Pharmacotherapy of Opioid Dependence Flashcards
Epidemiology of Opioid Dependence
Increased heroin purity have led to increased rates of intranasal use-only 37% of new users have injected heroin.
Trends in US heroin use:
Availability of high purity heroin-can be injected, snorted, smoked, or otherwise inhaled.
Expands the use of heroin to those who might be reluctant to inject drugs.
Conducive to experimentation.
Heroin addicts are undercounted-only those living in households are surveyed.
Population of heroin addicts is aging and encountering serious health problems after years of use.
Social and Health Consequences of Heroin Use
Danger of fatal overdose
Crime
Public Health concerns: Hepatitis B and C, HIV/AIDS, TB and STDs.
Difficult to overcome.
Methadone treatment
Substitution therapy
Greater than 900 treatment programs in the Us (170,000 patients).
Treatment capacity inadequate; 8 states have no program.
Synthetic, long acting mu opioid receptor agonist.
Tablets or solution; used for detoxification, maintenance and severe pain.
Peak blood levels at 2-6 hours.
Significant protein binding (>90%).
Readily crosses the BBB.
Extensive hepatic metabolism (N-demthylation).
Time Course of Opioid Withdrawal
Heroin
Symptoms begin 8-12 hours after last use, peak in 36-72 hours-symptoms may last 7-14 days.
Methadone
Symptoms begin 36-72 hours after last use; may last for several days to a few weeks.
Treatment: supportive measures (safe environment, nutrition, monitoring) and pharmacologic therapies to decrease symptoms.
Detoxification using Opioid Agonists
Cross tolerance: one opioid is replaced with another that is slowly tapered.
Methadone dose as needed for 2-3 days, then taper by 10-15% per day.
Bupenorphine 2 mg for 3 weeks then taper over 4 weeks.
Don’t give as high a dose to produce euphoria…
Detoxification using Nonopioid Medications
Clonidine (alpha 2 agonist, central effects); diminished norepinephrine activity during opioid withdrawal; most effective in suppressing autonomic signs and symptoms of withdrawal-sympathomimetic symptoms.
Less effective for subjective symptoms like craving, lethargy, and insomnia.
Adjunctive treatments may be needed: NSAIDs for myalgia, benzodiazepines for insomnia, antiemetics.
Rapid and Ultrarapid Opioid Detoxification
Use of an opioid antagonist (naloxone) causes an accelerated withdrawal response; goal of completing detoxification quickly, time periods from 8 days tops little as a few hours.
Clonidine, sedation, and general anesthesia: minimize acute withdrawal symptoms.
This rapid detox may minimize the risk for relapse; allows patients to enter post detox treatments more rapidly like naltrexone maintenance.
Rapid Opioid Detoxification (ROD) 3 day Protocol
24 hours prior-clonidine, lorazepam, prochlorperazine, haloperidol, clear liquids only.
Day 1: lorazepam, clonidine, naltrexone and monitor vital signs.
Day 2: Naltrexone and monitor vital signs.
Day 3: Naltrexone and then daily for a minimum of 30 days.
Anesthesia-assisted Rapid Opiate Detoxification (AAROD)-Potential Risks
Potential morbidity and mortality from anesthetic agents.
Loss of protective reflexes due to heavy oral sedation.
Patients coming out of anesthesia or conscious sedation often continue to experience psychological needs or cravings; leads to preoccupation with obtaining and using opioids.
Detox alters opioid receptor sensitivity and patients lose their high degree of tolerance that previously existed; resumption of the same high dose opioids result in overdose and death.
ASAM public policy statement on AROD-does not support the initiation of AAROD when part of a continuum of services that promote addiction recovery.
Appropriate for selected patients; assuming adequately trains staff and emergency medical equipment.
Benefits/risks/financial costs must be provided to all candidates.
Written informed consent recommended.
Sufficient period of medical monitoring needed.
More research needed.
Methadone Effects
Blocks many of the euphoric effects of exogenously administered opioids.
When injected has the potential for abuse.
Long term treatment results in tolerance; analgesic, sedative, and euphoric effects, minimal toxicity.
Long term side effects: constipation, weight gain, decreased libido, menstrual irregularities.
Pharmacokinetics of Methadone
N-demthylation of methadone to EDDP (inactive metabolite-cyclic, form a 3rd ring) via CYP3A4; possible minor involvement of CYP2C9 and CYP2C19.
Methadone and EDDP are both eliminated by the kidney and the liver; portion of methadone eliminated by the kidney increases with dose, length of treatment and urinary pH.
Mean oral clearance is slow (115 mL/min in health volunteers).
Elimination is slower in women than in men.
Methadone Drug Interactions
Mechanisms of Interaction: competition for metabolic pathways in the liver, competition at protein binding sites in plasma; changes in urinary pH. Methadone may prolong the QT interval: use with caution with other agents that may also prolong the QT interval: class 1 or class 3 anti arrhythmic drugs, calcium channel blockers, some antipsychotics, some antidepressants. Methadone metabolized through the CYP450 pathway; agents interacting with this pathway-alcohol, anticonvulsants, antiretrovirals, and macrolide antibiotics.
FDA Alert of Methadone
Methadone related reports of death and life threatening adverse events; respiratory depression and cardiac arrhythmias.
Possible causes: unintentional methadone overdoses, drug interactions, methadone cardiac toxicity (QT prolongation and Torsades de Pointes-unusual ventricular tachycardias).
Physicians instruct patients on use and risks, monitor initiation of treatment and dose changes.
Methadone Maintenance Therapy (MMT)
Admission criteria: currently addicted to an opioid with greater than 1 year history, informed written consent to treatment, for persons <18 years of age: two documented unsuccessful attempts within 12 months; short term detoxification or drug free treatment.
Admission exceptions to 1 year medical history for patients released from penal institutions: within 6 months after release, for pregnant patients, for previously treated patients (up to 2 years after discharge).
Control who comes into maintenance program.
Required OTP (opioid treatment program) services: adequate medical, counseling, vocational, educational, and other assessment/treatment services, initial medical exam services, special services for pregnant patients, initial and periodic assessment services, counseling services, drug abuse testing services (8 random drug tests per year in MMT), record keeping and patient confidentiality.
OTP medication, administration, dispensing and use; must be administered or dispensed by an appropriately licensed practitioner (may be an agent of the practitioner, RPh, RN, LPN); use only FDA approved agents like methadone and LAAM.
Use of oral dosage form formulated to reduce potential for parenteral abuse.
Drug administration and dispensing in accordance with product labeling.
Rules for unsupervised or “take-home” use: absence of recent drug or ETOH use, regular clinic attendance, absence of serious behavioral problems, absence of known recent criminal activity, stability of home/social relationships, lengths of time in comprehensive MMT, patient benefits outweigh potential risks of diversion.
Restrictions on take home use of amount.
Levo-alpha-acetylmethadol (LAAM)
Long acting derivative of methadone.
Metabolized to more potent metabolites that have a prolonged duration of action.
Peak blood levels in 4-8 hours.
Opioid withdrawal can be prevented for unto 72 hours dosing every 2-3 days.
Infrequent side effects, similar to methadone.
Doses of 30-100 mg 3 times/week.
Similar drug interactions to methadone.
