Transcript Presentation - Faculty of pain medicine

MEDICATIONS!
Role in Pain Management?
Dr Penny Briscoe
Pain Management Unit
Royal Adelaide Hospital
AUSTRALIAN CULTURAL BELIEFS –
“Quick fix” - REACH FOR A PILL
ASPRO
“for treatment of pain
AND depression”.......
“ASPRO IS A WOMEN’S BEST
FRIEND!”
THE ROLE OF MEDICATION
IN
CURRENT PAIN MANAGEMENT?
Pharmacogenetics analgesic drugs.
Estimated response
to over 25% common medications,
including analgesics,
is influenced by some genetic variation,
knowledge of which could be useful to prescribers.
BUT ALSO: Heritability of pain traits.
CREGG: BJ Pain: 2013: 7(4): 189
Pharmacogenetics analgesic drugs.
PAIN GENES:
Hereditary sensory and autonomic neuropathy I – IV
SCN9A: Voltage gated sodium channel – Nav 1.7
PHARMACODYNAMICS.
-opioid receptor gene (OPRM1)
STAT6
-arrestin 2
PHARMACOKINETICS.
CYP450 2D6
CYP450 3A4 or 3A5
UGT2B7
Multi-drug resistance gene
COMT
HTR3B
Cytokines
Pharmacogenetics analgesic drugs.
Nav1.7 ↑ - ↑ pain (ERYTHROMYELGIA)
Nav1.7 absence: Congenital insensitivity to pain.
CYP2D6 metabolism:
Poor metabolisers: minimal analgesia (tramadol).
Ultrarapid metabolisers: toxicity (codeine)
 Opioid receptor genetic varient: (OPRM1 118A>G)
10-15% Caucasians: 40-50% Asians.
Reduced mu-opioid receptor expression.
Increased opioid requirements.
theguardian
Winner of the Pulitzer prize
2003
CONNOR : CHIEF GLAXO : “OUR DRUGS DON’T WORK”
90% DRUGS ONLY WORK 30 –50% PEOPLE
“PERSONALISED MEDICINE”.
Most drugs don’t work in most people who take them.
– 90% drugs work in 30 – 50%patients
Patients with chronic illness often feel
they undergo a “trial and error” approach.
Future? DNA Testing – which drugs will work?
STEVE CONNOR: PHARMACOGENETICS
www.rense.com/general69/glax.htm
“The art of medicine
consists
of amusing the patient while
nature
cures the disease”
VOLTAIRE 1694 - 1778
Doctors put drugs
of which they know little
into bodies
of which they know less
for diseases
of which they know nothing at all.
VOLTAIRE 1694-1778
One of the first duties
of the physician
is to educate the masses NOT to take medicine
Sir William Osler 1849-1919
WHY DO PATIENTS GET
BETTER?
1. Appropriate treatments (antibiotics).
2. Natural history (acute back pain).
3. Nonspecific treatment effects: e.g. placebo.
JAMISON: IASP CLINICAL UPDATES: 2011
Informed drug choices? Neuropathic pain.
Undertreated.
Huge effect QOL.
Drugs have low treatment efficacy,
but doctors are ignorant about
how best to use available drugs.
LANCET NEUROLOGY: 2015
Informed drug choices? Neuropathic pain.
Estimation publication bias:
Searched trial data available on line but not in peer reviewed
journals (almost 10% studies).
Finnerup estimated:
publication bias leads 10% overstatement treatment effect.
NNT (50% relief) high – (4-10 in +ve trials)
Efficacy across range neuropathic pain conditions.
Studies looking at combination therapy haven’t been done.
BENNETT: LANCET NEUROLOGY: 2015
NNT (50% relief)
NNH (One patient w/d)
TCA’S
3.6
13.4
SNRI’S
6.4
11.8
SSRI’S
7.0
GABAPENTIN
6.3 (8.3)
26.1
PREGABLIN
7.7
13.9
TOPIRAMATE
7.4
6.3
OPIOIDS
4.3
11.7
CODEINE
12
TRAMADOL
4.7
CAPSAICIN 8%
10.6
9.0
FINNERUP: www.medscape.com
FINNERUP: LANCET NEUROLOGY: JAN 2015
TREATMENT NEUROPATHIC PAIN.
1st LINE
TCA’s, SNRI’s, gabapentin, pregablin
2nd LINE
Topical agents: lignocaine 5%, capsaicin 8%
Tramadol.
3rd LINE
Botulinum toxin A.
Strong opioids: recommendation to use declining.
(do have some efficacy BUT concerns ↑ re potential misuse)
Multiple mechanisms: can treatment (eventually) be targeted?
LANCET NEUROLOGY 2015
ONE IN FIVE RULE?
How good are you
at enabling a placebo response?
PAIN SPECIALISTS
recognise
current drugs –
limited role,
to manage Chronic Pain.
“DON’T JUST DO SOMETHING,
STAND THERE!”
Clinicians want to relieve suffering.
We find it difficult to do nothing.
Why do distressed patients get more opioids?
Why send in counseling teams after traumas,
knowing they possibly make things worse?
DOUST, DEL MAR: BMJ: 2004: 328: 474
But our drugs are safe,
aren’t they?
WHY ARE DRUGS
MISUSED?
Any centrally acting drug
can be misused / abused:
Opioids
Benzodiazepines
Mirtazapine
Quetiapine
Olanzapine
Gabapentinoids
TCA’s
‘Z drugs’: zopicolone, zolpidem
Dr Cameron Loy:
“We must refuse to write “scripts of death”
Australian Doctor: April 2014
Drugs tap into the brains communication system & disrupt way
nerves send, receive and process information:
1. Imitate brains natural chemical messengers.
2. Overstimulate the “reward circuits of the brain
↑ DOPAMINE:
PLEASURE & MOTIVATION
“A brain awash in dopamine”
www.drugabuse.gov
What Is Drug Addiction?
Addiction is a chronic, often relapsing brain disease that
causes compulsive drug seeking and use, despite harmful
consequences to the addicted individual and to those
around him or her.
Although the initial decision to take drugs is voluntary
for most people, the brain changes that occur over time
challenge an addicted person’s self-control and hamper
his or her ability to resist intense impulses to take
drugs.
NATIONAL INSTITUTE ON DRUG ABUSE
Why Do Some People Become Addicted While Others Do Not?
No single factor can predict whether a person will become addicted to drugs.
Risk for addiction is influenced by a combination of factors that include
individual biology, social environment, and age or stage of development.
The more risk factors an individual has, the greater the chance that taking drugs can lead
to addiction.
NIDA
Other Drugs
….variety medications become popular & are mostly smoked.
It is often hard to find the benefits of illicit use, … we keep an eye on medication use,
medications found during cell searches and become very suspicious when patients
start asking for medications by name and have the matching symptoms.
We try and reduce diversion by ensuring all administration of “popular” medications is
supervised but this is only partly effective.
In terms of popular medications (we do not allow a number medications no benzo’s except for alcohol/drug withdrawal to maximum 1 week),
Popular medications are
Quetiapine (this has dropped off as we restricted to Psychiatrist only):
Mirtazapine
Gabapentin
Pregablin.
We have tried to influence prescriber behaviour around best practice
As we “clamp down in one area another pops up”.
Central Adelaide Local Health Network
SA Prison Health Service
January 2015
√
BUPRENORPHINE
PATCHES (NORSPAN)
There have been ongoing concerns around diversion
of the contents of Norspan® patches.
Central Adelaide Local Health Network
SA Prison Health Service
January 2015
√
Staff need to be particularly vigilant
to check patches when they are removed
and carefully examine them
to ensure that the medication matrix
is still intact.
X
BUPRENORPHINE
PATCHES (NORSPAN)
X
Costs drugs on the street?
•
•
•
•
•
•
•
•
Endone 5mg $1 - 50
Valium $1-10
At $3 comment – reasonable!
Kapanol 100mg $50 Comment – reasonable!
Oxycontin 80mg $30 Not bad!
Oxycontin 10mg NSW $10 – Overpriced!!
Targin 10mg / 5mg $10 – Not bad!
Methadone 10mg (Kings Cross) $50 – Not bad!
Ritalin, Stilnox, Subutex, Seroquel
UK Pregablin 75mg £2.50 – 10
+ Gabapentin 400mg £10
streetRx: latest prices
STOPP.
Screening Tool Older Person’s Potentially
Inappropriate Prescriptions
Examples where benefits are outweighed by
potential harm include:
Potent opioids used non-palliatively.
NSAID’S
Anticholinergic drugs
Benzodiazepines.
SCOTT: MJA: 2014: 201(7)
FIRST DO NO HARM.
Polypharmacy (> 5 -10 medications) common among
older Australians
(>65 years).
1 in 4 community living older people
are hospitalised in a 5 year period.
15% report ADE over last 6/12.
SCOTT: MJA : 2014:201(7)
FIRST DO NO HARM.
ADR’s risk:
13% 2 drugs
38% 4 drugs
82% 7 or more drugs.
20% older Australians >10 prescription or OTC.
SCOTT: MJA:2014:201(7)
Simple Analgesics?
Paracetamol.
Aspirin.
Liver toxicity
Stephens Johnson Syndrome
Reyes Syndrome
Non Steroidal
Anti – inflammatory Drugs?
OTC Nurofen Plus?
Ibuprofen +Naproxen:
Stephens Johnson Syndrome
CODEINE:
Codeine is an addictive narcotic.
USA, Sweden and Germany have made it prescription
only.
Millions of dollars and doses, obscure a crucial
problem: there is a startling lack of evidence that
these drugs work better than paracetamol.
Canadian Pharmacists Association warned 36 years ago
– codeine can cause addiction, and are ineffective
CODEINE:
Codeine (like heroin) a pro-drug for morphine.
7-10% Caucasians don’t metabolise.
 5% “Ultra-rapid” metabolisers.
2009 UK parliamentary enquiry –
codeine can cause addiction in 3 days.
Profile OTC codeine abuser!
Highly functioning.
Working.
Higher socioeconomic status
Better education.
More social support.
WARANILLA admissions:
OTC abuse
200
180
160
140
120
100
80
60
40
20
0
174
Admissions
codeine
31
Antidepressants?
CASE REPORT: Recreational amitriptyline abuse: 2005: 62(6):397-8.
Two patients with a history of abuse with amphetamine and clonazepam were
admitted to the Clinic because of intoxication with amitriptyline.
They denied suicidal attempt and explained they used amitriptyline in a dosage of
100 to 200 mg per day as a drug of abuse.
On the day of admission one patient had increased the dosage to
600 mg which caused an acute intoxication.
Tricyclic antidepressants abuse, with or without benzodiazepines abuse,
in former heroin addicts currently in methadone maintenance treatment.
Eur Neuropsychopharmacol. 2008 Mar;18(3):188-93.
Street price: $1 a pop!!
Benzodiazepines?
Benzodiazepines 2002 and 2009
Diazepam
Oxazepam Temazepam Alprazolam
Total
2002
1,576,625
1,220,936
2,237,733
324,110
5,359,404
2009
1,639,952
1,015,080
1,840,222
413,526
4,908,780
+4%
- 17%
% change
Table: PBS prescriptions
- 18%
+28%
- 8%
Xanax 1mg / $10
Private prescriptions (non PBS) alprazolam comprise additional 32% of prescriptions / year
Antipsychotics?
J Subst Abuse Treat. 2015 Jan;48(1):8-12. doi: 10.1016/j.jsat.2014.07.006. Epub 2014 Jul
Misuse of atypical antipsychotics with alcohol and other drugs of abuse.
Malekshahi T
Non-medical use of atypical antipsychotics by substance abusers has been reported.
17.0% report misuse antipsychotics with alcohol, opioids, cocaine, methamphetamine and/or cannabis;
9.1% within the past year.
Most were male (76.0%), non-Caucasian (56.0%), and polysubstance abusers (84.0%).
Quetiapine, the most abused drug (96.0%), obtained primarily from doctors (52.0%) and
family/friends (48.0%).
Reasons for use: "recover" from other substances (66.7%), "enhance" the effects of other substances
(25.0%), and "experiment" (20.8%).
The most frequently reported positive effect was "feeling mellow" (75.0%).
SANSONE: PSYCHIATRY (EDGMONT):2010: JAN: 7(1): 13 -16
17% report misuse antipsychotics with alcohol, opioids,
cocaine, metamphetamines & / or cannabis
Street: $3- 8 /25mg
“quell”
“Susie-Q”
“baby heroin”
Anticonvulsants?
Pregabalin?
Gabapentin?
Misuse and Abuse of
Pregabalin and Gabapentin.
Increasing evidence of misuse.
Increasing levels prescriptions
and related fatalities.
Anecdotal reports growing black market.
SCHIFANO: CNS DRUGS: 2014
Misuse & Abuse
Pregabalin and Gabapentin.
WHY?
Potent binding Ca++ channel.
↓release excitatory molecules.
GABA-mimic properties
Possibly direct / indirect effects dopaminergic “reward”
system.
SCHIFANO: CNS DRUGS:2014
Misuse & Abuse
Pregabalin and Gabapentin.
WHY?
“Ideal psychotropic drug”
“Great euphoria”.
“Disassociation”
“Opioid buzz”
SPENSE GP GLASGOW: BMJ: 2013: 347.
Misuse & Abuse
Pregabalin and Gabapentin.
GABAPENTINOID EXPERIMENTERS:
History recreational polydrug misuse.
Self Administer doses in excess:
3 – 20x clinically advisable.
SCHIFANO: CNS DRUGS:2014
GABAPENTIN WITHDRAWAL :
SEVERE & POTENTIALLY DEADLY:
Delirium Tremens
Seizures
SHEBAK: J SUBS ABUSE ALCOHOL: 2014: 2(3)
theguardian
Winner of the Pulitzer prize
2015
One recent study showed there are
more than 1,800 inmates
in prisons in England and Wales
prescribed gabapentin or pregabalin:
this represents 3% of prison
population and is twice the rate of
prescribing in wider community.
THE GUARDIAN: 15TH JANUARY 2015
“misuse of two prescription drugs
(methadone + pregablin)
associated
chaotic,
uninhibited behaviour
amongst some heroin addicts, including
injecting in public”.
THE GUARDIAN: 15TH JANUARY 2015
Cannabinoids?
Marijuana?
FINNERUP: LANCET NEUROLOGY 2015:
SATIVEX: 9 Trials / 2 +ve.
 WEAK RECOMMENDATION AGAINST USE!
CANNABINOIDS?
NSW Government – medical use cannabis:
Terminal illness
Patients HIV / AIDS.
People at end of life use cannabis to relieve severe pain or
stimulate their appetite
should not be criminalised.
NSW LEGISLATIVE COUNCIL 2013
“Top medico
Alex Wodak
urges intervention
to curb
black market
for marijuana”.
Sydney Morning Herald: August 28th 2014
“The only way to protect people from questionable black market marijuana
is to regulate the supply of medicinal forms of the drug
that can be prescribed to suitable people”.
Marijuana.
Tetrahydrocannabinol (THC) produces the “high” effect seen with
marijuana.
Cannabidiol (CBD) plethora actions but fewer undesirable
psychoactive effects.
Sativex - CBD + delta 9-THC
Did not reach statistical difference from placebo for relief cancer pain
Pharmacological actions THC
Psychotropic
Initial euphoria & relaxation
Then a depressant period
Alteration memory & cognitive perceptual abilities.
Immune modulation
Cardiovascular
Tachycardia, orthostatic hypotension, vasodilation.
Analgesia
Anti-emetic
Appetite stimulant
Pharmacological actions CBD
Anticonvulsant
Analgesic
Anti-anxiety
Anti-psychotic.
Anti-inflammatory.
Anti-arthritic.
Sedative / hypnotic.
Immunosuppressive.
Neuropathic pain that failed standard Rx
Consider adequate trials other Rx & pharmaceutical cannabinoids 1st.
Not appropriate:
< 25 years
Hx psychosis
Current or past cannabis use disorder.
CVS disease, angina or arrythmia.
Pregnancy / or breastfeeding.
Full assessment, followup & document
START LOW – GO SLOW.
Specify % THC allowed.
CANNABINOIDS?
Advantages
Issues
Some benefit neuropathic pain.
Mild S/E: dizziness, sedation, nausea
Anxiety treatment in low doses.
Poor coordination, ataxia
Improved sleep
Paranoid thinking, agitation, dysphoria
PTSD: ↓nightmares, sleeplessness,
flashbacks
Impairments memory & cognition
No risk end organ failure.
Smoking - ↓resp function
? ↑ risk lung cancer
No risk lethal O/D
10% dependency syndrome
CANNABINOIDS? CAUTION!!
Paucity well designed studies,
evaluating medical cannabis for pain.
One systemic review –
cannabis moderately efficacious chronic pain.
Another – overall safe,
& modestly effective neuropathic pain.
SHIPTON X2: ANZJP: 2014: 48(4): 310
CANNABINOIDS?
CAUTION!!
EXTREME CAUTION IN PATIENTS:
History CVS disease.
History mental disorders.
Adolescents
SHIPTON X2: ANZJP: 2014: 48(4): 310
Melatonin?
Melatonin
Is a close derivative of serotonin
Pineal gland neuro-hormone (+GIT).
Implicated control sleep wake cycle.
↑ release darkness.
Melatonin has:
chronobiotic, antioxidant, antihypertensive anxiolytic, & sedative
properties
J PINEAL R: 2011
GUT: 2005
JPSM: 2013
Melatonin
Available Australia (Circadian) 2mg.
Doses required seem higher, in studies
Doses available OTC USA – 5-10mg.
Melatonin - what's all the fuss about?
David Kennaway, Senior Research Fellow/Senior Lecturer, Circadian Physiology Group,
Depart O & G, University of Adelaide,
AUST PRESCR 1997;20:98
“Melatonin is the new fad drug from the U.S.A. that everyone seems to be talking about.”
And then there is needle therapy!
ANTICONVULSANTS.
Affect pain indirectly -  sleep & mood.
• Carbamazepine
70% Trigeminal neuralgia improve - (level 1).
30% diabetic neuropathy (NNT 3.3)
Post-stroke pain - no better placebo:.
• phenytoin, valporate, clonazepam /
NO GOOD EVIDENCE
Education
+ self-management!