Week 10: Pain and Musculoskeletal - Opioids, Non opioids, NSAIDs, Arthritis Flashcards
What is pain?
- Signalling system - mechanical and nerve
- Unpleasant sensory and emotional experience
- Perception (independent of person experiencing it)
- No objective measuring system
- Symptom of underlying disease/injury (bodies warning system)
Pain is the activation of pain receptors
- A delta and C sensory fibers
- May be due to misfiring/dysfunction of nerves
Classification of pain
- Acute and chronic
- Types of pain
Acute
- Usually has anxiety and hyperactivity of SNS causing tachycardia, increased respiratory rate and increased blood pressure
Chronic
- Usually no sympathetic hyperactivity and may have depressed mood, fatigue, loss of appetite
Types of pain:
Nociceptive
- Pain related to damage of somatic or visceral tissue due to trauma or inflammation
- Examples = rheumatoid arthritis, osteoarthritis, gout
Non-nociceptive Neuropathic pain
- Pain related to damage of peripheral or central nerves
- Examples = painful diabetic peripheral neuropathy, postoperative neuralgia
Sensory hypersensitivity
- Pain without identifiable nerve or tissue damage
- Thought to result from persistent neuronal regularization
- Examples = fibromyalgia
Non pharmacological management of pain
- PT/OT
- CBT, meditation, counseling
- Mobility aids
- Heat
- Rest
- Ice
- Compression
- Elevation
Treating pain - WHO analgesic ladder
Step 1
- Non opioid +/- adjuvant
- E.g. aspirin, paracetamol or NSAID
Step 2:
- Weak opioid for mild to moderate pain +/- nonopioid +/- adjuvant
- E.g. codeine
Step 3
- Strong opioid for moderate to severe pain +/- non opioid +/- adjuvant
- E.g. morphine
Opioids
- MOA
- Pharmacological effects
- Unwanted effects
MOA
- Act on opioid receptor on neuronal cell membrane in CNS and PNS (specifically mu receptor)
- Mimic endogenous opioid such as b endorphin to reduce transmission of pain impulse
- Produce analgesia, respiratory depression, sedation and constipation
- Reduce transmission of pain impulse by acting pre and post synaptically in spinal cord and by modulating descending inhibitory pathway from brain
Pharmacological effects
- Analgesia/cough suppression/antidiarrheal (codeine)
Unwanted effects
- Analgesic tolerance
- Physical dependence
- Respiratory depression
- Constipation
- Nausea, vomiting, sedation (tolerance often develops)
Weak opioids
- Codeine (metabolism, contraindications and cautions)
- Dextropropoxyphene
Codeine
- Metabolised by kidney to morphine
- Not proven to be effective at OTC dosages (prescription only)
- Contraindications and cautions
> Elderly (reduce dose due to increase risk of cognitive impairment, sedation, respiratory depression and falls)
> Hepatic impairment (reduce dose and monitor)
> Children (usually contraindicated under 12 use with caution)
> Pregnancy (caution close to delivery)
> Breastfeeding (Do not use)
> Renal impairment (avoid)
> Contraindicated in comatose, epilepsy, hypotension, shock and neonates
Dextropropoxyphen
- Lots of ADR
- Prescribe must write special application
Examples of strong opioids
- Tramadol
- Fentanyl
- Morphine
- Hydromorphone
- Oxycodone
- Pethidine
- Methasone (for opioid addiction)
- Buprenorphine (partial agonist - longer onset of action)
Strong opioids - Tramadol
- MOA
- Contraindications and cautions
MOA
- Technically not an opioid
- Structurally not opiate but exhibits opioid characteristics
- Binds mu receptor but 10 time less affinity than codeine
- Inhibits reuptake of NA and 5HT
Contraindications and cautions
- Elderly (avoid over 75; avoid CR)
- Hepatic impairment (reduce dose in severe impairment; avoid CR)
- Children (avoid use except under specialist)
- Pregnancy (caution close to delivery)
- Breastfeeding (avoid)
- Renal impairment (avoid CR)
- Contraindicated within 14 days of stopping MAOI or other serotonergics
- Same contraindications as codeine
Strong opioids - morphine
- ADR
- Contraindications and cautions
- Morphine is benchmark for comparing opioid equivalence
- Stronger opioids have higher affinity and/or efficacy for opioid receptors
- Higher incidence of ADR including sedation, respiratory depression, GI effects, addiction/dependence and tolerance
Contraindications and cautions
- Elderly (reduce dose and titrate slowly)
- Hepatic impairment (Avoid in severe)
- Children (avoid in neonates, only when indicated by specialist in older children)
- Pregnancy (caution close to delivery)
- Breastfeeding (avoid repeated doses)
- Renal impairment (reduce dose in mild/mod and avoid in severe)
- Contraindicated in comatose, endocrine abnormalities, epilepsy and hypotension
Opioid overdose and dependence
- Naltrexone
- Opioid overdose can be hard to treat due to severe withdrawal symptoms
> Use methadone in step wise manner
Naltrexone - opioid antagonist
- Reversibly blocks effects of opioid for 24-72 hrs
- After it wears of patient more susceptible to effects of opioids (fatal overdose)
Non opioid analgesics
- Indications
- Causes
Indications - Neuropathic pain (described as burning, electric shock, shooting pain) > Hyperalgesia > Allodynia > Hyperpathia
Causes
- Phantom limb pain
- Diabetic neuropathy
- Postherapetic neuralgia
- Herpes zoster
- Fibromyalgia
Non opioid analgesic treatment options
Neuropathic pain treatment options
- Paracetamol
- Topical capsaicin
- Antidepressant - may inhibit nociceptive transmission via inhibition of NA and 5HT reuptake (TCA, SSRI, SNRI)
- Antiepileptic - decrease excitability of neurons by modifying action of voltage gated Ca2+ channels - reduced release of P, NA, and glutamate (gabapentin, pregabalin)
Local anaesthetics
- MOA
- Examples
- Practice points
MOA
- Block sodium channels in order to reversibly interrupt peripheral nerve impulse conduction
- Block ability of nerve cell to depolarise and send pain signals to CNS
Examples
- Lignocaine
- Prilocaine
- Cocaine
Practice points
- All cause vasodilation, which can make drug leak into surrounding tissue, limiting duration of action
- Usually given along with adrenaline (powerful vasoconstrictor) to keep anaesthetic localised and increase duration of action
Paracetamol
- Class
- Indication
- MOA
- Practice points
Class
- Analgesic and antipyretic
Indication
- 1st line for mild to mod pain in several situation
- Well tolerated
MOA
- Analgesia MOA may include inhibition of central prostaglandin synthesis and possible effect on serotonergic pain pathways
- Antipyretic effect probably due to reduced production of prostaglandins
- Negligible anti-inflammatory effects
Practice points
- Hepatotoxicity with excessive use and overdose
- Increase risk of adverse effects in hepatitis or chronic alcohol use
- Works best taken regularly at max recommended dose (especially chronic)
- Safe for children approx 4 weeks
- Safe for pregnancy and breastfeeding
- Dangerous in large overdose (liver failure and death)
Overdose of paracetamol
- Factors increasing risk of hepatotoxicity
Factors increasing risk of hepatotoxicity due to paracetamol
- Increased frequency of dosing
- Using higher than recommended doses for prolonged period
- Malnourished or dehydrated
- Fasting or vomiting
- Taking with other drugs such as antiepileptics
Common cause of paracetamol induced liver damage is inadvertently taking 2 paracetamol containing preparations at once
NSAID - Non steroidal anti inflammatory drugs
- Effects
- Examples
Effects
- Analgesic
- Antipyretic
- Anti inflammatory
Examples
- Aspirin
- Ibuprofen
- Diclofenac
- Naproxen
- Indomethacin
NSAID
- MOA
- Practice points
- Contraindications
MOA
- Inhibit synthesis of prostaglandins by inhibiting cyclo-oxygenase (COX) 1 and 2
See diagram
Practice point
- Non is more effective than other
- Dependent on patient response
Contraindications (many)
- CVD
- Asthma
- Therapy with anticoagulants
- Renal impairment
- Dehydration
- PUD/GORD/GIT complication
- Elderly
- Pregnancy
- Impending surgery
NSAIDS - Cox Enzymes
- Cox 1
- Cox 2
Cox 1
- Expressed in most tissue and responsible for synthesis of protective mucosal prostaglandins in GIT to maintain normal lining of stomach
- Also involved in kidney and platelet function
Cox 2
- Expressed in many tissues including brain, kidney, placenta, GIT
- Induced during inflammation and tissue repair
- May have significant role in renal function
Selective NSAIDs
- MOA
- Examples
- Practice points
MOA
- Selective inhibitors of COX2
- Maintain protective mechanisms of COX1 on GIT leading to fewer GIT side effects
Examples
- Celecoxib
- Meloxicam
Practice points
- May have higher incidence of CVD events
- Contraindicated in GORD/PUD however, preferred over NSAIDs
NSAID drug interactions
- Many between prescription, OTC and complementary medicines
- Include
> Warfarin
> ACE inhibitor
> Diuretic
> Sartans
> Lithium
> MTX
> Corticosteroids
Triple Whammy drug interaction
Diuretics - decreased plasma volume therefore reduced renal plasma flow
ACE-I - efferent arteriole dilation which decreases GFR
NSAID - block prostaglandin production which decreases glomerular perfusion
What is osteoarthritis?
Definition
- Metabolically active, ongoing process of degradation and synthesis involving different tissue types within effected joint (cartilage, bone, synovial, ligaments and muscle)
- Involves inflammation (mild to moderate and at least intermittently)
- As OA progresses cartilage synthesis disrupted by inflammation
- Synovial fluid starts to thin resulting in loss of joint lubrication and impaired ability to withstand weight bearing load
- Eventually cartilage and bone exposed and become damaged
Presentation of OA
- General
- Symptoms
- Pain
- Signs
General
- Patients generally over 50
- Spectrum of symptoms with diagnosis ranging from asymptomatic to severe joint pain and stiffness with limitation to daily function
- Joint involvement has asymmetrical distribution without systemic symptoms
Symptoms
- Cardinal symptoms are use related pain described as deep, aching, stiff
- Advanced cases can present during rest
- Weight bearing joints hindered by instability
- Stiffness generally lasts <30 min, limits range of joint motion, impairs daily activity and related to weather
- Psycho social aspect - depressed mood, loss of independence, anxiety
Pain
- Either acute by active inflammatory process or chronic resulting from peripheral and central sensitization
Signs
- Joints in asymmetrical pattern
- Common sites (distal finger, proximal finger, wrist, knee, hip, lower spine, big toe
Risk factors of OA
Systemic factors affecting joint vulnerability
- Increased age
- Female
- Genetic
- Nutritional factors
Intrinsic joint vulnerabilities
- Previous damage
- Bridging muscle weakness
- Increase bone density
- Malalignment
- Proprioceptive deficiencies
Use/loading factors
- Obesity
- Injury from physical activity
Management of OA
- Goals
Goals
- Education
- Pain control
- Maintaining or restoring mobility
- Minimize functional impairment
- Altering disease process and consequences
- Improve QALY
Management of OA
- Non pharmacological
- Weight reduction
- Exercise program
- Physiotherapy
- Thermotherapy
- TENS
- Acupuncture
- Surgery
- Insoles
- Splints/wraps
- Mobility aids
Management of OA
- Drug therapy 1st line
Paracetamol
- Regular divided doses
- Background therapy
- Controlled release option
Management of OA
- Drug therapy 2nd line
NSAIDS
- Lowest effective dose due to ADRs
- Topical or oral (rubs useful for many patients)
- Only use intermittently (before/after exercise or during flare of inflammation
- Should be on paracetamol for regular relief
Management of OA
- Drug therapy 3rd line
Opioids
- Only if 1st/2nd line don’t work or contraindicated
- Always start with weak opioid
Management of OA
- Alternative therapy
- Intra-articular corticosteroid injection
- Usually used if one large joint effected
What is rheumatoid arthritis?
Definition
- Degenerative, autoimmune disorder that attacks joints and associated tissue as well as other body systems
- Leads to inflammation of tissues
- Tends to effect smaller bones
- Significant morbidity and mortality
Pathophysiology of RA
Autoimmune of antibodies against joints, connective tissue and supporting muscles
- Recruitment of B cell and T cells
- Release of inflammatory mediators (cytokines)
- Results in synovial hypertrophy
- Chronic joint inflammation
Risk factors of RA
- Genetic link - HLA DR4
- Age
- Female
- Lifestyle
- Infection (periodontal)
- Nulliparity
RA symptoms and presentation
Mostly effects joints
- Pain/aching in more than one
- Stiffness
- Tenderness
- Bilateral symptoms
- Weight loss
- Fever
- Fatigue
- Weakness
RA complications
- Bony erosion
- Degradation of cartilage and tendons
- Joint deformity
- CVD (HT, hyperlipidaemia, hypercholesterolemia)
- Diabetes
- Obestiy
Ra treatment
- Non pharmacological
- Lifestyle modification
- Heat/cold packs
- Orthotics, splints
- PT/OT
- Daily living aids
RA treatment
- Pharmacological
Begin treatment at once
- Paracetamol
- NSAIDs/corticosteroids
- Antirheumatic tx
> Mild disease (sulfasalazine, hydroxychloroquine, corticosteroids)
> Moderate disease (low dose MTX, cytokine modulators, leflunomide)
Very individualized treatment - requires referral to specialist
RA treatment
1st line - csDMARDs
- Examples
Conventional synthetic disease modifying antirheumatic drugs
Examples
- MTX
- Leflunomide
- Sulfasalazine
- Hydroxychloroquine
While waiting for these to have effect or during flare consider corticosteroids
RA treatment 1st line - csDMARDs (methotrexate) - MOA - Effects - Practice points
MOA
- Folic acid antagonist - stops conversion of inactive folic acid to active form folinic acid by antagonising enzyme DHFR
- Reducing folinic acid inhibits DNA synthesis
Effects
- Cytotoxic
- Immunosuppressive
- Anti-inflammatory
Practice points
- Oral tablet - only take one day per week
- Hepatotoxic
- Tetratogenic
RA treatment
1st line - csDMARDs (methotrexate)
- Contraindication and cautions
Hepatic impairment
- Contraindicated as it is hepatotoxic
Children
- Under specialist
Pregnancy
- Avoid as tetratogenic
Breastfeeding
- Avoid
Renal impairment
- Contraindicated in mod to severe impairment
Avoid in those with immunodeficiency, GI ulcers, UC, active infections
RA treatment
1st line - csDMARDs (methotrexate)
- ADR
- Nausea and vomiting
- Blurred vision
- Oral mucositis
- Pulmonary toxicity - dyspnoea, chest pain, cough, fever
- Hepatoxicity
- Rash/itch/photo sensitivity
- Neurotoxicity
- Myelosuppression
- Immunosuppression
RA treatment
2nd line - bDMARDs
- Examples
Biological disease modifying antirheumatic drugs
Examples
- Abatacept
- Adalimumab
- Certolizumab
- Etanercept
- Infliximab
Begin combining treatments
- Individualized concerning what can be tolerated, severity of symptoms and comorbidity
RA treatment
2nd line - bDMARDs (Infliximab)
- MOA
- Effects/administration
MOA
- TNF alpha antagonist blocking he cytokine stops the inflammatory and immune response
Effects/administration
- Usually used with MTX
- Only IV administration
- Lots of ADR
- Can take 12 weeks to see effect
- Given every 6-8 weeks once reach maintenance dose
RA treatment
2nd line - bDMARDs (Infliximab)
- Contraindication and cautions
Hepatic impairment
- Hepatoxic - avoid
Children
- Not indicated in juvenile RA
Pregnancy
- Avoid
Breastfeeding
- Specialist advice
Cannot be given with certain vaccination
Contraindicated if malignancy in last 5 yrs, active infection, blood dyscrasias, heart failure, MS, lupus
