominal cramps
– Insomnia
– Multifocal myoclonus or abrupt spasms (rare)

Oxford Textbook of Palliative Medicine (2010) 51

Addiction

• Addiction: Psychological dependence leading to craving,

impaired control over drug use, and compulsive use to get
psychic effects despite harm.
– Behaviors associated with addiction
• Compulsive drug-seeking -strong (sometimes
overwhelming) desire
• Unauthorized use or dose escalation
• Use despite harm to self or others 
• Progressive neglect of alternative pleasures or
interests
• Stealing, multiple prescription

52
Addiction = “drug dependence” syndrome: ICD 10 –
generally four criteria required
 

• A strong (sometimes overwhelming) desire or sense

of compulsion to take the drug  
• Progressive neglect of alternative pleasures or
interests
• Persistent use despite harmful consequences,
depressive mood or cognitive impairment
• Evidence of tolerance
• Physiological withdrawal state
What makes a drug addictive?
key drug principles
•speed of onset = faster is better
e.g. heroin > codeine
•route of use  speed of onset
e.g. i.v./smoking > i.m./oral
•speed of offset = faster is more addictive
•drug efficacy - more = better
e.g.
fentanyl>pethedine>morphine>buprenorphine
Pseudoaddiction

• When the dose of opioids is not enough to relieve pain, some

patients may become anxious about opioid availability and
may demonstrate some behaviours that you see in patients
with addiction, such as
– Asking for the next dose before it is due
– Taking medications not prescribed to them
– Taking illegal drugs
– Using deception to obtain medications

Oxford Textbook of Palliative Medicine (2010) 55

Risk of addiction in medical use of opioids
• The correct answer is E: less than one-half of 1 percent
• According to the World Health Organization:

– A systematic review of research papers concludes that only

0.43% of patients with no previous history of substance abuse

treated with opioid analgesics to relieve pain abused their
medication and

– only 0.05% developed dependence syndrome

• Fishbain et al (2008): Among chronic pain patients with no history of
opioid abuse/addiction, incidence of abuse/addiction is 0.19%

56
Pseudoaddiction

• These behaviours go away after the dose has been increased

and pain has been relieved
• It is important to distinguish pseudoaddiction from addiction:
patients with pseudoaddiction stop seeking medications once
their pain has been effectively treated

Oxford Textbook of Palliative Medicine (2010) 57

 Management of addiction
• Psychological therapy
• behavioural therapy
• Rehabilitation
• Exclude Pseudo Addiction
Summary

• Morphine is most effective

• Morphine is safe for long term use
• Morphine is useful in low doses in majority of the needy ones
• Breakthrough pain can be controlled with rescue doses
• No ceiling dose
• Morphine has side effects
• Tolerance ,Dependence, addiction

59
Thank you
References

• African Palliative Care Association. Beating Pain: a pocketguide for pain management in Africa,
2nd Ed. [Internet]. 2012. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/beating_pain.pdf

• African Palliative Care Association. Using opioids to manage pain: a pocket guide for health
professionals in Africa [Internet]. 2010. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/using_opiods.pdf

• Amery J, editor. Children’s Palliative Care in Africa [Internet]. 2009. Available from:
http://www.icpcn.org/wp-content/uploads/2013/08/Childrens-Palliative-Care-in-Africa-Full-
Text.pdf

• Kopf A, Patel N, editors. Guide to Pain Management in Low-Resource Settings [Internet]. 2010.
Available from: http://www.iasp-pain.org/files/Content/ContentFolders/Publications2/
FreeBooks/Guide_to_Pain_Management_in_Low-Resource_Settings.pdf

• The Palliative Care Association of Uganda and the Uganda Ministry of Health. Introductory
Palliative Care Course for Healthcare Professionals. 2013.

61
 Case 1
• 37. Patient A is 25 years old and this is his first
day following abdominal surgery. As you enter
his room, he smiles at you and continues
talking and joking with his visitor. Your
assessment reveals the following information:
BP = 120/80; HR = 80; R = 18; on a scale of 0 to
10 (0 = no pain/discomfort, 10 = worst
pain/discomfort) he rates his pain as 8.
• A. On the patient’s record you must mark his
pain on the scale below. Circle the number that
represents your assessment of Andrew’s pain.
0 1 2 3 4 5 6 7 8 9 10
“Among the most powerful remedies that God bestowed to
mankind in order to ease our suffering none is as
efficient or as universal as opium” Thomas Sydenham,
the famous 17th century English Physician.
64