Narcotic Analgesics and Anesthesia Drugs Narcotic Analgesics.
Pain and Analgesics Dr Ian Coombes, Judith Coombes, Dr Lisa Nissan University of Queensland Schools...
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Transcript of Pain and Analgesics Dr Ian Coombes, Judith Coombes, Dr Lisa Nissan University of Queensland Schools...
Pain and Analgesics Pain and Analgesics
Dr Ian Coombes, Judith Coombes, Dr Lisa NissanUniversity of Queensland Schools of Medicine and
Pharmacy Safe Medication Practice Unit, Queensland Health
Dr Ian Coombes, Judith Coombes, Dr Lisa NissanUniversity 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”
Noxious Stimulus,Tissue Damage Pain Sensation
Psychological FactorsSexAge
Cognitive LevelPrevious Pain
Family LearningCulture
Situational Factors
Expectation
Control
Relevance
Emotional FactorsFear
StressAnxiety
Frustration
Acute pain (e.g. sprain, surgery) • Limited duration
• related specifically to an event or trauma
• bodies’ natural “healing” process
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 self-esteem issues +++
Palliative Carecomponents of bothe.g. incident pain,
disease progression
Acute vs Chronic
• Acute Pain
– Passive patient
– Short term planning
– “hands-on” Tx
– Rest
– PRN Tx (inc. Meds)
– Resume usual life
• Chronic Pain
– Active patient
– Long term planning
– “hands-off” Tx
– Activity
– Regular Tx (inc.Meds)
– 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
•NSAID
•Non-opioid (paracetamol)
•Adjuvant Medication
•NSAID
•Non-opioid (paracetamol)
•Weak Opioid (codeine, tramadol)
•Adjuvant Medication
•NSAID
•Non-opioid (paracetamol)
•Strong Opioid (morphine, oxycodone)
•Adjuvant Medication
STEP 1STEP 1
STEP 2STEP 2
STEP 3STEP 3
• 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
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
Arachidonic acidArachidonic acid
COX-1COX-1 COX-2COX-2
thromboxane / prostaglandins prostaglandins
NSAIDs CoxibsCoxibs
Primarily support platelet function
Primarily protect GI mucosa
Maintenance Induced
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 EffectsSide effects Cautions
• hypersensitivity/allergy
• GI (GORD/PUD)
• platelet inhibition
• sodium retention, oedema
• renal toxicity
• hepatic toxicity
NSAIDs- Adverse EffectsSide 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?
Descending Inhibition
Brain
Nociceptors
Spinal Cord
DorsalHorn
Nociceptive primary afferent
Ascending Activation
Opioids
OpioidsDescending Inhibition
Brain
Nociceptors
Spinal Cord
DorsalHorn
Nociceptive primary afferent
Ascending Activation Descending Inhibition
Brain
Nociceptors
Spinal Cord
DorsalHorn
Nociceptive primary afferent
Ascending Activation
Opioids
Opioids
How do Opioids Act?
• Interact with specific cell-surface receptors in – CNS and PNS– other tissues (GIT, immune cells, other tissues)
2nd messenger systems
G-proteins 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 0.125x 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)
x 3x 1
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
CR/SR
12-24
morphine-6-glucuronide (M6G), morphine-3-glucuronide (M3G – toxic)
yes
Oxycodone (A) 3-4
CR/SR
12-24
oxymorphone no
Pethidine (A) 2–3 norpethidine (CNS +++) yes; contraindicated
Tramadol (A) 3–6 desmethyl tramadol yes
Buprenorphine (partial agonist)
6–8 norbuprenorphine no Reference: AMH
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)
Reaction No. of reports Confusion 36 Hallucinations 30 Convulsions 26 Serotonin syndrome 20 Increase in blood pressure 14 Hypersensitivity reactions 12 Hepatic reactions 10 Warfarin interaction 5
More serious ADR’s with tramadol
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 PainNeuropathic 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
Eg.AmitriptylineDesipramineparoxetine
Eg.Lidocaine patch
Capsaicin
Eg.Tramadol
oxycodone
Eg.CBZ
Gabapentinpregabalin
Topicalagents
OpioidsAnticonvulsants
DRUGS
PAIN TYPE
Nociceptivee.g. fracture
Neuropathiceg neuralgia
Inflammatory e.g. rheumatoid arthritis
Paracetamol Effective when taken regularly at max. dose
Less effective Effective, but not anti-inflammatory
Opioids Effective May be effective(agent + dose)
May be effective (depends on 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?