Transcript Drugs used in treatm..

Drugs used in treatment
of addiction
What is Addiction?
•
It is well known that the initial decision to use
drugs is voluntary
• Addiction is a chronic, relapsing brain disease
characterized by:
 compulsive behavior of a person
 continue taking drugs despite their many
adverse health and negative consequences
 craving
Reward pathway
Regions of the brain
The Reward Pathway and Addiction
Major structures of the reward pathway
1. Ventral tegmental area (VTA)
2. Nucleus accumbens
3. Prefrontal cortex
• VTA is connected to both the nucleus
accumbens and the prefrontal cortex.
• Neurons of the VTA contain the
neurotransmitter dopamine
• Rewarding stimulus  activation of
reward pathway  release of dopamine
from VTA neurons into nucleus accumbens
and the prefrontal cortex
Rats self-administer heroin
Activation of the reward
pathway by an electrical
stimulus
Dopamine Spells reward
Release
Recycle
Activate
Addiction
A state in which an organism engaged in a
compulsive behavior
Even when faced with negative consequences
Behavior is reinforcing (pleasurable or
rewarding)
Loss of control in limiting intake
via increasing dopamine
neurotransmission
Globus pallidus
Tolerance
• A state when organism no longer respond to normal
dose of a drug.
• Higher dose is required to achieve desirable effect.
• Tolerance develops at the level of the cellular targets
(receptor desensitization).
• The development of tolerance is not addiction
• Detected within 12-24 hours of morphine administration
• Sensitivity returned to normal within about 3 days of
removing the drug
• Extends to most of the pharmacological effects of
morphine, but with different degree
Tolerance to analgesic effect of
morphine
• The development of tolerance to the
analgesic effects of morphine involves
different areas of the brain and separate
from those in the reward pathway.
• The two areas involved here, the thalamus,
and the spinal cord (green dots).
• Both of these areas are important in
sending pain messages and are responsible
for the analgesic effects of morphine.
• The parts of the reward pathway involved in
heroin or morphine addiction are shown for
comparison.
thalamus
spinal cord
Dependence
• Organism functions normally ONLY in the
presence of the drug
• Two components involved
1. Physical dependence
2. Psychological dependence
Physical dependence
• Characterized by physical disturbance (withdrawal symptoms) when
drug removed.
•
•
Resembling severe influenza
Extreme restlessness and distress
• Neurons adapt to the repeated drug exposure and only function
normally in the presence of the drug.
• Can be mild (e.g., for caffeine) or even life threatening (e.g., for
alcohol)
• In the case of heroin, withdrawal can be very serious and the abuser
will use the drug again to avoid the withdrawal syndrome.
• Lasting for a few days
• Precipitated by removal or antagonizing drug (e.g. μ-receptor
antagonists, naloxone)
• Rapidly abolished by re-administration of drug
Psychological dependence
• Associated with craving
• Lasting for months or years
• Rarely occurs in patients being given opioids
as analgesics
Drugs of addiction
Stimulants
- stimulate the central nervous system
- amphetamines, cocaine, nicotine
Depressants
- depress the CNS
- alcohol, barbiturates, benzodiazepines
Analgesics
- powerful painkillers
- from opium poppy , morphine, heroin
Hallucinogens - dramatically alter perception
- LSD, cannabis, Marijuana
of Addiction
 No single treatment is appropriate
for all individuals
 Pharmacological (medications)
 Psychological
 Behavioral Therapies
 Medical and Social Services
 Family Services
• Social interventions
– Adjusting environmental triggers
– Improving occupational, legal, financial situation
– Attention to social circle, including self-help meetings
• Psychological interventions
– Psychotherapy for depression, anxiety, etc. (individual,
group, family therapies)
– Skills training to prevent relapse, education about
addiction, relaxation training, self-care, contingency
management
• Biological interventions
– Medications
– Drug testing
– Alternative therapies (e.g., acupuncture, exercise,
massage, etc.)
Aim of Pharmacological Treatment
• Treatment of withdrawal (“detox”): medications
used to alleviate withdrawal symptoms
• Treatment of psychiatric symptoms
• Reduction of cravings
• Substitution therapy
• Relapse prevention
Medications for Drug Addiction
Medications are an important element of treatment for many
patients, especially when combined with counseling and other
behavioral therapies.

Alcohol: Naltrexone, Disulfiram, Acamprosate

Opiates: Naltrexone, Methadone, Clonidine

Nicotine: Nicotine replacement (gum, patches, spray),
Bupropion

Stimulants: [None to date]
Treatment of Chronic
Alcoholism
•Hospitalization,
psychotherapy
and
nutritional therapy may be needed.
 Drug therapy includes:
•Benzodiazepines e.g. Diazepam (Valium),
Lorazepam (Ativan), others are used to
prevent alcohol withdrawal symptoms.
They are preferred over barbiturates
because of their wide margin of safety.
The dose must be tapered slowly over 1-7
days to prevent withdrawal symptoms,
seizures, and delirium
Alcohol Relapse Prevention
The Disulfiram
drug given by (Antabuse)
itself to nondrinkers
has little effects however, it causes extreme
discomfort to patients who drink alcohol
(Flushing,
throbbing
headache,
nausea,
vomiting,
sweating,
hypotension
and
confusion).
Disulfiram acts by inhibiting aldehyde
dehydrogenase thus, alcohol is metabolized
as usual but acetaldehyde accumulates.
Acetaldehyde
will
form
the
toxic
intermediates; methanol and formaldehyde.
• Naltrexone is an opioid receptor antagonist
used primarily in the management of alcohol
dependence and opioid dependence (blocking
the drugs’ euphoric effects) by adjusting natural
endorphin levels in the brain
• Acamprosate (Campral) reduces alcohol relapse
rates by treating post-acute withdrawal
syndrome from alcohol : stabilize the chemical
balance in the brain by modulating glutamatergic Nmethyl-D-aspartate receptors and gamma
aminobutyric acid(GABAA) receptors
Treatment of opioid addiction
Hospitalization
Opioid Withdrawal
• Clonidine cocktail
– Clonidine (stimulating α2-receptors in the brain), antiinflammatory drugs, medications for nausea, diarrhea,
cramping, etc.
– Most common approach
• Substitution and taper
– Can use any opioid; tramadol (Ultram) is commonly used;
can also use methadone, buprenorphine, etc.
• Ultra-rapid detox
– Opioid blocker (e.g., naltrexone or naloxone) administered
under general anesthesia
– Expensive and now a discredited approach
Opioid Relapse Prevention
• Naltrexone
– Opioid blocker
– Compliance is often the issue
• Methadone
– Full opioid agonist
– “Gold standard” for past 50 years
– Only administered for addiction at federally licensed
opioid treatment programs (“OTP’s”)
• Buprenorphine (Suboxone, Subutex)
– “Next generation” methadone
Methadone
 Pharmacologically similar to morphine
 It has less sedative action
 Its duration of action is considerably longer
(plasma half-life >24 hours)
 The physical withdrawal syndrome and
psychological dependence are less than with
morphine
 Widely used to treat morphine and diamorphine
addiction
 In the presence of methadone, an injection of
morphine does not cause the normal euphoria
• Buprenorphine (Subutex, Suboxone)
Advantages
– Partial opioid agonist  has properties of
both a blocker and activator
– Reduces cravings
– Less abusable than methadone
– Less dangerous in overdose than
methadone
– Legally possible to prescribe in standard
outpatient clinic  easier to access than
methadone clinics
Opioid Antagonists
Naloxone
 The first pure opioid antagonist, with affinity for all three
opioid receptors
 It blocks the actions of endogenous opioid peptides as
well as those of morphine-like drugs
 Given on its own, naloxone produces very little effect in
normal subjects
 It produces a rapid reversal of the effects of morphine
and other opioids
Disadvantages
• Its effect lasts only 2-4 hours (shorter than that of most
morphine-like drugs)
Opioid Antagonists
Naltrexone
• very similar to naloxone but with the
advantage of a much longer duration of
action (half-life about 10 hours).
Tobacco
• Nicotine Replacement Therapy
• Bupropion (Wellbutrin, Zyban)
• Varenicline (Chantix)
Nicotine Replacement Therapy
• Many forms
– Patch
– Gum
– Lozenge
– Inhaler
• Usually not prescribed long enough; pts may
need to be on NRT for months, years, or even
lifetime (benefits outweigh costs)
Bupropion
• “Zyban” is specifically approved by FDA for
smoking cessation, but not different from
generic bupropion or “Wellbutrin” approved
for depression
• Unclear mechanism, but reduces reward from
smoking cigarettes and reduces craving
Varenicline “Chantix”
• MOA ; Partially activates same receptors that
nicotine does
• Analogous to Buprenorphine (Suboxone) for opioid
addiction
• Start taking it 1 week before quit date
• Very expensive
• Some reports of adverse psychiatric effects
Treatment of Stimulant Dependence
• There are no proven medications for the
treatment of stimulant addiction
• Symptomatic treatment
• Behavioral therapies effective for treating
stimulant addiction
• Slowly decrease dose
• Medications to treat withdrawal symptoms
– Anxiety
– Depression
* NIDA
Medications for Stimulant Dependence
• Medications used to treat stimulant-induced
psychiatric symptoms:
– Antidepressants
– Antipsychotics
– Anti-anxiety agents
– Medications to treat agitation, violence
• ER and outpatient settings
• Medications to treat co-occurring psychiatric
disorders
Medications for Stimulant Dependence
• Disulfiram (Antabuse)
– Has been shown to reduce cravings for cocaine,
possibly by increasing dopamine levels
• Bupropion (Wellbutrin)
– Chemical structure is closely related to that of
amphetamine; reported to reduce cravings for
amphetamines
• Tricyclic antidepressants
- TCAs have been shown to reduce cocaine relapse
rates in patients with major depression