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Adjuvant Analgesics Flashcards

1
Q

Define Adjuvant Analgesics

A
  • Any drug that has a primary indication other than pain, but is analgesic in some painful conditions
  • “Co-analgesic” in palliative care
    • administered with primary analgesic
    • enhance pain relief
    • treat refractory paihn
    • allow reduction of primary analgesic to limit side effects
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2
Q

Limitations of adjuvants

A
  • less reliable than opioids
  • higher side effects
  • slower onset
  • best to optimize opioids first, then add adjuvant if necessary
  • if another indication exists for adjuvant (depression, for ex), can use earlier
  • larger interindividual and intraindiviudal variability
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3
Q

List 6 major classes of adjuvant analgesics

A
  • Multipurpose adjuvants
  • Adjuvants for neuropathic pain
  • Topical Analgesics
  • Adjuvants for Bone Pain
  • Adjuvants for MBO
  • Adjuvants for MSK pain
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4
Q

Multipurpose analgesics

A

Antidepressants

  • TCA
  • SNRI
  • SSRI
  • Other

Alpha 2 adrenergic agonists

  • Clonidine
  • Tizanidine

Corticosteroids

  • Dex
  • prednisone, methylprednisone
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5
Q

Antidepressants : TCAs

A
  • Amitriptiline, Nortriptyline, Desipramine
  • 10-25 mg qhs - 50-150 mg po qhs
  • Analgesic efficacy in chronic and neuropathic pain
  • only evidence for pain in cancer population
  • Evidence strongest for Amitriptiline, but nortriptyline preferred as it has lower toxicity and side effects
  • Side effects:
    • sedation
    • confusion
    • orthostatic hypotension
    • heart block
    • weight gain
    • arrythmia Qtc
    • Ach effects
  • Caution:
    • with SSRIs
    • Ach
    • lithium
    • tramadol
    • Glaucoma, recent MI
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6
Q

TCAs: interactions and side effects

A
  • Cardiac
    • Qtc
    • caution with BB
    • Class c antiarrythmics
  • ACH
    • mixing with Ach drugs = toxicity
  • Serotonin syndrome
    • MAOIs, Ondansetron, Serotonerigic opioids (tramadol, methadone, fentanyl)
  • Bleeding risk
    • Caution with NSAIDS
  • CNS depression
  • CYP 2D6 interactions
    • SNRIs/SSRIs (venlafaxine, fluoxetine, paroxetine, citalopram, duloxetine, mirtazapine)
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7
Q

What CYP enzyme metabolizes TCAs?

A

CYP 2D6

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8
Q

SNRIS

A
  • Evidence for analgesia: neuropathic pain, post op mastectomy pain
  • Duloxetine 20 mg po od - 60 mg po od
  • Venlafaxine 37.5-300 mg po od
  • Risk of serotonin syndrome with MAOIs, TCAs, buproprion, buspirone, SSRIs
  • SE:
    • nausea
    • headache
    • somnolence
    • tremor
    • anxiety
    • hypertension
    • sexual dysfunction
    • seizure
    • hypertension
  • caution in renal failure; dose reduxe venlafaxine
  • lowers seizure threshold
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9
Q

Serotonin (or Antidepressant) discontinuation syndrome

A
  • Headache
  • Anxiety
  • Flu like sx
  • Gait instability
  • Malaise
  • Irritablity
  • Insomnia
  • Rebound depression
  • fatigue
  • nausea
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10
Q

SNRIS : drug interactions

Venlafaxine and Duloxetine

A
  • no CYP
  • increased serotonin risk when combined with MAOIs, TCAs, buproprion, SSRIs
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11
Q

Precautions with SNRIS

A
  • LOWER seizure threshold
  • Hypertension
  • Dose reduce in renal impairment
  • Avoid in hepatic dysfunction
  • Discontinuation syndrome
    • taper gradually
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12
Q

Bupropion

A
  • NO CYP
  • increased effects of NE, D
  • some evidence for neuropathic pain
  • Useful for :
    • depression
    • smokinsg
    • ADHD
    • activating!
  • Side effects:
    • SEIZURE
    • well tolerated
    • fewer weight, sex sx
    • some ha, insomnia, tachycardia
  • DO NOT USE IN SEIZURE DISORDER
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13
Q

Buproprion dose

A

75 mg po od -

150 mg po bid/tid

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14
Q

Contraindications to Buproprion

A
  • seizure disorder (lowers threshold)
  • anorexia/bulimia
  • MAOI within 14 days (serotonin syndrome)
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15
Q

Steroids as adjuvants : when are they useful?

A
  • improve appetite, nausea, malaise, QOL
  • limited by toxicity/ side effects
  • Helpful for :
    • neuropathic pain?
    • bone pain
    • headache from ICP
    • arthralgia
    • obstruction of hollow viscus
    • liver capsular pain
  • MOA:
    • reduce peritumour edema
    • oncolytic effect on lymphoma
  • Taper after 2 weeks to avoid adrenal insufficiency (can be fatal)
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16
Q

Why is dexamethasone often preferred as adjuvant in palliative care?

A
  • Lower mineralocorticoid effects
  • less sodium and fluid retention. less K excretion
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17
Q

Comparison of steroids : equivalent doses and antiinflammatory effect

A

Equivalent dosing and antiinflammatory effect relative to hydrocortisone

  • Short acting:
    • Hydrocortisone 20 mg : 1
    • Cortisone acetate 15 mg : 0.8
  • Intermediate acting:
    • Prednisone 5 mg : 4
    • Prednisolone 5 mg : 4
    • Methylprednisolone 4 mg : 5
  • Long acting
    • Dexamethasone 0.75 mg : 30
    • Betamethasone 0.6 mg : 30
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18
Q

Starting dexamethasone (dosing)

A

Severe pain, SCC, SVC syndrome

  • 16 mg /day

Less severe pain, weakness, low energy

  • 2-4 mg/day

Should rarely exceed 24 mg / day

half life 36 hours

Divide dose to reduce GI side effects

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19
Q

Alpha 2 AGONISTS

A
  • Clonidine, tizanadine
  • some evidence for cancer pain, diabetic neuropathy, myofascial pain syndrome
  • not usually used
  • limited evidence in advanced cancer
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20
Q

Approach to neuropathic pain

A
  1. Gabapentinoid
  2. Analgesic antidepressant
  • duloxetine
  • TCA
  1. Steroids
    * short term pain crisis
  2. Topicals if localized
    * lidocaine
  3. Opioids (IR, then CR)
    * usually go with adjuvants
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21
Q

Gabapentin and pregabalin

A
  • Gabapentin
    • 100 mg po tid
    • max 3600 mg/day
  • Pregabalin
    • 25-75 mg po od-bid
    • 150-300 mg po
  • Calcium channel antagonists
  • pain relief in 1-2 weeks
  • NNT 4.2-6.4
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22
Q

Gabapentin/PRegabalin: contraindications and precautions

A
  • Renal dysfunction
    • dose reduce if milkd-mod
    • avoid in severe renal dysunfciton
  • Discontinuation syndrome
    • headache, insomnia, pain, nausea, diarrhea
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23
Q

Gapapentin / pregabalin drug interactions and side effects

A
  • NO significant interactions
  • NO CYP
  • SE: sedation, edema
24
Q

Lacosamide

A
  • 50 mg po bid-400 mg po bid
  • Renal, hepatic dose reduction
  • SE:
    • nausea, dizziness, drowsiness, fatigue
  • no drug interactions
  • limited use in pall care
25
Q

Lidocaine

A
  • non selective sodium channel blocker
  • used for chronic neuropathic pain
  • injured nerves develop spontaneous active sodium channels along injrued site and along nerve and dorsal root ganglion
  • lidocaine suppresses abnormal firing at concentrations that do not affect normal nerve or cardiac function.
  • Metabolized in liver, excreted in kidneys
  • negative inotropic effect
26
Q

Lidocaine : who to use it on and exclusions

A
  • patients with severe pain syndrome not responding to standard therapies
  • Patients with severe neuropathic pain who understand other less invasive medications will be used long term to maintain

Exclusions:

  • cognitively impaired/delirious.
  • severe allergy to local anesthetics
  • liver failure (bili > 25)
  • cardiac failure or 2nd/3rd degree heart block
  • seizures
  • Hypertension (Sys > 160 mmHg)
  • Hypokalemia
27
Q

Lidocaine dosing

A
  • 5-10 mg/kg intermittent dosing
  • Day 1 : 5 mg/kg over 60-120 minutes
  • Day 2 if no response : 7 mg/kg
  • Day 3 if no response : 10 mg/kg
28
Q

Lidocaine Adverse effects

A
  • Local anesthetic toxicity
    • drowsiness, agitation, vomiting, muscle twitching
    • seizure
    • bradycardia, heart block, hypotension
    • circumoral parethesias, metallic taste, tinnitus
  • Rare:
    • light headedness
    • anxiety, euphoria, confusion, tinnitus, blurred vision
    • rare: asystole, cardiac arrest
    • apnea, respiratory arrest
29
Q

Ketamine : MOA

A
  • NMDA receptor antagonists
  • binds also to mu receptors at high doses
  • dissociative anesthetic
    • acts on cortex and limbic system
    • release of catecholamines ( epinephrine, norepi)
  • reduces polysynaptic spinal reflexes
  • Anesthetic, sedative
  • mainstains respiratory drive
  • no effect on hemodynamics (no hypotension)
30
Q

Ketamine indications

A
  • Severe pain
  • that has failed traditional modalities
  • possibly for total pain, anxiety, depression in palliative care
31
Q

Ketamine contraindications

A
  • Conditions where significant elevations in blood pressure would be a hazard
    • severe uncontrolled HTN
    • CHF
    • Aneurysms
    • recent MI
    • NOT CONTRAINDICATED IN TBI or elevated ICP
  • Caution
    • psychotic disorders
    • thyrotoxicosis
    • tachycardia
    • seizures
32
Q

Ketamine Drug Interactions CYP

A
  • CYP 3A4
  • if also taking CYP3A4 inhibitor, ketamine levels will be increased
33
Q

Ketamine Adverse Effects

A
  • increased heart rate and BP
  • Arrythmia, bradycardia rare
  • Psychomimetic effects:
    • hallucinations
    • vivid dreams
    • startle reflex
  • tonic clonic movements
  • nausea and vomiting
  • airway resistance
  • drowsiness, confusion, dry mouth
  • INCREASED SECRETIONS
34
Q

Ketamine Burst Protocol

A
  • can pre-treat with haldol 2.5 sc 30 min prior (or benzo)
  • test dose 10 mg IV/SC
  • Burst Protocol
    • Day 1
      • 4mg/hour IV/SC continuous
    • Day 2
      • if effective, continue 4 mg/hour x 3 days total
      • if ineffective, increase to 12.5 mg/hour continuous infusion
    • Day 3
      • if effective at 12.5/hour, continue for total 72 hours
      • if ineffective, increase to 20 mg/hour continuous infusion. Discontinue at end of Day 5.
  • if psychomimetic, schedule haldol bid
  • no dosing adjustments for renal dysfuntion
  • dose reduce for hepatic failure
35
Q

Ketamine dosing for pain

A
  • 0.2- 0.3 mg/kg single push
    • 10-20 mg IV push (or better slowly given over 15 minutes)
  • Low dose infusion 0.1-0.3 mg/kg/hour
    • 7-20 mg/hour

Analgesic dosing 0.1-0.3 mg/kg

Partial dissociation 0.4-0.8 mg/kg

Full dissociation (induction dosing) 1-2 mg/kg

36
Q

Synthetic THC : Drobinol

A
  • indications:
    • pain, neuropathic HIV
    • CINV
    • AIDS
    • anorexia
  • MOA:
    • CB1
  • AE: dizziness, tachycardia, euphoria/dysphoria, anxiety, hallucinations
    • mania
    • dry mouth
    • psychoactive s/e
    • MI risk
  • CYP 2C9
  • CYP 3A4
37
Q

Synthetic THC : nabilone

A
  • CB1 and CB2 receptors
  • Indications:
    • NAUSEA and vomiting
    • Pain, nausea, appetite
    • CINV, peripheral neuropathy HIV
  • Dose
    • 0.5 mg -1 mgqhs - 3 mg po bid
  • AE:
    • dizziness, dry mouth, fatigue, drowsy
38
Q

THC/CBD combination : Sativex

A
  • CYP 2C9, 3A4
  • CB1 and CB2 receptors
  • Indications:
    • MS spasticity
    • peds epilepsy
    • maybe refractory pain
  • Dose:
    • 1 spray bid – 4-8 bid
  • Same adverse effects
39
Q

Which part of cannabinoids cause psychoactive SE?

40
Q

Topicals for adjuvant therapy

A
  • lower risk systemic toxicity
  • direct delivery to site of pain
  • Capsaicin
  • NSAIDS
  • Topical TCAs
  • Topical lidocaine
41
Q

Capsaicin for pain

A
  • inhibits primary afferent nociceptive neurons (C fibres)
  • may be helpful in neuropathies
  • can be painful to apply
  • has long term effect with no systemic side effects
42
Q

Topical NSAIDS

A
  • MSK pain
  • Some systemic absorptions
43
Q

Topical anesthetics

A
  • low risk systemic toxicity, but if applied to mucous membrane or open wounds, risk is there
  • topical lidocaine 5%patch or gel
44
Q

Adjuvant treatment for bony pain

A
  • Radiation
  • NSAIDS
  • Steroids
  • Calcitonin
  • Bisphosphonates
45
Q

Calcitonin for bony pain

A
  • mixed evidence
  • side effects n/vx
46
Q

Bisphosphonates for bony pain

A
  • Pamidronate sc q 4 weeks, zometa 4mg sc q4 weeks
  • Evidence :
    • useful for analgesia in breast and MM patients
    • some evidence for pain relief in lung, GI, prostate ca
  • Single dose, can repeat after 7 days x 1.
  • 50-70% of patients have 30% pain reduction in one week.
47
Q

Buscopan

A
  • Hyoscine Butylbromide
  • NO CYP
  • ACH
    • decreased peristalsis
    • decreased secretions
    • decreased colic
    • decreased nausea
  • AntiM effects
  • Does not cross BBB
48
Q

Baclofen

A
  • inhibits transmission of monosynaptic reflexes at spinal cord
  • muscle spascticity
  • 5-10 mg po tid prn
  • Discontinuation syndrome - must taper
  • dizziness, nausea, vomiting, drowsiness, confusion
49
Q

Methotrimeprazine

A
  • may have analgesic properties
  • may choose if pain complicated by delirium/agitation
  • sedation, ACH SE, hypotension
  • paradoxical effects
50
Q

Cannabinoids : evidence

A
  • very mixed
  • one meta analysis : moderate evidence of reduction of chronic non cancer pain by 30%
    • AE hihg
    • NNT 24, NNH 6
  • no data to support smoked, vaporized, ingested for cancer pain
  • use cannot be recommended (UTD)
  • Sativex (synthetic) may be considered adjunct for cancer pain refractory to opioids
  • Nabilone second line
51
Q

Cannabinoids MOA

A
  • endocannabinoid system
  • CB1 (CNS, PNS)
  • CB2 (organs/tissues/lymph)
  • CB1:
    • inhibition of neurotransmitter release
    • ? attentuate synaptic transmission of pain
  • CB2:
    • inhibits cytokine release
    • modulates immune system
    • ? anti inflammatory effect
52
Q

Cannabinoids Side Effects

A
  • dry mouht
  • n/vx
  • somnolence
  • euphoria
  • fatigue
  • disorientation
  • confusion
  • hallucinations
  • CV : orthostatic hypotension, arrythmias, MI
53
Q

How to approach a situation where clinican is concerned about patient’s motive for medical marijuana?

A
  • Random urine drug screen
  • discuss with patient
  • contract of use
  • consult with psychiatrist
  • ensure consistent team approach
  • limit prescriber
  • limited dispensing
  • written contract if needed
54
Q

Sodium channel blockers for pain :

Carbamazepine and oxcarbamazepine

A
  • Trigeminal neuralgia

Side Effects:

  • leucopenia
  • cognitive SE
  • drowsiness
  • ataxia
  • diplopia
  • hyponatremia
  • bone marrow suppression

CI:

  • AV block
  • hepatic impairment

Metabolism:

  • CYP3A4
    • ​may decrease levels of drugs metabolized by CYP3A4
  • CYP2C19
55
Q

Topiramate for pain

A
  • Sodium channel blocks, glutamate and GABA antagonist
    • Neuropathic pain
  • Shit drug, poorly tolerated
  • may decrease serum bicarb

Side effects:

  • COGNITION
  • metabolic acidosis
  • nausea,
  • abnormal vision
  • glaucoma

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