Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Palliative > Opioid Therapy > Flashcards

Opioid Therapy Flashcards

1
Q

Opioid: Definition

A
  • Natural occurring, sem-synthetic, and synthetic drugs that produce their effects by combining with opioid receptors and are antagonised by nalaxone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Opioid receptor: Mu (endogenous ligand and site)

A

Mu

Endogenous Ligand

  • Beta-endorphin
  • leu and met encephelin
  • Endomorphins

Site

  • Both A and C delta febres
  • Peripheral inflammation
  • Pre and post synaptic neurons in the spinal cord
  • Periaqueductal grey
  • Nucleus raphe magnus
  • Thalamus
  • Cortex

Notes

  • Clinically most important, main receptor responsible for inhibition of nociceptive pathways and exploited by all exogenous opioids
  • Many unwanted side effects also related to this receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Opioid receptor: Kappa (endogenous ligand and site)

A

Kappa

Endogenous Ligand
- Dynorphins

Site

  • Spinal cord
  • Supraspinal
  • Hypothalamus

Notes:

  • Involved in pain, particularly in response to inflammation
  • Activation causes a number of unpleasant side effects (including nausea, vomiting, and dysphoria)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Opioid receptor: Delta (endogenous ligand and site)

A

Delta

Endogenous Ligand

  • Encephalins
  • Beta endorphin

Site

  • Olgactory centres
  • Motor integration areas in cortex
  • Limited distribution in nociception areas

Notes
- Appears to modulate activity of mu agonists (e.g. administration of delta agonists increases potency of mu agonists)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Opioid receptor: Nociceptin orphanin (endogenous ligand and site)

A

Nociceptin orphanin

Endogenous Ligand
- Nociceptin

Site
- Spinal cord

Notes:
- Modulates a range of biologic functions, including stress response, movement, CV, and renal mechanisms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Opioid receptors - names

A
  • Mu (MOP)
  • Kappa (KOP)
  • Delta (DOP)
  • Nociceptin orphanin (NOP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Effect of mu receptor activation

A

Inhibitor effect via:

  1. Inhibition of adenylyl cyclase
  2. Increased opening of potassium channels, leading to hyperpolarization of postsynaptic neurons and reduced transmission
  3. Inhibition of calcium channels, leading to decreased presynaptic neurotransmitter release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Pharmacogenomics and opioids

A
  • Most familiar with impact of genetic variation in CYP2D6, where codeine is of variable analgesic effect
  • Pharmacogenetic factors thought to play an important role in variability of response to opioid analgesics and side effects
  • Number of polymorphisms in the mu receptor, identification of which may provide a basis for drug selection in the future
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Acid/base status of opioids

A
  • All opioids are weak bases

- Relative proportion of free and ionized fractures dependent on plasma pH and pka of the opioid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Dose response curves of opioids

A
  • Generally steep for opioids
  • If dose is near minimum effective analgesia concentration, very small fluctuations in plasma or effect-site concentrations can lead to large changes in level of analgesia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Effect of prolonged infusion of opioids

A
  • Significant sequestration in fat stores and other body tissues can occur for highly lipid soluble opioids (e.g. fentanyl)
  • Elimination half life may become prolonged as drug moves out of tissues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Factors impacting pharmacokinetics and pharmacodynamics of opioids

A

Age

  • Metabolism and volume of distribution often reduced in the elderly
  • Increased free drug concentrations in the plasma
  • Reduced opioid clearance due to reduced hepatic blood flow
  • Increased CNS sensitivity in elderly

Hepatic disease
- Unpredictable effects, although may be little clinical difference unless there is coexisting encephalopathy

Renal failure
- May significant effect patients on opioids with reanlly excreted active metabolites (morphine, codeine, diamorphine)

Obesity
- Larger volume of distribution, prolonged elimination halflife

Hypothermia, hypotension, hypovolemia
- variable absorption and altered distribution and metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Efficacy (definition)

A

Maximal response induced by administration of the active agent

Typically ‘S’ shaped

  • In practice, determined by the degree of analgesia produced following dose escalation, with the range of escalation limited by the development of adverse effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Potency (definition)

A
  • Reflects the dose-response relationship, which is influenced by pharmacokinetic factors and affinity to drug receptors

E.g. if Drug A produces the same response as B but at a lower dose, it is more potent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Agonist (definition)

A

Drug that has affinity for and binds to cell receptors to induce changes in the cell that stimulate physiologic activity

E.g. Morphine, HM, fentanyl, methadone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Antagonist (definition)

A

Drugs with no intrinsic pharmacological action, but interfere with the action of an agonist.

Competitive antagonists - bind to the same receptor and compete for receptor sites

Non-competitive antagonists - block the effects of the agonist in some other way (e.g. changing receptor site affinity, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Opioid antagonists

A

Naloxone (short acting)

Naltrexone (long acting)

Block mu, delta, kappa receptors equally

Generally used to reverse respiratory depression associated with an opioid overdose. Also reverse analgesia.

Naltrexone combined with an opioid can help to prevent or manage opioid induced constipation

Methylnaltrexone (relistor) - antagonist used to relieve side effects of opioids, especially constipation, but cannot cross the blood brain barrier and thus has minimal effect on analgesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Opioid mixed agonist-antagonist

A
  • Produce agonist effects at one receptor and antagonist effects at another

E.g. Pentazocine, nutorphanol, nalbuphine - effects at kappa receptors, weak mu angatonist actions
- Produces kappa-mediated psychotomimetic effects and analgesia, with psychotomimetic effects being dose limiting

  • If administered with a pure agonist, the antagonist effect at the mu receptor can generate an acute withdrawal syndrome

Lower abuse potential than agonist opioid analgesics

Limited role in chronic cancer pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Opioid partial agonist

A
  • Low intrinsic activity (efficacy), such that dose response curve exhibits a ceiling effect at less than the maximum effect produced by a full agonist

E.g. buprenorphine

  • Increasing the dose of such a drug above its ceiling does not result in any further increase in response
  • If administered with a full agonist, may displace the agonist and even generate a withdrawal syndrome
  • May be reasonable for relatively opioid-naive patients where pain can be managed with lower doses
  • Naloxone ineffective at reversing opioid effects based on limited evidence
  • May be useful in renal dysfunction (excreted by GI tract)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Mixed mechanism drugs - Tramadol

A
  • Centrally acting analgesics with agonist action at the mu recepter, but also block serotonin and norepi reuptake
  • No evidence that tramadol is superior to pure mu agonists for cancer pain and likely less effective than stronger opioids

Caution
- Risk of serotonin syndrome, especially if combined with SSRIs or SNRIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Dose response relationship of opioids

A
  • No ceiling to the analgesic effects of full agonist opioids
  • As the dose increases, analgesic effects increase as a log linear function
  • In practice, adverse reactions (confusion, sedation, respiratory depression, etc.) limit the useful dose of an opioid agonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Equinalgesia/relative potency

A

Studies have provided guidelines for dose selection of an opioid when the drug or route of administration is changed, but many variables may influence the appropriate dose for an individual patient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

WHO analgesic ladder

A
  • Initially developed as a structured approach to medication selection for cancer pain
  • Provides adequate relief to 70-90% of patients

Step 1: Mild cancer pain:

  • Non-opioid analgesics, combined with adjuvant drugs if a specific indication exists
  • EG patient with mild arm pain due to radiation induced brachial plexopathy may benefit from regular acetaminophen with a TCA

Step 2: Moderate pain (or inadequate relief with step one)

  • ‘Weak’ opioid
  • E.g. Tylenol combined with codeine
  • Escalated until the maximum dose of the non-opioid analgesic is attained

Step 3: Severe pain (or inadequate relief with step 2)

  • ‘Strong’ opioids
  • No inherent superiority of one opioid over another, treatment should be individualised
  • May be combined with non-opioid analgesics or adjunct
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Reasons for omitting second step on the opioid ladder

A
  • Improved understanding of problems associated with metabolism of codeine
  • Wider range of Step 3 opioids and comfort using these at lower doses
  • Thoughts that using a low dose of a Step 3 opioid is more effective than using Step 2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Opioids for mild to moderate pain

A
  • Codeine* (CBM)
  • Dihydrocodeine
  • Dextropropoxyphene
  • Oxycodone
  • Tramadol* (CBM)
  • Tapentadol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Codeine

A
  • Loss potent than morphine
  • Exerts activity by binding at mu receptor with weaker affinity than morphine
  • Wide variation in oral bioavailability between individuals, depending on CYP2D6 activity (10% do not have adequate activity for its transformation and experience little to no analgesia)

Metabolites

  • Codeine-6-glucuronide (main metabolite)
  • Norcodeine
  • Morphine
  • Morphine 3- and 6- glucuronides (M6G has analgesic effects, while M3G does not and is felt to contribute to neurotoxic adverse effects)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Dihydrocodeine

A
  • Semisynthetic analogue of codeine
  • Equinalgesic to codeine when given PO, but double when given parenterally
  • Poorer bioavailability (hepatic pre-systemic metabolism)

Reports of severe toxicity in patients with advanced renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Oxycodone

A
  • Semi-synthetic congener of morphine
  • Metabolised to oxymorphone (may accumulate in renal failure)
  • Acts on the mu-receptor
  • Often combined with acetaminophen or ASA
  • Relative potency compared to morphine: 1.5:1 (more potent than morphine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Tramadol

A
  • Centrally acting analgesic with opioid agonist properties and may also activate monoaminergic spinal inhibition of pain
  • Also inhibitors noradrenaline and serotonin re-uptake
  • Modest affinity with mu receptors, weak affinity to kappa and delta receptors
  • Reversed by naloxone
  • Similar side effect profile to morphine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Tapentadol

A
  • Mu opioid receptor agonist
  • Noradrenaline reuptake inhibitor with minimal serotonin reuptake inhibition
  • Limited studies in cancer pain
  • Limited protein binding, no active metabolites, no significant enzyme induction or inhibition = low potential for drug interactions
  • Contraindicated in those using MAOIs
  • Could cause serotonin syndrome when used with TCAs, SNRI, SSRIs, or MAOIs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Morphine

A
  • Mu- agonist drug
  • Available as liquid, IR, or CR

Absorption
- Upper small bowel (more alkaline medium, morphine is a weak base)

Half life
- 2-3 hrs

Duration of analgesia
- 4-6 hours

Elimination

  • Liver (pre-systemic)
  • Kidney (excretion of active metabolites takes longer with deteriorating function and may contribute to toxicity)

Metabolism

  • Predominantly in liver
  • Morphine-3-glucuronide (M3G) - no analgesic effects, believed to contribute to neurotoxic effects
  • Morphine-6-glucuronide (M6G) - binds to opioid receptors, half as potent as morphine and has analgesic properties

Cautions:
- Not contraindicated in renal failure, but use with caution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Morphine conversions

A

PO to parenteral ratio of 1:3 or 1:2, depending on single dose vs chronic dosing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Sustained release morphine

A
  • Rather than peak plasma within the first hour, SR has a peak of 3-6 hours an concentrations can be sustained over 12 to 24 hours
  • Not appropriate for acute pain or breakthrough pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Diamorphine

A
  • AKA heroin
  • When taken orally, metabolised to morphine and is an inefficient of delivering morphine
  • Poorly absorbed SL (no point in giving this way)

Some advantages given parenterally:

  • Twice as potent as morphine
  • Quicker onset of action when given IV
  • Greater sedation and less vomiting (due to differences in receptor binding)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Methadone

A
  • Synthetic opioid with activity at opioid receptors and as an NMDA receptor antagonist
  • Oral to parenteral potency ratio of 1:2

By single doses, only marginally more potent than morphine, but much more potent with repeated administration. Higher risk of toxicity.

  • Long half life (12-150 hrs) with considerable variability

Useful in cases of:

  • Inability to tolerate other opioids
  • Patients in renal failure or on dialysis
  • Need for opioid rotation due to high doses of other opioids with adverse effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Meperidine/pethidine

A
  • Synthetic opioid
  • Mu agonist
  • Significant disadvantages limiting utility for chronic pain (accumulates with repetitive dosing)
  • Also not recommended for acute pain given alternatives

Adverse effects with repeated dosing:

  • CNS excitability - mood effects, tremors, myoclonus, occasionally seizures
  • Naloxone does not reverse seizures, and could even precipitate seizures by blocking depressant action of pethidine and allowing norpethidine to stimulate convulsive activity
  • Accumulation most likely in patients with renal disease
37
Q

Hydromorphone

A
  • Morphine congener (semi-synthetic)
  • 5x as potent as morphine
  • Mu agonist
  • High concentrations available for subcut infusions
  • Neither inferior nor superior to morphine

Metabolism
- Partially metabolised by the liver to hydromorphone-3-glucuronide (excreted by kidneys)

38
Q

Levorphanol

A
  • Morphine congener (semi-synthetic)
  • 5x as potent as morphine
  • oral to parenteral potency ratio of 1:2
  • Mu agonist, also acts on kappa and delta
  • NMDA antagonist

Similar to methadone in that it has a long half life (12-16 hrs) but shorter duration of analgesia (4-6 hrs) that can predispose to drug accumulation, though appears to be less of an issue than for methadone

39
Q

Oxymorphone

A
  • Lipophilic congener of morphine
  • PO IR and SR formulations
  • less likely to induce histamine response - useful for patients who develop an itch with opioids
  • Avoids CYP3A4 and 2D6 metabolism
  • Half life 1.2-2 hrs
  • Duration of action 3-5 hrs
  • 10x as potent as morphine
40
Q

Fentanyl

A
  • Semi-synthetic opioid
  • Highly selective mu agonist
  • 80x - 100x as potent as parenteral morphine in non-tolerant acute pain patient
  • Extremely lipophilic
  • Rapid onset with parenteral, intranasal, SL, or buccal administration
  • Also prescribed as a skin patch
  • Elimination half life dependent on prior administration/fat sequestration, ranging from 3-12 hrs
  • No known active metabolites: Ideal for patients with renal insufficiency
  • May cause less constipation than other opioids
  • Short duration of action when used IV (0.5-1 hrs) due to rapid re-distribution of drug into body tissues
41
Q

Transdermal fentanyl

A
  • TD absorption facilitated by low molecular weight and high lipid solubility
  • After application, serum fentanyl concentration increases gradually, then levels off at 12-24 hrs (90% of peak levels achieved at 24 hrs)
  • After removal, serum concentration falls by 50% in 17 hours
  • Avoid in patients with escalating or unstable pain, as it is difficult to titrate rapidly given the long half life. If a patient is already on a fentanyl patch, consider rotating to IR or subcut opioid until the pain is under better control

Slow onset and slow decline in effect due to subcutaneous depot of drug maintaining the plasma concentration

Starting a patch:

  • Effective analgesia takes 8-12 hrs when placing the patch (requires alternative analgesia - liberal use of short acting opioid)
  • If rotating from another regular opioid, continue previous regular opioid for at least 12 hours after initiation of the patch
  • Start early in the day so as to ensure overdose does not occur during sleep

Patch placement

  • Minimal skin movement (upper anterior chest wall, lower back)
  • All areas of skin absorb the drug at the same rate
  • Consider using a nonirritant tape to provide extra security
  • Severely cachectic patients may have suboptimal serum fentanyl levels, but debatable as to how clinically significant this is - monitor for analgesic effect. WHO recommends AGAINST use in cachectic patients, manufacturer recommends ‘caution’

While using a patch

  • Watch for temperature-dependent increases in fentanyl release (e.g. hot tubs etc
  • 3 day duration of action
  • If dosing needs to be adjusted, continuing absorption following patch removal should be taken into account
42
Q

Indications for a fentanyl patch

A
  • Intolerance of PO meds (e.g. head and neck cancers, esophageal obstruction, GOO, or bowel obstruction)
  • Poor compliance with PO meds (e.g. due to patient factors or variable LOC)
  • Unfavourable reaction to other opioids
  • Stable opioid dosing
  • Anxiety or preoccupation with medication regimens
  • Adverse effects with other opioids

Avoid if:
- Unstable pain (3 day duration of action)

When starting:

  • Education around correctly applying a patch
  • Caution about safe disposal of used patches
43
Q

Oral transmucosal fentanyl

A
  • A lozenge on a stick where the drug is absorbed buccally
  • Absorbed rapidly, time to onset is 5-10 minutes (most oral IR formulations take 30 mins)
  • Rapid and effect relief of breakthrough pain
  • Successful dose is difficult to predict and may not be related to daily dose for background pain

Side effects:
- Somnolence, nausea, dizziness

44
Q

Rapid onset oral fentanyl preparations

A
  • Fentanyl given either buccally or SL
  • Nasal fentanyl also available
  • Limited studies, but early data suggests could be more efficacious than oral morphine for BT pain
45
Q

Indications for starting opioid therapy

A
  • Trial for all patients with pain of moderate or greater severity, irrespective of underlying mechanism
  • Dose titration until adequate analgesia occurs, or adverse effects supervene
46
Q

Drug selection in initiating opioid therapy

A
  1. Pain severity
    - Consider opioid vs non-opioid analgesic, or combination
    - Consider previous trials of opioid therapy
  2. Pharmacokinetic formulations
    - Start with a shorter half life opioid (morphine, hydromorphone, oxycodone)
    - Oral route if possible, otherwise, consider subcutaneous (less disruptive than suppositiories or IV)
  3. Coexisting disease
    - Renal impaitment (consider active metabolites, especially with morphine)
    - Fentanyl, buprenorphine, HM may be useful in renal impairment
47
Q

Oral administration

A
  • Most appropriate in routine practice
  • Slower onset of action, delayed peak time, longer duration of effect with availability of SR formulations
  • Peak effect typically within 60 minutes

Contraindications:

  • Impaired swallowing
  • Gastrointestinal obstructin
  • Requirement for rapid onest of analgesia
48
Q

Rectal administration

A
  • Alternative to parenteral route for patients unable to take PO opioids
  • Available for morphine, HM, oxymorphone, oxycodone
  • Pharmacokinetics/bioavailability may cary from oral absorption due to delayed/limited absorption and partial bypassing of pre-systemic hepatic metabolism
  • Often not used as patients would prefer subcutaneous infusion
49
Q

Parenteral infusion

A
  • Used for patients with impaired swallowing or GI obstruction, rapid onset of analgesia, or very high doses
  • Can be delivered by IV, IM, or subcut routes

Boluses can be complicated by ‘bolus’ effects (toxicity at peak concentration or pain breakthrough at the trough)

IM is generally not recommended as it is painful and offer no pharmacokinetic advantage. IV or subcut is a good alternative. 25-27g subcut butterfly can be left undert he skin for up to a week.

50
Q

Continuous infusions

A
  • Avoid the problems associated with the ‘bolus’ effect (peaks with toxicity, breakthrough pain at troughs)
  • Variety of ambulatory infusion devices
  • Can be given subcut or IV with no difference in blood levels
  • May give a drug combination if there is need for an antiemetic, neuroleptic, or anxiolytic
  • Ensure to check that drug combinations are compatible and avoid combinations of more than 3 drugs
51
Q

Epidural, intrathecal, and intraventricular administration

A
  • Opioid receptors are present in the dorsal horn of the spinal cord
  • Intraspinal opioid delivery provides longer duration of analgesia at lower doses than required for systemic administration
  • May add local anesthetic (e.g. bupivicaine) to an epidural or intrathecal opioid to improve analgesia without increasing toxicity

For morphine:

  • Epidural is 1/10 of systemic dose
  • Intrathetical is 1/10 of epidural dose (1/100 of systemic dose)
52
Q

Sublingual administration

A
  • Bioavailability poor with less lipophilic drugs

- Best with buprenorphine, methadone, and fentanyl

53
Q

Topical administration

A
  • May be a role for this in limited situations, such as cutaneous ulcers or tumour with cutaneous inflammation
  • No evidence for this in RCTs with non-malignancy cutaneous pain (e.g. burns etc.)
54
Q

Scheduling opioid administration

A
  1. Around the clock dosing
    - Provide patients with continuous relief with scheduled dosing
    - If the patient is opioid naive, start low and go slow!
    - Start with IR formulations, then once a dose is established, move to SR
    - Morphine 5mg PO q4H
    - HM 1mg PO q4H
    - Oxycodone 2.5mg PO q4H
  2. Breakthrough dosing
    - Supplemental dose as needed, typically identical to the regular opioid (except with methadone or TD fentanyl)
    - Provides a method for rational dose titration upward
    - Offer q1H for PO, up to q30 minutes for subcut
    - May start with only PRN dosing in opioid naive patients
    - In general, should be 10% of total daily scheduled opioid dose
    - Titrate along with scheduled dosing
    - If more than three BTs used per day, consider a dose increase of the regular opioid
55
Q

Initial dose of opioids in opioid naive patients

A
  • For severe pain not controlled with a step 2 opioid-nonopioid combo, patients should begin opioid agonists at a dose equivalent to 5-10mg morphine PO q4H reg
  • Morphine 5mg PO q4H
  • HM 1mg PO q4H
  • Oxycodone 2.5mg PO q4H
  • Early follow up, particularly if pain is unstable (e.g. in 1 or 2 days)
  • Note that some physicians suggest patients take a double dose of regular IR opioid at bedtime for convenience. There is no good evidence to support this practice.
56
Q

Titration of opioid doses

A
  • Analgesic response to opioids increases linearly with the logarithm of the dose
  • Escalations of less than 30-50% not likely to improve analgesia significantly
57
Q

Opioid tolerance

A
  • Need for escalating doses is complex, and often related to disease progression or increasing psychological distress rather than physiologic tolerance
  • Most patients reach a dose that remains constant for a prolonged period of time

Tolerance of respiratory depression, somnolence, and nausea develops rapidly

Tolerance to opioid-related constipation may occur slowly, if at all

58
Q

Opioid rotation

A
  • Dose reduce to 75% of the equianalgesic dose with appropriate breakthrough, due to incomplete cross tolerance
  • If dose reduction from the equianalgesic conversion tables is not used, can result in overmedication
  • Be prepared to titrate the drug further after rotation
  • If rotating to fentanyl, note that incomplete cross tolerance is BUILT INTO the manufacturer’s table
  • If pain is unstable, do not switch from one long acting oral opioid to another - use IR

Indications:

  • Change of route of administration
  • Pain is escalating or under suboptimal control and unable to escalate the current opioid further due to unacceptable side effects or neurotoxicity
59
Q

Factors predictive of opioid adverse effects

A

Drug-related

  • Pethidine/meperidine has a bad side effect profile, and codeine can lead to toxicity
  • Otherwise no opioid is inherently worse than others regarding side effects, though TD fentanyl may be less constipating than PO morphine

Route
- No significant difference, though TD fentanyl seems to be less constipating than PO morphine

Patient-related

  • Individual variability in sensitivity, likely related to co-morbidity, age, genetics
  • Ageing contributes to diminished clearance and volume of distribution
  • Addition of other drugs

Initiation and escalation

  • Dose-response relationship, especially with CNS side effects
  • N/V more common initiation, but then tend to resolve (though persist for some)
  • Little dose-response relationship with constipation
60
Q

GI side effects of opioids

A
  • Nausea
  • Vomiting
  • Constipation
61
Q

Autonomic side effects of opioids

A
  • Xerostomia
  • Urinary retention
  • Postural hypotension
62
Q

CNS side effects of opioids

A
  • Drowsiness
  • Cognitive impairment
  • Hallucinations
  • Delirium
  • Myoclonus
  • Seizure disorder
  • Hyperalgesia
63
Q

Cutaneous side effects of opioids

A
  • Itch

- Sweating

64
Q

Approaches to treating adverse effects

A
  • Rule out other causes of adverse effects

Then consider:

  1. Dose reduction
    - If pain is managed, may maintain control with gradual reduction of dose by 25%
    - Otherwise, consider addition of non-opioid co-analgesic, an adjuvant, alternative therapies (e.g. rads for bony pain), or regional anesthetic/neurosurg technique
  2. Specific therapy to reduce AE
    - Very little evidence to support
    - Always give laxatives prophylactically with opioids
  3. Opioid rotation
    - May improve cognitive impairment, sedation, hallucinations, N/V, and myoclonus
    - Outcomes may be unpredictable and patients at risk of under or over dosing
  4. Change route
    - Switching routes may from PO to subcut may help with some adverse effects (especially N/V, perhaps constipation)
    - Evidence is weak
65
Q

Ddx of side effects of opioids

A

CNS

  • Cerebral mets
  • Leptomeningeal mets
  • CVA
  • Extradural hemorrhage

Metabolic

  • Dehydration
  • HyperCa
  • HyperNa
  • Renal failure (myoclonus)
  • Liver failure (myoclonus)
  • Hypoxemia

Sepsis/infection

Bowel obstruction

Iatrogenic

  • TCAs
  • Benzos
  • Abx (n/v)
  • Vinca alkaloids (constipation)
  • Flutamide (constipation)
  • NSAIDs (nausea, drowsiness)
  • Chemo
  • Rads
66
Q

Management of opioid induced constipation

A
  • Prophylactically prescribe laxatives (e.g. PEG, senokot, lactulose)
  • Not a side effect that improves with time
  • Avoid bulk laxatives (e.g. bran, psyllium)
  • Methylnaltrexone may be helpful (antagonises opioid receptors peripherally, but not centrally - costly, however)
  • If a patient has short gut syndrome, observe closely
67
Q

Management of opioid related nausea and vomiting

A
  • Opioids stimulate medullary CTZ, increase vestibular sensitivity, and effect the GI tract (delayed emptying, diminished motility)
  • Ensure patients have access to an antiemetic if issues occur - prokinetic is often first line
  • Nausea typically resolves over a few days, but if it persists will likely be a chronic problem
  • Consider scheduled prokinetic if nausea is more than mild
68
Q

Management of confusion and delirium related to opioids

A
  1. Discontinue al non-essentially centrally acting medications
  2. If analgesia is satisfactory, reduce opioid dose by 25%
  3. Exclude sepsis/metabolic derangements
  4. Exclude CNS tumour involvement
  5. If delirium persists, consider neuroleptic (e.g. haldol), rotation, change in opioid route to intraspinal with a local anesthetic, or trialling alternative analgesic options
69
Q

Management of sedation related to opioids

A
  • Sedation is typical when beginning opioid therapy or after significant dose escalation until tolerance develops, usually days to weeks
  • Limited evidence for treatment with methylphenidate or dextroamphetamine
  • Rotation to another opioid may help
  • Consider opioid-sparing adjuvants to try to decrease the dose of opioid, or other treatments like rads or interventional analgesia
70
Q

Respiratory depression related to opioids

A
  • Sedation is usually an early indicator of CNS toxicity
  • Respiratory compromise with tachypnea and anxiety is NEVER related to opioids
  • Tolerance typically develops rapidly, but respiratory depression can occur if pain is suddenly eliminated without a reduction in opioid dose (e.g. after a neurolytic procedure)

Patients at higher risk:

  • Rapid titration
  • Drug errors (e.g. in conversion, or patients taking long acting as BT)
  • Pre-existing underlying lung disease
  • Multiple opioids given simultaneously

Management:

  • Supportive tx with oxygen
  • Can treat with naloxone, but can precipitate a pain crisis and should only be used if absolutely necessary
  • Dilute naloxone to 1:10 and titrate to respiratory rate and level of consciousness - may require ongoing infusion until the opioid is metabolised
  • If peak effect is already reached and patient is bradypneic but rousable, simply hold next dose and monitor until improvement occurs
71
Q

Myoclonus related to opioids

A
  • Mild and infrequent myoclonus is common
  • If distressing/frequent, consider dose reduction or rotation
  • May be treated symptomatically with a benzo (esp clonazepam) or gapapentin
72
Q

Hypogonadism related to opioids

A
  • Chronic opioid therapy inhibits the HPA axis and interferes with GnRH, resultingin lower levels of LH and FSH
  • Clinically, may manifest as fatigue, muscle wasting, ED, reduced libido, menstrual changes, and vaginal dryness
  • If bothersome, may be worth considering HRT
73
Q

Metabolism and opioids

A
  • Opioids associated with weight gain, hyperglycemia, worsening DM
  • May be due to central action on the sympathetic nervous system and impaired insulin secretion
74
Q

Urinary retention related to opioids

A
  • Opioids increase smooth muscle tone and can cause bladder spasm or urinary retention (increased sphincter tone)
  • Tolerance typically develops rapidly, but cath PRN
75
Q

Opioid induced hyperalgesia

A
  • Paradoxical increase in pain with increasing or high doses of opioids
  • Underlying mechanism likely due to central sensitization, central neuro-inflammatory response, alterations in the balance between anti-nociceptive and facilitatory descending systems

Management

  • Dose reduction
  • Opioid rotation (differential binding at opioid receptor subtypes)
  • Use of NMDA antagonists (ketamine)
76
Q

Opioids and driving

A
  • Advise patients not to drive or engage in other skilled activities (e.g heavy machinery) while starting an opioid
  • Once initial sedative effects have resolved, and patient/clinician are confident, driving can restart
  • Remind patients to critically self-examine before ever stepping behind the wheel
77
Q

Opioids and allergy

A
  • Morphine and other opioids can induce a histamine response (asthma or urticaria)
  • Always ask about what the allergy was - may actually be adverse effects rather than true allergy
78
Q

Screening for opioid abuse risk

A
  • Screener and Opioid Assessment for Pain Patients (best validated)
  • 14 item self report
  • 5 point Likert scale, possible score of 0-56
  • 7 is the cut off (sensitivity of 91%, specificity of 69%), but will have a high number of false positives
79
Q

Safe application of a fentanyl patch

A
  • Don’t touch sticky part of the patch - if this occurs, rinse with water (don’t use soap etc.)
  • Ensure the patch is not torn or damaged (may cause drug to release too quickly)
  • Apply the patch to a dry, flat skin area on upper arm, chest, or back, where the skin is not very oily and is free of scars, cuts, burns, or irritation
  • Do not apply the patch to areas that have received radiation treatment.
  • If the patch is applied to an area with hair, clip the hair with scissors to ensure adherence but do not shave the area
  • If required, clean the area before applying the patch with ONLY plain water and ensure area is complete dry
  • Remove the liner covering the sticky side of the skin patch, then press the patch firmly in place with the palm of the hand for a minimum of 30 seconds.
  • In young children or persons with decreased mental alertness, place on the upper back to avoid the patch being accidentally removed

Trouble shooting:

  • If the patch becomes loose, tape the edges with first aid tape.
  • If the patch falls off after applying it, throw it away and apply a new patch in a different area.
  • If you need to apply more than 1 patch at a time, place the patches far enough apart so that the edges do not touch or overlap each other.

Afterwards:

  • Wash your hands with a lot of clear water after applying the medicine. Do not use soap or other cleansers.
  • Remove the patch after 3 days (72 hours), or as directed by your doctor.
  • Choose a different place to apply the next patch. If possible, use a place on the other side of your body. Wait at least 3 days before using the first area again.
80
Q

Safe disposal of a fentanyl patch

A
  • To dispose of the Duragesic® patch, fold the patch in half with the sticky side inside. Place in a sharps container and bring back to the pharmacy for safe disposal.
  • If the patch has not been used, take it out of the pouch and remove the liner that covers the sticky side of the patch before folding it in half.
  • Do not flush the pouch or the protective liner down the toilet.
81
Q

Long acting preparations of opioids

A
  • Typically administered q12, but some patients have end of dose failure and do better with these SR medications dosed q8H
  • Do not crush or chew these medications and ensure patients are aware of this
82
Q

Rotating from IR to SR opioids

A
  • Use same total daily dose (duh)
  • CBM suggests ensuring some overlap due to slower onset of SR opioids by 3-4 hrs, but in reality, correctly dosed breakthrough medications should provide adequate coverage
83
Q

Rotation from TD fentanyl back to other opioids

A
  • Use the fentanyl conversion table when changing from other opioids to fentanyl, but not the other way around
  • WHO recommends 100 mg OME~1000 mcg Fentanyl ratio when converting FROM transdermal fentanyl - but caution if there were any concerns regarding absorption (e.g. in a severely cachectic patient) as this may overestimate their needs
  1. Remove the TDF patch.
  2. For the first 12 hours after patch removal, use only the previously prescribed rescue opioid only for pain that occurs.
  3. Twelve hours after patch removal, begin with 50% of the calculated scheduled opioid regimen, and continue to offer the rescue opioid as needed.
  4. Twenty-four hours after patch removal, increase to 100% of the calculated scheduled opioid regimen, and continue to offer the rescue opioid as needed.
84
Q

Rotating TO Fentanyl

A
  • Manufacturer’s table may risk underdosing patients

In practice:

  • Use a 2:1 ratio: Every 2 mg oral morphine per day ~ 1 mcg per hour TDF
  • Another way to word this is the number of mcg per hour of TDF should be about half the number of milligrams of oral morphine per day
  • For example, 50 mg per day of oral morphine ~ 25 mcg/h TDF
85
Q

Incident pain

A
  • Type of breakthrough pain that occurs with movement that is not typically painful
  • May result in severe pain with certain activities, but little or no pain otherwise

Difficulty in treating:

  • By the time a typical BT dose is used, the painful activity may be over and the patient is left simply sedated
  • Increasing background opioid may leave the patient too sedated

Strategy:

  • Use BT dosing proactively before predictably painful activities
  • Use rapid acting medications (e.g. fentanyl given bucally, SL, intranasally, or subcut - onset will be in 5 minutes, peak at 15-30 mins, then rapidly redistributed)
  • Consider other treatments (e.g. rads for bony pain)
86
Q

Opioids in renal failure

A
  • Fentanyl and methadone are the least problematic
87
Q

Opioid neurotoxicity

A
  • Serious adverse effect that may happen at high opioid doses

Presentation:

  • Somnolence
  • Vivid/distressing dreams
  • Delirium
  • Hallucinations
  • Changes in pain perception (allodynia, hyperalgesia)
  • Myoclonus (early signs)
  • Seizures (rare and late)

Causes

  • Any opioid, especially at higher doses
  • Dehydration and renal impairment increase the risk
  • Assumed to be due to accumulation of opioid metabolites

Management

  • Dose reduction
  • Hydration
  • Rotation (most typical)
88
Q

How to manage recreational drug use in the context of opioid prescribing

A
  1. Consider a random urine drug screen for other drug use that may not have been prescribed
  2. Have a frank discussion about the need to distinguish between recreational substance use and medical use
  3. Ensure that patient agrees not to take recreational substances without informing the care team given risks of toxicity
  4. Request a consult with a psychiatrist with expertise in recreational substance use to support the team in prescribing analgesia appropriately
  5. Ensure consistent team approach (limited number of prescribers, frequent urine drug testing, acknowledgement that pain control may not be as good as it may be otherwise)
  6. If difficulties continue, physician should suggest a written contract to ensure the patient will agrees not to divert medications, escalate doses without discussing with the team, and to disclose any recreational drugs being taken.

Palliative (71 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions