DSA21 - Opioid Abuse and Treatment

What is the most important subtype of Opioid receptors for abuse and dependence?

Mu/µ

Where are Opioid Mu receptors expressed?

Selectively on GABAergic neurons in the Ventral Tegmental Area (VTA) --> decrease firing of DA neurons

What happens if Opioid Mu receptors are activated (stops GABA activity on VTA)?

Increases DA neuronal activity w/ increased DA release into Nucleus accumbens (reward center)

Describe how Opioid Abuse occurs

-Euphoria (may take multiple uses)

-More frequent use at higher dose (oral/skin popping --> smoking/injecting)

Morphine MoA

Opioid Agonist; obtained from opium poppy

Morphine S/E

Abused via prescription diversion - more potent parentally

Heroin MoA

Opioid Agonist - morphine + 2 acetate groups; more lipid soluble than morphine (quicker access to brain); PRO-DRUG (metabolized to morphine in brain)

Heroin Effects

Often mixed w/ Fentanyl --> 1 min effects = Warmth, "Rush", Intense Euphoria then Modest Euphoria (45-60 min)

Fentanyl MoA

Opioid Agonist - more potent than other opioids

Methadone MoA

Opioid Agonist - HIGHEST ORAL POTENCY; Effects ~ 24 hrs

Methadone Uses

Tx of Cancer Pain & Tx of Opioid addiction, Replacement-Maintenance Therapy (long-half lives to keep opioid receptors occupied)

Oxymorphone MoA

Opioid Agonist

Hydromorphone MoA

Opioid Agonist

Oxycodone MoA

Moderate Efficacy Opioids; time release formula

Oxycodone S/E

Significant abuse liability

Hydrocodone MoA

Moderate Efficacy Opioids

Hydrocodone S/E

Significant abuse liability

Codeine MoA

Low Efficacy Opioids; obtained from opium poppy - converted to morphine by liver --> binds to Sigma receptor (with higher dose --> unpleasant psychotomimetic effects)

Codeine S/E

Abuse potential

Tramadol MoA

Low Efficacy Opioids; Schedule IV; Very WEAK Mu-receptor effects + Pain-Relief (acts on NE & Serotonin)

Tramadol S/E

Less Abuse potential

Rate of Opioid Tolerance development varies among agents but general develops faster with more () and/or () doses

potent; higher

What does it mean to say that there's specificity of tolerance development with Opioids?

Means there's little to no tolerance to the miosis-producing and constipating effects of opioids

What are S/S of Opioid Withdrawal?

-DRUG CRAVING

-RHINORRHEA

-Lacrimation

-YAWNING

-CHILLS

-Piloerection

-Hyperventilation

-Hyperthermia

-MYDRIASIS

-Vomiting

-Diarrhea

-ANXIETY

When does Opioid Withdrawal occur in relation to cessation of substance use?

-Short Acting Opioid = 6-12 hrs after last dose

-Long Acting Opioid = 72+ hrs after last dose

What should be done to Tx Opioid Withdrawal?

NOTHING (Non-lethal) --> Detox w/ Methadone or Buprenorphine

Buprenorphine MoA

Low Efficacy Opioids; Schedule III; Weak Mu partial agonist w/ slow dissociation from Mu receptors (clings tightly to receptors --> high dose = all Mu receptors covered)

Buprenorphine Uses

Tx of Opioid Dependence, Replacement-Maintenance Therapy, Replacement-Maintenance Therapy (long-half lives to keep opioid receptors occupied)

Buprenorphine S/E

Likelihood of abuse --> Add Naloxone to reduce likelihood

Clonidine MoA

Alpha2 Agonst - acts in brainstem to reduce Sympathetic activation

Clonidine Uses

Tx of Opioid Withdrawal (part of supportive Rx to minimizeSNS Activation of Withdrawal s/s WITHOUT maintaining independence)

Lofexidine MoA

Alpha2 Agonst - acts in brainstem to reduce Sympathetic activation

Lofexidine Uses

Tx of Opioid Withdrawal (part of supportive Rx to minimizeSNS Activation of Withdrawal s/s WITHOUT maintaining independence)

What are the Primary S/S of Opioid O/D?

-Lethargy or coma

-Depressed respiration

-Pinpoint pupils (normoxic)

-Needle marks

What are the Secondary S/S of Opioid O/D?

-Hypotension

-Hypothermia with cold or clammy skin

-Pulmonary edema

-Convulsions (primarily in children)

-Hypoxia with dilated pupils (just before death)

Naloxone MoA

Opioid Antagonist - Short Acting

Naloxone Uses

Injectable for Opioid O/D (used in ED), Intranasal, Used in SUBLOXONE (Sublingual form; Buprenoprhine + This --> reduce abuse likelihood)

Naltrexone MoA

Opioid Antagonist - Long Acting

Naltrexone Uses

Oral, Tx Chronic Opioid Abuse OR Alcoholism

What should be done to prevent Opioid Abuse Relapse?

Medication-Assisted Therapy