Pharm III - Substance Use Disorder

Med effects pts can grow tolerance to

Euphoria, sedation, respiratory depression

Med effects pt do NOT grow tolerance to

Anxiolytic affects, analgesia, constipation, miosis

Primary neurotransmitter in reward system

Dopamine

Area of the brain that the reward pathway connects?

Nucleus accumbens and ventral tegmental area

*stimulate VTA -> nucleus accumbens -> DA -> prefrontal cortex, enhancing reward pathway (reinforcing)

Withdrawal sx: nausea/vomiting, diarrhea, "goose flesh", chills, yawning, flu-like sx

Opioid withdrawal

Pharmacotherapy for opioid withdrawal

Methadone

Buprenorphine

Naloxone

Naltrexone

Methadone MOA

Mu-opioid receptor agonist

Buprenorphine MOA

partial mu agonist

Naloxone/Naltrexone MOA

Mu receptor antagonists

Mu receptor effects

Pain - innervations to the brain

Cravings/compulsion - reward center of brain

Physiological withdrawal - brainstem, spinal cord

Methadone SE

Dry mouth, constipation, nausea, loss of appetite, anxiety, insomnia, decreased sex life

Methadone BBW

Concurrent use w benzodiazepines -> risk of OD and death

Why is Naloxone added to Buprenorphine?

Minimize IV injection misuse

*should be SL for opioid tx

Buprenorphine SE

HA, nausea, sweating, constipation, stomach pain, sleep issues, SL irritation, cavities

Buprenorphine BBW

Concurrent benzodiazepines -> risk of OD and death

Acute pain management in patients receiving OMT

Buprenorphine - divide total daily dose into 3-4 doses

Methadone - additional methadone

Pharmacological effects of alcohol

Alcohol facilitates GABA action -> decreased CNS excitability. Long term it causes a decrease in GABA receptors -> tolerance

Also acts as NMDA receptor antagonist -> decreased CNS excitatory tone. Chronic use leads to increased number of NMDA receptors -> more glutamate

Mainstay tx for ACUTE ethanol withdrawal

Benzodiazepines

Treatment for alcohol DEPENDENCE (chronic tx)

Disulfiram, naltrexone, acamprosate

Ethanol MOA

EtOH -> acetaldehyde (step 1 metabolized by alcohol dehydrogenase, rate limiting step)

Acetaldehyde -> acetic acid (aldehyde dehydrogenase)

-> CO2 + H2O

Disulfiram MOA

Interferes w aldehyde dehydrogenase (step 2) -> excessive aldehyde levels -> N/V, hypotension, headaches

In which patients should you prescribe disulfiram?

Extremely motivated patients; disulfiram-alcohol reaction promotes abstinence

Naltrexone use in chronic alcoholism

Long acting opioid antagonist -> reduces craving

Which alcoholic pt should you avoid using naltrexone in

Any pt who is taking opioids for chronic pain

Acamprosate use in chronic alcoholism

Decreases glutamatergic transmission, modulates neuronal hyperexcitability during withdrawal

When should Acamprosate be considered when tx chronic alcoholism

Considered an alternative to naltrexone for pts who are also taking opioids or have significant hepatic impairment

Prescription drug monitoring program components

Patient tracking of records

Prescriber tracking of records

Surveillance/monitoring/research

What would you NOT find on the PDMP

Other state info (statewide program)

Methadone/buprenorphine under federal programs

Basic observations of CSMD report

Persistent or continued randomness of similar meds including escalating-deescalating doses, variation in doses

What are opioid doses compared to?

All opioids are compared to morphine on a mg/mg basis

*MEDD should be used anytime an opiate is prescribed

Milligram Morphine Equivalent (MME)

value assigned to opioids to represent their relative potencies

*Risk of OD doubles >50 MME/day*

MUST be under 90

CDC recommendations for outpatient pain prescribing

Extra precaution when increasing to >50 MME per day

- monitor and assess pain

- discuss reducing dose/tapering

- consider offering Naloxone PRN

*avoid increasing dose to >90 MME per day

Who should you prescribe outpatient Naloxone to?

Patients who are prescribed opioids > 50 MME

Naloxone use in opioid overdose

ONLY way to reverse opioid OD

Reverses effects by binding to same sites as opioids so breathing can be restored (30-90 min)

Not possible to OD on Naloxone, pt will go into temporary withdrawal

Where should you administer IM Naloxone

Outer thigh

When are prescribers required to check PDMP

Before prescribing opiates or cocaine derivatives in Schedule II drugs or benzodiazepines