Transcript Pharmacologic Treatment Options for Alcohol Dependency

Pharmacologic Treatment
Options for Alcohol Dependency
Damon Landreau, D.O.
LCDR/USPH/USCG Flight Surgeon
Objectives
• Review basic neurobiology
• Review “road ahead” views of Alcohol
Dependency
• Review treatment options
• Look at a few Coast Guard Pictures
Neurobiology 101
• Neurons are the functional unit of the nervous
system
• They release neurotransmitters(NT) via electrical
impulses – we currently know of about 60
• Neurotransmission occurs in 3 basic stages
– Sending neuron releases NT via electrical impulses via
flow of Na and K
– Receiving neuron binds the NT at a receptor
– Chemical changes happen that are similar to the
process of the sending neuron
Understanding this process is the
key to understanding dependency
Implications
The process for neurotransmission is highly
regulated on the molecular level.
1. Dysregulation is the core molecular problem
of dependency
2. Symptoms of dysregulation may be overcome
with treatment.
Mesolimbic Dopamine System (MDS)
• Primal emotional center of the brain
• Components
– Anterior cingulated cortex – autonomic nervous
system, cognition, decision making
– Ventral tegmental area – primary site of drug
actions
– Nucleus accumbens - pleasure center
– Frontal/prefrontal cortex – executive functions
– Amygdala – emotional center
Drug Dysregulation
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Down/Up regulates production of NT
Depletes NT stores
Blocks release of NT
Inhibits NT transport systems
Binds to receptors blocking NT
Blocks the second messenger - electrical and
chemical impulses caused by NT
USCG Medical Mission
• Provide Healthcare to active duty and reserve
personnel to support USCG missions
• Maintain medical and dental readiness for
world wide deployment
• Oversight of occupational and preventative
services
USCG Clinics
Alaska
Hawaii
Drugs Effects - Molecular Level
Drug
Effects
Nicotine
Acetylcholine
Amphetamine , Cocaine
Dopamine
Marijuana
Endocannabinoids
Opiates
Endorphins
Benzo’s
Gamma-aminobutyric Acid (GABA)
LSD
Serotonin
Note – very specific actions
The Neurobiology of Addiction, Erickson, C.K. , 2009 pg 33
Alcohol
Neurotransmitter system
Effects of alcohol
Gamma-aminobutyric acid (GABA)
Enhance
Glycine
Enhance
Acetylcholine
Enhance
Serotonin
Enhance
Adenosine triphosphate (ATP)
Inhibit
Glutamate
Inhibit
Voltage-gated (several)
Enhance + inhibit
Principles of addiction medicine, 3d ed, 2003, page 104 [ISBN = 1-880425-08-4].
Compliments of Dr David Franz
Genetic Predisposition
Drugs
% Dependency Over Time
Nicotine
32%
Heroine
23%
Crack
20%
Cocaine
17%
ETOH
15%
Stimulants
11%
Opiates
9%
Sedatives
9%
Marijuana
9%
The Neurobiology of Addiction, Erickson, C.K. , 2009 pg 47
47’ Motor Life Boat
22 knot cruising speed
Twin 435 HP diesel engines
Self rights in 10-30 seconds
Road Ahead
• Approaching Dependency as a Chronic Disease
– Expect relapse
– Success greatly depends on behavioral changes
– Medications may help
• Disease Management Systems
• Exploring Medications as more Neurobiology
is understood
• More research and doing away with the
untreatable stigmata
25’ Defender Class Boat
45 knot
Twin 225 HP motors
Security and River patrols
Medications
• Will not cover alcohol detox
• FDA and non-FDA options
• Much is expert opinion
Clev Clin J Med 2006;73:641 [PMID = 16845975]. Compliments of Dr David Franz
Naltrexone
• Opioid Antagonist
• Decreases the acute pleasure of drinking by
blocking endogenous opioids that reinforce
the pleasure
• Reduces relapse frequency in ~ 50% of
alcoholics
• More effective when there is a strong Family
History of ETOH
Naltrexone
• Dosage
• Oral 50-100 mg/day for 12 weeks
– Some advocate 6-12 months of treatment
• Depot naltrexone – 380 mg IM (gluts) q 4
weeks.
– Monitor for local injection site complications
• FDA approved
Naltrexone
• Contraindications
– Opioid Use – consider drug testing
– Acute Hepatitis
– Acute liver failure
• Side Effects
– Nausea, headache, dizziness – most common
210’ Medium Endurance Cutter
Acamprosate (Campral)
• Exact mechanism is unknown, but it targets
the glutamate system
• May helps in decreasing the amount of ETOH
used
• Renal clearance – consider with liver disease
• FDA approved
Disulfiram (Antabuse)
• Increases amount of acetaldehyde after ETOH
• Causes a noxious reaction
• Not very effective – it has shown to decrease
the amount ETOH but not abstinence
• FDA approved
H-65 "Dolphin" - Short Range Recovery Helicopter
Ondansetron (Zofran)
• Affects the corticomesolimbic dopamine
pathway and effects the reward pathways that
are activated by alcohol
• Most effective for early onset alcohol
dependence.
• Not FDA approved
Topiramate (Topamax)
• Increases GABA and decreases glutamate
function (opposite of ETOH)
• Reduces # of heavy drinking days
• Increased # abstinent days
• Not FDA approved
Baclofen
• Alcohol alters the balance between gammaaminobutyric acid (GABA) and glutamate
• Baclofen increases GABA function
• May reduces alcohol cravings and leads to a
higher rate of abstinence
• Not FDA Approved
National
Maritime
Center
Varenicline (Chantix)
• Antagonizes nicotinic acetylcholine receptors
• May reduce the rewarding properties and
cravings
• Not FDA approved
SSRI
• May be more effective when:
– Co-Morbid depression
– Older age with onset of ETOH
– Not a strong family history
Pharmacologic Strategies to Reduce
Drinking Behavior
• Reduce ETOH seeking and craving
– Naltrexone, ondansetron, topiramate
• Reduce dysphoria and sxs of acute and protracted
withdrawal
– Acamprosate, sedatives, baclofen, anti-epileptics
• Reduce ETOH bioavailability
– Kudzu, alpha 2 antag (clonidine)
• Reduce impulsivity/attention deficits
– Dopamine agonist and antagonist, ondansetron
• Treat comorbid psychiatric disease
– TCA, SSRI, antipsychotics, buspirone
Adapted from Pharmacologic Interventions for the Treatment of Addiction – Dr. Marvin Seppala
Questions?