Slide 1

Report
How to Keep The Patient
in Pain Sleeping at Night
(and you awake in the
morning )
Barry Bass
University Center for Pain
Medicine
UTHSC, Houston
Pain
Management
For
Objectives
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•
•
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To identify types of pain
To clarify principles of pain assessment
To clarify the basic principles of prescribing
To discuss the basic pharmacological principles of opioid
and adjuvants used in pain management
• To discuss the practical application of drugs used in
analgesic therapy with emphasis on patient safety , risk
benefit comparisons and cost containment
Acute Pain
An unpleasant reaction/sensation
secondary to tissue damage
Acute Pain
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•
Corresponds to the degree of injury
Is self limiting
Serves a purpose
Responds to conventional therapy
Attracts sympathy and concern from
family and caregivers
• Minimal affective response
• Treatment is cost effective
• Good outcomes
Chronic Pain
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Outlasts the initial injury
Subjective exceeds the objective findings
Poor response to conventional therapy
Serves no beneficial purpose
Poor response from family and care givers
Cost ineffective therapy
Accompanied by major psycho-social comorbidity
• High incidence of substance abuse
Definition of Persistent (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
PAIN
SUFFERING
DEPRESSION
LOSS OF
FUNCTION
DRUG ABUSE
FINANCIAL
LOSS
DOMESTIC
DISRUPTION
Scope of The Problem
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•
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•
One in four Americans has persistent pain
Commonest reason for PCP office visits
Over 50% of Cancer patients have severe pain
60% of the elderly have persistent pain
Commonest cause of disability
Health care costs related to persistent pain is
$100 billion and rising rapidly
• Lost work hours secondary to persistent pain
can double the costs
• Rising rate of substance abuse
rate-item
The Good
ACUTE PAIN
tg/stores/d
The Bad
cavorite-lis
n
-fGET
tg/stores/d
communit
rate-item
cust-rec
just-say-no
true
m/justsay
Persistent
nociceptive Pain
The Ugly
Neuropathic Pain
communit
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
Types of Persistent Pain
• Nociceptive
–
–
–
–
Musculo skeletal
Joint
Ligamentous
Visceral
• Neuropathic
– Central
– Somatic
– Sympathetic
• Psychogenic
• Mixed
Neuropathic Pain
Pain secondary to
biochemical and
structural changes within
the central and peripheral
nervous system.
Pain Transduction
Pain conduction
Pain processing
Pain perception
Pain expression
Pain Assessment
• The pain itself
–
–
–
–
Intensity
Radiation
Type
Relieving exacerbating factors
• Functional assessment
• Behavioral assessment
• Medication usage
Pain Assessment
• Characterize the pain
• Characterize the disease, relationship
between pain and disease and potentially
treatable etiologies
• Clarify syndromes and infer
pathophysiology
• Determine need for urgent therapy
• Identify other needs
• Develop a therapeutic strategy
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)
(Cleeland, 1991; Jacox et al, 1994)
Moderate (5 – 6)
Severe (7 – 10)
Red Flags in Pain Assessment
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Poor function
Pain always a 10 out of 10
Behavioral co morbidity
Obsession with drugs
Altercations with staff
Focus on particular medications
Multiple admissions for pain therapy
Frequent ER visits
Illegal drug usage
Alcohol and tobacco abuse
Poor motivation
Guidelines in Pain Therapy
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Assess the pain frequently
Pain assessment must be dynamic and not static
Be pre-emptive
Be mechanistic
Use around the clock therapy (ATC)
Treat and assess breakthrough pain aggressively
Where possible use oral route
Consider age, previous drug usage, hepato- renal
function
• Monitor for abuse
• Monitor and treat side effects
• Be cost effective
Neuro -Physiology of Pain
TRANSDUCTION
CONDUCTION
PERCEPTION
CONDUCTION
Descending
Modulation
EXPRESSION
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.
Mechanistic Approach to Drug
Therapy in Persistent Pain
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Decrease peripheral sensitization
Delay or block conduction
Suppress automaticity
Inhibit central amplification
Increase descending inhibition
Modify central perception
Modify expression
The Opioids
Cancer Pain……… Palliation
Non Malignant Pain………Rehabilitation
Efficacy of Opioids in
Persistent Pain States
• Nociceptive pain
• Visceral pain
• Neuropathic pain
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
Deer T, Winkelmuller W, Erdine S, et al. Intrathecal therapy for cancer and nonmalignant pain:
patient selection and patient management. Neuromodulation 1999;2:55-66.
Breakthrough Pain
• End of dose
• Pathological
• Incidental
• Tolerance
Principles of Breakthrough Pain
Therapy
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Should not exceed 25% of the daily dose
Should stay within the therapeutic window
Should have minimal side effects
Should not be randomly escalated
If needed more than 4 hrly. Increase ATC.
Assess for abuse vs tolerance
Opioids Used for Pain Management
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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
Routes of Administration
• Intravenous
– PRN nurse administered
– PCA
• Oral
– PRN
– Around the clock
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•
Transdermal
Rectal
Transmucosal……oral or nasal
Neuraxial
– Intrathecal
– epidural
The PRN Scenario
20 minutes
The PCA
PHARMACOKINETIC GOALS
SIDE EFECTS
NO PAIN
PAIN
HOURS
Indications for PCA
• Moderate to severe pain requiring
opioids
• Pain anticipated to last >10-12 hours
• Patients willing to control their
analgesia
• Patient able to understand PCA
• Oral route is not appropriate
• Procedural pain
Choice of Opioid in PCA
• Depends on:
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Allergies
Renal function
Liver function
History of abuse
Individual response
Previous surgical history
• Cost consideration
Loading Dose
• Morphine 50 mg/kg q 10 minutes
– 80 kg = 50 X 80 = 4,000 mg = 4 mg
• Fentanyl 0.5 mg/kg q 5 minutes
– 80 kg = 0.5 X 80 = 40 mg
• Hydromorphone 10 mg/kg q 10 minutes
– 80 kg = 10 X 80 = 800 mg = 0.8 mg
Maintenance Dose
• Morphine 25 mg/kg q 10 minutes
– 80 kg = 25 X 80 = 2,000 mg = 2 mg
• Fentanyl 0.25 mg/kg q 5 minutes
– 80 kg = 0.25 X 80 = 20 mg
• Hydromorphone 5 mg/kg q 10 minutes
– 80 kg = 5 X 80 = 400 mg = 0.4 mg
III. PCA
• Morphine 1 mg / ml (5 mg/ml)
• Fentanyl 10 mg/ml (50 mg/ml)
• Hydromorphone 0.2 mg/ml
(1 mg/ml and 5 mg/ml)
• Meperidine 10 mg/ml
The Demand Dose with PCA
• <0.5 mg MS is associated with poor analgesia
• >2 mg MS associated with over sedation
• Excessive demands
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Poor pain relief or change in medical status
Pump failure
Patient confusion…………..elderly
Family interference………..elderly and children
Inappropriate patient use…….abuse
• Adjust bolus dose if poor pain relief with >4
demands per hour
• With line occlusion alarm set for 3 failed
demands
The Lockout Interval
• Time interval to assure full effect and to
minimize sedation…..a safety feature
• Too long a lockout will reduce the
effectiveness of the PCA
• Too short a lockout will increase risk of
sedation
• Lockout of 7 -11 minutes for morphine
• Lockout of 6-10 minutes for
hydromorphone
• Lockout 5-8 minutes for fentanyl
Ginsberg. Pain.1995:62:95
The Lockout Interval
• Time interval to assure full effect and to
minimize sedation…..a safety feature
• Too long a lockout will reduce the effectiveness
of the PCA
• Too short a lockout will increase risk of
sedation
• Lockout of 7 -11 minutes for morphine
• Lockout of 6-10 minutes for hydromorphone
• Lockout 5-8 minutes for fentanyl
Ginsberg. Pain.1995:62:95
Basal Infusions with PCA
• Infusion will continue regardless of sedation
level
• Responsible for most instances of oversedation ..1-3% cf. <0.5% with demand
• Removes the feed back loop
• Does not offer improved pain relief
• Does not offer improved sleep
• No difference in number of demands
• Does increase total opioid delivered
• Increased risk of programming errors
• Only to be used if patient is opioid tolerant
with knowledge of daily requirements
Rudolph.Anes.Analg.1999.89:1226
Inadequate Analgesia with PCA
• Check
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–
Demands
The machine
The IV
The lesion being treated
• Abuse potential
Inadequate Analgesia with PCA
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Increase the bolus dose
Decrease the lockout
Educate the patient
Start basal infusion
Change the route
Change the opioid
Add an adjuvant
– Antidepressant
– Anticonvulsant
– Anti inflammatory
• Treat the lesion
Extreme Caution with Basal Infusion
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Children
Elderly
OSA disease
Morbidly obese
Hypovolemia
Renal impairment……….when using morphine
and Demerol.
• Inexperienced nursing staff
• With concurrent epidural infusion
Etches. Can. J. Anes. 1994.41:125
Continuous Infusion
• Not routine
• Start an infusion if:
– Inadequate analgesia over >6 hours
– Opioid-tolerant patient
• Infusion rate based on hourly use over previous 6
hours
– Opioid-naïve 25-50% of hourly requirement
– Opioid-tolerant 50-75% of hourly requirement
PCA Dosing in Children
Lockout 6-10 minutes
Drug/Potency
Morphine/1
Hydromorphone
(Dilaudid/5
Fentanyl/20
PCA dose
Basal
10-20mcg/kilo
5-30mcg/kilo/hr
2-6mcg/kilo
1-6mcg/kilo/hr
0.5-1mcg/kilo
0.25mcg/kilo/hr
Used in children over the age of 6 years
Patient
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Education PCA
Assess patient competency
Allay fears regarding addiction
Press the button before pain is intolerable
Family not to press the button
Nurses not to press button
Do not clock watch
Hit button whenever you want
Reassure fears of sedation
Meperidine…….Demerol
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Short acting
Toxic metabolites
Metabolites with long half life >12 hrs
Increased risks in renal failure
High addiction potential
Expensive
High incidence of caregiver diversion
Gradually being phased out
Normeperidine Toxicity
Asymptomatic
Shaky
Feelings
Tremors/
Twitches
Myoclonus/
Grand mal
19
20
9/9
8/2
Days of
administration
1.2 (0.1)
1-2
8.0 (1.2)
(1-22)
6.7 (1.9)
(1-30)
5.9 (1.0)
(3-10)
Rate of admin.
(mg/day)
170 (18)
(75-380)
350 (52)
(59-1080)
370 (66)
(46-1100)
420 (37)
(260-540)
Patient Group
N
Kaiko RF et al, Ann Neurol 1983;13(2):180-5
Equianalgesic Dosing
Drug
Oral po
Morphine
30 /1
200/1
Oral SR durn
3-5
10
2-3
100
.5-1
2-4/2
3-4
10/1
oxycodone 10/1
20/2
methadone
3-4
3-4
demerol
fentanyl
dilaudid
30-60
IV
hydrocodone
10
6-8
im peak Half life
2-3
unpred
0.1
30
1
45
0.5
30
2-3
2 mins
4-5
3-4
8
1
15-30
Opioid Equivalencies/ Conversions
Drug
PARENTERAL
oral
factor*
MSO4
10 mg
30mg
3
Oxycodone
--------
15-20
---
Methadone
10MG
20mg
2
Dilaudid
1.5 mg
7.5 mg
5
codeine
130 mg
hydrocodone
-------
200mg
10-20mg
propoxyphene
Tramadol
----50-100
------- 50-100
duration
3-4hrs
3-4 hrs
4-8 hours
2-3 hours
1.5
---
----------
3-4 hours
3-4 hours
3-4 hours
3-7 hours
Conversion to Oral
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Calculate total daily requirement with PCA
Convert to IV morphine
Convert to Oral morphine
Convert to alternate opioid
75 % as ATC 25% as rescue
Factor in incomplete cross tolerance especially
with oxycodone and Methadone
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
• multimodal therapy started to be used
PCA to Oral Oxycodone
Conversion Table
MSO4
HydroFentanyl
morphone
OxyContin
Q 12 h
Oxycodone
IR (q 3h prn)
24-hour opioid
< 20 mg
< 4 mg
< 300 mg
0
5-10 mg
30 mg
6 mg
500 mg
10 mg
5-10 mg
40 mg
8 mg
650 mg
20 mg
5-10 mg
50 mg
10 mg
800 mg
30 mg
10 –15 mg
60 mg
12 mg
1000 mg
30 mg
10 –15 mg
70 mg
14 mg
1200 mg
40 mg
10 –15 mg
80 mg
16 mg
1400 mg
40 mg
10 –15 mg
Ginsberg B, Anesthes & Analgesia 1998
Oral Opioid Comparison
Oxycodone
Hydromorphone
Hydrocodone
• Long track record
• Avoids “M” word
• No toxic
metabolites
• ? immune function
• Formulations
–Immediate
release
–Controlled
release
• Long track record
• Avoids “M” word
• No toxic
metabolites
• ? immune function
• Formulations
–Immediate
release
–Sustained
release (Fall
2001)
• Long track record
• Avoids “M” word
• No toxic
metabolites
• ? immune function
• Formulations
– Immediate
release
– Combinations
Acetaminophen
o Ibuprofen
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
Long Acting Opioids for ATC
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MS Contin 15,30,60 mgm
Oxycontin 10,20,40,60,80 mgm
Methadone 5, 10, 20 mgm
Fentanyl patch 25, 50,75,100 mcg
Methadone (Dolophene)
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Long acting
Lower addiction potential
Cheap
Lower tolerance profile
For the opioid addict
No active or toxic metabolites
No renal excretion
No dependence on hepatic function
Long elimination half life
8-12 hour analgesic action
Methadone
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Start of at lowest dosage
5 mgm Q 12 hourly
Warn patient about dangers of PRN
Increase only after 72 hours if needed
If indicated increase to 5 mg Q 8 hourly
Increase to 10 or 7.5 mg slowly
Strongly advise against iv administration
Oxycodone
• High bioavailability
compared to MSO4
• No toxic metabolites
• Less tolerance
compared to MSO4
• Higher incidence of
euphoria
• Expensive
• No “M” word
The Fentanyl Patch
• Indications for use
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Around the clock delivery of opioids
Allergy to long acting oral opioids
Severe nausea and vomiting
Unable to swallow
Severe constipation
• Beware
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Opioid naïve
Febrile patient
Elderly
Drug abuser
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
(Adapted from Duragesic PI, 2001)
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
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Methadone
Dilaudid
Oxycodone
Hydrocodone
Morphine
Fentanyl
Demerol
NEUROTOXICITY
SEDATION
TOLERANCE
Liver Failure
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Methadone
Dilaudid
Oxycodone
Hydrocodone
Morphine
Fentanyl
Demerol
All pretty much
OK, but halve
dose
Side Effects of Opioids
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Nausea
Sedation
Constipation
Pruritus
Myoclonus
Sweating
Dependence
• Physical dependence
• Psychological dependence
• Pseudo addiction
Recognizing the Addict
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Refuses drug screen
Focus on narcotics
Wants demerol or fentanyl
Wants Xanax and soma
Hourly or daily escalations
Conflicts with care givers
Family issues
Obvious stigmata
Strength
10 mgm
2o mgm
40mgm
80mgm
160 mgm
Licit Retail
$1.25
$2.30
$4.0
$6.0
$14
Illicit Retail
$5-10
$10-20
$25-40
$65-80
$100-200
Cincinatti Police Department
50c to $1.5 per milligram oxycodone
Non Opioid Adjuvants
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Antidepressants
Anticonvulsants
Anti-inflammatories
Acetominophen
Tramadol
Acetaminophen
Guidelines
• Short-term
NHCOCH3
– < 4 gm / day
• Long-term
– < 3.2 gm /day
– < 2.4 gm /day,
elderly, debilitated
OH
Acetominophen Content
Tylenol
Tylenol liquid
Tylenol drops
Tylox
Vicodin
Lortab
Norco
zydone
Wygesic
160
325 500
80
160 500
80
100
500
500 750
500
650
325
400
650
650
Tricyclic Antidepressants:
Adverse Effects
• Commonly reported AEs Fewest
(generally
AEs
anticholinergic):
• Desipramine
– blurred vision
– cognitive changes
– constipation
– dry mouth
– orthostatic hypotension
– sedation
– sexual dysfunction
– tachycardia
– urinary retention
• Nortriptyline
• Imipramine
• Doxepin
Most
AEs
• 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
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Coumadin
Alcohol ( cold medications)
Appetite suppressants
Quinolone antibiotics
Antihistamines
Tramadol
Anti epileptics
Bronchodilators
The Anti Epileptic Drugs
• Carbamazapine (Tegretol)
• Gabapentin (Neurontin)
• Oxcarbezapine (Trileptal)
•
•
•
•
•
Topiramate ( Topramax)
Zonisamide ( Zonergan)
Levetiracetam( Keppra)
Lamotragine ( Lamictal)
Valproate ( Depakote)
Gabapentin in Neuropathic
Pain Disorders
•
•
•
•
FDA approved for postherpetic neuralgia
Anticonvulsant: uncertain mechanism
Limited intestinal absorption
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 3,600
mg/d (tid–qid)*
*Not approved by FDA for this use.
Suggestions with Gabapentin
•
•
•
•
•
•
•
•
Start as low as possible…..100 mgm q HS
Increase slowly by 100 mgm every three days
Caution regarding driving
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
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
Selective
COX-2
Inhibitor
Inflammation
Pain
Needleman P, et al. J Rheumatol. 1997;24: 6-8.
Simon LS, et al. J Clin Rheumatol. 1996;2:135-40.
COX-2–Specific Inhibitors
Generic Name
Celecoxib
Brand Name
Celebrex®
Approval Year
1998
Rofecoxib
Vioxx®
1999
Valdecoxib
Paracoxib
Etoricoxib
Bextra®
2001
The COX 2 Inhibitors
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•
Rofecoxib 25-50 mg daily (Vioxx)
Celecoxib 100-200mg daily (Celebrex)
Valdecoxib 10-20 mg daily (Bextra)
Etrocoxib
Paracoxib (iv use)
•
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Contra Indications to COX2
Therapy
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
The Muscle Relaxants
• Most act by central mechanisms
• Most produce sedation
• Most have anticholinergic side
effects
• Some are highly addictive
• Most produce little local relaxation
The Muscle Relaxants
• Centrally acting relaxants
–
–
–
–
Metaxalone(Skelaxin)
Cyclobenzaprine (Flexeril)
Methocarbamol (Robaxin)
Carisprodol (Soma)
• GABA agonists
– Alprazolam (Xanax)
– Diazepam (Valium)
– Lioresal (Baclofen)
• Alpha 2 agonists
– Tizanidine ( Zanaflex)
Beware of
sedation,
addiction and
anticholinergic
side effects
The Muscle Relaxants
• Centrally acting relaxants
–
–
–
–
Metaxalone(Skelaxin)
Cyclobenzaprine (Flexeril) 10mg and max at 40mg
Methocarbamol (Robaxin)
Carisprodol (Soma) highly addictive
• GABA agonists
– Alprazolam (Xanax) highly addictive
– Diazepam (Valium) high abuse potential
– Lioresal (Baclofen) 10 mg daily and max at 40mg.
• Alpha 2 agonists
– Tizanidine ( Zanaflex) 2mg q hs and escalate to 8mg
Case Example
•45 y.o. female with sickle cell disease
•Admitted with severe back and left hip pain
•Frequent visits to the ER for pain. Gets demerol
•Takes Soma, Xanax and Vicodin for pain
•History of cocaine, tobacco and THC abuse
•Hb 5gms, severe muscle spasm lower back, decreased ROM left
hip.
•Placed on demerol 25-50 mg iv q 2 hourly PRN, Vicodin 10/500
tabs 1-2 q 4-6 hrly.
•Continual demands for more demerol and yelling at nurses
Take Home Message
• Identify the pain generator
• Identify and treat underlying disease(diabetes, HIV,
Depression)
• Assess before you treat
• Start low and go slow
• Use rational poly-pharmacy, but not shotgun Rx.
• Factor in age, hepato-renal function
• Monitor for abuse and document
• Identify and treat side effects early
• Be cost effective
• Communicate with patient and family
• Obtain pain service consult when you feel necessary
Hermann Acute
Pain Service
713-606-7100 Pager
713-704-3010 0ffice
Good Luck and Thank
You for Your Attention
Questions?

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