Pharmacology Update of Pain

Relievers and Other

Controlled Substances
Dr. Elizabeth VandeWaa, Ph.D.
University of South Alabama
College of Nursing
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Prescribing Problematic Drugs
• Drugs for pain--Opiates
• Drugs for anxiety, insomnia—BZDs, BZD-like
• Drugs for weight loss--Stimulants
• Other controlled substances that have “gains”
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Controlled Substances
• Any drug whose use is controlled by the
Federal Government.
• Drugs are put into Schedules I-V depending on
abuse potential
 Controlled Substances Act of 1970
• All Schedule II prescriptions must be written in
ink
– Dated the same day as signed, no refills
• DEA number
• Drugs in Schedules III-V may not be filled after 6
months after issuance of prescription
• Dynamic? Static? No State may place something
lower in the schedule than the Feds have
 CSA and DEA
• The DEA regulates every step of controlled
substances—from manufacture to dispensing
• The goal is to prevent diversion from legitimate use
• States may require more stringent regulations than
the Controlled Substance Act mandates
• Federal law governing the issuance and filling of
prescriptions can be found in the Code of Federal
Regulations, Title 21, Section 1306 and the United
States Code (USC) - Controlled Substances Act, Title
21, Section 829.
 Orders for Controlled Substances
• Must be issued for legitimate medical
purposes
• By a practitioner in the usual course of his/her
professional practice
• Not for self-use
– Even if this is not mandated by law
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
In 1900…the Magic Ingredient?
Morphine! Available OTC
 Why Opiates Are Controlled
• Abuse/Overuse potential
• Danger of use--REMS
• Side effects/Toxicities
• Diversion
• Physical and psychological addiction
• Bridging
 Assessment of Pain
• Evaluate prior to opioid administration and about 1 h
after
• Assess pain location, type of pain (dull, sharp,
stabbing, throbbing, etc.), what makes pain better,
worse, how pain changes with time.
• Some patients over-report (drug seekers)
• Some patient under-report (fear of addiction, fear of
treatment, feel a need to be stoic, men—to female
HCP, etc.).
 Types of Pain
• Acute Pain: Recent onset, transient, from an
identifiable cause.
• Chronic Pain: Persistent or recurrent; lasting beyond
the usual course of illness or injury or more than 3-6
months, and which adversely affects the individual’s
well-being.
• Breakthrough or Flare-up Pain: transient pain which
is severe or excruciating; unpredictable. May
indicate changes in underlying disease.
 Actions of the Opioids
• Opioids decrease the release of inflammatory
mediators from C fibers presynaptically.
• They reduce activity of interneurons, dendrites, and
output neurons in the pain pathway.
• They inhibit neuronal activity via GABAergic
pathways in the substantia gelatinosa. All of
these reduce ascending pain
transmission
 Actions of the Opioids
• Opioids relieve pain by binding to the mu
receptor. Endogenous opiates (enkephalins,
endorphins, dynorphins) stimulate this
receptor as well and modulate the pain
response.
• Opioids are better at relieving dull, chronic
pain than sharp, acute pain. Sharper pain
needs higher doses.
 Actions of the Opioids
• Analgesia
• Euphoria
• Sedation
• Cough suppression
• Biliary colic
• Emesis
• Elevation of ICP
• Miosis
• Neurotoxicity
• Hormonal changes with prolonged use
– Highlighted items are often associated with opiate side effects
 Precautions--General
• Decreased respiratory reserve—use with caution in
COPD (low dose), or in patient taking other meds
that decrease respiratory rate
• Pregnancy
• Labor and delivery—watch respiration
• Head injury—watch respiration with increased ICP
• Infants and elderly
• Hypotensive patient or patient with reduced blood
volume
 Risk Factors Associated With
Chronic Opioid Use
• In the patient using these for chronic non-
cancer pain
• Tolerance/poor pain control
• Hyperalgesia
• Physical dependence
• Abuse
• Toxicity
 Opioid Tolerance
• With prolonged opioid exposure, cellular adaptations
occur that make the drug less effective than it
previously was. Tolerance develops to sedation,
analgesia, and euphoria.
• Some tolerance is also seen to respiratory
depression.
• No tolerance to miosis or constipation.
• Cross-tolerance is seen to all opioid agonists.
– Decreased sensitivity to opioids
 Hyperalgesia
• Emergence of a new pain syndrome refractory
to treatment
• Seen with prolonged opioid use
• Atypical, unrelated to original pain
– Abnormal sensitivity to both painful and
nonpainful stimuli
– Increased sensitivity to pain
 Physical Dependence
and the Opioids
• Defined as the presence of an abstinence
syndrome if the drug is discontinued.
• Body now requires the presence of the
drug in order to function normally.
• Usually takes about 3 weeks of regular
use, but may be seen earlier
 Physical Dependence
and the Opioids
• Begins about 10 hours after last dose with
symptoms of yawning, rhinorrhea, sweating.
Then anorexia, irritability, tremor, gooseflesh.
Peaks with violent sneezing, weakness, NVD,
muscle spasms (legs). May last for 7-10 days,
and is rarely life-threatening.
• Withdrawal can be lessened by tapering
doses; is rarely seen in patients receiving
acute treatment.
 Bridging--Defined
• Patients addicted to prescription (or illicit)
opiates or sedatives may use other
prescription opiates to minimize symptoms of
withdrawal until they can once again get their
drug of choice
– Tolerance and potential overdose are outcomes
– Commonly abused bridging agents include
Methadone, Buprenorphine and Tramadol
• Sedatives becoming common bridging agents, too
 Risk Factors for Opioid Abuse
• Family history of substance abuse
• Serving time in prison
• Living in poor, rural environment
• Younger age
• Male gender
• White race
• Pain-related functional limitations
• PTSD or mental illness
– N. Sehgal, J. Colson and H.S. Smith (2013). Expert Rev. Neurother. 13:1201-1220.
 Opioid Overdose/Toxicity
• Overdose presents with a triad of symptoms
– Coma—may be profound
– Respiratory depression—may be as low as 2-4
breaths/min
– Pinpoint pupils—may dilate as hypoxia sets in
• Treatment is ventilatory support and naloxone
 Opioid Overdose
• Most opioid-related deaths are due to
increased use of hydrocodone, oxycodone and
methadone
• Chronic pain patients on long-term therapy
and those with non-medical use are at highest
risk
• Predisposing factors include concomitant use
of CNS depressants, sleep apnea, obesity,
substance abuse
 Death Due to Opioid Overdose
• Most deaths occur at night and often in
patients with comorbid CV, respiratory,
cerebrovascular disorder
– Initiate opioid at lowest possible dose!
• Sudden death is due to cardiotoxicity
– Prolongation of QT is seen with methadone, ER
Morphine, Buprenorphine
– For methadone, a screening EKG is necessary,
repeat at 1 mo, then yearly
 REMS
• Risk Evaluation and Mitigation Strategies are a
way to decrease adverse outcomes with these
drugs. They include:
• Medication guides with pertinent patient
information
• Black box warnings to alert the prescriber to
potentially harmful side effects
• Additional prescriber education, if needed
– For instance, “Dear Prescriber” letters, drug-
company-sponsored education, pharmacy registration
 Risk Evaluation and
Mitigation Strategies
• REMS is a way to decrease the risks associated
with long-term opiate use/abuse—long-acting
drugs were included first
– Morphone, morphine SR, hydromorphone ER,
methadone, oxycodone CR, oxymorphone ER,
transdermal fentanyl and transdermal
buprenorphine, morphine/naltrexone ER
– IR opiates have since been included in REMS
 Classification of Drugs That Act
at Opiate Receptors
• Pure Agonists: Activate mu and kappa receptors.
Produce analgesia, sedation, euphoria, respiratory
depression, physical dependence, constipation, and
cough suppression.
• Partial Agonists: Produce analgesia in the opiate
naïve patient; withdrawal in the opiate user.
• Antagonists: Block the mu and kappa receptors to
cause a reversal of sedation and respiratory
depression caused by opioid overdose.
 Morphine
• 11 formulations available
– Controlled release (MS Contin, Oramorph), extended
release (Avinza), sustained release (Kadian), standard PO
solution (MSIR), concentrated PO solution (Roxanol)
• Advise patient NO ALCOHOL with extended or sustained release
preps as this enhances drug delivery to dangerous levels
– Rectal suppositories (RMS)
– Standard solution for injection (Astramorph, Duramorph,
Infumorph)
– Soluble tablets for injection
– Extended liposomal tablets for injection (DepoDur)
 Morphine
• 11 formulations available
– First-pass effect after PO administration is
extensive, hence PO doses are large. Doses are
individualized. Avinza given every 24 h.
– IM and SubQ routes unreliable and should be
avoided.
– IV injection should be done slowly to minimize
hypotension.
– Epidural route preferred to intrathecal.
 Fentanyl
• Preparations include Sublimaze, Duragesic,
Actiq, Fentora, Abstral, Lazanda, Onsolis
• Potency is 100 x that of morphine!
• Parenteral—Sublimaze, Alfentanil, Sufantanil,
Remifentanil
– Used for induction and maintenance of anesthesia
• Transdermal (Duragesic)
– Patch applied to upper torso, reaching effective
levels within 24 h.
 Fentanyl
• Using the Duragesic Patch
– Indicated for severe, persistent pain in the opioid tolerant
patient
– Not for use in children <2 years old, or in adults weighing
less than 110 pounds
– Patch sizes include 12, 25, 50, 75, 100 mcg/hr delivery
systems—use smallest effective patch and monitor
respirations!!
– Do not apply heat to patch.
– Treat breakthrough pain with short-acting opioid
 Immediate Release Opioids
• Fentanyl Products (Abstral, Onsolis, Actiq, Fentora)
– The transmucosal products are ONLY approved for
those 18 years and older who are opiate tolerant
• Taking for one week or longer, 60 mg PO morphine/day, or
30 mg PO oxycodone/day, or 25 mg PO oxymorphone/day,
or 8 mg PO hydromorphone/day, or 25 mcg fentanyl/hr.
• Not approved for acute pain
• May cause respiratory depression and/or shock in opiate-
naïve patients
• Are not interchangeable with each other on a mg-for-mg
basis!
 Fentanyl
• Using Actiq—transmucosal fentanyl
– Available as 200, 400, 600, 800, 1200, and 1600 mcg strengths.
– Approved ONLY for breakthrough cancer pain in OPIOID TOLERANT
(needing more than 60 mg morphine/day) patients.
– Patients should suck on lozenge—some will be absorbed thru mucosa,
some across GI tract.
– Start with 200 mcg unit; if pain persists, patient may have another 15
min after the first.
• Using Fentora—buccal fentanyl
– Same indications as above but the two are not interchangeable
– Absorption is more complete
– Follow dosing directions when switching patient from one formulation
to the other
– Place between cheek and gum near rear molar
– Initial dosage should be 100 mcg
 Other Formulations
• Abstral—Fentanyl sublingual tablet is available
only through enrollment in ABSTRAL REMS
program
• Onsolis—buccal film is available only through
enrollment in the FOCUS program
 Label Changes to the Opioids--IR
Products Recently Added to REMS
• Fentanyl Products
• Approved products with the brand names
Abstral, Actiq, Fentora, Lazanda, Onsolis
– Indicated to treat cancer breakthrough pain in
opioid-tolerant patients
• Added to REMS because of high home use and
high potential for abuse or accidental misuse
 Codeine
• For mild to moderate pain. 30 mg produces
about as much pain relief as 325 mg
acetaminophen. But together…
• Cough suppression dose is 10 mg.
• Alone, codeine is Schedule II; in combination,
often a Schedule III. In cough medicines, often
a Schedule V.
– Codeine metabolism….be careful!!!
• Ultra-rapid metabolizers are extremely sensitive
 Oxycodone
• Available alone in immediate release and controlled
release tablets; as PO solution; in combination with
aspirin (Percodan), acetaminophen (Percocet) and
ibuprofen (Combunox). All formulations are
Schedule II.
• OxyContin is to be dosed q 12 h and is NOT PRN.
• Abusers crush OxyContin and snort powder or
dissolve it for injection.
– Newer formulations form gelatinous substance, making
this difficult
 Other Oxycodone Formulations
• “Abuse-Proof” formulations include ER oxycodone
reformulated with plastic polymer that transforms
into a viscous gel when in contact with most solvents
• IR Oxycodone (Oxecta) that contains proprietary
aversive agents should the drug be crushed and
snorted
• Xartemis XR—extended release oxycodone (7.5 mg)
plus acetaminophen (325 mg) for acute pain
• Several other forms of oxycodone with abuse
deterrent technologies are in development
 Hydrocodone
• Available as Vicodin, Vicoprofen, Norco, Xodol
and in many other formulations including
cough syrups (Tussionex)
• All are currently Schedule II drugs
 Hydrocodone ER
• Hydrocodone ER
– Available in 10, 15, 20, 30, 40, 50 mg strengths
– Schedule II CS
– Reserved for patients for whom other pain
medications are not tolerated, are not an option,
are inadequate to provide pain relief
• Not indicated for prn pain relief
• Opioid naïve—10 mg every 12 h
• Opioid tolerant—50 mg or total daily dose of 80 mg
– BBW for respiratory depression, abuse potential,
REMS
 Hydrocodone ER
• Zohydro—sustained-release hydrocodone
with NO abuse-deterrent properties
– Several groups are calling for its approval to be
revoked
– 2 tablets could cause fatal respiratory depression
in the opiate-naïve individual
– 1 tablet could be fatal in a child
 Meperidine
• Meperidine (Demerol) is available for PO, IV,
IM, or subQ use.
• Use is declining due to frequent dosing (q 4 h),
many drug-drug interactions, and the
potential for accumulation of normeperidine,
a toxic drug metabolite. Avoid use in the
elderly. Treatment should not exceed 48 h.
 Methadone
• Used 2% of the time for pain relief
• Responsible for 33% of deaths due to opioid
overdose
• Patient monitoring, dose adherence, tapering,
cardiac toxicity should all be part of prescribing
education
– Watch with CYP3A4 inhibitors!
• On the Preferred Drug List in 33 states for
publically funded health care
 Methadone
• Methadone (Dolophine, Methadose) is
available for PO, IM, and subQ use.
• Analgesic dose is 2.5-20 mg repeated q 3-4 h
PRN.
– Significantly more potent with repeated dosing
due to active metabolite
• One of the most widely abused opiates.
• When used for detox or maintenance, will
cause tolerance to ALL opiates
 Use Caution With Methadone
And…
• Levels of methadone may be increased in
patients who are also taking:
– Azole antifungals, amphetamines,
antipsychotics, ciprofloxacin, CYP3A4
inhibitors, CYP2B6 inhibitors, MAOIs,
Interferons, SSRIs, Succinylcholine, grapefruit
juice.
• Screening EKG; repeat at 1 mo and then
annually
 Hydromorphone, Levorphanol,
Oxymorphone
• Hydromorphone (Dilaudid)
– ER tablet under development in the US
• Levorphanol (Levo-Dromoran)
– Abuse-proof tablet under development
• Oxymorphone (Numorphan)
• All Schedule II for moderate to severe pain.
• Watch for respiratory depression, miosis,
constipation
 Pentazocine
• Partial agonist, so indicated for mild to moderate
pain. Agonist at kappa receptors, but antagonist at
mu receptors.
• Get sedation, analgesia, limited respiratory
depression, but no euphoria.
– Schedule IV
• Will precipitate withdrawal in an addicted patient
• Available as PO preps (Talwin, Talwin Compound,
Talacen)and Talwin for IM, IV, or subQ injection.
 Butorphanol, Nalbuphine
• Butorphanol (Stadol) may be given IM and IV,
or by nasal spray. Schedule IV. Increases
cardiac work, so avoid in MI patient.
• Nalbuphine (Nubain) is given by IV, IM, or
subQ injection. Low abuse potential so it is
not a CS.
 Buprenorphine
• Buprenorphine (Buprenex, Butrans, Subutex,
Suboxone) is a partial agonist at mu receptors
and an antagonist at kappa receptors.
– May cause dependence; Schedule III.
– Tolerance does not seem to develop.
– Buprenex by injection IM or IV
– Subutex or Suboxone SL for management of
opioid addiction
 Buprenorphine (Butrans)
• Transdermal for moderate to severe pain
• Applied once every seven days to hairless area
• 5, 10, 20 mcg/hr patches.
• Eight application sites: upper side of chest,
upper back, upper front of chest, upper outer
arm—right and left sides of body. Sites must be
rotated. No site reused within 21 days.
• Breakthrough pain managed with
acetaminophen, NSAID or short-acting opioid.
 Opioid Antagonists--Considerations
• Main uses are treatment of opioid overdose,
reversal of post-op opioid effects, and
management of opioid addiction.
• Preps available include Naloxone (Narcan),
Naltrexone (ReVia, Vivitrol), Methylnaltrexone
(Relistor) and Alvimopan (Entereg)
• Reverse analgesia, sedation, euphoria,
respiratory depression, constipation
 News About Opioid Antagonists
• Naloxone Auto-Injector Pen (Evzio) was fast-
tracked through FDA approval process for use
to rapidly reduce overdose of prescription or
illicit opioids
• Family member/caregiver follows step-by-step
instructions via audio recording
– State rules may affect prescribing
– Some states claiming they will not make the drug
available
Naloxone Auto-Injector
 Drug Interactions with the Opioids
• CNS Depressants
– Barbiturates, benzodiazepines, alcohol
– Intensify sedation and respiratory depression caused
by opioids
– Some opioids “dose dump” when combined with
alcohol (Avinza, Embeda, Nucynta, Opana)
• Anticholinergics
– Antihistamines, TCAs, OTCs
– Worsen constipation, sedation and urinary retention
caused by opioids
 Drug Interactions with the Opioids
• Hypotensive Drugs
– Any blood-pressure-lowering medication will have
an additive effect with the opioids
• MAOIs
– Watch with Meperidine. Causes fever, excitation,
delirium, seizures and severe respiratory
depression. Avoid MAOI + opioid use.
 Drug Interactions with the Opioids
• Partial Agonist Opioids
– Pentazocine, buprenorphine, butorphanol,
nalbuphine
– Will precipitate withdrawal syndrome in patient
taking pure opioid agonists
 Label Changes to Opioids
• Label Changes Affects ER opiates
– ER-oxycodone (Oxycontin), transdermal fentanyl
(Duragesic), ER oxymorphone (Opana), ER morphine
(MS-Contin)
• These had been recommended for persistent
moderate to severe chronic pain requiring an
around the clock opiate
• New labeling states that these drugs are for
SEVERE pain only, for which alternative treatments
are INADEQUATE
 Label Changes to Opioids
• As a prescriber, your patient must meet the
assessment criteria
– These drugs are NOT for as-needed pain relief
• Boxed warnings include ‘aberrant behavior’
risk, implicit in which is drug abuse
– Overdose, death, respiratory depression when
initiating treatment or increasing dose, neonatal
abstinence syndrome all now described
 Aberrant-Related Drug Behaviors
• Correlate with substance abuse and addiction
• These include:
– Sedating oneself
– Using opiods for non-pain reasons
– Increasing dose without authorization
– Having felt intoxicated by opioids
– N. Sehgal, J. Colson and H.S. Smith (2013). Expert Rev. Neurother. 13:1201-1220 .
 Label Changes to Opioids
• Further Studies
– FDA is requiring further studies on the ER opiates
to quantify incidence of aberrant behaviors
• Overdose, death
– Further studies are ongoing to examine tolerance
and hyperalgesia
– Protocols for these studies are to be submitted in
early 2014; reports will be issued in 2018
 Chronic Opioid Therapy
• Is your patient a candidate? Assessment tools:
– Opioid Risk Tool (ORT)
– Screener and Opioid Assessment for Patients With
Pain (SOAPP)
– Diagnosis, Intractability, Risk, and Efficacy Score (DIRE)
• To identify misuse during treatment:
– Pain Medication Questionnaire (PMQ)
– Current Opioid Misuse Measure (COMM)
– Prescription Drug Use Questionnaire (PDUQ)
• American Academy of Pain Medicine; American Pain Society
 Chronic Opioid Therapy
• Morphine sulfate (Avinza, Kadian, Embeda)
• Fentanyl (Duragesic)
• Methadone (Methadose, Dolphine)
• Oxycodone (Oxycontin)
• Oxymorphone (Opana)
• Hydromorphone (Exalgo)
• Buprenorphine (Butrans)
• Tapentadol (Nucynta)
 Chronic Opioid Therapy:
Theory vs. Reality
• What SHOULD effective chronic opioid therapy do?
– Provide clinically significant pain relief
– This pain relief is sustained over years
– It improves physical activity, sleep, mood, quality of life
• What DOES chronic opioid therapy do?
– 50-70% of patients fail chronic therapy
– Of those who report relief, the reduction in pain is mild
to moderate, and short-term
 Very Few LONG-Term Studies
• Of opiate users who use them for years for
conditions such as diabetic neuropathy,
osteoarthritis, low back pain, neuropathic pain,
the reductions in pain are modest (20-30%).
• Opioids not significantly better than NSAIDs,
TCAs or anticonvulsants for LBP or other CNCP
– Due to tolerance, hyperalgesia
• Overall, users report more severe pain, poorer
QoL, more healthcare utilization
• N. Sehgal, J. Colson and H.S. Smith (2013). Expert Rev. Neurother. 13:1201-1220.
 Functional Outcomes and
Adverse Effects
• Frequency of ADEs increased with more daily doses,
higher doses, polypharmacy, long-term Tx,
decreased renal or hepatic function
• Of note: sexual dysfunction and
hypogonadism seen with intrathecal,
transdermal, sustained release opioids
– Opioids inhibit the release of GnRH and CRH
– LH, FSH are effected, as are end hormones—
estrogen, progestins, testosterone
 Functional Outcomes and
Adverse Effects
• Cognitive function is most often affected, but
data are mixed; maintaining a stable dose is
the most helpful
• GI, CNS adverse effects are the worst
– Dry mouth, constipation, nausea, somnolence,
decreased cognition, weight gain, pruritus,
sweating
 Tips For Prescribing Opiates
• Remember the following….
• Go low and slow
• Watch for tolerance
• Watch for abuse/diversion issues
• Patients being weaned off of high-dose
morphine equivalent doses reported no
decrease in pain relief—don’t be afraid to try
this!
 Is Opioid Rotation Acceptable?
• If patient is not responding well
• Is not compliant
• Cannot afford a certain medication
• Has drug-drug interactions
• There are concerns about diversion
• Use the equianalgesic table and DECREASE dose
of new opiate by 25-50% to account for
polymorphisms or enhanced sensitivity to new
opiate
Switching Between Opiates
Equianalgesic Table
 Opioid Rotation
• If switching to an opioid other than fentanyl or
methadone, use an equianalgesic table as a
guide, and then select a dosage 25-50% lower
than recommended by the table
• When using methadone, the dosage reduction
should be 75-90% lower than the calculated
dose
– Consider an EKG
• When switching to transdermal fentanyl use
prescriber information
 Legal Issues with
Prescribing Opioids
• Need to satisfy 2 agencies: DEA and state
licensing board
• As a prescriber, you also need to “satisfy” the
patient…
– While undertreatment of pain has been called a
“national problem”, this is usually in cases of
cancer pain, not CNCP
• DEA looks for “legitimate prescribing”
 Hydrocodone
Prescribing/Medicare
 When Prescribing Opioids…
• Perform a thorough history and physical exam
• Try non-opioid analgesics first
• Stay within recommended dosage ranges
• Reevaluate monthly. If pain is not resolving, refer
patient to a pain specialist
• Have rules and stick to them!
– Use 1 pharmacy, 1 clinician
– Written agreement to rules
– Terminate relationship if patient is noncompliant
 Tools to Use
• Patient-Prescriber Agreement
– 1 prescriber, 1 pharmacy, meds will be locked,
meds will not be sold/shared, follow-up visits,
plan for med disposal, exit strategy, etc.
• Assessment tools
• Urine drug testing
• Medication reconciliation
• Family/caregiver interviews
 To Ensure Safe Practice and
Prescribing for Nurse Practitioners
• American Pain Society and American Academy
of Pain Medicine have put together strategies
for safer prescribing
• For the patient on Chronic Opiate Therapy
(COT)—14 recommendations
– A thorough history including that of prior
substance abuse
– Risk/benefit ratio should be explained
– COT management plan with endpoints
 COT Plan, Continued
• A plan for continuance of COT
• Patient monitoring, including urine drug
screens
• Discuss referral to a specialist if addiction
issues arise
• Discontinue patients suspected of diverting
• Treat opioid ADRs including constipation,
sedation, itching, respiratory depression
 COT Plan, Con’t
• Use of psychotherapeutic cointerventions
• Educate patients about cognitive changes caused by
COT
• Patient must have continuous access to a primary
HCP
• Educate patient about breakthrough pain
• Educate patient regarding the use of COT (or NOT) in
pregnancy
• Keep abreast of current treatments and guidelines
and laws
 Use Care With ER/LA Opioids
• In substance abusers (use tools to evaluate)
• In the elderly, frail
• In children—not approved for those under 18
– Fentanyl transdermal the exception
• Dosage individualized in every case
• Watch with co-prescribed agents!
 Discontinuing ER/LA Opioid Use
• Treatment goals are not met
• Adverse effects outweigh benefits
• Patient demonstrates aberrent drug-related
effects/events
• Taper the dose
– Tapers range from 10% per week to 25-50% over
several days
– At high doses (200mg/day morphine eq) initial
taper may be more rapid
 Options to Opiates for Pain
• There are many!
• NSAIDs
• Acetaminophen
• Anticonvulsants—Gabapentin, Pregabalin
• Antidepressants—TCAs, Venlafaxine, Duloxetine
• Muscle relaxants (use caution here!)
• Local anesthetics—Lidocaine, Capsaicin
• Combinations—balanced analgesia
Non-Opioids for Pain
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Why Sedatives Are Controlled
• Abuse potential
• Side effects/Toxicities
• Physical addiction liability
• Diversion rate is very high
 Sedatives and Scheduling
• Pentobarbital, Secobarbital (II); Phenobarbital (IV)
• Butalbital combinations (III)
• Alprazolam, Butorphanol, Chloral hydrate,
Chlordiazepoxide, Clonazepam, Clorazepate,
Diazepam, Flurazepam, Lorazepam, Meprobamate,
Midazolam, Modafinil, Oxazepam, Temazepam,
Triazolam, Zaleplon, Zolpidem (IV)
• Pregabalin (V)
 Barbiturates
• Indications: Seizure disorders, adjuncts to
anesthesia, daytime sedation, induction of
sleep.
• Ability to cause tolerance, dependence,
respiratory depression, and general CNS
depression is high, so widespread use as drugs
for sleep and anxiety is very limited.
– Abuse of these agents is increasing
 Benzodiazepines
• Indications: Depending on the agent, these drugs
may be used for sleep disorders, muscle spasms,
seizure disorders, skeletal muscle relaxants, as
adjuncts to anesthesia, for panic disorder, or for
sedation.
• They are first-choice drugs for anxiety
– Long-term use is associated with a withdrawal syndrome
– Alprazolam and Lorazepam are most often prescribed for
anxiety; Chlordiazepoxide, Clorazepate, Diazepam,
Oxazepam also approved
 Benzodiazepine Use
• Withdrawal syndrome may be mistaken for anxiety
symptoms
– Withdraw patient slowly over several months
• If used for insomnia, encourage intermittent use
– Rebound insomnia upon discontinuance
• Overdose or toxicity presents with excessive
drowsiness or lethargy; dangerous when combined
with other CNS depressants
– Flumazenil (Romazicon) is the antidote
 Benzodiazepine-Like CS for Sleep
• Zolpidem (Ambien, Ambien CR, Zolpimist)
– Promotes falling asleep. CR formulation also maintains sleep.
Mist formulation useful in patient with swallowing difficulty.
• Zaleplon (Sonata)
– Short duration of action makes it more useful to promote
falling asleep (4 h).
• Eszopiclone (Lunesta)
– Approved for longer-term use
• All three may cause sleep-driving, eating, amnesia, etc.
 Recent Data Show…
• The 3 “Z”’s
• Zolpidem, Zaleplon and ‘Zopiclone users are 3
times more likely to die prematurely
– Stronger link seen in smokers
– Long-term use more tightly associated with
mortality
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Why Stimulants Are Controlled
• High abuse potential!
• Many “gains” in stimulant use and abuse
– Feeling of euphoria, weight loss, feeling of
increased energy
• Diversion risk is very high
• New routes for abuse
• Lisdexamfetamine—one of the top 10 drugs
prescribed in the US!
 Stimulants and Scheduling
• Methylphenidate, Dexmethylphenidate,
Dextroamphetamine, Amphetamine,
Lisdexamfetamine, Methamphetamine (II)
• Modafinil, Armodafinil (IV)
What are Prescription Stimulants?

• A class of drugs that enhance brain activity

including attention span and goal-oriented
activity.
• Prescription stimulants were used historically
to treat asthma, obesity, neurological
disorders, and a variety of other ailments,
before their potential for abuse and addiction
became apparent.
 What are the Effects of Stimulants?
• Stimulants increase the amount of
norepinephrine and dopamine in the brain,
which increases blood pressure and heart
rate, constricts blood vessels, increases blood
glucose, and increases breathing. Effects can
feel like increased alertness, attention, and
energy along with a sense of euphoria.
 Usually Prescribed For…
• Narcolepsy
• Attention-deficit hyperactivity disorder
(ADHD) –hyperactivity, impulsivity, inability to
concentrate
• Depression that does not respond to other
treatment
 In Normal Use….
• The normal user of stimulants should take
them once a day (early)
• Drug holidays are encouraged
– Weekends
– School holidays
– Spring break, Christmas, Summer vacation
• Regular assessment should be done to
determine if continued use is necessary
 Effects of Short-Term Use
• Elevated blood pressure
• Increased heart rate
• Increased respiration
• Suppressed appetite
• Sleep deprivation
• Dilated pupil
• A “wearing off” effect as short-term drugs stop working.
This can be lessened with caffeine (Mountain Dew,
coffee, energy drink—use caution here! Consider age of
patient—may be more appropriate for adults, late teens)
 Effects of Long-Term Use
• Potential for physical dependence and
addiction
• Stimulants have many “desirable” gains…
increased alertness, attention, weight loss
• Euphoric feelings are most intense when the
user snorts or injects the drug
• Increased risk for cardiovascular effects,
seizures, paranoia, hostility, agitation
 Federal Classification
and Penalties
• Many stimulants are Schedule II
– Schedule II drugs must have a written prescription
to be refilled
– One-month supply on hand only—pharmacy may
hold more
– Class A felony for illicit trading in these drugs
• Strattera is an exception—it is a non-
controlled substance
 Drug Interactions With Stimulants
• OTC decongestant medications (Sudafed,
Phenylephrine, Coricidin)—high BP, irregular HR
• Antidepressants, unless supervised by prescriber
(Nardil, Prozac, Paxil)—psychosis, high HR
• Some asthma medications (Proventil)—high HR
• Any drug that raises blood pressure is a dangerous
combination (energy drinks??)
– Energy drinks typically contain large amounts of caffeine, B
vitamins and taurine
• Any drug that affects mood should be assessed
(alcohol!)
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Why the GI Drugs Are Controlled
• Risk for diversion
• Side effects/Toxicities
 Antiemetics, GI Drugs
and Scheduling
• Belladonna and Opium (II), Paregoric (III), Diphenoxylate (V)
– Excessive doses can cause morphine-like effects. These may be reversed
with naloxone.
• Dronabinol (Marinol) (III) and Nabilone (Cesamet)(II)
– Derivatives of THC, with some of the effects of THC—dissociation,
depersonalization, dysphoria.
• Diethylpropion, Phentermine (Adipex), Sibutramine (Meridia)
(IV)
– Sibutramine may increase HR and BP; has some drug interactions, so use
should be monitored
– Diethylpropion and Phentermine are related to amphetamines and can
cause increased alertness, nervousness, insomnia. Watch for abuse.
• Contrave
– Bupropion plus naltrexone
Topiramate/Phentermine (Qsymia)
• A combination of phentermine/topiramate in
varying amounts—highest amounts are
15mg/92 mg
– Schedule IV CS for weight loss
– Topiramate may cause cleft palate and also
decreases effectiveness of contraceptives
• Monitor for neuropathies
– Phentermine causes CNS effects, high blood
pressure
 Lorcaserin (Belviq)
• Lorcaserin (Belviq) is a Schedule IV CS
• Watch for Serotonin Syndrome, migraines,
hypoglycemia, valvular disease, confusion,
hallucinations, memory deficits
• Causes modest reductions in weight, but also
can help modulate blood glucose
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
 Hormones and Other Drugs
and Scheduling
• Methyltestosterone, Nandrolone, Fluoxymesterone,
Testolactone, Testosterone (III)
– Used mostly for replacement, catabolic states, male
hypogonadism, delayed puberty, and female breast cancer
• May be abused for effects on growth; risk for diversion is high
– When used for “low T” syndrome, monitor for
adverse cardiovascular events including chest pain
and MI
• Consider risk/benefit here!
 Topics Covered
• Controlled Substances and the Schedules
• Prescribing Opiates
• Prescribing Sedatives
• Prescribing Stimulants
• Prescribing GI Drugs—Antidiarrheals and Drugs for
Weight Loss
• Prescribing Anabolic Hormones
• Controlled Substances and the NP
• Summary
Controlled Substances and the NP
• Judicious prescribing
• Drugs with danger associated with use
– Risk for addiction (physical, psychological)
– Side effect profile
– Risk for diversion
– Interactions of note
– Risk for abuse…
DEA Standards for CS Prescriptions
• Keep prescription pads in safe place; minimize
the number of pads in use
• Write out the actual number in addition to a
numerical value
– “Thirty” as well as 30
• Use pad only for prescriptions and not for
note-taking
DEA Standards for CS Prescriptions
• Never sign prescription pads in advance
• Work cooperatively with pharmacy to verify
accuracy of prescriptions
• Contact nearest DEA office to obtain/provide
suspicious prescription activities
• Use tamper-resistant prescription pads
 Indications That a Patient May Be
Abusing or Diverting Drugs
• Demanding to be seen immediately
– “Need something to tide me over”
– “Traveling through the area and need something
until my own prescriber can be seen”
• Appearing to feign symptoms
– Watch for LBP, kidney stones, migraine
• Indicating that nonopioids “don’t work”
• Requesting a particular opioid, particular
strength
 Indications That a Patient May Be
Abusing or Diverting Drugs
• Stating that a prescription has been stolen or
lost
• Requesting more refills than originally
prescribed
• Using pressure or threatening behavior to
obtain a prescription
• Showing visible signs of abuse
 Inappropriate Prescribing—
What the DEA Looks For…
• Large quantity of CS or large numbers of prescriptions
issued compared to other clinicians in a given
geographic area
• No physical exam given
• Warnings given to patients to fill prescriptions at
different drug stores
• Knowledge that the patient will divert the medication
• Ordering unnecessary tests (even excessive urine
testing—insurance fraud!)
 Inappropriate Prescribing—
What the DEA Looks For….
• Issuing the Rx in exchange for money or sexual
favors
• Prescribing CS at intervals inconsistent with
legitimate medical treatment
• Use of street slang to describe CS
prescribed/used in practice
• No relationship between the drugs prescribed
and the clinical condition described in the chart
 Other Things That Will Cause
Revocation of Your DEA # or Worse
• Charging a patient an “initiation fee”, or any fees
to remain a patient in a practice
• Violating the CS laws
• Giving an Rx for a CS without a clinician-patient
relationship
• Issuing Rx with a fraudulent name
• Issuing several Rx’s at once for combinations of
potent CS
• Abuse of CS by the practitioner
 Licensing Boards and CS
• BON have disciplined NPs for prescribing CS to
addicts/diverters
– Standards of appropriate assessment or ongoing
monitoring were not met
– Typically, patients presented with symptoms of
LBP, fibromyalgia, knee pain, major depressive
disorder
– In several parallel cases, NPs were disciplined
more severely than MDs!
 Licensing Boards and CS
• Aspects of cases that are examined include:
– Are patient and practitioner easily identifiable?
– Is the drug prescribed appropriate for the
condition diagnosed?
– Is the pharmacy geographically relevant to the
patient?
– Is the drug prescribed one with a history of
potential abuse? How about the patient?
 Licensing Boards and CS
• Aspects of cases that are examined include:
– Is the prescription consistent with patterns for this
prescriber including the type of drug and amount?
– Any prior disciplinary action involving the
prescriber?
– Is this drug consistent with this prescriber’s scope of
practice?
– Does the prescription list contain an unusual
combination of drugs?
– Are quantities or refills questionable?
 Remember
• Drug overdose is now the LEADING CAUSE of
injury death in the United States
 Of the Top Ten Most Abused
Prescription Drugs….
• Hydrocodone
• Codeine
• Fentanyl
• Morphine
• Diazepam
• Alprazolam
• Zolpidem
• Eszopiclone
• Methylphenidate
• Dextroamphetamine
 The List vs. Schedule
• Hydrocodone (II)
• Codeine (II)
• Fentanyl (II)
• Morphine (II)
• Diazepam (IV)
• Alprazolam (IV)
• Zolpidem (IV)
• Eszopiclone (IV)
• Methylphenidate (II)
• Dextroamphetamine (II)
• ALL OF THEM ARE CONTROLLED SUBSTANCES.
• MAKE SURE YOU TAKE CONTROL OF PRESCRIBING THEM!
 Changes Are Coming…
• Prescriber education
• States rights
• Prescription Drug Monitoring Programs
• Alternative therapies
• Safety for Patients, Prescribers, Pharmacists