Transcript Opioid and non-opioid analgesics: pharmacology and

Palliative Care
Dr Philip Lee
Senior Staff Specialist
Palliative Medicine
Westmead Hospital
Palliative Care Definitions
To cure, occasionally
To relieve, often
To comfort, always
Anonymous (16th Century)
Death should simply become a
discreet but dignified exit of a
peaceful person from a helpful
society … without pain or suffering
and ultimately without fear.
Philippe Ariès, 1977
The Hour of Our Death
Palliative Care provides for all the medical
and nursing needs of the patient for whom
cure is not possible and for all the
psychological, social and spiritual needs of
the patient and the family, for the duration of
the patient’s illness, including bereavement
care.
Roger Woodruff
Palliative Medicine
2nd Edition
Palliative Care
Caring for a person with an active,
progressive, far advanced disease
with little or no prospect of cure and
for whom the primary treatment goal is
quality of life
PALLIATIVE CARE - WHEN?
ACTIVE TREATMENT
PALLIATIVE
CARE
BEREAVEMENT
ACTIVE TREATMENT
BEREAVEMENT
PALLIATIVE
CARE
PALLIATIVE CARE - WHERE?
 Palliative
Care is a Network
 Services are provided by Teams
 Services are available in:
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Community, home and aged care facilities
Acute hospitals
Private Hospitals
Specific inpatient units eg St Joseph’s, Mt Druitt,
Neringah, Greenwich, Braeside Hospitals
PALLIATIVE CARE - COMMUNITY
 GP
“case manager”
 Generalist Community Nurse - GCN
 Clinical Nurse Specialist - CNS
 Clinical Nurse Consultant - CNC
 Palliative Care Medical Officer
 Community Palliative Care Specialist
WHAT DOES PALLIATIVE CARE
OFFER?
 Pain
control
 Other symptom control
 Terminal care
 Family support
 Bereavement support
Cancer pain
 30-50%
of cancer patients undergoing active
treatment
 70-90% of cancer patients with advanced
disease
 Prospective
studies indicate that as many as
90% of patients could attain adequate pain relief
with simple drug therapies.
The Context
Symptoms of debility
Non-cancer pathology
Side effects of therapy
Cancer
Loss of social position
Loss of job prestige
and income
SOMATIC SOURCE
Friends not visiting
Loss of role in family
Chronic fatigue
and insomnia
Bureaucratic bungling
DEPRESSION
TOTAL
PAIN
ANGER
Unavailable doctors
Sense of helplessness
ANXIETY
Disfigurement
Fear of hospital
or nursing home
Worry about family
Fear of death
Spiritual (existential) unrest
Delays in diagnosis
Fear of pain
Family finances
Loss of choices
Uncertainty about future
Irritability
Therapeutic failure
WHO analgesic ladder
Pain
Pain persists
or increases
Pain persists
or increases
3.
2.
1.
Non-opioid
± adjuvant
Weak opioid
± non-opioid
± adjuvant
Strong opioid
± non-opioid
± adjuvant
Guidelines for opioid use
Preferably oral
 Continuous rather than PRN
 Commence with immediate release
 Once stable convert to slow release +
immediate for breakthrough pain relief
 If more than 2 episodes of breakthrough pain
increase regular dose
 Laxatives
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Analgesic Classes
Aspirin
 Paracetamol
 NSAIDS
 Opioids
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Opioids
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Weak opioids
Codeine
 Dextropropoxyphene
 Tramadol
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Strong opioids
Oxycodone
 Morphine
 Methadone
 Fentanyl
 Hydromorphone
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Opioid receptors
All opioids produce analgesia and other
effects by mimicking the actions of
endogenous opioid compounds
(endorphins) at multiple subtypes of the
three major opioid receptors in the brain
stem, spinal cord and peripheral tissues.
Opioid actions
The perception of pain is altered both by a
direct effect on the spinal cord,
modulating peripheral nociceptive input,
and by activation of the descending
inhibitory systems from the brain stem
and basal ganglia.
Patients’ concerns about
narcotics
Addiction & withdrawal
 Tolerance
 Implications of taking morphine
 Side effects
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Side effects
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Sedation
Hallucinations
Nausea & vomiting
Constipation
Urinary retention
Myoclonus
Respiratory depression
Pruritus
Cognitive impairment
Some sedation early in use of morphine
 Tolerance develops
 Prior sleep deprivation due to poor pain
control
 Other causes of cognitive impairment
need to be excluded
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Opioid
Dose
Duration of Action
Morphine (oral)
20 mg
4 hrs
Morphine (parenteral)
10mg
4 hrs
Codeine
130 mg
4-6 hrs
Pethidine (IMI)
80 mg
2-3.5 hrs
Methadone *
2-5 mg
8-12 hrs
10-20 mg
4 hrs
Tramadol
200 mg
4-6 hrs
Fentanyl
200 mcg
1-2 hrs
4 mg
4 hrs
Oxycodone
Hydromorphone
Routes of administration of
morphine
Oral
 Subcutaneous
 IVI
 Epidural & intrathecal
 Rectal
 Topically
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Morphine metabolism
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Primarily metabolised in the liver
 Metabolites excreted in urine
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Morphine-3-glucuronide (M3G)
Morphine-6-glucuronide (M6G)
Caution in renal impairment
 M6G potent morphine agonist
 M3G no significant analgesic action
 Liver disease not reported to alter
pharmacokinetics
Morphine
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Pros
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“Gold Standard”
Well understood
Readily available
Usually well tolerated
No “ceiling”
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Cons
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Accumulates in renal
failure
Constipating
Nausea
Sedation
Misconceptions
Morphine Preparations
Morphine mixture
(Ordine)
4 hrs
1, 2, 5, 10, 20, 40 mg/ml
Kapanol caps
24 hrs
10, 20, 50, 100 mg/ml
MS Contin tabs
12 hrs
5, 10, 15, 30, 60, 100, 200 mgs
MS Contin susp
12 hrs
30, 60, 100, 200 mgs
MS Mono caps
24 hrs
30, 60, 90, 120 mgs
Morphine sulphate
amps
4 hrs
5, 10, 15, 30, 50 mgs/ml
Morphine tartrate amps
4 hrs
120 mgs/1.5 mls, 400mgs/5mls
Oxycodone
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Pros
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Various dose forms,
immeadiate & slow
release
Neuropathic pain
“New”
OK in renal failure
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Cons
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Constipating
Nausea
Confusing names
Oxycodone & Tramadol
Endone Tabs
4 hrs
5 mg
Oxynorm
4 hrs
5, 10, 20 mgs
Oxycontin
12 hrs
5, 10, 15, 20, 30, 40,
80 mgs
Tramadol caps
4-6 hrs
50 mg
Tramadol SR Tabs
12 hrs
100, 150, 200 mgs
Tramadol amps
4-6 hrs
100 mg/2 mls
Fentanyl
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Pros
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Less constipation
Less nausea
Less psychotomimetic
effects
Convenient
OK in renal failure
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Cons
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Reliant on good fat stores
Inflexible dosing
Difficult to titrate
Expensive
Breakthrough medications
Hydromorphone
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Pros
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Less sedating
Less constipating
Less hallucinations
Less nauseating
OK in renal failure
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Cons
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Availability
Methadone
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Pros
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Neuropathic pain
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Cons
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Stigma
Difficult dosing schedule
Variable half-life
Fentanyl, Methadone &
Hydromorphone
Fentanyl Patches (Durogesic)
72 hrs
25, 50, 75, 100 mcg/hr
Fentanyl sublingual liquid
1-2 hrs
100 mcg/ml
Fentanyl lozenges (ACTIQ)
1-2 hrs
200, 400, 800, 1200, 1600 mcg
Methadone
8-100 hrs
10 mg
Hydromorphone tabs
(Dilaudid)
4 hrs
2, 4, 8 mgs
Hydromorphone liquid
4 hrs
1 mg/ml
Hydromorphone Extended
Release (Jurnista)
24 hrs
8, 16, 32, 64mgs
Hydromorphone amps
4 hrs
2mg/ml, 10mg/ml, 50mg/5mls,
500mg/50mls
Pethidine
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Repetitive dosing leads to accumulation of the
toxic metabolite norpethidine
Norpethidine accumulation causes
CNS hyper-excitability & subtle mood changes
 Tremors
 Multifocal myoclonus
 Seizures
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Common with repeated large doses, eg 250 mg
per day