Download ASTHMA MANAGEMENT

Pain and Analgesics
Dr Ian Coombes, Judith Coombes, Dr Lisa Nissan
University of Queensland Schools of Medicine and
Pharmacy
Safe Medication Practice Unit, Queensland Health
The University of Queensland
Outline
• What is pain
• Pain assessment
• Principles of Pain Management
• Drug therapies
• Neuropathic Pain and adjuvant therapy
• Role of the Pharmacist / other health professionals
You have been asked to recommend a
patient’s analgesia including
medication choice dose and duration…
What patient factors do you need to
consider?
What is Pain?
• A signaling system : mechanical and nerve
• Unpleasant sensory & emotional experience – IASP
• A perception : unlike taste or hearing
– cannot define independent of person experiencing it
• Only know in pain by statements & actions
– Pain is what the patient says “hurts”
Psychological Factors
Sex
Age
Cognitive Level
Previous Pain
Family Learning
Culture
Noxious Stimulus,
Tissue Damage
Pain Sensation
Situational Factors
Expectation
Control
Relevance
Emotional Factors
Fear
Stress
Anxiety
Frustration
Acute pain (e.g. sprain, surgery)
• Limited duration
• related specifically to an event or trauma
• bodies’ natural “healing” process
Palliative Care
Chronic pain
• pain
persists beyond time of healing
• often no specific pathology identified
•  changes in the CNS
•  development of NP
• complex interplay physical +psychological
• Often - sleep disturbances, fatigue,
depression, social withdrawal, and selfesteem issues +++
components of both
e.g. incident pain,
disease progression
Acute vs Chronic
• Acute Pain
• Chronic Pain
– Passive patient
– Active patient
– Short term planning
– Long term planning
– “hands-on” Tx
– “hands-off” Tx
– Rest
– Activity
– PRN Tx (inc. Meds)
– Regular Tx (inc.Meds)
– Resume usual life
– Retraining, readjustment
Examples of acute pain
• Acute post operative pain
• Sprains and strains
• Sports injuries
• Period pain
• Headaches
• Toothache / dental
Types of chronic pain
• Chronic back or neck pain
• Total body pain
• Chronic daily headaches
• Musculoskeletal pain
– Include: OA,RA, polymyalgia
• Painful diabetic neuropathy (PDN)
• Post-herpetic neuralgia (PHN)
• Phantom limb pain
Cancer Pain – 4 sources
• Malignancy
– E.g. infiltration of tumor, fractures
• Treatment Pain
– E.g. radiotherapy, mucositis
• Debility
– E.g. bed sores
• Unrelated
– E.g. history of underlying lower back pain
Types of pain
mechanical
inflammatory
neuropathic
Two Main categories
• Nociceptive Pain
– Pain due to stimulation of superficial or deep
tissue pain receptors as a result of injury or
inflammation
• Neuropathic Pain
– Pain due to dysfunction or primary lesion in the
central or peripheral nervous system
Patient Assessment
Goal to individualise analgesic therapy
Assess patient characteristics:
- indication for analgesia
- age, sex, weight
- culture
- vital signs
- allergies/ADRs
- opioid tolerance
- respiratory status
- renal/hepatic function
- other medical co-morbidities
- mental state
- other Rx
- availability of oral/rectal routes
Assessment
• Pain History (LINDOCARRF)
–
–
–
–
–
–
–
–
–
–
Location
Intensity
Nature
Duration
Onset, Offset
Concomitants
Aggravating
Relieving
Radiating
Frequency
Verbal Rating Scale:
On a scale of 1-10 …..
How would you rate your pain?
Sometimes add –
“where 10 is the worst ever and
zero is no pain”
Principles of Analgesic Prescribing
• Analgesic Ladder
• Adjuvants – TCA
– Anti-convulsants
– Anti-arrhythmic
STEP 1
STEP 3
STEP 2
•NSAID
•NSAID
•Non-opioid
(paracetamol)
•Non-opioid
(paracetamol)
•Strong Opioid
(morphine,
oxycodone)
•Non-opioid
(paracetamol)
•Weak Opioid
(codeine,
tramadol)
•Adjuvant
Medication
•Adjuvant
Medication
•Adjuvant
Medication
•NSAID
Paracetamol
• Analgesic, antipyretic, Act centrally (PGs)
• Not useful as an anti-inflammatory
• Few SE if taken at therapeutic doses
– Onset of effect 30 - 60 min
• Dosing:
– 500 –1000mg QID Max 4g for adult
Paracetamol
• Should be 1st line therapy
– minor, non-inflammatory pain
• As effective as aspirin/NSAID in relieving acute pain
• Similar antipyretic actions to aspirin, NSAID
• No. 1 choice mild to moderate pain in children
• May be given chronically:
– 1g QID, or for example in people with OA
– ALTERNATE Extended release: 1330mg TDS
Paracetamol
• Dosing in Children - Often under dosed!
• Appropriate:
• 15mg/kg Q4H MAX 60mg/kg (community)
• 15mg/kg Q4H MAX 90mg/kg (hospital)
• Can use in Combination with Ibuprofen
• Careful with other OTC products
– Esp. cough and cold medications
– “cumulative paracetamol”
Side-effects
• major risk: is poisoning with overdose
• Paracetamol can damage the liver (mainly OD)
• Risk of toxicity  - dehydrated, malnourished,
alcohol (chronic)
• Common: N/V, dizziness, sedation
• Less common: headache, skin rash
• *NOTE: paracetamol & NSAID can be used together
How do they work? - NSAID v COX2
Maintenance
Arachidonic acid
COX-1
Induced
COX-2
NSAIDs
thromboxane / prostaglandins
Primarily support
platelet function
Coxibs
prostaglandins
Primarily protect
GI mucosa
Primarily mediate
inflammation, pain & fever
COXib Withdrawal 2004
• Vioxx® withdrawn 2004   CV risk
• MOA CV risk
– COX-2 is the main source of the prostacyclin PGI2
• PGI2 acts in opposition to thromboxane
• TXA2 generated by COX-1
•
PGI2 = anti-clotting (anti-thrombotic)
•
TXA2 = pro-clotting (pro-thrombotic)
– Therefore, inhibiting COX-2   PGI2 synthesis 
“pro-thrombotic” effect (TXA2)  risk of MI, stroke
Non-Steroidal Anti-inflammatory Drugs
(NSAID)
• Analgesic, antipyretic
• Anti inflammatory - several days dosing
– must dose constantly at least several days
– prn not significant anti-inflammatory action
• Onset of action / effect 30 – 60 min
• difference in half-life and SE
• NOTE:
– elderly patients should not be on NSAID's with long half-lives
– can be even more prolonged in elderly
NSAIDs- Adverse Effects
Side effects
• hypersensitivity/allergy
• GI (GORD/PUD)
• platelet inhibition
• sodium retention, oedema
• renal toxicity
• hepatic toxicity
Cautions
NSAIDs- Adverse Effects
Side effects
Cautions
• hypersensitivity/allergy
- asthma
• GI (GORD/PUD)
- GI bleeding/ulceration
• platelet inhibition
- coagulation disorders
- warfarin therapy
• sodium retention, oedema - hypertension
- cardiac failure
- ACEI/ARA/diuretics
• renal toxicity
- renal impairment
- gentamicin therapy
• hepatic toxicity
- hepatic impairment
NSAIDs – Caution!
Major cause of ADEs and hospital admissions
 use lowest effective dose for shortest possible time
 use paracetamol as alternative or to reduce NSAID dose
 COX-2 inhibitors
- similar adverse effects to non-selective
- increase risk of thrombotic events (stroke; MI)!
 little difference in efficacy between NSAIDs
 avoid aspirin < 18 yrs in viral illness (Reye’s syndrome)
 elderly - increased risk of adverse effects
Continue only if effective. Avoid if possible!
Where do Opioids Act?
Brain
Opioids
Opioids
Ascending Activation
Descending Inhibition
Dorsal
Horn
Nociceptors
Nociceptive primary afferent
Spinal Cord
How do Opioids Act?
• Interact with specific cell-surface receptors in
– CNS and PNS
– other tissues (GIT, immune cells, other tissues)


G-proteins
2nd messenger
systems

G-protein
Pharmacological Effects of
Opioid Agonists
• Desired Action – analgesia
• Unwanted actions
– Analgesic tolerance
– physical dependence
– Respiratory depression
– Nausea, vomiting sedation
Tolerance often develops
Other unwanted effects
– Constipation
• inhibition of GIT motility
• slowing of oral-caecal transit times
• Never forget laxatives
– Endocrine effects
• may alter male sex hormones in chronic dosing
• Must monitor in chronic therapy
– Neuro-excitatory SE
• e.g. myoclonus, allodynia, seizures
– very high doses
No tolerance
Opioids – Precautions
 hypotension, shock
 concomitant CNS depression
 impaired respiration /↓ respiratory reserve
 elderly
 hepatic impairment
 renal impairment
 epilepsy/recognised seizure risk
 biliary colic or surgery
What are Opioids?
• Step 2 / 3 - Moderate to severe pain
• Definite role in cancer + non-cancer pain
• Mu, Kappa, Delta receptors
• Many available
• Typical SE profile
– Nausea, Drowsiness, Respiratory Depression
– Constipation, Sweating, Itch
• Caution in hepatic and renal impairment
Opioids – what to do?
• Assess requirements – calculate dose
• Conversion table as a guide (if on other opioids)
• Can start on one Short Acting opioid and titrate
• Conversion to SR / CR preparation when possible
• Adding it up …..
• If currently on multiple Tx - Use conversion table
• E.g. convert all to oral morphine equivalent
Opioids – what to do? ******
• Start low go slow …..
• When converting between opioids
• Reduce calculated total daily dose ~20-30%
• Breakthrough (incident pain – esp. in cancer)
• Calculate as: 1/6th – 1/12th of TDD
– Or ~ 50% of the dose just given (if e.g. Q4H)
DRUG
DOSE x CONVERSION FACTOR
Pethidine (oral)
Pethidine (IV)
x 0.125
x 0.4
Methadone
x 1.5
Oxycodone
x 1.5
Buprenorphine
x 50
Codeine
x 0.16
Dextropropoxyphene
x 0.1
Morphine (IV)
Morphine (oral)
x3
x1
Oral
Morphine
equivalent
* 100mg tramadol ~ 60mg codeine ~ 10mg oral morphine
Drug / action
Duration of
action
Active metabolites
Adjust dose in renal
impairment
Codeine (A)
3-4
Morphine
Yes
Dextropropoxyphene (A)
4-6
Nordextropropoxyphene (toxic)
Yes
Fentanyl (A)
0.5-2 (iv)
No
no
Hydromorphone
2-4
hydromorphone-3-glucuronide
(H3G - toxic)
yes
Methadone (A)
Variable
(>24hr)
No
no
Morphine (A)
2-3
yes
12-24
morphine-6-glucuronide (M6G),
morphine-3-glucuronide (M3G –
toxic)
3-4
oxymorphone
no
CR/SR
Oxycodone (A)
CR/SR
12-24
Pethidine (A)
2–3
norpethidine (CNS +++)
yes; contraindicated
Tramadol (A)
3–6
desmethyl tramadol
yes
Buprenorphine
(partial
agonist)
Reference:
AMH
6–8
norbuprenorphine
no
Regular vs PRN Analgesia




regular analgesia is better in setting of continuous pain
PRN only if pain intermittent and unpredictable
in most settings, pain is predictable
problems with using only PRN analgesia
- dose prescribed by Dr/administered by nurse
- patients don’t ask for medication
 inadequate or infrequent dosing → unrelieved pain
 keeping up with pain is easier than catching up with pain
 prn dose = 1/6 →1/12 total regular daily dose
Tramadol (Tramal)
• Centrally acting analgesic with a dual MOA
• 1st - opioid effects similar to morphine (mu)
– Active Metabolite M1
– M1 - 6x tramadol as analgesic, 200x binding
• 2nd - inhibit re-uptake of NA / 5-HT
– descending pain inhibitory pathway
• Hepatic Metab. Via CYP 2D6 (P450)
– similar to codeine
•  doses in renal and hepatic impairment
• 50 – 100mg 4-6 hrs (Max 400mg) or SR equiv.
• Interactions:
– SSRI, TCA, carbamazepine, MAOI, warfarin ( INR)
• Can cause serotonin syndrome by itself!
• Start low – go slow ……. Short term use only!
• Start on IR then (switch to SR if appropriate)
More serious ADR’s with tramadol
Reaction
Confusion
Hallucinations
Convulsions
Serotonin syndrome
Increase in blood pressure
Hypersensitivity reactions
Hepatic reactions
Warfarin interaction
No. of reports
36
30
26
20
14
12
10
5
Australian Adverse Drug Reactions Bulletin - Volume 22, Number 1, February 2003
NNT > / = 50% relief 3.5 (2.4 to 5.9)
NNH = 7.7 (4.6 to 20)
Neuropathic Pain
•
Pain or abnormal sensations due to a
dysfunction of, or damage to, a nerve or group
of nerves
• primarily peripheral nerves, although pain
due to CNS damage (“central pain”) may share
these characteristics
Neuropathic Pain
• Can be due to a central or peripheral component
• Opioids not particularly effective
• Post Herpetic Neuralgia: acute herpes zoster
• Phantom Limb Pain
• Postoperative Pain
• Diabetic neuropathy
• May be lancinating (shooting, stabbing)
• non-lancinating (dull, aching)
• burning (dysesthesia)
TREATMENTS FOR NEUROPATHIC PAIN
Antidepressants
Anticonvulsants
Opioids
Eg.
Amitriptyline
Desipramine
paroxetine
Eg.
CBZ
Gabapentin
pregabalin
Eg.
Tramadol
oxycodone
Topical
agents
Eg.
Lidocaine patch
Capsaicin
DRUGS
Nociceptive
e.g. fracture
Paracetamol Effective when
taken regularly
at max. dose
Opioids
Effective
PAIN TYPE
Neuropathic Inflammatory
eg neuralgia
e.g. rheumatoid
arthritis
Less effective Effective, but not
anti-inflammatory
May be
May be effective
effective
(depends on
(agent + dose) dose)
NSAIDs
Effective
Not effective
Effective
TCAs,
parenteral,
local
anaesthetics
antiepileptic
Rarely used
(clonidine may
be effective as
adjunct)
May be
effective
Rarely used (may
be effective as
adjunct)
Adapted from Table 3-1, Australian Medicines Handbook
Things to think about when
reviewing Prescriptions
• Regular dosing of pain medications
• Dosage form issues
– Crushing, breaking SR/CR
– Appropriate level of breakthrough medication
• Managing SE
– Importance of laxative use
– Increasing needs ? More breakthrough
• Interactions ….. Watch OTC / complementary
Monitoring – making it work
• Frequent assessment is essential
• Important to maintain communication with
– Doctor, patients, carers
• Nursing staff and pharmacist ……
– Monitor for response to therapy
• Include increase in need
• Change in pain “type” or “origin”
• Change in severity
– ADR / SE
• Esp. laxatives with opioids
Key Messages







individualise analgesic therapy
choose analgesics judiciously
use multimodal analgesia
regular pain monitoring is critical to outcomes
regularly review and revise analgesic doses
adjust regular dose according to breakthrough usage
anticipate and manage analgesic-associated adverse
events
 avoid NSAIDs – major cause of morbidity/mortality!
 avoid tramadol, dextropropoxyphene, pethidine
Questions?