Current and novel treatment for Addiction Flashcards
Treatments (2)
CBT + pharmacotherapy
Phases of Substance Use that are
Targets for Pharmacotherapy(5)
- intoxication/overdose
-withdrawal/detoxification
-abstinence initiation/use reduction
-relapse prevention
-sequelae (psychosis, agitation, etc.)
Some Pharmacological
Treatment Strategies for SUDs (4)
-Agonist/partial agonist
(replacement/substitution)
- antagonist (blockade)
- aversive (negative reinforcement)
- correction of underlying/associated
disorders (such as depression, etc.)
Substances for which
Pharmacotherapy
is Available (4)
Opioids
Alcohol
Benzodiazepines Tobacco (nicotine dependence)
Substances for which
Pharmacotherapy
is NOT Available (5)
Cocaine
Methamphetamine
Hallucinogens
Cannabis
Solvents/Inhalants
Opioids- Dependence treatment (4)
Lofexidine (non-substitute method of detoxification)
- Central ⍺2-agonist, suppresses some components of withdrawal syndrome = inhib NA release (pre-synap)
Methadone (substitution method of detoxification)
- Long-acting drug, no euphoria to morphine
Naltrexone, opioid antagonist, prevents euphoria to opioids
- Given daily to addicts to prevent lapses
Buprenorphine (substitution method of detoxification)
Loefixidine (2)
increased NA release = withdrawal symptoms
so this drug binds with ⍺2r =inhib the release of NA
Opioid Dependence
Maintenance Therapy - Methadone (6)
Methadone (must be administered through a registered narcotic treatment program - substitutes heroine) = occupies all mu r (not as much euphoria)
Characteristics:
- Long acting mu agonist
-Duration of action: 24-36hrs
-Dose: important issue and philosophical issue for many programs
-30-40 mg will block withdrawal, but not craving
- Illicit opiate use decreases with increasing methadone dose
- 80-100 mg is more effective at reducing opioid use lower doses (e.g.: 40-50 mg/d)
Methadone
Benefits (5)
- Lifestyle stabilization: can’t stop taking it though (otherwise withdrawal)
-Improved health and nutritional status
-Decrease in criminal behaviour
- Employment
- Decrease in injection drug use/shared needles
Naltrexone- Why antagonist therapy? + side effects + dosage (8)
- Block effects of a dose of opiate : can’t give to heroine user = withdrawal - needs abstinence
-Prevent impulsive use of drug
-Relapse rates high (90%) following detoxification with no medication treatment
-Dose (oral): 50 mg daily, 100 mg every 2 days, 150mg every third day
-Blocks agonist effects
- Side effects: hepatotoxicity, monitor liver function tests every 3 months
- Biggest issue is lack of compliance; but those who “test” naltrexone by taking a dose of opioid and experiencing no effect do better with the medication
- Injectable naltrexone not currently approved for opioid dependence, but likely to also be effective
Buprenorphine (5)
Partial MOPr/KOP antagonist
Advantage/disadvantage over methadone?
-Lower risk of respiratory depression
- Lower retention rate
- Also used with Naloxone (Suboxone).
- Lower risk of withdrawal symptoms/lower
craving for opioids
Endogenous opioid control of
reinforcement - 2 ways of actions (3)
substitutes opioids like methadone w/o inducing such a big euphoric effect
however : it will activate mu r = euphoria(DA release)
- acts on ka r too( activation of ka = dysphoria (big relapse factor)) - drug blocks -ve reinforcement
2 ways of action
Opioid overdose treatment??? (3)
NALOXONE
- blocks the r heroine/fentanyl binds to = almost reverses the effects induced (RD)
-NHS: epipen of naloxone
= harsh reaction = acute withdrawal symptom but save their life from RD
Treatment of alcohol dependence (6)
- Benzodiazepines (e.g. diazepam) effective against seizures
-Clonidine ⍺2-adrenoceptor agonist-(inhibits excessive transmitter release)
-Propranolol β-blocker (blocks excessive sympathetic activity)-
-Acamprosate, weak NMDA antagonist (interferes with synaptic
plasticity): reduced craving
-Disulfiram, causes accumulation of acetaldehyde making alcohol consumption unpleasant
-Naltrexone, opioid antagonist reduces alcohol-induced reward
Alcohol Dependence
Pharmacotherapy - 2 phases (3)
Two Phases of Alcohol Dependence:
1. Acute Alcohol Withdrawal
- Relapse Prevention: Maintenance Medications To
Prevent Relapse To Alcohol Use (FDA approved):
- Disulfiram
- Naltrexone (oral and injectable)
- Acamprosate
Note: monitor any patient being treated for a SUD for emergence of depression/anxiety/ suicidality as this can occur in the course of treatment
Alcohol - tolerance + dependence (5)
when alc stops = withdrawal symptoms because:
- inc. voltage-gated Ca2+ channels
– dec. GABAA receptors
– Marked abstinence syndrome, changes in Ca2+ channels lead to
excessive neurotransmitter release
*Tremor, nausea, sweating, fever, hallucinations
* Seizures, confusion, agitation, aggression
– Alcohol dependence (alcoholism) is common (4-5% of population)
– Susceptibility to dependence, genetic factors
* Linked to alcohol metabolism (alcohol dehydrogenase)
Anxiolytic BZDs: Diazepam/
Lorazepam treat alc withdrawal (3)
need to inc inhib in brain = GABAa r
BZD + GABAa = cl- channels open up = hyperpolarisation inhib
GABAa has alpha1 subunit = BZD biding site = enhances the cl- channels opening
Benzodiazepines
for acute withdrawal - not w/ alc (5)
- DO NOT MIX W/ALC = Overdose:
– Prolonged sleep without CVS or respiratory depression
– Can become life threatening (respiratory depression etc.) with
other CNS depressants e.g. alcohol
– Reversed with flumazenil (competitive antagonist) - Tolerance & Dependence:
– Tolerance – gradual escalation of dose needed to produce
required effect (Q Any suggestions what might cause that?)
– Dependence – stopping treatment causes marked inc. in anxiety + tremor / dizziness, insomnia
What about Benzo’s for Alcohol Dependence? (8)
Clinical Pearls: If your patient is alcoholic, try to avoid prescribing a BZD.
- BZD produce cross-tolerance with alcohol
-High risk of abuse of BZD
-High risk of relapse to alcohol use
-Combined use of alcohol and prescribed BZD can be very
impairing and produce significant toxicity
-If patient complains of anxiety:
- consider use of serotonin reuptake inhibitors SSRI’s (this
is 1st line treatment of anxiety disorders (not
Benzos)), - refer to psychotherapeutic interventions (e.g.:
cognitive-behavioural therapy), - consider relapse to alcohol
Alcohol Relapse Prevention Meds:
Disulfiram (Antabuse) (3)
How it Works:
Blocks alcohol metabolism= increase in blood acetaldehyde
levels; aims to motivate individual not to drink
because they know they will become ill if they
do
- Antabuse reaction: flushing, weakness
nausea, tachycardia, hypotension
-Contraindications: cardiac disease, esophageal
varices, pregnancy, impulsivity, psychotic
disorders, severe cardiovascular, respiratory, or renal disease, severe hepatic dysfunction: transaminases > 3x upper level of nl
Pharmacotherapy of Alcohol
Dependence: Naltrexone (2)
- Oral Naltrexone Hydrochloride: 50 mg per day
-Extended-Release Injectable Naltrexone (Vivitrol) : 1 injection per month
Naltrexone Pharmacology (4)
Similar structure to naloxone (Narcan)
-Potent inhibitor of Mu opioid receptor
binding
-may explain reduction of relapse because endogenous opioids involved in the reinforcing (pleasure) effects of alcohol (endorphins + enkephalins)
-May explain reduced craving for alcohol
because endogenous opioids may be
involved in craving alcohol
Naltrexone for alc - Cochrane review of NTX (5)
decreased relapse to heavy drinking [RR =
0.64]
decreased return to any drinking [RR =
0.87 ]
NTX increased the time to first drink
NTX reduced craving
NTX was superior to acamprosate in
reducing relapses, drinks and craving
Nicotine dependence treatment (3)
- Nicotine replacement therapy:
** Relieves psychological and physiological withdrawal syndrome
** Reduces cigarette consumption (carcinogens) but not nicotine abstinence - still giving nicotine over longer duration (smoking = goes straight to brain = addiction) - Bupropion
** Developed as antidepressant (blocks monoamine reuptake)
** Nicotinic antagonist
** May inc. [DA] in nucleus accumbens
** Can induce seizures, eating disorders and mania (bipolar disorder)
-Varenicline (Champix) - most effective!!!!
** Partial a4b2 nAChR agonist, full agonist for AChR
** More effective than NRT
