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RC Study > OPIOIDS : Principles of opioids and optimizing outcomes > Flashcards

OPIOIDS : Principles of opioids and optimizing outcomes Flashcards

1
Q

Pharmacokinetics

A
  • What the body does to the drug
  • ADME
    • Absorption
    • Distribution
    • Metabolism
    • Excretion
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2
Q

Pharmacodynamics

A

What the drug does to the body

*

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3
Q

Factors that affect pharmacokinetics of opioids

A
  • Age
    • metabolism, volume of distribution, reduced in elderly
    • increased free concentrations in plasma
    • hepatic flow declined
    • increased CNS sensitivity
  • Hepatic disease
    • Unpredictable
    • severe failure = marked sensitivity
    • reduction in plasma protein = increased plasma concentrations of drugs
  • Renal failure
    • renally cleared metabolites accumulate
  • Obesity
    • volume of distribution larger, longer half life, elimination
  • Hypothermia, hyperthermia, hypotension, hypovolemia
    • variable absorption
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4
Q

Pharmacokinetics : Absorption

A
  • across lipid cell membrane
  • passive process concentration gradient
  • occurs in small bowel
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5
Q

List causes of altered absorption

A
  • delayed gastric emptying
  • medications that delay emptying (opioids, ach)
  • sustained release formulations need to stay in small bowel to be fully absorbed
    • may be reduced absorption if increased GI transit (maxeran, domperidone)
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6
Q

Pharmacokinetics : Bioavailability

A
  • percentage of drug that gains access unchanged to systemic circulation
  • oral administration most relevant
  • Extensive first pass metabolism in liver
    • low bioavailability of some drugs
  • differences in bioavailability = challenges in safe dose selection between oral and parenteral
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7
Q

List reasons that can alter bioavailability

A
  • hepatic dysfunction
  • exposure to drugs that induce or inhibit P450 system
  • eg:
    • chronic liver disease, blood shunted from portal to venous system
    • bypasses hepatic enzymes and first pass effect
    • increased bioavailability of drug
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8
Q

Pharmacokinetics : Distribution

A
  • volume of distribution :
    • theoretical volume for total amount of drug needed to be uniformly distributed to achieve targeted blood concentration
  • Volume for lipophilic drugs can be 4-5x body size

High volume of distribution

  • drugs leaves plasma and goes intro extravascular components of body
  • higher dose required to achieve blood concentration
  • longer half life elimination

Low Volume of distribution

  • more likely to stay in plasma
  • lower dose required
  • shorter half life
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9
Q

List factors that affect the volume of distribution

A
  • acid base disturbances
    • basic drugs tend to be more lipophilic
    • leave systemic circulation, higher volume distribition
    • acid drugs like albumin and bind to it, stay in plasma
  • Lipophicility of drug
    • higher VD
    • Hydrophilic meds stay in plasma
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10
Q

Diffusable fraction of opioids

A
  • proportion of opioid that is unbound to plasma proteins
  • capable of diffusing to site of action
  • determines speed on onset of clinical effect
    • concentration of diffusable fraction
    • lipid solubility
    • diffuses across BBB
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11
Q

Compare onset of action and reason for morphine and fentanyl

A
  • Morphine:
    • high diffusable fraction, low lipid solubility
    • slow onset
  • Fentanyl
    • high diffusable fraction, high lipid solubility
    • fast onset
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12
Q

Pharmacokinetics : metabolism

A
  • occurs in liver
  • Phase I reactions :
    • oxidation, reduction, hydrolysis, isomerization
    • Oxidation catalyzed by CYP450 family of enzymes most important
  • Phase II reacions:
    • conjugations, glucoronidation, methylation
  • goal is to produce water soluble products that can be excreted by kidneys
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13
Q

Pharmacokinetics : Elimination

A
  • Liver
  • Kidneys
  • Clearance is volume of blood completely cleared of drug in unit of time
  • determines half life and steady state
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14
Q

Pharmacokinetics : define Half Life

A
  • measure of time taken for half the drug in the body to be removed
  • correlates closely with duration of action

Concerns:

  • long half life accumulates for prolonged period of time
  • concentration can surpass effective therapeutic range
  • toxicity
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15
Q

Pharmacokinetics : Steady State

A
  • 5-6 half lives requried to reach steady state
  • regardless of route of adminstration
  • aim is to achieve intended effect without side effects
  • swings between trough and peak:
    • amount depends on eliminimation half life and frequency of administration
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16
Q

How much time does it take to reach steady state?

A
  • depends on half life
  • 5-6 half lives
  • 95% of steady state drug concentration achieved with 4 half lives.
  • relevant for first order kinetics (most drugs)
  • Eg: half life of morphine is 2-4 hours.
    • given q4h
    • steady state 95% will be at 4x4 hours = 16 hours
    • can titrate every day then to ensure dose changes are at steady state
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17
Q

Pharmacodynamics

A
  • drugs produce effects by:
    • binding with receptors
    • modifyign enzyme processes
    • direct chemical or physical actions
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18
Q

Opioid receptors

A
  • Mu (MOR)
  • kappa (KOR)
  • delta (DOR)
  • ORL-1 Orphan
    • opioid like receptor
    • (nociceptin peptide receptor NOR)
    • spinal cord
    • modulates stress response, movement, etc
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19
Q

List endogenous opioids

A
  • Encephalins
  • Endorphins
  • Dynorphins
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20
Q

Mu Opioid receptor

A
  • Gene OP3
  • Expression
    • CNS (cortex, thalamus, hypothalamus, periaqueductal gray, amygdala)
    • Spinal cord
    • Peripheral nervous system
    • Immune cells
  • Endogenous ligand
    • beta endorphin
    • encephalins
    • endomorphins
  • Function
    • inhibits nociceptive pathways
    • all exogenous opioids can bind
    • analgesia
    • resp depression
    • reduce GI motility
    • mioisis
    • euphoria
    • sedation
    • dependence
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21
Q

Kappa Opioid Receptor

A
  • Gene OPRK1
  • Expression:
    • CNS, same as Mu
    • no amygdala
    • spinal cord
    • PNS
  • Endogenous ligand
    • Dynoprhins
  • Function
    • modulation of pain
    • chemical and visceral and thermal pain
    • analgesia
    • responsible for lots of side effects
      • nausea and vomiting
      • dysphoria
    • mioisis
    • dysphoria
    • hallucinations
    • sedation
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22
Q

Delta Opioid Receptor

A
  • Gene OPRD1
  • Expression
    • CNS (cortex, striatum, olfactory bulb)
    • PNS
  • Endogenous ligand
    • encephalines
    • betaendorphins
  • Function
    • analgesia
    • resp depression
    • reduced GI motility
    • tolerance
    • mood regulation
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23
Q

Opioid AGONISTS

A
  • binds to cell receptors to induce changes in cell that stimulate physiological activity
  • no ceiling effect to analgesia
  • log linear function of analgesia until either analgesia or adverse side effects occur
  • most opioids are Full agonists
    • morphine,
    • HM,
    • oxycodone,
    • methadone,
    • fentanyl
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24
Q

Partial AGONISTS

A
  • low intrinsic efficacy
  • lack of linear response in analgesia after dose escalation
  • ceiling effect at less than maximum effect compared to full agonist
  • Buprenorphine
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25
Q

Potency

A
  • dose response relationship
  • intensity of effect of different drugs
  • equianalgesic effects
  • ratio of doses of 2 analgesics required to produce the same effect
  • by convention, it is compared to 10 mg IV morphine
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26
Q

Efficacy

A
  • maximal reponse by active drug
  • degree of analgesia after dose escalation through a range limited by adverse effects
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27
Q

Opioid Mixed agonist / antagonists

A
  • Agonist effects at one receptor
  • Antagonist effects at another
  • Eg. Nalbuphine
  • Pentazocine
  • when mixed antagonist-agonist is given with an agonist, the antagonist effect at mu receptor can cause withdrawal.
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28
Q

Opioid ANTAGONISTS

A
  • Interfere with action of agonist
  • have no pharmacological action intrinsically
  • competitive antagonists bind to same receptors as agonists
  • non competitive antagonists block in other ways
  • Eg Naloxone, Naltrexone
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29
Q

List GI Side Effects of Opioids

A
  • nausea
  • constipation
  • dry mouth
  • vomiting
  • Ileus
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30
Q

List CNS side effects of opioids

A
  • Somnolence
  • COnfusion
  • Myoclonus
  • Nightmares
  • hallucinations
  • hyperalgesia
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31
Q

List GU side effects of opioids

A
  • Urinary retention
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32
Q

List respiratory side effects of opioids

A
  • decreased cough
  • respiratory depression
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33
Q

List skin side effects of opioids

A
  • diaphoresis
  • pruritis
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34
Q

List Endocrine side effects of opioids

A
  • Hypogonadism
  • Immunosuppression
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35
Q

Define Adverse drug effect

A
  • unwanted or harmful reaction to drug
  • when given under normal circumstances
  • suspected to be related to drug
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36
Q

Pharmacokinetic drug interactions

A
  • changes in rate and extent of absorption
  • rate of metabolism
  • distribution
  • renal exretion
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37
Q

Common drug interactions

A
  • GI tract
    • metoclopramide, ACh alter gastric emptying
    • alters speed of absorption
    • drugs that bind in GI tract (PPI, iron, cholestyramine) : decrease bioavailability
  • Liver
    • changes in bioavailability
    • miss first pass metabolism
    • decreased clearance
  • CYP450 interactions
    • inducers/inhibitors
  • Kidney
    • loop diuretics compete for active tubular secretion
    • NSAIDS
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38
Q

What happens if you give buprenorphine with Morphine?

A
  • morphine induced analgesia reversed or limited by competetition of partial agonist buprenorphine.
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39
Q

Immediate and Sustained Release

A
  • IR:
    • absorbed in stomach and small bowel
    • complete in 1-2 hours of ingestion
  • SR
    • smoother concentration profile in blood
    • extended duration and reduction in pill burden
40
Q

Transmucosal administration

A
  • avoids first pass metabolism
  • higher bioavailability
  • faster onset of action
41
Q

Transdermal

A
  • Lipid soluble drugs well absorbed through skin
  • caution in cachexia and fever
42
Q

Opioid pharmacogenomics

A
  • CYP2D6 allele
  • genetic polymorphisms
  • 4 phenotypes
    • poor metabolizers (10% caucasions, no analgesia)
    • intermediate
    • extensive
    • ultra metabolizers (3%, adverse effects, toxicity)
  • CODEINE partially metabolized by CYP2D6
  • Fatal neonatal opioid toxicity in children breastfed by mothers who are ultrarapid metabolizers
43
Q

Mixed mechanism Drugs

A
  • Tramadol / Tapentadol
  • centrally acting anaglesics
  • Mu agonist AND monamine SE, NE reuptake inhibition
  • ceiling dose
44
Q

WHO Analgesic ladder for Cancer Pain

A

Step 1 Mild Pain

  • non opioid +/- adjuvant

Step 2 Moderate Pain

  • Weak opioid +/- non-opioid +/- adjuvant

Step 3 Severe Pain

  • Strong opioid +/_ non-opioid +/- adjuvant
45
Q

Why do some clincians prefer to omit the second step of the WHO ladder and move directly to step 3?

A
  • Improved understanding of the metabolism of codeine
  • Wider range of step 3 opioids available. Can use low dose of these
  • Low dose strong opioid more efficient than switching mutiple times
46
Q

Codeine

A
  • naturally occuring opium alkaloid
  • low affinity for mu receptors, bioavailability 60-90%
  • metabolized to morphine
    • codeine 6 glucoronide
    • M3G and M6G
  • CYP 2D6 with ++ genetic polymorphism
  • 1/2 life 2 hours, peak 1.5-2 h, duration 3-6h
  • dose 30-60 mg po
47
Q

Oxycodone

A
  • semi-synthetic congener of morphine
  • high oral bioavailability 60-90%
  • metabolized to oxymorphone in liver (not active)
  • pure mu agonist
  • more potent than morphine (1.5 :1)
  • accumulates in renal failure
  • CYP 3A4 and CYP 2D6
48
Q

Tramadol

A
  • CYP 3A4 and 2D6
  • Mu agonist
  • Monoamine inhibitor (Serotonin and NE)
  • Modest affinity for mu, weak affinity to delta and kappa
  • can be reveresed by naloxone
  • ceiling effect
  • Side effects similar to morphine
49
Q

Tapentadol

A
  • mu agonist
  • NE reuptake inhibitor
  • minimal 5HT inhibition
  • no active metabolites, no drug drug interactions
  • CI with MAOI
  • limited evidence
50
Q

Morphine

A
  • potent mu agonist
  • liquid, IR, CR

Absorption

  • Absorption is complete in upper small bowel

Metabolism

  • pre systemic first pass metabolism in liver
    • bioavailability 20-30%
  • t1/2 2-3 hours, duration 4-6 hours
  • rectal bioavailability similar to oral
  • M3G - no analgesic effects
    • does not bind to mu receptors
  • M6G - active metabolite, binds to opioid receptors
    • potent analgesic
    • may cause toxicity

Excretion

  • liver first pass
  • Kidney excretes metabolites

Other

  • Hydrophilic
    • epidural this means no systemic absorption, long 1/2 life in spinal fluid. extensive rostral redistribution
51
Q

Morphine potency and conversions

A
  • 1:3 or 1:2 IV: oral
  • Single dose vs chronic dosing
  • M6G accumulation may be greater with oral than parenteral administration
52
Q

Sustained release morphine

A
  • peak of 3-6 hours
  • duration 12-14 hours
  • do not use for titration period
53
Q

Methadone

A
  • Synthetic opioid at mu receptor NMDA receptor antagonist
  • oral : parenteral potency 1:2
  • single doses, potency similar to morphine
  • repeated doses = increased potency
  • half life 12-150 hours with variability
  • Steady state 1 week
  • Ratios:
    • 4:1 MEDD < 90
    • 8:1 MEDD 90-300 mg
    • 12:1 MEDD >300 mg
54
Q

Meperidine

A
  • synthetic opioid
  • mu agonist
  • active metabolite is norpethidine:
    • twice as potent as a convulsant
    • half as potent as analgesic
    • accumulates ++ with repeated dosing
  • CNS excitability, mood , tremor, myoclonus, seizure
  • naloxone not effective for seizures, may even preciptate seizure by blocking anti seizure action of meperidine
  • Accumulation in renal function
  • 5HT4 syndrome with MAOI combination
  • NOT USEFUL IN CANCER PAIN
55
Q

Hydromorphone

A
  • semi synthetic morphine congener
  • 5x as potent at morphine
  • potency ratio:
    • equianalgesic ratio for parenteral HM : M differs
      • 7:1 when going morphine to HM
      • 4:1-8:1 when going HM to morphine
    • Oral equianalgesic ratio
      • 7.5-1
    • IV hm : oral HM 1:2
  • mu agonist
  • high concentrations available for sc infusion
  • Metabolism:
    • oral bioavailability 60-80%
    • partially metabolized in liver
    • H3G metabolite
    • largely excreted unchanged in liver
56
Q

Fentanyl

A
  • semi synthetic opioid
  • highly selective mu agonist
  • 100X as potent as parenteral morphine
  • ++ lipophilic
  • rapid onset 3-5 minutes
  • duration 30-60 minutes
  • t 1/2 3-12 hours (longer with repeated administration –> fat sequestration)
  • NO active metabolites
  • some evidence less constipating
57
Q

Transdermal fentanyl

A
  • TD absorption bc low molecular weight and high lipid solubility of fentanyl
  • serum {} increases gradually, levels of at 12-24 hours
  • after removal, serum [] falls to 50% at 17 hours
  • avoid in patients with unstable pain
  • subcutaneous depot of drug that maintains plasma concentration

Rotating to patch

  • takes 8-12 hours to get analgesia
  • need to continue IR original opioid until then

Patch placement

  • minimal skin movement
  • cachexia may not absorb
  • no heat pads
  • watch for fever
  • cold = less absorption
58
Q

When you might choose a fentanyl patch

A
  • loss of oral route (head and neck ca, obstruction)
  • poor compliance with po meds
  • opioid toxicity or intolerance of other opioids
  • stable opioid dosing
  • patient preference

Avoid if unstable pain

++ Education when starting

59
Q

Oral Transmucosal fentanyl

A
  • Lozenge
  • Rapid absorption
  • Onset 5-10 minutes
  • Good for incident pain
  • Dose is not dependent on MEDD

Also can be given :

  • sl
  • nasal fentanyl spray (esp for kids)
60
Q

When should opioid therapy be initiated?

A
  • moderate or greater pain
  • regardless of mechanism (neuropathic, somatic, visceral)
  • dose titration until analgesia or side effects
61
Q

Buprenorphine

A
  • PARTIAL mu agonist
  • true partial mu agonist
  • ceiling effect in higher doses
  • oral not effective as all elimated in first pass metabolism
  • injectable, sl, patch
  • single doses of 0.3 mg iv are equal to 10-15 mg morphine IM
  • LONG duration of action (6-9 hours)
  • onset 30-60 minutes
62
Q

Nalbuphine

A
  • mixed agonist-antagonist
  • produce analgesia in opioid naive, but withdrawal in people already dependent on opioids
  • mu ANTAGONIST, and kappa AGONIST
  • Not useful for repeated dosing for pain, limited role
  • low incidence of euphoria or respiratory depression
  • useful for opioid induced pruritis
63
Q

Factors to consider when selecting an opioid

A
  1. Pain severity
    * opioid vs non-opioid
  2. Pharmacokinetic formulations
  • start with a shorter half life opioid
  • oral route if possible, or IV/sc
  1. Co-existing disease
  • renal impairment
  • hepatic impairment
  1. Response to previous opioids
64
Q

Rectal administation

A
  • morphine, hydromorphone, oxycodone
  • may be different from oral admin
  • bioavailabilty might be different
  • bypasses first pass hepatic metabolism
65
Q

Parenteral administation

A
  • Bolus effects:
    • toxicity at peak concentration
    • breakthrough pain at trough concentrations
  • IV bolus most rapid onset, depends on lipid solubility
66
Q

Epidural / Intrathecal dosing

A
  • opioid receptors present in dorsal horn of spinal cord
  • Epidural 1/10 of MEDD
  • Intrathecal 1/100 MEDD (or 1/10 of epidural dose)
67
Q

Sublingual administration

A
  • bioavailability poor with less lipophilic drugs
  • works for SL fentanyl, buccal methadone, buprenorphine
68
Q

Scheduling opioids

A
  1. Around the clock
  • start low and go slow
  • IR formulations, then SR
  • Morphine 5 mg po q4h, HM 1mg po q4h, oxycodone 2.5 mg po q4.
  1. Breakthrough dosing
  • q1h po or q30 min IV/sc
  • usually same as regular opioid (except methadone and fentanyl
  • 10% daily dose
  • or 1/6 of 4 hourly dose of opioid (ie same as 4 hourly dose)
  • If more than 3 breakthrough doses/day, consider titration of base opioid
69
Q

Titration

A
  • log linear increase in analgesic compared to dose
  • escalations of < 30-50% are not likely to improve analgesia significantly
70
Q

Opioid tolerance

A
  • Tolerance to analgesic effect:
    • need for increasing doses to maintain same effect in the abscence of other factors that would explain increase in pain.
  • true tolerance is less common than disease progression or psychological distress
  • true tolerance is from changes at receptor level.
  • Tolerance to side effects varies:
    • Respiratory depression, somnolence, nausea RAPID tolerance
    • Constipation SLOW Or NO tolerance
71
Q

List side effects of opioids that resolve quickly (tolerance develops rapidly)

A
  • somnolence
  • nausea/vomiting
  • respiratory depression
  • urinary retention
72
Q

Opioid Rotation

A
  • dose reduction of 25-50% for incomplete cross tolerance
    • to reduce toxicity, overdose, and minimize underdosing.
  • Always done to reduce opioid side effects.
  • Usually improves :
    • cognition
    • delirium
    • sedation
    • myoclonus
    • nausea/vomiting
73
Q

List common opioid adverse effects

A

Gastrointestinal

  • nausea/vomiting
  • constipation

Autonomic

  • xerostomia
  • urinary retention
  • postural hypotension

CNS

  • sedation
  • cognitive impairment
  • hallucinations
  • delirium
  • respiratory depression
  • myoclonus
  • seizure
  • hyperalgesia

Cutaneous

  • Itch
  • sweating

Endocrine

  • hypogonadism
  • impaired adrenal hormones - blunted stress reponse
  • obesity - diabetes
74
Q

List factors that predict opioid adverse effects

A
  • Drug related
    • fentanyl less constipating
  • Route related
  • Patient related
    • age
    • renal function (M6G)
    • hepatic function
    • Other drugs
  • Dose related
    • CNS side effects increased with increased dose
    • GI effects weaker dose reponse
    • constipation universal and not related to dose
75
Q

Approach to treating adverse effects

A
  • Rule out other causes of adverse effects
  • Then consider
  1. Dose reduction 25%
  • if pain is well controlled
  • use of non opioids or adjuvants
  • targeted therapy : radiation, chemo, surgery
  • regional anesthesia, blocks, etc
  1. Specfic therapies to treat AE
  2. Opioid rotation
  3. Change route
  • switching routes from po to sc may help
  • poor evidence
76
Q

Differential diagnosis of opioid adverse effects : delirium/drowsiness/cognitive impairment

A

CNS:

  • mets
  • leptomeningeal disease
  • CVA
  • extradural bleed

Metabolic

  • dehydration
  • hyper CA
  • Hyper/hypo NA
  • Renal failure
  • hepatic failure
  • hypoxemia

Sepsis/infection

Iatrogenic

  • tcas
  • benzos
  • NSAIDS
  • chemo/rads
77
Q

Differential diagnosis of opioid adverse effects : nausea/vomiting and constipation

A

Bowel obstruction

Medications:

  • antibiotics
  • vinca alkaloids (constipation)
  • Flutamide (constipation)
  • NSAIDS
  • chemo/rad (nausea and vomiting)

Metabolic

  • hyper Ca
  • Hyper/hypoNA
78
Q

Management of opioid induced constipation

A
  • prophylactic laxative (PEG, senna)
  • does not improve with time
  • avoid bulk laxatives
  • methylnaltrexone
79
Q

Management of opioid related nausea and vomiting

A
  • Often resolves over days-week
  • opioids stimulate CTZ, delay gastric motility, delayed emptying
  • either prn antiemetic effective at CTZ (prokinetic)
  • scheduled prokinetic if nausea persistent
80
Q

Management of confusion and delirium related to opioids

A
  1. Discontinue all non essential centrally acting medications
  2. If analgesia satisfactory, reduce opioid dose by 25%
  3. Exclude sepsis
  4. Exclude CNS tumour involvement
  5. If delirium persists, consider neuroleptic, rotation, change in route, different analgesic options.
81
Q

Management of sedation related to opioids

A
  • sedation typical wehn beginning opioid therapy or dose increase
  • tolerance within days to weeks
  • limited evidence to treat with methylphenidate if persistent
  • rotation may help
  • opioid sparing adjuvants (rads, interventional)
82
Q

Respiratory depression related to opioids

A
  • can be early indicator of CNS toxicity
  • tachypnea and anxiety never related to opioids
  • tolerance develops rapidly
  • respiratory depression can occur if pain eliminated suddenly (neurolytic, epidural)

High risk

  • rapid titration
  • high dose
  • pre -existing underlying lung disease
  • multiple opioids given suddenly

Management:

  • supportive with 02
  • naloxone with caution, Titrate to RR
  • naloxone infusion if long acting
  • if peak effect already reached and patient bradypneic but rousable, can simply hold next dose and monitor
83
Q

Naloxone

A
  • pure mu antagonist, displaces opioids at receptor
  • IV/IM/SC/intranasal
  • Dosing:
    • IV/SC/IM 0.4-2.0 mg single dose –> withdrawal
    • 0.02-0.2 mg for patients with opioid tolerance/dependence IV/SC/IM
    • 20 ug IV push
  • Continuous infusion
    • 2/3 of effective bolus dose given hourly
    • 0.25-0.6 mg/hour
84
Q

Myoclonus from opioids

A
  • can be normal, very common
  • If distressing/frequent, consider dose reduction or rotation
  • can treat with benzo (clonazepam) or gabapentin
85
Q

Hypogonadism secondary to opioids

A
  • chronic opioids inhibitis HPA axis
  • interferes with GnRH
  • lower levels of LH and FSH
  • clinical presentation:
    • fatigue
    • muscle wasting
    • Erectile dysfunction
    • reduced libido
    • menstrual changes
    • vaginal dryness
  • Can consider HRT
86
Q

Metabolism and opioids

A
  • Weight gain
  • Hyperglycemia
  • Worsening DM
  • Central action of sympathetic nervous system and impaired insulin secretion
87
Q

Urinary retention and opioids

A
  • Opioids increase smooth muscle tone
  • bladder spasm or urinary retention
  • increased sphincter tone
  • Tolerance develops rapidly
  • cath prn
88
Q

Opioid induced hyperalgesia

A
  • paradoxical increase in reported pain with increasing or high doses of opioids
  • central sensitization
  • Management:
    • dose reduction
    • opioid rotation
      • genetic variation in opioid respose
      • differentia binding at receptor subtypes
    • NMDA antagonist (methadone), etc
89
Q

Opioids and driving

A
  • provincial guidelines
  • no driving while dose is titrated or initiated
  • once sedation has resolved and dose stable, may resume driving
  • self assessment by patient
90
Q

Opioid Allergy

A
  • morphine and other opioids can induce histamine release from cutaneous mast cells (asthma, urticaria)
    • pseudoallergy and adverse effect
    • rarely life threatening
    • commonly morphine, codeine, meperidine
    • rare : fentanyl, sufentanil, tramadol
  • True allergy rare (< 2%). IgE mediated:
    • anaphylaxis
    • urticaria
    • EM
    • severe hypotension
    • bronchospasm, edema
    • angioedema
  • difficult to distinguish, testing challenging
  • assume likely pseudoallergy
  • can switch to another class with less histamine release
  • concurrent H1/H2 blocker can be considered
91
Q

Opioid misuses and addiction

A
  • Abuse :
    • intentional self adminstration of medication for non medical purpose or use of illegal drug
  • Addiction:
    • primary chronic disease
    • impaired control over drug use, compulsive use despite harm, craving.
  • Risk of developing addictive behaviours with medical use of opioids for palliative care needs is low
  • We overestimate risk of addiction
  • confuse physical dependence and addiction
  • reluctance to prescribe and use them
92
Q

Therapeutic dependence

A
  • Patient require a specific drug to control a disease process or symptom are dependent on therapeutic efficacy of drugs in question.
93
Q

Psychological dependence

A
  • effects mediated in CNS most likely to lead to misuse.
  • continued craving and abherrent drug seeking behaviour
  • use despite harm to self or others
94
Q

Physical dependence and Withdrawal

A
  • withdrawal when abruptly discontinued or opioid antagonist administered.
  • Withdrawal:
    • anxiety
    • irritability
    • chills/hot flashes
    • salivation, lacrimation, rhinorrhea, sneezing, sweating
    • nausea
    • abdo cramping
    • insomnia
  • Time course of withdrawal function of half life of opioid
  • Abstinence sx within 6-12 hours, peak at 24-72 hours for short acting opioids
  • Sx onset 36-48 hours for long acting (methadone)
  • must decrease / taper dose.
  • usual daily dose to prevent withdrawal if 75% of previous daily dose
95
Q

Pseudoaddiction vs addiction

A
  • pseudoaddiction :
    • intense concern about availablity of opioids an drug seeking behaviour
    • resolves once pain is relieved with dose escalation
  • addiction
    • does not resolve.
96
Q

Screening for misuse and abuse risk

A
  • all patients should be screened
  • validated tools (self report) : SOAPP, COMM
  • require multidisciplinary team to manage

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