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Pain Management
Dr. Lamya Alnaim
Pain is a Very Significant Problem

Pain has negative effects on sleep, work,
enjoyment of activities, sexual function, and
personal interactions

Multiple studies show pain of all types is
under treated
Pain is a Very Significant Problem

Good medications and treatments are
available

Barriers (patient and caregiver) include lack
of education, attitudes (myths, cultural
differences), and regulatory/legal issues
Definition: Acute Pain
An unpleasant sensory and emotional
reaction/sensation secondary to tissue damage
 Arises from injury, trauma, spasm, or disease
of the skin, muscles, somatic structure or
viscera.
 Corresponds to the degree of injury
 Self limiting- limited duration

Definition: Acute Pain

Serves a purpose
 By
inducing an organism to withdraw from or
avoid a noxious stimulus.
Responds to conventional therapy.
 Decreases in intensity as the damaged area
heals and tissue repair takes place.

Definition of Chronic Pain
 Any
pain that
Persists
beyond the expected time after a physical
or emotional injury
Subjective complaints are magnified
Pain is out of proportion to clinical signs
Is accompanied by severe psycho-social issues
Responds poorly to conventional therapy
Persistent Pain
SUFFERING
DEPRESSION
LOSS OF
FUNCTION
DRUG ABUSE
FINANCIAL
LOSS
DOMESTIC
DISRUPTION
PAIN
Who Gets Persistent Pain ?
Systemic disease
Diabetes mellitus
hypothyroidism
HIV/AIDS
Hepatitis C
Malignancy
Neurological disease….ALS, MS
Rheumatoid related syndromes
 Obesity
Psychiatric co-morbidity

ACUTE PAIN

Meaningful, linear,
reversible

Well defined, recent
onset, clear definable
cause

Observable responses

Readily responds to
analgesics

Usually nociceptive in
origin
CHRONIC PAIN
 Meaningless, cyclical,
irreversible

Persists over time

Adaptation

Less amenable to
analgesics alone

Multiple etiologic
components
Cancer Pain

20-50 % at time of diagnosis

Incidence varies with tumor type

55-95% with advanced disease

50-70% report pain of moderate to severe
intensity

30% report excruciating pain
Pain Experience in Ambulatory
Cancer Patient Population
Disease
Pain
71%
Pain due to
Disease
83%
Worst Pain
>5
60%
Negative
PMI
43%
Breast
GI
61%
91%
58%
41%
GYN
55%
80%
71%
54%
GU
64%
84%
66%
38%
Lymphoma
53%
66%
63%
63%
Lung
74%
85%
63%
34%
Other
74%
85%
64%
42%
Pain Classification Schemes
1-Neurophysiologic:
Nociceptive
(somatic, visceral)
Neuropathic
2-Duration: acute vs. chronic
3-Temporal pattern:
continuous
intermittent
 incident
 Breakthrough
 End-of-dose
failure
Pain Classification Schemes
4-Severity
5-Specific cancer pain syndromes
(etiology):
 Tumor infiltration of bone, nerve, viscera.
 Treatment related.
Types of Persistent Pain
Nociceptive
Musculo skeletal
Joint
Ligamentous
Visceral
 Neuropathic
Central
Somatic
Sympathetic
 Psychogenic
 Mixed

Types of Pain: Nociceptive vs.
Neuropathic
Nociceptive mediated by normal nervous
system:
 Somatic - dull, aching, well-localized. Bone
metastasis, invasion of soft tissue
 Visceral - vague distribution, referred. Bowel
obstruction, carcinomatosis, pleural effusion
Types of Pain: Nociceptive vs.
Neuropathic
Neuropathic mediated by damaged nervous
system:
 Localized to an area of sensory abnormality
 Pain in response to non-painful stimuli
 Pain in the absence of ongoing tissue damage
 Painful peripheral neuropathy, post mastectomy
pain, brachial plexopathy
Behavioral
Physiologic
Manifestations of Pain
Acute
Increased BP, P, R.
Dilated pupils.
Sweating.
Focuses on pain
Reports pain
Crying, moaning
restless
Grimace
Chronic
Normal
Normal
Dry skin
Easy distraction
No report
Quiet, sleep, rest
Blank or normal
facial expression
Key Principles in Assessment

Pain is a multidimensional, subjective, and
uniquely personal experience

Pain is what ever the person says it is,
occurring whenever the person says it does

Reliance on observable physiologic and
behavioral manifestations in order to verify
existence and severity of pain is inadequate
Goals of Assessment

Estimate severity of pain (0-10 scale, visual
analog scale)

Form clinical impression regarding etiology

Determine need for additional diagnostic
testing

Formulate therapeutic recommendations which
take into account the patient’s medical and
psychosocial status
Symptom Assessment
PQRST
 P: Palliative or precipitating factors
 Q: Quality
 R: Region or Radiation
 S: Subjective Description of severity
 T: Temporal factors
Symptom Assessment
Site
 Onset
 Temporal pattern
 Quality
 Relieving/Provoking
factors
 Associated signs/
symptoms

Impact of function
and QOL.
 Impact on
psychological state.
 Response to prior
therapy.
 Treatment
preferences.

Pain Assessment

Characterize the pain

Location of the pain

Past Medication and Current Medication

Pain Intensity
Pain Intensity Rating Scales
• Visual Analogue Scale (VAS)
No pain
----------------------------------- Worst pain
• Numerical Rating Scale
0 ------------------------------------------- 10
Worst pain
imaginable
No pain
• Categorical Scale
None (0)
Mild (1 – 4)
Moderate (5 – 6)
Severe (7 – 10)
Guidelines in Pain Therapy
Assess the pain frequently
 Pain assessment must be dynamic and not static
 Use around the clock therapy (ATC)
 Treat and assess breakthrough pain aggressively
 Where possible use oral route
 Consider age, previous drug usage, hepatorenal function
 Monitor for abuse
 Monitor and treat side effects

Treatment Goals
Decrease Intensity and duration of pain
 Decrease conversion from acute to chronic
 Decrease suffering and disability
 Decrease psychological and socioeconomic of
sequel of untreated pain.

Treatment Goals
Optimize drug therapy
 Improve quality of life and optimize ability to
perform activities of daily living
 Minimize adverse effects of therapy
 Minimize inappropriate use

Overall Treatment Strategies
 Analgesic
 Physical
and adjuvant medications
therapies
 Psychological
 Anesthetic
interventions
and neurolytic procedures
Mechanistic Approach To Therapy
Modify
expression..anxiolytics
Decrease
inflammatory
response.
NSAIDS, local
anesthetics,
steroids
Increase
inhibition..
Amitryptiline
venlafaxine,
clonidine
Prevent
centralization
Decrease
conduction
gabapentin,
carbamazepine,local
anesthetics, opioids
cox2,opioids,
ketamine,alpha
2 agonists.
WHO Three-Step Analgesic
Ladder
 Step
1: Mild pain
Non-opioid, + Adjuvant
 Step 2: Mild to moderate pain
Opioid for mild to moderate pain, + nonopioid, + Adjuvant
 Step 3: Moderate to Severe Pain
Opioid for moderate to severe pain , +
non-opioid, + Adjuvant.
WHO Analgesic “Ladder” for
Cancer Pain
Freedom from Pain
Proposed 4th Step
Intrathecal Opioid Delivery
Pain persisting or increasing
Step 3
Opioid for moderate to severe pain
± Nonopioid ± Adjuvant
WHO 3-Step
Analgesic
Ladder
Pain persisting or increasing
Step 2
Opioid for mild to moderate pain
± Nonopioid ± Adjuvant
Pain persisting or increasing
Step 1
± Nonopioid
± Adjuvant
Pain
Algorithm for Medication Selection
in Various Pain Syndromes
Neuropathic pain
Shingles, DM, HIV, antiretroviral drugs, Vinca
Alkaloids.
 Sharp, lancinating, burning, hot, electrical,
shocking, paresthesia

Myofascial pain
From muscle, bone, joints, or connective tissue
 Muscle pain from exertion→NSAIDs
 myositis → injection of local anasthetic
 Inflammatory muscle disease → low dose
steroids

Sickle Cell Disease
Acute infarctions and necrosis of organs
 Mild to moderate pain: NSAIDs,
acetaminophen
 Sever acute pain: opiates

Cancer Pain

Cancer: Tumor expansion, nerve compression,
infiltration by tumor, malignant obstruction,
infection of malignant ulcers.

Treatment: radiation → mucositis pain
Principles of Analgesia for cancerRelated pain





Follow WHO Ladder
ATC dosing for continuous pain
Rescue dosing for intermittent pain
Oral route unless contraindicated
No PRN
 It
is reactive not preventive
 Requires larger doses to reestablish control which may lead
to side effects
Principles of Analgesia for cancerRelated pain
ATC dosing

Small fixed doses on a schedule to prevent
pain
Rescue dosing
Fixed doses on a flexible schedule
 Analgesia is administered in response to pain
or to prevent predictable pain
 Key to success of pain management
 Similar to NG in angina
 Use immediate release opioid or NSAIDs

Calculating Rescue dosing
1.
25-50% of the 4hrly ATC

2.
3.

If ATC is 60 mg MS q 4 hrs, rescue can be 15 mg
2-5% of the 24 hr ATC dose
Based on response, 50% relief from 2 mg
morphine →4 mg should provide ≈ 100%
relief
All rescue should be prescribed q 4 hrs
Titrating dosage

If 3 or more rescue doses in 24 hr
↑ based upon total opioid dose ( ATC+
rescue) taken in the previous 24 hrs.
 ↑ both the ATC and breakthrough
 Calculate

Increase by the following guidelines
> 7 , ↑ dose by 50-100%
 Pain 4-7, ↑ dose by 25-50%
 Pain < 4, ↑ dose by 25%
 Pain

When patient uses < 2 rescue, sustained
release opioid should be started
Mild-Moderate Pain
NSAIDs
Ceiling dose.
Contraindications.
Side effects
Effective in bone metastasis because block
PGE2
Reduce stiffness, swelling and tenderness
 ± Weak opioid
Codeine, hydrocodone, propoxyphene.
Limitation of combination formulations.

Mild-Moderate Pain

+ Adjuvant
Corticosteroids: inhibit PGE2 in bone
Mets
bisphosphonates
Moderate to Severe Pain
 Strong Opioid
Morphine, hydromorphone, fentanyl,
methadone, oxycodone, levodromoran.
Moderate to Severe Pain
 + Adjuvant
 NSAIDs or Corticosteroids
1. No data to support analgesic superiority
among NSAIDs. Selection based on
patient report, side effects, chemical class
(ibuprofen, naprosyn)
2. Gastric protection: PPIs
3. If nerve compression use dexamethasone
Opioids

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Morphine Sulphate
Hydromorphone (Dilaudid)
Strong Opioids
Demerol
Fentanyl
Methadone
Buprenorphine
Partial
agonists
Pentazocine
Oxycodone (Roxycodone, Tylox, Percocet)
Weak
Hydrocodone (vicodin, lortab, Norco)
Propxyphene ( Darvon, Darvocet)
opioids
Codeine
Opioids
Three Classes:
 Phenanthrene: morphine, hydromophine,
levorphanol
 Phenylpiperidines: mepridine,fentanyl
 Diphenylheptanes:methadone, prpoxyphene
Opioids

Opioid Agonist: bind w/ opioid receptor site in
PNS & CNS = pain relief

No Ceiling

Titrate to pain relief or side effects

Opioid Antagonist: blocks relief. Naloxone

Opioid Agonist-antagonist: + pain relief.
Stadol, Nubain, Talwin (not recommended)
Opioids

No rationale for combining two opioids, use
same agent for ATC and rescue pain.
Routes of Administration

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Intravenous
 PRN nurse administered
 PCA
Oral
 PRN
 Around the clock
Transdermal
Rectal
Transmucosal……oral or nasal
Neuraxial
 Intrathecal
 epidural
Potent Opiates: Morphine,
Hydromorphone.
µ-receptors, κ-receptors
 Treat acute, chronic, sever, or terminal
malignant pain
 Orally, rectally, IV Infusion, epidural ,
intrathecal
 Immediate release analgesic effect 4 hrs

Morphine, Hydromorphone.

Doses according to
 Prior
exposure
 Pain severity
 Hepatic, renal function
 Route of administration

Oral: parental, 5:1
Morphine

Opioid of choice
 Available
in multiple routes and formulations
 Extensive clinical experience in dosing, route
change and side effects.
Meperidine…….Demerol
Used for traumatic and postoperative pain
 1/10 potency of morphine
 Oral or parenteral
 Short acting
 Toxic metabolites: nomeperidine

 Can
accumulate in renal dysfunction and cause
CNS stimulation and seizures
Metabolites with long half life >12 hrs
 High addiction potential
 Expensive

Methadone
Equivalent potency to morphine
 Orally, IV, rectally, epidurally/intrathecally
 Long acting
 adjust dose q 5-7 days
 Lower addiction and tolerance potential
 Cheap
 No active or toxic metabolites
 8-12 hour analgesic action ( give Q8-12 hrs)

 Longer
intervals in hepatic failure
Methadone

CNS depression lasts for 36 hrs after overdose
 Needs
CIVI Naloxone for reversing effect.
No renal excretion
 Dependence on hepatic function (p-450)

 Watch
for drug-drug interaction
Fentanyl


>100 potent than morphine
IV, intraspinally as preoperative anesthetic
agent
Rapid


onset, short duration of action
Transdermal patch: Consistent dosing
Oral lollipop
The Fentanyl Patch

Indications for use
 Severe
nausea and vomiting
 Unable to swallow
 Children
 Patients with poor compliance
 Concern of drug diversion

Beware
 Opioid
naïve
 Febrile patient
 Elderly
 Drug abuser
The Fentanyl Patch

disadvantages
 Delay
in onset of analgesia
 Residual activity after the patch is removed
25,50,75,100 mcg
 Duration 72hrs
 Steady state requires 24 hrs, use supplemental
short acting to cover initial period.

Weak Opioids
Codiene, oxycodone, propoxyphene
 For mild to moderate pain

Oxycodone
Analgesic effect 4 hrs
 High bioavailability compared to MSO4
 No toxic metabolites
 Less tolerance compared to MSO4
 Higher incidence of euphoria
 Expensive

Tramadol
Activity against opioid and serotonergic and
noradrenergeric pathways in CNS.
 Moderate to sever pain
 Advantages

 Lower
abuse liability
 Lower risk of respiratory depression

Disadvantages
 Dizziness,

dry mouth, sedation, constipation.
Use lower doses in elderly
Oral Opioid Comparison
Oxycodone
• Long track record
• No toxic
metabolites
• Formulations
–Immediate
release
–Controlled
release
Hydromorphone
• Long track record
• No toxic
metabolites
• Formulations
–Immediate
release
–Sustained
release
Hydrocodone
• Long track record
• No toxic
metabolites
• Formulations
– Immediate
release
– Combinations
Acetaminophen
o Ibuprofen
Equianalgesic Dosing
MEDICATION
IV
PO
RATIO DURATION
Morphine
10
30
3
4-5
Hydromorphone
1.5
7.5
5
3-6
Oxycodone
Meperidine
15
75
Hydrocodone
Codeine
300
3-5
4
200
130
200
2-4
4-6
.75
3-5
Dose Conversion
Equianalgesic
dose of current
opioid
24 hrs dose
current opioid
Equianalgesic dose
of desired opioid
=
24 hrs dose current
opioid
Drug Delivery
No evidence that other routes are superior or
have less SE.
 Choice of route depends on pragmatic
consideration e.g. inability to swallow
 Can only be done safely with knowledge of
equianalgesic dosing.

Oral
Route of choice
 Simple, noninvasive
 Reasons for failure: inadequate dose,
parenteral to oral conversion made too quickly,
dosing intervals too long
 Formulation and dose dependent upon pattern
of pain and severity
 Long Acting Combined with Short Acting for
Chronic Pain
Sublingual, buccal
 Simple,
noninvasive
 Unable to tolerate oral dosing, unable to
swallow rapid onset, drug not subject to
first-pass effect
 fentanyl
Intravenous
Most efficient for rapid titration, dose finding,
immediate analgesic effect.
 Bolus, continuous, PCA.
 Steady state better maintained with CI.
 Full effects of increase CI will not be felt until
steady state or approximately 5-6 half-lives.
Therefore with IV Morphine 12-18 hours.
 Morphine, hydromorphone, fentanyl,
methadone

Rectal
Morphine, hydromorphone
 Conversion from oral at 1:1 ratio
 Sustained release tablets of morphine can be
used by this route.

Subcutaneous
Morphine, hydromorphone
 Equivalent to IV in efficacy and side effects

Conversion to Oral
Calculate total daily requirement with PCA
 Convert to IV morphine
 Convert to Oral morphine
 Convert to alternate opioid
 75 % as ATC 25% as rescue

Prior to Oral Conversion
Patient able to tolerate oral fluids
 Oral therapy started prior to removal of PCA
 Pain control predictable and stabilized
 IV to oral conversion calculated
 Side effects under control

Example of Conversion
Total morphine for 24 hours on PCA= 60mg
Want to convert to Oxycodone.
60 mgm of MS IV( x 3) = 180 mgm oral.
To convert to oxycodone x by 1.5 = 120 mg
oxycodone
75% as ATC = 90 mg = 40 mg Q 12 , but factor in
50% less for ICT = 20 mg q 12 hourly
25% as rescue = 30 mg or 5 mg Q 4-6 hourly PRN

Conversion Chart for Starting Dose
of Transdermal Fentanyl
Fixed-combination short-acting
opioids (6/day):
– Lorcet 5 mg/500 mg
– Lortab 5 mg/500 mg
– Percocet 5 mg/325 mg
– Percodan 5 mg/325 mg
– Tylenol + Codeine 30 mg/325 mg
– Tylox 5 mg/500 mg
– Vicodin 5 mg/500 mg
One 25 mcg/h
transdermal
fentanyl
patch/3 days
(72 hours)
Long-acting opioids(2/day):
– OxyContin 20 mg
– MS Contin 30 mg
Multiple patches may be used
for doses exceeding 100 mcg/h.
Doses up to 6oo mcg/h have
been evaluated in clinical trials.
Renal Failure
Methadone
 Dilaudid
 Oxycodone
 Hydrocodone
 Morphine
 Fentanyl
 Demerol

NEUROTOXICITY
SEDATION
TOLERANCE
Liver Failure
Methadone
 Dilaudid
 Oxycodone
 Hydrocodone
 Morphine
 Fentanyl
 Demerol

All pretty much
OK, but halve
dose
Side effects of opioids


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Constipation
Sedation
Mental clouding
Respiratory depression
Nausea and vomiting
Orthostatic hypotension
Urinary retention
Pruritus
Myoclonus
Constipation
Decreased gastric,
pancreatic, biliary
secretions.
 Decrease motility
 Delayed passage

Tolerance does not
develop
 Dose dependent
 Preventative
approach
 Bulk and stimulant
laxatives

Sedation



Common with start,
increase, change drug,
pain relief in sleep
deprived.
Tolerance to sedative
effects 2-7 days.
Other causes:
sedatives, sepsis,
metabolic imbalances,
hypoxia.
Strategies:
 change dose,
frequency, type of
opioid
 Stimulants: Caffeine,
dextroamphetamines,
methylphenidate
Respiratory Depression
Direct action on brain  Rapid tolerance
stem respiration
 Short acting
receptors; decreased  Goal: gradual reversal
responsiveness to
without analgesic
CO2 levels
withdrawal
 Pain is physiologic
 Naloxone 0.4
antagonist
mg/10cc; 0.5 cc q 2-3
 Risk factors
mins

Nausea - Vomiting

Common with start or increase dose

Tolerance within 2-3 days

Rule out other causes

Treatment:
treat constipation, use antiemetics,
change opioid
Withdrawal
Physical dependence
 Causes: abrupt discontinuation, rapid
dose reduction, antagonist, agonistantagonist
 Onset dependent upon elimination halflife
 Signs and symptoms
 25% of daily dose

Dependence
Physical dependence
 Psychological dependence
 Pseudo addiction

Definitions

Physical Dependence: involuntary,
adaptation, withdrawal with abrupt
reduction or discontinuation

Psychological Dependence (addiction):
compulsive use despite harm, for effects
other than pain relief
Definitions

Tolerance: decreased effect over time (not
universal)

Pseudo addiction: behavioral manifestations
of inadequate treatment

Iatrogenic addiction: psychological
dependence as consequence of exposure
(RARE < 0.1%)
Non Opioid Analgesics
NSAIDS
 Acetominophen

NSAIDS

Mechanism of action
-
Inhibition of prostaglandin synthesis
-
Synergism with opioid analgesics

Mild to moderate pain

Different side effect profile from opioids

No tolerance or dependence

Ceiling effect

Limited routes
NSAIDS

Pain from injury, surgery, trauma, arthritis, or
cancer

Very effective for bone pain

Predominant effect on PNS→synergistic

All are equipotent

Patient response varies
The Arachidonic Acid Cascade and COX-1
and COX-2 Inhibition
Arachidonic acid
COX-1
X
Body Homeostasis
• Gastric integrity
• Renal function
• Platelet function
COX-2
Traditional
NSAID
X
X
Inflammation
Pain
Selective
COX-2
Inhibitor
The COX 2 Inhibitors
Rofecoxib 25-50 mg daily (Vioxx) →W
 Celecoxib 100-200mg daily (Celebrex)
 Valdecoxib 10-20 mg daily (Bextra) →W
 Etrocoxib
 Paracoxib (iv use)

The COX 2 Inhibitors

Minimal effect on
 Gastric
integrity
 Renal function
 Platelet function

Potent inhibition of PGI2 →↑ risk if CV events
(MI)
Contraindications to COX2 I

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Previous side effects with COX2 inhibitors
Allergy to sulpha drugs
History of previous GI bleed
pregnancy
History of perforated gastric ulcer
Esophageal varices
Bronchospastic disease
Renal dysfunction
Coronary artery disease needing aspirin
Congestive heart failure
Acetaminophen





Same analgesic potency as ASA
No neuropsychological and little GI SE
Orally, or rectally
For musculoskeletal or visceral pain
Can be used in 3 ways
ATC 1g q 4 hrs as 5 doses in 24 hrs
2. As rescue with ATC opioid 1g q4 PRN
3. As an adjuvant analgesic
1.
Adjuvant Medications
Enhance analgesic
effect of opioids
 Treat concurrent
symptoms
 Provide independent
analgesia

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Antidepressants
Neuroleptics
Anticonvulsants
Local anesthetics
Antispasmodics
Muscle relaxants
Psychostimulants
Corticosteroids
NMDA receptor
antagonism
Anticholinergics
Bisphosphonates
Antidepressant
TCA, MAOIs,
 Clinical effects

 Improve
mood
 Improve sleep
 Anoxiolytics
 Decreased pain perception

TCA more easier to use
Antidepressant

TCA inhibit reuptake of serotonin and
norepinephrine
 Serotogergic
processes are part of endogenous pain
inhibitory mechanisms
TCA have analgesic properties related to
ability to increase pain tolerance
 Faster onset than antidepressant effect
 Have local anesthetic properties

Antidepressant
Improve sleep disturbances and depression
associated with chronic pain.
 1-3 weeks for effect
 Amitriptyline most commonly used for painful
conditions 50-150 mg/day
 Anticholinergic side effects

TCA: Adverse Effects
 Commonly
reported AEs
Fewest
(generally anticholinergic): AEs
blurred vision
cognitive changes
constipation
dry mouth
orthostatic hypotension
sedation
sexual dysfunction
Most
tachycardia
AEs
urinary retention

Desipramine

Nortriptyline

Imipramine

Doxepin

Amitriptyline
Caveats With the Antidepressants
•Start at lowest dose available
•Escalate slowly…every 10 -14 days
•Slow weaning, over a week
•Beware of drug interactions
•Check for
•Glaucoma
•Prostatic obstruction
•Heart block
Drug Interactions With
Antidepressants
Coumadin
 Alcohol ( cold medications)
 Appetite suppressants
 Quinolone antibiotics
 Antihistamines
 Tramadol
 Anti epileptics
 Bronchodilators

Neuroleptics
Fluphenazine, methotrimeprazine
 For mild to moderate pain
 Improve sleep
 Similar analgesic effects to morphine without
addictive properties or respiratory depression
 Side effects

 High
sedative and anticholinergic effects
 Extrapyramidal
Anticonvulsants
Carbamazapine (Tegretol)
 Gabapentin (Neurontin)
 Oxcarbezapine (Trileptal)
 Topiramate ( Topramax)
 Zonisamide ( Zonergan)
 Levetiracetam( Keppra)
 Lamotragine ( Lamictal)
 Valproate ( Depakote)

Anticonvulsants
Carbamazapine and valproate
 for lancinating, burning pain. (neuropathic)
 Neural
invasion by cancerous tumor
 Surgical scarring
 Trigeminal neuralgia
For opioid induced myoclonus
 dosing start at 100-200mg/d in cancer pain
 Plasma levels need to be monitored

Anticonvulsants
Carbamazapine and valproate
 Side effects
 Bone
marrow suppression
 Ataxia, diplopia, Nausea
 lymphadenopathy, hepatic dysfunction

Monitoring
 LFTs
 CBC
 Serum
Drug levels
Gabapentin in Neuropathic
Pain Disorders
FDA approved for postherpetic neuralgia
 Neuropathic pain in patients who do not respond to
CBZ and TCA.
 Neuropathy, multiple sclerosis, migraine
 Usually well tolerated; serious adverse effects rare


dizziness and sedation can occur
No significant drug interactions
 Peak time: 2 to 3 h; elimination half-life: 5 to 7 h
 Usual dosage range for neuropathic pain up to 12004800 mg/d

Suggestions with Gabapentin








Start as low as possible…..100 mgm q HS
Increase slowly by 100 mgm every three days
Caution regarding driving ( sedation)
Increase to 1200 mgm and assess pain relief
If > 50% relief, wait two weeks and reassess
Increase to maximum of 3600 mgm
Do not exceed 1200 mgm in elderly
Elixir in children mgm/kilo
Local anesthetics

Lidocaine For neuropatheic pain
 Short
duration
Mexiletine longer acting
 Doses same as antiarrhythmic dose
 Side effects

 Dizziness,
lightheadedness, ataxia, N/V
 High dose lead to tremor and convulsion

Lidocaine available as patches which have
lower SE
Local anesthetics

Ketamine
 At
the N-methyl-D-aspartate (NMDA) receptor
 Analgesic at subanesthetic doses
 For neuropathetic pain
 25 mg q 6 hrs , titrate by 25 mg q 24-48hrs
 Side effects

Psychotomimetic, tachycardia, high BP , ↑ intracranial
pressure
Benzodiazepines
Diazepam, midazolam
 Skeletal muscle relaxant and anxiolytic → ↑
pain threshold.
 Side effects

 Sedation,
cognitive impairment, depression
 Addictive
 Serious
withdrawal symptoms such as seizures
Corticosteroids
Prednisone, Dexamethasone
 No ceiling effect
 Opioid sparing effect
 Dexamethasone

 4-16
mg/d in divided doses
 Oral or IV

Other non-analgesic effects
 Relief
of nausea and vomiting
 Increase energy
Corticosteroids

Indications
 Bone
metastases
 Visceral pain
 Neuropathic pain
 Nerve compression from tumor
 Soft tissue or musculoskeletal pain from
inflammatory lesions
 Headache from ↑ intracranial pressure
 Pain from spinal cord compression
Bisphosphonates
Analgesic and prevents skeletal complications
of malignancy
 Treatment of hypercalcemia
 Indications

 Wide
spread painful bone metastases at risk of
complications
 Multiple painful sites of disease at risk of
hypercalcemia
 Osteolytic bone disease where radiation is CI
Bisphosphonates
Pamidronate, zoledronic acid
 given IV q 4 wks

Nonpharmacologic therapy
Surgery
 Neuroablative blocks and neurolysis
 Central and peripheral nervous system
stimulation
 Physical therapy
