Download Neil Sandson

11/2/2011
Chronic Pain in the Patient with
Mental Health Issues
Neil B. Sandson, M.D.
Psychiatrist, Veterans Affairs Maryland
Health Care System
„ Director, Psychopharmacology Consultation
Service; Sheppard Pratt Health System
„ Clinical Associate Professor, University of
Maryland Medical School, Department of
Psychiatry
„
Core Concepts
Understand the physiologic causes and
types of chronic pain.
„ Identify mental health issues that may
produce and/or aggravate chronic pain.
„ Elucidate the interplay between mental
illness issues and physiologic issues in the
expression and experience of chronic pain.
„
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Core Concepts
„
Craft a comprehensive treatment plan that
addresses all physiologic and mental health
dimensions of the ppatient’s condition
‹ Multidisciplinary and concurrent, when
possible
‹ Communication and collegiality
‹ Monitor adherence
Chronic Pain - Classifications
General Somatic Pain
„ Visceral Pain
„ Bone Pain
„ Muscle Spasm
„ Peripheral Neuropathy
„ Vasculopathy
Vasculopathy--Induced
„ Headaches
„
Chronic Pain - Classifications
„
General Somatic Pain
‹ Skin/muscle injury or other pathology
‹ Includes fibromyalgia
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Chronic Pain - Classifications
„
Visceral Pain
‹ Pain arising from pathology involving
internal organs
 Chronic pancreatitis
 Chronic cholelithiasis
 Chronic active hepatitis
Chronic Pain - Classifications
„
Bone Pain
‹ Arthritis
‹ Osteomyelitis
‹ Osteoporosis
‹ Bone Cancer
Chronic Pain - Classifications
„
Muscle Spasms
‹ Often involved in chronic back pain
‹ Quite variable with activity
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Chronic Pain - Classifications
„
Peripheral Neuropathy
‹ Radiculopathies, like sciatica
‹ Herpetic neuralgia
‹ Diabetes
Diabetes--induced
Chronic Pain - Classifications
„
Vasculopathy-Induced
Vasculopathy‹ Basically chronic ischemic pain
 Diabetes
 Tobacco use
 Autoimmune diseases
 Claudication
Claudication--induced
 Reflex Sympathetic Dystrophy
Chronic Pain - Classifications
„
Headaches
‹ Migraine
‹ Tension
‹ Sinus
‹ Cluster
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Mental Health Issues
Depression
„ Anxiety
„ Psychosis
„ Drug/Alcohol Abuse
„
Mental Health Issues
„
Depression
‹
‹
‹
‹
‹
‹
‹
‹
‹
Dysphoria
Anhedonia
Increased/decreased sleep
Weight/appetite change
Anergia
Psychomotor changes
Poor concentration
Guilt
Suicidality
Mental Health Issues
„
Depression
‹ The PHQPHQ-9 is a quick and easy
assessment tool ideally suited to primary
care settings.
 www.agencymeddirectors.wa.gov/Files
/depressoverview.pdf
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Mental Health Issues
„
Depression
‹ Can markedly increase sensitivity to pain
and decrease ability to tolerate
discomfort.
‹ Of course, undertreated chronic pain can
produce or exacerbate depression.
Mental Health Issues
„
Anxiety
‹ Generalized Anxiety Disorder
‹ Panic Disorder with or without
agoraphobia
‹ PTSD
‹ Obsessive Compulsive Disorder
‹ Others
Mental Health Issues
„
Anxiety
‹ As with depression, anxiety symptoms
can undermine the patients ability to
participate in and/or benefit from
treatment of chronic pain, but
undertreated pain can also produce or
greatly worsen anxiety symptoms.
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Mental Health Issues
„
Psychosis
‹ Delusions
‹ Hallucinations
‹ Thought Disorder
‹ Bizarre behaviors
Mental Health Issues
„
Psychosis
‹ For obvious reasons, active psychotic
symptoms can undermine the patient
patient’ss
ability to participate in and comply with
treatment of chronic pain
‹ Undertreated pain can exacerbate
psychosis, particularly paranoia, and
associated impulsivity.
Mental Health Issues
„
Drug/Alcohol Abuse
‹ Alcohol/other sedativesedative-hypnotics (BZDs)
‹ Cocaine/stimulants
‹ Cannabis
‹ Opioids
‹ PCP/ketamine/hallucinagens
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Mental Health Issues
„
Drug/Alcohol Abuse
‹ This poses perhaps the greatest challenge
to patients and clinicians alike, because
more than any other psychiatric
comorbidity, sequalae of these illnesses
often undermine the trust at the heart of a
healthy and productive doctor
doctor--patient
relationship.
Mental Health Issues
„
Patients
‹
‹
‹
„
Will he/she really listen to and believe me?
Can I be honest with my doctor?
If I am, might he/she restrict my treatment options?
Clinicians
‹
‹
Is my patient being honest with me?
Can I trust them to adhere to treatment and not misuse
and/or divert the medications that I am providing to
them?
Mental Health Issues
„
Drug/Alcohol Abuse
‹ Pseudoaddiction: A drugdrug-seeking
behavior that simulates true addiction,
which occurs in patients with pain who
are receiving inadequate pain medication.
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Treatment
„
„
Physiologic
‹ PCP
‹ Appropriate
pp p
specialists
p
((neurology,
gy orthopedics,
p
pain service, etc.)
Mental Health
‹ Medication management (psychiatrist or NP)
with appropriate psychotherapies and
psychosocial supports
Treatment
„
Multidisciplinary Approach
‹ Shared/Group Clinics or defined Pain
Service
‹ Open lines of communications
‹ Clearly defined roles/responsibilities –
Who does what?
‹ Case conferences
Specific Topics: Drug-Drug Interactions
„
A DDI occurs when one drug exerts an influence
upon the action of another drug.
ƒ Pharmacodynamic
Pharmacodynamic:: one drug’s alteration of
another drug
drug’ss action at its intended site of
action (eg: MAOI with SSRI leads to serotonin
syndrome)
ƒ Pharmacokinetic
Pharmacokinetic:: one drug’s alteration of
another drug’s movement through the body,
often resulting in changes in blood levels
(fluoxetine added to NTP raises NTP levels).
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Specific Topics: Drug-Drug Interactions
„
Cytochrome P450 System: A family of
enzymes (usually hepatic) which performs
oxidative metabolism on a broad array
y of
substances (substrates).
‹ “Number
“Number--letter
letter--number” sequence
identifies enzyme in a manner analogous
to “family“family-genus
genus--species” for animals.
Specific Topics: Drug-Drug
Interactions
„
Substrate: An agent that is metabolized by
Substrate:
an enzyme into a metabolic end product and
eventuallyy excreted.
Specific Topics: Drug-Drug
Interactions
„
Inhibitor:: An agent which interferes with the
Inhibitor
ability of a given enzyme to metabolize a given
substrate.
‹ This is usually competitive (by a coco-substrate)
rather than nonnon-competitive (impairs enzyme
functioning).
‹ The introduction of inhibitors generally leads to
rapid increases in the blood levels of substrates.
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Specific Topics: Drug-Drug
Interactions
„
Inducer:: An agent which causes an increase
Inducer
in the production of the enzyme(s)
responsible
p
for metabolizingg a ggiven
substrate.
‹ The introduction of inducers generally
leads to gradual (1 to 3 weeks) decreases
in the blood levels of substrates.
Specific Topics: Drug-Drug
Interactions
„ Coadministration
of substrates and
inhibitors of the same enzyme leads to
increases in substrate blood levels
levels.
„ Coadministration of substrates and
inducers of the same enzyme leads to
decreases in substrate blood levels.
Specific Topics: Drug-Drug
Interactions
„
Metabolic variability
‹ Poor metabolizers (PMs): blood levels of
substrates are higher than expected at
standard doses.
 genetic polymorphisms
 acquired PM status through the
addition of an inhibitor
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Specific Topics: Drug-Drug
Interactions
„
Metabolic variability
‹ Extensive (rapid) metabolizers – normal
 significant variability even within the
bounds of “normal” – 10
10--30
30--fold
variations in efficiency of 3A4 function
without polymorphisms
Specific Topics: Drug-Drug
Interactions
„
Metabolic variability
‹ Ultraextensive/ultrarapid metabolizers
(UEMs): blood levels of substrates are
lower than expected at standard doses.
 extra allelic copies of the wildwild-type
enzyme
Specific Topics: Drug-Drug
Interactions
„
Phase II metabolism: Also referred to as
glucuronidation, this is the “capstone” to phase I
(P450) metabolism. It increases the hydrophilicity
off metabolites
t b lit andd thus
th makes
k them
th more readily
dil
excretable.
‹ There are substrates, inhibitors, and inducers,
just like P450.
‹ “UGT” is the main phase II enzyme system
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Specific Topics: Drug-Drug
Interactions
„
„
Nonnarcotic analgesics
‹ Cyclooxygenase
Cyclooxygenase--2 (COX(COX-2) Inhibitors
‹ Aspirin
‹ Acetaminophen
‹ Nonsteroidal Anti
Anti--Inflammatory Drugs (NSAIDs
(NSAIDs))
Narcotic analgesics
‹ Phenylpiperidines
‹ Morphine and related compounds
‹ Methadone, Propoxyphene,
Propoxyphene, and Tramadol
Nonnarcotic Analgesics
„
COX-2 Inhibitors
COX‹ Celecoxib (Celebrex)
 Metabolized by: 2C9
2C9, unspecified
UGTs
 Inhibits: 2D6
 Induces: None
Nonnarcotic Analgesics
„
COX-2 Inhibitors
COX‹ Diclofenac (Voltaren)
 Metabolized by: 2C9, 3A4, UGT 1A9, UGT
2B7 (to
(t hepatotoxic
h t t i metabolite)
t b lit )
 Inhibits: UGT 2B7
 Induces: None
 DDI issues: PMs for 2C9 or
coadministration of 2C9 inhibitors increases
hepatotoxicity via increased use of UGT 2B7
pathway.
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Nonnarcotic Analgesics
„
COX-2 Inhibitors
COX‹ Etodolac (Lodine)
 Metabolized by: 2C9
2C9, UGT 1A9
 Inhibits: 2C9 (weak)
 Induces: None
Nonnarcotic Analgesics
„
COX-2 Inhibitors
COX‹ Meloxicam (Mobic)
 Metabolized by: 2C9
2C9, 3A4
 Inhibits: 2C9, 3A4
 Induces: None
Nonnarcotic Analgesics
„
COX-2 Inhibitors
COX‹ Nabumetone (Relafen)
 Pro
Pro--drug
 Metabolized by: unspecified phase I
enzyme and unspecified UGTs
 Inhibits: None
 Induces: None
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Nonnarcotic Analgesics
„
Aspirin
‹ Pro
Pro--drug
‹ Metabolized by:
y deacetylation
y
to salicylic
y acid,
which is then metabolized by UGT 2B7 and
other UGTs, as well as glycine conjugation
‹ Inhibits: UGT 2B7, betabeta-oxidation, possibly
other UGTS (all via salicylic acid)
‹ Induces: None
Nonnarcotic Analgesics
„
Aspirin
‹ DDI issues: Coadministration (at least
325 mg/day) with VPA can increase free
VPA levels more than 44-fold.
Nonnarcotic Analgesics
„
Acetaminophen
‹ Metabolized by: UGTs 1A1, 1A6, 1A9,
2B15; sulfation; 2E1, 3A4, and 1A2
‹ Inhibits: None
‹ Induces: None
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Nonnarcotic Analgesics
„
NSAIDs
‹ Diflunisal (Dolobid)
‹ Fenoprofen
p
(Nalfon)
(
)
‹ Flurbiprofen (Ansaid)
‹ Ibuprofen (Advil, Motrin)
‹ Indomethacin (Indocin)
‹ Ketoprofen (Actron, Orudis)
‹ Ketorolac (Toradol)
Nonnarcotic Analgesics
„
NSAIDs (cont)
‹ Meclofenamate (Meclomen)
‹ Mefenamic Acid (
(Ponstel))
‹ Naproxen (Aleve, Naprosyn)
‹ Oxaprozin (Daypro)
‹ Piroxicam (Feldene)
‹ Sulindac (Clinoril)
‹ Tolmentin (Tolectin)
Nonnarcotic Analgesics
„
NSAIDs
‹ Metabolized by:
 Generally 2C9
• Except for: tolmentin (3A4), diflunisal,
fenoprofen, and sulindac
 Generally UGT 2B7
‹ Inhibits: Generally UGT 2B7
 Except for: flurbiprofen, ketorolac.
oxaprozin, piroxicam, and tolmentin, none of
which inhibits any enzymes
‹ Induces: None
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Nonnarcotic Analgesics
„
NSAIDs
‹ DDI issues
 All 2C9 inhibiting NSAIDs can raise
free PHT levels.
 All NSAIDs, except for aspirin and
sulindac, can raise lithium levels (20%
to 200%).
Narcotic Analgesics
„
Phenylpiperidines
‹ Fentanyl (Duragesic)
‹ Meperidone (Demerol)
Narcotic Analgesics
„
Fentanyl
‹ Metabolized by: 3A4
‹ Inhibits: 3A4
‹ Induces: None
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Narcotic Analgesics
„
Meperedine
‹ Metabolized by: 2B6, 3A4, 2C19, possibly
some UGTs
‹ Inhibits:
I hibit None
N
‹ Induces: None
‹ DDI issues: Coadministration of 3A4 inducers
can lead to increased production of the longlonglived, neurotoxic, normeperidine metabolite.
There are known cases with chronic ritonavir
and phenobarbital.
Narcotic Analgesics
„
Morphine and related compounds
‹ Buprenorphine (Buprenex)
‹ Codeine
‹ Hydrocodone (Vicodin - with acetaminophen)
‹ Hydromorphone (Dilaudid)
‹ Morphine
‹ Oxycodone (Oxycontin)
Narcotic Analgesics
„
Buprenorphine
‹ Metabolized by: 3A4, UGT 2B7, UGT 1A3
‹ Inhibits: None
‹ Induces: None
‹ DDI issues: When coadministered with narcotic
analgesics, it is likely to displace them from mu
receptors and reduce analgesic efficacy.
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Narcotic Analgesics
„
Codeine
‹ Pro
Pro--drug
‹ Metabolized by: 2D6 (into morphine), 3A4,
UGT 2B7 (80%)
‹ Inhibits: UGT 2B7
‹ Induces: None
‹ DDI issues: Coadministration with 2D6
inhibitors, or 2D6 PM status, is likely to impair
the conversion to morphine and reduce
analgesic efficacy.
Narcotic Analgesics
„
Hydrocodone
‹ Pro
Pro--drug
‹ Metabolized by: 2D6 (into hydromorphone),
3A4
‹ Inhibits: None
‹ Induces: None
‹ DDI issues: Coadministration with 2D6
inhibitors, or 2D6 PM status, is likely to impair
the conversion to hydromorphone and reduce
analgesic efficacy.
Narcotic Analgesics
„
Hydromorphone
‹ Metabolized by: 2D6, 3A4, UGT 1A3,
UGT 2B7, possibly other UGTs
‹ Inhibits: None
‹ Induces: None
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Narcotic Analgesics
„
Morphine
‹ Metabolized by: UGT 2B7, UGT 1A3,
slightly by 3A4 and 2D6
‹ Inhibits: UGT 2B7
‹ Induces: None
Narcotic Analgesics
„
Morphine
‹ DDI issues: UGT 2B7 converts morphine into
morphine--6-glucuronide (M6G), which is, in
morphine
vitro, 50 times more potent as a mu agonist than
parent morphine. It is theoretically possible,
but as yet not demonstrated, that
coadministration of UGT 2B7 inhibitors (such
as most NSAIDs) could impair morphine’s
analgesic efficacy.
Narcotic Analgesics
„
Oxycodone
‹ Metabolized by: 2D6, 3A4, metabolites
then by UGT 2B7
‹ Inhibits: None
‹ Induces: None
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Narcotic Analgesics
„
Methadone
‹ Metabolized by: 3A4, 2B6, 2D6 (minor)
‹ Inhibits: 2D6, 3A4, UGT 2B7
‹ Induces: None
‹ DDI issues
 Beware coadministration with inhibitors or
inducers of 3A4 (or 2B6).
 Beware coadministration with other QT
prolongers.
Narcotic Analgesics
„
Tramadol
‹ Pro
Pro--drug
‹ Metabolized by: 2D6 (into M1)
M1), 3A4,
3A4
2B6, unspecified UGTs
‹ Inhibits: None
‹ Induces: None
Narcotic Analgesics
„
Tramadol
‹ DDI issues
 Coadministration with 2D6 inhibitors, or
2D6 PM status,
t t iis lik
likely
l to
t impair
i
i the
th
conversion to M1 and reduce analgesic
efficacy, as well as further lower the seizure
threshold.
 Coadministration with other serotonergic
agents may predispose to serotonin
syndrome, but this is not overwhelmingly
likely.
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Other Analgesic Agents
Gabapentin (Neurontin)
„ Duloxetine (Cymbalta)
„ Venlafaxine (Effexor)
„ TCAs
„ Pregabalin (Lyrica)
„
Other Analgesic Agents
„
Gabapentin
‹ Metabolized by: None -- purely renally
excreted
‹ Inhibits: None
‹ Induces: None
Other Analgesic Agents
„
Duloxetine
‹ Metabolized by: 1A2, 2D6
‹ Inhibits: 2D6
‹ Induces: None
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Other Analgesic Agents
„
Venlafaxine
‹ Metabolized by: 2D6 (major), 3A4 and
2C19 (minor)
‹ Inhibits: 2D6 (weak)
‹ Induces: None
Other Analgesic Agents
„
TCAs
‹ Metabolized by: 2D6 (all); 2C19, 3A4, and 1A2
(tertiary amines)
‹ Inhibits:
I hibit 2D6 ((mild
ild to
t moderate),
d t ) mild
ild
inhibition of assorted P450s depending on
which specific TCA is considered
‹ Induces: None
‹ DDI issues: low therapeutic index, caution with
2D6 and other inhibitors.
Other Analgesic Agents
„
Pregabalin
‹ Metabolized by: very little – mostly
excreted unchanged
‹ Inhibits: none
‹ Induces: none
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Meet the Enzymes
3A4
„ 2D6
„ 1A2
„ 2C9
„ 2C19
„ 2E1
„ 2B6
„
3A4
„
Notable substrates
‹
alprazolam
carbamazepine
calcium channel blockers
clopidogrel
cyclosporin/tacrolimus
ethinylestradiol/progesterone
several “statins” – atorvastatin, lovastatin, and
simvastatin
steroid compounds
tertiary amine TCAs (IMI, AMI, etc.)
‹
zolpidem/zaleplon
‹
‹
‹
‹
‹
‹
‹
‹
3A4
„
Notable inhibitors
‹ azole antifungals
‹ cimetidine
‹ ciprofloxacin/norfloxacin
‹ diltiazem/verapamil
‹ fluoxetine/fluvoxamine
‹ grapefruit juice
‹ HIV protease inhibitors
‹ macrolide antibiotics (except azithromycin)
‹ nefazodone
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3A4
„
Notable inducers
‹ barbiturates
‹ carbamazepine
‹ modafinil
‹ oxcarbazepine (for ethinyl estradiol only)
‹ phenytoin
‹ rifampin
‹ ritonavir
‹ St. John’s wort
‹ topiramate
2D6
„
Notable substrates
‹ ß-blockers
‹ codeine → morphine
p
‹ hydrocodone → hydromorphone
‹ risperidone → 9-OH risperidone (paliperidone)
‹ tamoxifen → 4-hydroxytamoxifen (endoxifen)
‹ TCAs
‹ tramadol → M1
2D6
„
Notable inhibitors
‹ bupropion
‹ cimetidine
‹ duloxetine
‹ fluoxetine
‹ paroxetine
‹ quinidine
‹ ritonavir
‹ sertraline (>150 mg/d)
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2D6
„
No known inducers
1A2
„
Notable substrates
‹ caffeine (and other xanthines, like
theophylline)
‹ clozapine
‹ cyclobenzaprine
‹ olanzapine
1A2
„
Notable inhibitors
‹ caffeine
‹ cimetidine
‹ ethinylestradiol
‹ fluoroquinolones
‹ fluvoxamine
‹ grapefruit juice
‹ ticlopidine
‹ zafirlukast
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1A2
„
Notable inducers
‹ large amounts of cruciferous vegetables
(broccoli, brussel sprouts, cauliflower,
etc.) or charchar-grilled meats
‹ carbamazepine
‹ rifampin
‹ tobacco smoking
2C9
„
Notable substrates
‹ glipizide/glyburide
‹ phenytoin
‹ S-warfarin
2C9
„
Notable inhibitors
‹ cimetidine
‹ clopidogrel
‹ fluconazole
‹ fluoxetine/fluvoxamine
‹ metronidazole
‹ ritonavir
‹ sulfamethoxazole
‹ valproate
‹ zafirlukast
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2C9
„
Notable inducers
‹ carbamazepine
‹ phenobarbital
‹ phenytoin
‹ rifampin
2C19
„
Notable substrates
‹ diazepam
‹ phenytoin
‹ tertiary amine TCAs
2C19
„
Notable inhibitors
‹ cimetidine
‹ disulfiram
‹ ethinylestradiol
‹ fluoxetine
‹ fluvoxamine
‹ modafinil
‹ omeprazole
‹ ritonavir
‹ topiramate
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2C19
„
Notable inducers (same as 2C9)
‹ carbamazepine
‹ phenobarbital
‹ phenytoin
‹ rifampin
2E1
„
Notable substrates
‹ acetaminophen
‹ ethanol
2E1
„
Notable inhibitors
‹ disulfiram
‹ isoniazid
‹ watercress
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2E1
„
Notable inducers
‹ chronic ethanol use (leads to increased
hepatotoxicity following acetaminophen OD
due to increased production of NAPQI).
‹ isoniazid
‹ obesity
‹ retinoids
‹ tobacco smoking
2B6
„
Notable substrates
‹ bupropion
‹ cyclophosphamide/ifosfamide
‹ tamoxifen
2B6
„
Notable inhibitors
‹ fluoxetine
‹ fluvoxamine
‹ nefazodone
‹ paroxetine
‹ sertraline
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2B6
„
Notable inducers
‹ phenobarbital
‹ phenytoin
‹ rifampin
Phase II Metabolism
„
Notable substrates
‹ lamotrigine
‹ olanzapine
‹ several NSAIDs
‹ morphine
‹ codeine
‹ bilirubin
‹ AZT
‹ valproate
Phase II Metabolism
„
Notable Inhibitors
‹ valproate
‹ probenecid
‹ sertraline
‹ milk thistle
‹ significant competitive inhibition with
other substrates
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Phase II Metabolism
„
Notable Inducers
‹ phenobarbital
‹ carbamazepine
‹ phenytoin
‹ ethinylestradiol
‹ oxcarbazepine
‹ rifampin
Case Vignettes
Sad and Sore
„ More Bang for the Buck
„ The Tremulous Triathlete
„ Gradual Withdrawal
„
Case Vignettes
„
Sad and Sore
‹ Fluoxetine was added to hydrocodone.
‹ 2D6 was inhibited.
‹ Hydrocodone was not able to be
metabolized into hydromorphone.
‹ Loss of analgesia resulted.
‹ Analgesia returned with removal of
fluoxetine.
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Case Vignettes
„
More Bang for the Buck
‹ A patient was given small doses of codeine for
a cough due to bilateral pneumonia, soon after
which the patient developed lifelife-threatening
opioid intoxication.
‹ Genotyping revealed 3 or more functional
alleles for 2D6 (UM phenotype).
‹ Codeine → morphine via 2D6
‹ Codeine + 2D6 UM phenotype can yield
increases in morphine levels up to 800%!
Case Vignettes
„
The Tremulous Triathlete
‹ Indomethacin was added to lithium.
‹ Inhibition of p
prostaglandin
g
synthesis
y
interfered with the excretion of lithium.
‹ The lithium level increased significantly
(about 50% in this case), resulting in
polyuria, feeling “spacey”, and tremor.
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Case Vignettes
„
Gradual Withdrawal
‹ Carbamazepine was added to chronic
methadone.
‹ 3A4 was induced.
i d d
‹ The blood level of methadone decreased
significantly (by about 60%).
‹ Opioid withdrawal resulted.
‹ This could also have occurred if PHT or
phenobarbital was added to methadone.
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
The most vexing issue is whether, and
under what conditions, to administer
narcotic analgesics
g
to ppatients with
comorbid drug/alcohol abuse.
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
What are the problems?
‹ Abuse
‹ Diversion
‹ Overdose
 suicide
 inadvertent
‹ Interactions with drugs and alcohol
 CNS depression, arrhythmias, etc.
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11/2/2011
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
Prudent Measures
‹ When possible, obtain objective evidence of
physiologic derangements that would justify
administration of narcotic analgesics.
‹ Treatment “contracts”
 Critical component: Patient will report
inadequate tx of pain, anxiety, etc., rather
than unilaterally pursue “self“self-treatment”
‹ Drug/alcohol screens – frequent and random
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
Warning Signs
‹ Premature refills
‹ Loss/destruction of meds
‹ Excessive somnolence
‹ Marked changes in manifest symptoms when pt
is unaware of being observed vs. aware of such
observation, protean symptoms, etc.
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
What to do if “irregularities” emerge
‹ Explore concerns with the patient
‹ Check area pharmacy records
‹ Increase intensity of monitoring
‹ If safety issues are too compelling or if
clear abuse/diversion is occurring, then
taper and discontinue narcotic analgesics.
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11/2/2011
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
Key consideration
‹ If we underunder-treat the pain and anxiety of our
patients, we make it quite difficult for them to
comply with our treatment contracts.
Therefore, if/when irregularities emerge, we
need to ask ourselves the question, are these
irregularities potentially attributable to such
under--treatment?
under
Specific Topics – Comorbid
Chronic Pain and Drugs/Alcohol
„
Corollary Ethical Consideration
‹ All other things being equal, as clinicians, what
is our more compelling ethical imperative?
 To minimize underunder-treatment, even if we
thus run a greater risk of allowing abuse and
diversion to occur, OR
 To minimize the risk of abuse and diversion,
even if we thus run a greater risk of underundertreating our patients.
DDI References
„
Clinical Manual of Drug Interaction
Principles for Medical Practice, by Gary
Wynn,
y
M.D., Jessica Oesterheld, M.D.,
Kelly Cozza, M.D., and Scott Armstrong,
M.D.
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11/2/2011
DDI References
„
„
„
„
Drug-Drug Interaction Primer: A Compendium of
DrugCase Vignettes for the Practicing Clinician, by
Neil Sandson, M.D.
Dr. Oesterheld’s site is at:
http://www.mhc.com/Cytochromes
DDI program is at www.genelex.com
Pub med is at:
http://www.ncbi.nlm.nih.gov/pubmed
DDI References
„
Dr. Flockhart’s site is at: www.drug
www.drug-interactions.com (hyperlinks to pub med)
„
The Physicians’
y
Desk Reference online is at:
www.pdr.net
Existing drug interaction programs (ePocrates,
ePocrates RxPro, MICROMEDEX, etc.) are not
great (in my humble opinion), but they are a good
deal better than nothing.
„
Take-home message
Calculated risks of abuse are taken in order to
preserve higher values.
Warren E. Burger
37