Download - Drugs for Pain Management Rev 2011
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Drugs For Pain
Management
Nicolaski Lumbuun
Faculty of Medicine
Univ. Pelita Harapan
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Case Study A 20 yo cross country runner complains
ofpain in her foot. She runs more than
35 miles per week and has been havingfoot pain for almost 10 days. She ask
you whether she should take aspirin,
prednisolone or codein, or
What should you do??
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Pain
An unpleasant sensory and emotional experienceassociated with actual or potential tissue damage.
Pain is always subjectivepain is what the
patients says it is. So, All pain management is base on individual
perceptions & response
Many persons would rather be dead than unloved,abandoned and too often, left in pain.
(Margaret Somerville Death of Pain: Pain, Suffering and Ethics. Proceedings of the 7thWorld Congress on Pain, 1993.)
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Classification
Physiological
Nociceptive
Neuropathic
Psychological
Clinical
Acute
Chronic
Malignant
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Two Major Types of Pain
Nociceptive Pain
Normal process of stimuli that damages normal tissues
or has the potential to do so if prolonged; usually
responsive to nonopioids and/or opioids.
Neuropathic Pain
Abnormal processing of sensory input by the peripheral
or central nervous system; treatment usually includes
adjuvant analgesics.
Somatic Pain
Arises from bone, joint,
muscle, skin, or connective
tissue. It is usually aching
or throbbing in quality and
is well localized.
Visceral Pain
Arises from visceral
organs, such as the GI tract
and pancreas. This may be
subdivided:
Tumor involvement ofthe organ capsule that
causes aching and fairly
well-localized pain.
Obstruction of hollowviscus, which causes
intermittent cramping and
poorly localized pain.
Centrally GeneratedPain
Deafferentation pain:Injury to either the
peripheral or central
nervous system.
Examples: Phantom pain
may reflect injury to the
peripheral nervous system;burning pain below thelevel of a spinal cord lesion
reflects injury to the
central nervous system.
Sympatheticallymaintained pain:
Associated with
dysregulation of the
autonomic nervous system.
Examples: May include
some of the pain associated
with reflect sympathetic
dystrophy/causalgia
(complex regional pain
syndrome, type I, type II).
Peripherally GeneratedPain
Painfulpolyneuropathies: Pain is
felt along the distribution
of many peripheral nerves.
Examples: diabeticneuropathy, alcohol-
nutritional neuropathy, and
those associated withGuillain-Barr syndrome.
Painfulmononeuropathies:
Usually associated with a
known peripheral nerve
injury, and pain is felt at
least partly along the
distribution of the
damaged nerve. Examples:nerve root compression,
nerve entrapment,
trigeminal neuralgia.
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Pathophysiology
Pain:
Involves four physiological processes:
- Transduction
- Transmission
- Modulation
- Perception
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Noxious stimulusNSAIDSrelease of inflammatory substances
(PG, Hst, Srn, Brdks, Sub.P)
Transduction
(generation & electrical impulses)
Transmission
Pathophysiology
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Opioids Transmission(conduction by nerve fibers)
Opioids Modulation
(descending pathways)
Opioids Perception
Pathophysiology
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Nerve pathways
Ascending TractsTract Signal function
Dorsal columnsVibration, tactile sensation, conscious
proprioception
Spinocerebeller Proprioception
Spinothalamic (lateral andanterior)
Pain, temperature, itch (lateral), crude
touch (anterior)
SpinoreticularPain
Spinomesencephalic Pain
Spino-cervico-thalamic Pain (touch?)
Spinohypothalamic Pain
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Pain( neuroexcitatory)transmitter:
Glutamate, Ach, NE,Srn, Substance P
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Intervention for Pain
LA = Local Anesthesi
TENS = Transcutaneus Electric Nerve Stimulation
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Medical management of pain
WHO Ladder
1. Mild pain
NSAID + adjuvant
2. Moderate pain
weak narcotic +
NSAID + adjuvant
3. Severe pain strong narcotic +
NSAID + adjuctant
4. Regional analgesia
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Drugs Intervention for Pain
1. Non-narcotics
Simple analgetic (Paracetamol)/NSAIDs
2. Narcotics3. Adjuvant analgesic or coanalgesics
tricyclic antidepressants
antiepileptics corticosteroids
bisphosphonates
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NSAIDs
Principally have same mechanism of action
Pharmacokinetics (route of administration,
concomitance disease like peptic ulcers,impairment of kidney or liver)
Issue of side effects cox selectivity
Drug-drug interaction, drug-disease interaction
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Highly COX-1 Selective Flurbiprofen, Ketoprofen
Relatively COX-1 selective Fenoprofen, PiroxicamSulindac
Equally Selective Aspirin, Ibuprofen,Ketorolac, Indomethacin,Naproxen, Oxaprosin,Tenoxicam, Tolmetin
Relatively COX-2 Selective Diclofenac, Etodolac,
Meloxicam, Nabumetone,Nimesulide
Highly COX-2 Selective Rofecoxib, Celecoxib,
Etoricoxib, Valdecoxib,Parecoxib, Lumiracoxib
Classification of NSAIDs
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Principles ofOpioid Analgesic
Pharmacodynamic - Intrinsic Effect
Receptor :
(Mu), (Delta), and (Kappa), (Sigma)?
Full agonists, partial agonists, and antagonists
Example :
Morphine is a full agonist at the opioid receptor
Codeine functions as a partial receptor agonist
Naloxone, a strong receptorantagonist
Receptor Subtypes Location Function
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Receptor Subtypes Location Function
delta () 1, 2 Brain
opontine nuclei
oamygdala
o
olfactory bulbsodeep cortex
analgesia
antidepressant
effects
physical dependence
kappa () 1, 2, 3 Brain
ohypothalamus
operiaqueductal gray
o
claustrumspinal cord
osubstantia gelatinosa
Spinal analgesia
Sedation
Miosis
Inhibition ofADHrelease
mu () 1, 2, 3 brain
ocortex (laminae III and
IV)othalamus
operiaqueductal gray
spinal cord
osubstantia gelatinosa
1:
Supraspinalanalgesia
physical dependence2:
respiratory depression
miosis
euphoria
reduced GI motility
physical dependence
http://en.wikipedia.org/wiki/Delta_Opioid_receptorhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Ponshttp://en.wikipedia.org/wiki/Amygdalahttp://en.wikipedia.org/wiki/Olfactory_bulbshttp://en.wikipedia.org/wiki/Cerebral_cortexhttp://en.wikipedia.org/wiki/Analgesiahttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Hypothalamushttp://en.wikipedia.org/wiki/Periaqueductal_grayhttp://en.wikipedia.org/wiki/Claustrumhttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Substantia_gelatinosahttp://en.wikipedia.org/wiki/Sedationhttp://en.wikipedia.org/wiki/Miosishttp://en.wikipedia.org/wiki/Antidiuretic_hormonehttp://en.wikipedia.org/wiki/Mu_Opioid_receptorhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Cerebral_cortexhttp://en.wikipedia.org/wiki/Thalamushttp://en.wikipedia.org/wiki/Periaqueductal_grayhttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Substantia_gelatinosahttp://en.wikipedia.org/wiki/Supraspinalhttp://en.wikipedia.org/wiki/Supraspinalhttp://en.wikipedia.org/wiki/Analgesiahttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Respiratory_depressionhttp://en.wikipedia.org/wiki/Respiratory_depressionhttp://en.wikipedia.org/wiki/Miosishttp://en.wikipedia.org/wiki/Euphoriahttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Euphoriahttp://en.wikipedia.org/wiki/Miosishttp://en.wikipedia.org/wiki/Respiratory_depressionhttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Analgesiahttp://en.wikipedia.org/wiki/Supraspinalhttp://en.wikipedia.org/wiki/Substantia_gelatinosahttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Periaqueductal_grayhttp://en.wikipedia.org/wiki/Thalamushttp://en.wikipedia.org/wiki/Cerebral_cortexhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Mu_Opioid_receptorhttp://en.wikipedia.org/wiki/Antidiuretic_hormonehttp://en.wikipedia.org/wiki/Miosishttp://en.wikipedia.org/wiki/Sedationhttp://en.wikipedia.org/wiki/Substantia_gelatinosahttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Claustrumhttp://en.wikipedia.org/wiki/Periaqueductal_grayhttp://en.wikipedia.org/wiki/Hypothalamushttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Kappa_Opioid_receptorhttp://en.wikipedia.org/wiki/Physical_dependencehttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Analgesiahttp://en.wikipedia.org/wiki/Cerebral_cortexhttp://en.wikipedia.org/wiki/Olfactory_bulbshttp://en.wikipedia.org/wiki/Amygdalahttp://en.wikipedia.org/wiki/Ponshttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Delta_Opioid_receptor -
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Opiate receptor interactions
Drug Receptor
mu kappa deltaFull Agonists
Morphine +++ ++ +
Fentanyl ++++ +
Alfentanil +++ ?
Sufentanil +++++ +
Hydromorphone +++ ++
Methadone +++ ++
Meperidine ++ ++
Codeine +
Levorphanol +++ ++
Buprenorphine P +++
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Opiate receptor interactions
Drug Receptor
mu kappa delta
Mixed agonist-antagonists
Nalbuphine --- +++Pentazocine - +++
Nalorphine - P
AntagonistsNaloxone --- - -
Naltrexone --- - -
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Principles ofOpioid Analgesic
PharmacokineticsAbsorption : Most opioid well absorbed, but have first pass
metabolism effect. Interpatient variability making prediction of an
effective oral dose difficult.
Distribution : Highest concentrations in tissues that are highlyperfused such as the brain, lungs, liver, kidneys, and spleen.
Metabolism Phase 2 Metabolism (conjugation with glucuronid) : morphine
Phase 1 & 2 : heroin, remifentanil
Phase 1 : meperidine, fentanil, alfentanil, sulfentanil, codein
Excretion : Mainly in the urine, only a small portion in faeces
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Table Common Opioid AnalgesicsGeneric Name Trade
Name
Approximately
Equivalent
Dose (mg)
Oral:Parenteral
Potency Ratio
Duration
of
Analgesia
(hours)
Maximum
Efficacy
Morphine 1 10 Low 45 High
Hydromorphone Dilaudid 1.5 Low 4
5 High
Oxymorphone Numorphan 1.5 Low 34 High
Methadone Dolophine 10 High 46 High
Meperidine Demerol 60100 Medium 24 High
Fentanyl Sublimaze 0.1 Low 11.5 High
Sufentanyl Sufenta 0.02 Parenteral only 11.5 High
Alfentanil Alfenta Titrated Parenteral only 0.250.75 High
Remifentanyl Ultiva Titrated2
Parenteral only 0.053
High
Levorphanol Levo-Dromoran
23 High 45 High
Codeine 30604 High 34 Low
Hydrocodone 4 510 Medium 46 Moderate
Oxycodone1,5 Percodan 4.56 Medium 3
4 Moderate
Propoxyphene Darvon 601206
Oral only 45 Very low
Pentazocine Talwin 30506
Medium 34 Moderate
Nalbuphine Nubain 10 Parenteral only 36 High
Buprenorphine Buprenex 0.3 Low 48 High
Butorphanol Stadol 2 Parenteral only 3
4 High
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Clinical Use of Opioids
For a patient in acute severe pain, opioid analgesic
is usually considered a primary part of the overall
management plan.
Determining : route of administration (oral, parenteral, intrathecal)
duration of drug action
ceiling effect (maximal intrinsic activity)
duration of therapy
potential for adverse effects
patient's past experience with opioids
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Clinical Use of Opioids
Analgesia Pain associated with cancer and other terminal illnesses
must be treated aggressively, require continuous use ofpotent opioid analgesics tolerance & dependence.
Administer opioid regularly (not PRN) if pain is presentmost of day. A regular dose at a scheduled time is moreeffective in achieving pain relief than dosing on demand.Use controlled release preparation (morphine (MST continus),fentanyl patch transdermal)
severe pain of renal and biliary colic the drug-inducedincrease in smooth muscle tone cause a paradoxicalincrease in pain.An increase in the dose of opioid isusually successful in providing adequate analgesia.
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Clinical Use of Opioids
Acute Pulmonary Edema The relief produced by intravenous morphine
Sugessted mechanism of morphine :
reduced anxiety
reduced cardiac preload (reduced venous tone)
afterload (decreased peripheral resistance)
Morphine can be particularly useful when treating painful
myocardial ischemia with pulmonary edema
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Clinical Use of Opioids
Cough obtained at doses lower than for analgesia.
Recently the use of opioid analgesics to allay cough hasdiminished largely because a number of effectivesynthetic compounds (eg. Dextrometorphan, noscapin)have been developed that are neither analgesic noraddictive.
Diarrhea
from almost any cause can be controlled with the opioidanalgesics, but if diarrhea is associated with infectionmust not use.
Now synthetic opioid with more selective gastrointestinaleffects and few or no CNS effects, eg, diphenoxylate
(Lomotil
), loperamide are used.
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Clinical Use of Opioids
Shivering
Although all opioid agonists have some
propensity to reduce shivering, meperidine is
reported to have the most pronounced anti-shivering properties.
Meperidine blocks shivering through its action
on subtypes of the 2 adrenoceptor
vasoconstriction
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Clinical Use of Opioids
Applications in Anesthesia Frequently used as premedication before anesthesia and surgery
Also used intraoperatively both as adjuncts to other anesthetic
agents and, in high doses (eg, 0.020.075 mg/kg of fentanyl), as a
primary component.
Also be used as regional analgesics by administration into the
epidural or subarachnoid spaces of the spinal column have
demonstrated long-lasting analgesia with minimal adverse effects
(epidural administration of 35 mg of morphine, followed by slow
infusion through a catheter placed in the epidural space).
Epidural application of morphine might selectively produce
analgesia without impairment of motor, autonomic, or sensory
functions. Currently is favored ???
In rare cases, chronic pain management surgically implant a
programmable infusion pump connected to a spinal catheter for
continuous infusion of opioids or other analgesic compounds.
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Adverse Effects of Opioid
Tolerance & Dependence A strong agonist is associated w/ more severe withdrawal sign & symptoms
Tolerance develops most readily when large dose are given at short intervals.Generally manifest after 2-3 weeks of frequent exposure to ordinarytherapeutic doses.
Physical Dependence signs and symptoms : rhinorrhea, chills, gooseflesh (piloerection), hyperventil,
hypertherm, mydriasis, musc ach, vomit, diarrhea, anxiety
time of onset, intensity, duration depend on the drug.
morphine/heroin start within 610 hours after. Peak effects at 3648 hours,after that most of the signs and symptoms gradually subside.
meperidine, the withdrawal syndrome largely subsides within 24 hoursmethadone several days to reach the peak of symphtom, and last as 2 weeks
Psychologist Dependence euphoria, indifference to stimuli, and sedation (iv) promote compulsive use
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Opioid ADR Monitoring
Constipation always prescribe laxatives
Nausea/Vomiting
Metoclopramide
Ondansetron
Respiratory depression
Naloxone
Histamine release
Antihistamines
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Principles ofOpioid Analgesic Use
in Acute and Cancer Pain
Individualize route, dosage, and schedule
Administer analgesics regularly (not PRN) if
pain is present most of day Become familiar with dose / time course of
several strong opioids
Give infants / children adequate opioid dose Follow patients closely, particularly when
beginning or changing analgesic regimens
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Clinical Outcome in Pain management
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ThankYou
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