pain mgmt Flashcards
Types of pain?
Nociceptive, Neuropathic, Referred, Ischemic
Duration to consider pain - “chronic pain”
4-6 weeks, to some 3 months
What are the stages to nociceptive pain?
Transduction, Transmission, Modulation, Perception
Types of nociceptive pain?
Somatic, Visceral
What is somatic pain described as?
Throbbing, aching, stabbing. Localized to injury site and constant
What are the stimulus that cause somatic pain?
Chemical, mechanical, thermal
What fibres are the nociceptive pain signals carried by?
Small myelinated A-Delta fibres (for mechanical and thermal stimulus)
C fibres to the dorsal horn of spinal cord (for all type types of pain stimulus)
What are visceral pain mediated by?
Stretch receptors
What is visceral pain described as?
Dull, gnawing, cramping. Poorly localised
What causes neuropathic pain?
Damage to nerves due to diseases or treatment
What are the types of neuropathic pain?
Peripheral, Central
What is the pathophysiology of peripheral neuropathic pain
Abnormal nerve generation + Nerve sprouts formation
Ectopic neuronal pacemaker formation
What is the pathophysiology of central neuropathic pain?
Reorganisation of central somatosensory processing leading to
1) Deafferentation of pain
2) Sympathetically maintained pain
How is neuropathic pain described?
Tingling, numbing, electric shock-like, burning, prolonged
How is referred pain described as?
Pain is located away from point of origin
What causes referred pain?
Signal from different pain of the body travels along the same pathway going to the spinal cord and the brain
What causes Ischemic pain ?
Loss of blood flow to tissue, lack of perfusion, leading to tissue hypoxia and damage
Tissue hypoxia causes the release of inflammatory mediators and chemicals that stimulate the nociceptors.
Autonomic signs associated with pain?
Increased RR, HR, BP and diaphoresis
What are the components of SOCRATES framework?
Site, Onset, Character, Radiation, Associations, Time course, Exacerbating/Relieving factors, Severity
What are assessment tools use to assess pain?
FLACC scale, Wong-Baker Faces rating scale, Numerical rating scale, Visual analog scale, Adjective rating scale, McGill Pain Questionnaire
What are the pharmacological therapies available for pain?
Non-opioids analgesics, Opioids analgesics, Nerve blocks, Adjuvant analgesics
What are the electrical stimulation therapies available for pain?
Transcutaneous electrical nerve stimulation (TENS)
Percutaneous electrical nerve stimulation (PENS)
What are the alternative therapies available for pain?
Acupuncture, physiotherapy, chiropratic, surgery
What are the pharmacologic treatments suggested by WHO ladders?
Mild pain - Non-opioids +/- adjuvants
Moderate pain - Weak opioids +/- adjuvants
Severe pain - Strong opioids +/- adjuvants
What are recommendations made by WHO for management of cancer pain?
1) Oral administration of analgesic (if possible)
2) Analgesics should be given at regular intervals
3) Dosing of pain medication should be adapted to the individual
4) Analgesic should be prescribed according to pain intensity as evaluated by a scale of intensity of pain
5) Analgesics should be prescribed with a constant concern for detail
Pharmacological options for mild pain?
Acetaminophen, NSAIDs (1st line: Ibuprofen)
Benefits of COX-2 selective NSAIDs?
Lesser GI side effects, no platelet inhibition
What are the uses of adjuvants?
Co-administered to improve analgesia
Adjuvants used for neuropathic pain?
Gabapentin, Pregabalin, Antidepressants, Antiepileptics, Topical lidocaine, Corticosteroids
Adjuvants used for bone pain?
NSAIDs, Corticosteroids, Bisphosphonates
Adjuvant used for intestinal colic?
Hyoscine butylbromide
Adjuvant used for muscle cramps/ spasms?
Muscle relaxants, benzodiazepines
Corticosteroid is an adjuvant indicated for?
Bone pain, neuropathic pain, raised intracranial pressure pain, liver capsule stretch pain
MOA of opioids?
Modifies central perception of pain by binding to Mu-1, Mu-2, Kappa and Delta opioid receptors
Examples of Weak opioids?
Codeine, Tramadol
Examples of Moderate opioids?
Tapentadol
Examples of Strong Opioids?
Morphine, Fentanyl, Oxycodone, Pethidine, Methadone
Conversion of PO codeine to PO morphine?
10:1 , 100 mg of PO codeine = 10 mg of PO morphine
Codeine is a substrate of?
CYP2D6, CYP3A4
DDIs of Codeine?
CYP2D6 inhibitors such as Chlorpromazine, Fluoxetine can decrease the effects of codeine
Indication for Codeine?
Moderate pain
Indication of Tramadol
Moderate pain
MOA of Tramadol
Opioid receptor agonist, inhibitor of noradrenaline and serotonin uptake
Onset of Tramadol?
1 hour
Duration of Action of Tramadol
9 hours
Absorption of Tramadol?
Rapid and complete
Onset of Codeine?
Oral: 0.5-1 hours
IM: 10-30 mins
Duration of action of Codeine?
4-6 hours
Metabolism of Codeine?
Hepatically to morphine
Excretion of codeine?
Urinary
What is codeine available as?
Injection and tablet
Dosing adjustment for codeine in patient with renal impairment?
CLCR 10-50ml/min: 75% dose
CLCR <10 ml/min: 50%
Dosing adjustment for codeine in patient with hepatic impairment?
Necessary in hepatic insufficiency
ADR of Codeine?
Drowsiness, Constipation
Metabolism of Tramadol?
Extensively hepatically by CYP2D6 via 1) Demethylation 2) Glucuronidation 3) Sulfation to active metabolite O-desmethyl tramadol
Excretion of tramadol?
Urine
Conversion of PO tramadol to PO morphine?
5:1, 50mg PO Tramadol = 10 mg PO morphine
Dosing adjustment for Tramadol in patient with renal impairment?
Immediate release:
CLCR < 30ml/min: 50-100 mg q12h (Max: 200mg)
Extended release:
Should not be used in patient with CLCR <30ml/min
Dosing adjustment for Tramadol in patient with hepatic impairment?
Immediate release:
Cirrhosis: 50mg q12h
Extended release:
Should not be used in pts with severe hepatic dysfunction
Tramadol is a substrate of?
CYP2D6, CYP3A4
DDIs of Tramadol?
CYP2D6: Chlorpromazine, Fluoxetine
Carbamazepine: Decreases half life of tramadol
Increases risk of tramadol induced seizure: Naloxone Neuroleptic agents SSRIs Tricyclic antidepressants
Warfarin: Elevation of prothrombin times
ADR of Tramadol
Dizziness, Constipation, Nausea, at high dose decreases the seizure threshold
Indication of Morphine
For moderate to severe pain
Conversion of PO Morphine to IV morphine
3:1, 30 mg of PO = 10mg of IV
Tramadol is available as?
Injection and tablet
Benefits of Tramadol over other opioids?
Lesser cardiovascular and respiratory adverse effects, lower potential of abuse.
Onset of action for Morphine?
Oral (immediate release): 30 minutes
IV: 5-10 minutes
Absorption of Morphine
Variable
Metabolism of morphine
Hepatic via conjugation via glucuronic acid to
1) Morphine-3-glucuronide (inactive)
2) Morphine-6-glucuronide (active)
3) Morphine-3,6-diglucuronide
4) Normorphine (active)
5) 3-ethereal sulfate
Excretion of morphine
Mainly in urine, 10% in bile
Morphine is available as?
Tablet, capsule, injection, mixture
Dosing adjustment for Morphine in patient with renal impairment?
CLCR 10-50 ml/min: 75% dose
CLCR < 10 ml/min: 50%
Dosing adjustment for Morphine in patient with hepatic impairment?
No change in mild liver disease, excessive sedation may occur in cirrhosis
DDIs of Morphine
Antipsychotic agent: Increase hypotensive effects of morphine
Increase effect/toxicity:
CNS depressant, MAO inhibitors
DFIs of Morphine
Ethanol: Increase CNS depression
Herb/Nutraceutical: Valerian, St John’s Wort, Kava Kava, Gotu Kola increases CNS depression
Side effects of Morphine (more important ones)
Hypotension, Pruritus, Drowsiness, Urinary retention, N/V, Constipation
Indications of Fentanyl
Indicated for severe pain
Onset of action of Fentanyl?
IM: 7-15 mins
IV: Almost immediately
Metabolism of Fentanyl?
Hepatically, primarily via CYP3A4
Excretion of Fentanyl
Urinary, mainly as metabolites
Conversion of TD Fentanyl to PO Morphine
Refer to manufacturer guide
12 MCG TD= 30 MG PO /24 hours
Dosing adjustment for Fentanyl in patient with renal impairment?
Nil
Dosing adjustment for Fentanyl in patient with hepatic impairment?
Monitor
SE of Fentanyl (more impt ones)
Hypotension, N/V, Constipation, Respiratory depression, Drowsiness
Availability of Fentanyl
Injection and Dermal patch
What kind of patients are TD Fentanyl indicated for?
1) Intolerable SE from Morphine
2) Renal failure
3) Dysphagia
4) ‘Tablet phobia’ or poor oral compliance
Bioavailability of TD Fentanyl?
> 92%
Time taken to reach steady state for TD Fentanyl?
36-48 hours
Elimination half-life of TD Fentanyl?
13-22 hours after removing patch
Duration of action of TD Fentanyl?
72 hours, for some pts 48 hrs
MOA of Methadone?
Mu-opioids receptor agonist, NDMA receptor channel blocker, Presynaptic blocker of serotonin re-uptake
Bioavailabilty of Methadone?
80% (range from 40-100%) PO
Onset of action of Methadone?
30 minutes PO
Metabolism of Methadone?
Hepatically. N-demethylation primarily via CYP3A4, CYP2B6, CYP2C19
Excretion of Methadone?
Urine, increased with urine pH <6
Methadone is a substrate of?
CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (major)
DDIs of Methadone?
CYP3A4 inducers, may decrease levels /effects of methadone
CYP3A4 inhibitors, may increase levels/ effect of methadone
Agonist/antagonist analgesics: May decrease analgesic effect of methadone
DFIs of Methadone?
Ethanol: Increase CNS effects
Herb/ Nutraceuticals like St John’s Wort (may decrease Methadone levels as well), Valerian, Kava Kava, Gotu kola increases CNS effects
Dosing adjustment for Methadone in patient with renal impairment?
CLCR < 10 ml/min: 50-75% dose
Dosing adjustment for Methadone in patient with hepatic impairment?
Avoid in severe liver disease
Significant SEs of Methadone?
Hypotension, Constipation, Sweating, Drowsiness, N/V, Respiratory depression
Conversion of PO Oxycodone to PO Morphine
1:2, 10 mg Oxycodone = 20 mg Morphine
Bioavailability of Oxycodone?
75% PO (60-87% range)
Onset of action of Oxycodone
20-30 mins PO
Duration of action of Oxycodone
4-6 hours; 12 hours for m/r
Metabolism of Oxycodone
Hepatically by CYP2D6 to oxymorphone (active), BY CYP3A4 to noroxycodone
Excretion of Oxycodone?
Via Urine
Dosing adjustment for oxycodone in patient with renal impairment?
Use with caution. Renal impairment decrease the clearance of oxycodone, noroxycodone and conjugated oxymorphone
Dosing adjustment for oxycodone in patient with hepatic impairment?
Reduce dosage in pts with severe liver disease
Significant SEs of Oxycodone?
Drowsiness, Constipation, N/V
Main difference in dosing between Oxycodone and Morphine?
Oxycodone is given q6h rather than q4h
Oxycodone is the substrate of?
CYP2D6, CYP3A4
DDIs of oxycodone?
CYP2D6 inhibitors: Decrease effect of oxycodone (Chlorpromazine, Fluoxetine)
DFIs of oxycodone?
Ethanol
Valerian, St John’s wort, Kava Kava, Gotu kola
Indication of Tapentadol?
Acute moderate to severe pain
MOA of tapentadol
Mu-opioid receptor, inhibits reuptake of noradrenaline
Metabolism of Tapentadol?
Metabolized primarily via phase 2 glucuronidation to glucuronides, all metabolites are pharmacologically inactive
Excretion of Tapentadol?
Urine
Absorption of Tapentadol?
Rapid
Distribution of Tapentadol?
Widely distributed, enters human milk
Dose of Tapentadol?
50-100mg q4h or q6h for acute moderate/acute pain
Administration of Tapentadol?
Orally with or without food, long acting formula must be swallowed whole
Dosing adjustment for Tapentadol in patient with renal impairment?
No dose adjustment for mild/moderate impairment
Dosing adjustment for TAPENTADOL in patient with hepatic impairment?
No dose adjustment for mild impairment
Common SEs of Tapentadol?
N/V, Dizziness, Drowsiness
Indication of Pethidine
ACUTE SEVERE PAIN
Onset of Pethidine?
SC: 10-15 mins
IV: 5 mins
Duration of Pethidine effect?
SC: 2-4 hours
Metabolism of Pethidine?
Hepatically to
1) Meperidinic acid (inactive)
2) Norpethidine (active)
Excretion of Pethidine?
Urine as metabolites
Dose of Pethidine?
IV 75-100mg q3h
Dosing adjustment for Pethidine in patient with renal impairment?
Avoid repeated administration in renal dysfunction
CLCR 10-50 ml/min: 75%
CLCR <10 ml/min: 50%
Dosing adjustment for Pethidine in patient with hepatic impairment?
Increase effect in cirrhosis, may need to reduce dose
Why do we avoid Pethidine in Palliative care?
1) Quick onset, short duration of action. Not suitable for regular analgesia
2) Toxic metabolite (Norpethidine) accumulate if given regularly
3) More emetogenic than morphine
When switching from one opioid to another consider _____ dose reduction?
25-50%
Exceptions for opioid dose reduction?
1) No dose reduction when converting to TD Fentanyl
2) Patient in severe pain
3) Converting to Methadone required larger reduction (75-90%)
4) Elderly patients or those with organ dysfunction, consider reduction
Choice and dose of opioid depends on?
Severity of pain
Dose of breakthrough dose?
1/6 of total daily dose
Which drug is used for opioid overdose rescue?
Naloxone
When to use Naloxone?
When patient is non responsive, cyanosed, RR < 8/min
When to “wait and see”?
When patient RR >8/min, easily arousable and not cyanosed
Metabolism of Naloxone? Excretion of Naloxone?
In the liver, excreted by kidney
Onset of action of Naloxone?
Around 2 mins (IV)
Availability of Naloxone?
400 mcg/ml IV injection
Dosing of Naloxone
Adults: IV 100-200 mcg, can be repeated every 2 mins. Max: 10mg
Child: IV 5-10 mcg/kg, can be repeated every 2 mins
Common SEs of Opioid therapy?
Somnolence, mental clouding, constipation, N/V
Management of Sedation and cognitive dysfunction?
Psychostimulants like
Caffeine (100-200mg PO daily)
Dextroamphetamine (2.5-10mg PO BDS)
Methylphenidate (5-10 mg PO BDS)
Management of Myoclonus?
Clonazepam (0.5-2mg PO TDS) and anticonvulsants
Monitoring outcomes of Opioid Tx?
Pain relief, SEs, Function (Physical and Psychosocial), Drug related behaviour