Transcript What is Alcohol?

Chapter 4
Pharmacology Of Alcohol
Associate Prof. Dr. Jawad AlMusaw (2016
)
What is Alcohol?
Alcohol is a sedative
It’s is primarily used for recreation not
medicine
2nd Largest used psychoactive drug in
the world (first is caffeine)
Alcohol’s chemical composition
CH3 CH2OH
Yellow – H Black – C Red – O
The Phamacokinetics of Alcohol Absorption
Alcohol is both soluble in fat and water
This means alcohol is absorbed though
the gastrointestinal tract and through
the Blood Brain barrier
20% is absorbed through the stomach
the other 80% through the upper
intestine
The Phamacokinetics of Alcohol Distribution
Alcohol easily crosses the Blood-Brain
barrier because it is lipid soluble
Alcohol can even cross the placental
barrier where there can be an
occurrence of fetal alcohol syndrome
(FAS). FAS occurs in 30% to 50% of all
alcoholic mothers
The Phamacokinetics of Alcohol
– Metabolism and Excrection
95% of all alcohol is digested (metabolized)
by an enzyme called alcohol dehydrogenase
85% via the liver
15% via the stomach – a full stomach can
metabolize more
Alcohol is exposed to first-pass metabolism
5% is excreted via the lungs
Metabolism of Alcohol by Men
and Women
Since men have naturally less fat than
woman and bigger blood vesicles, men have
a lower Blood Alcohol Concentration (BAC)
than woman
Also, woman have 50% less enzyme then
men, thus the metabolism rate is slower
Remember – Alcohol metabolism is zero order
Blood ethanol concentrations (mM)
10
Non-alcoholic Women
10
Alcoholic Women
Intravenous
300
10
Non-alcoholic Men
300
300
10
Alcoholic Men
300
Time after ethanol administration (minutes)
Oral
How the Liver Metabolizes
Alcohol
1. NAD+ + Ethanol  NADH + Acetaldehyde
Enzyme: Alcohol Dehydrogenase
2. NAD+ + Acetaldehyde  NADH + Acetic
acid
Enzyme: Aldehyde Dehydrogenase
3. Acetic acid  Water + CO2
Uses ATP ATP  AMP
Disulfiram inhibits Aldehyde Dehydrogenase
Step 2 is the rate limiting step
More on Metabolism
BAC is measured in grams of alcohol
per liter
.08 is the legal limit in New York
An average person can metabolize 8 to
10 milliliters of pure alcohol per hour
More than that, BAC increases
Weight is a big determiner in the
concentration of alcohol
Phamacodynamics of Alcohol
Suppresses Calcium-ion Currents
Alterates of cAMP and the SodiumPumps
Also effects Glutamate systems
(excitatory) and GABA Systems
(inhibitory)
Effects Serotonin and Dopamine
Systems
Glutamate Receptors
Inhibitor of NMDA-subtype of Glutamate
Receptors
Depresses responsiveness of NMDA
receptors
Acoamprosate an anti-craving drug to
alcohol interacts with NMDA receptors
Glutamate Antagonist
GABA Receptors
Ethanol is a GABA agonist, binds to a
subunit of the GABAA receptor
It increases Cl- ions thus
hyperpolarizing the cell
Low doses of alcohol can reduce panic
and anxiety
Other pharmacodynamic effects
Chronic use of Alcohol changes mRNA
of the Neuron
As a result, Ach, DA, opioid and
serotnin systems are effected
Abuse potential maybe due to increase
in dopamine
Pharmacological Effects
Alcohol effects many different functions
of the brain
Alertness, motor functions, and
intellectual abilities decrease
Combined with other sedatives
(benzodiapines), this increase the
sedativeness of alcohol
Pharmacological Effects – Cont.
Alcohol dilates blood vessels, thus releasing
more body heat and decreasing blood temp.
Large doses of Alcohol increases the risk of
heart failure
Small Doses decrease the risk of coronary
disease
Alcohol is a diuretic – it decrease the amount
of diuretic hormone thus increasing the
excretion of water
Psychological Effects
Low amounts of Alcohol have minimal
Change in behavior < .04 BAC
From .04 - .10 BAC, your 4x more likely
to get into an accident
.12-.18 Likelihood increases to 25x
.23-.29 your in a stupor
.30 - .33 your in a coma
.39 and greater, your dead
Psychological Effects – Cont.
50% of all highway crimes and
accidents are alcohol related
Health Effects
Alcohol is highly caloric but has little
nutritional value
Vitamin and trace element deficiencies
are linked to alcohol
Liver and stomach cancers
Tolerance
Metabolic Tolerance – Increase of alcohol
digesting enzyme by the liver
Behavioral Tolerance – Brain adapts to
amount of drug present. A tolerant person
can have a BAC 2x the amount of a
nontolerant and act the same
Environmental – the same environment over
time when drinking increases tolerance.
Changing the environment decrease tolerance
Dependence
Many be do to either increase in dopamine
and/or the effect of decreased anxiety
Withdrawal and alcohol seizures may occur in
10% of people who stop taking alcohol
This is due to the neuron producing more
glutamate to counteract the effects of
increased GABA
When GABA leaves, there is an
overabundance of glutamate, thus causing a
seizure
Dependence – Cont.
Other effect of withdrawal include
hallucinations, psychomotor, agitation,
confusion
This syndrome is also known as
delirium tremens (DT)
Side effects and Toxicity
Liver damage – 75% of all deaths due
to alcoholism are caused by cirrhosis of
the liver, the 7th most common cause of
death in the US
Other effects are Panreatitis and chronic
gastritis causing peptic ulcers
Side effects and Toxicity – Cont.
The metabolizing of alcohol produces
free radicals, causing cancer in the liver
and some hypothesis breast cancer also
Alcohol has immunosuppressive effects
thus promoting tumor growth
Teratogenic Effects
FAS – Fetal Alcohol Syndrome is
accountable for 3 to 5 birth defects in
1000
Causes low intelligence, mental
retardation, behavioral abnormalities
There is retard body growth
Facial Abnormailities
Teratogenic Effects – Cont.
Adolescents engage in anti-social
behavior
These people are slow learners
Congenital heart defects
The point is – drinking is bad if you are
pregnant, do not do it.
Alcoholism & It’s
Pharmacological Treatment
1950s : American Medical Association
recognized the syndrome of alcoholism
as an “ILLNESS”
 1970s : Alcoholism redefined as a
“CHRONIC, PROGRESSIVE, AND
POTENTIALLY FATAL DISEASE.”
Alcoholism & It’s Pharmacological
Treatment – Cont.
1992: Alcoholism is characterized by impaired
control over drinking, preoccupation w/the
drug “alcohol”, use of alcohol despite adverse
consequences ( impairments in such areas as
physical health, psychological functioning,
interpersonal functioning, and occupational
functioning, as well as legal financial, and
spiritual problems) , and distortions in
thinking, most notable DENIAL!
Alcoholism & It’s Pharmacological
Treatment – Cont.
Denial is nearly always the major
obstacle (integral part)
Environmental Factors seem to be
less important than Genetic Factors
Alcoholism is used as a “selfmedication” of psychological distress.
Alcoholism & It’s Pharmacological
Treatment – Cont.
Often times alcoholism is associated
with addiction to other drugs,
depression, manic-depressive illness,
anxiety disorder, or antisocial
personality
30-50% meet criteria for major
depression
Alcoholism & It’s Pharmacological
Treatment – Cont.
33% have a coexisting anxiety disorder
many have anti-social personalities
some are schizophrenic
36% are addicted to other drugs
14 million Americans have serious alcohol
problems. 7 million considered Alcoholics
100,000 Americans die each year of
alcoholism
Pharmacotherapies for
Alcoholic Abuse & Dependence:
Eliminating the taking of alcohol is an
obvious therapeutic strategy
Vaillant 60 has proven POOR long-term
outlook of alcoholism treatment (both
pharmacologic or behavioral)
Goals of Pharmacotherapy for
Alcohol Dependence & Abuse
Reversal of the severe pharmacological
effects of alcohol
Treatment & prevention of withdrawal
symptoms & complications
Maintaining abstinence & preventing relapse
by :
-using agents that decrease craving for alcohol
-stop the loss of control over drinking
-make it unpleasant to ingest alcohol
Goals of Pharmacotherapy for Alcohol
Dependence & Abuse – Cont.
Treatment of coexisting psychiatric disorders
that complicate recovery
Note:
No agent can reverse the acute
pharmacologic effects of alcohol
Pharmacotherapies are available for the
treatment & prevention of withdrawal
symptoms & complications in alcoholdependent people who are decreasing or
discontinuing alcohol
Pharmacotherapies for Alcohol
Withdrawal
Benzodiazepines are the drug of
choice for acute alcohol withdrawal
- Improve symptoms
- Prevent seizures & DTs
- Substituting this long-acting drug
prevents or suppresses w/drawal
symptoms
Pharmacotherapies for Alcohol
Withdrawal – Cont.
- The “longer-acting” benzodiazepine is
either:
- 1. Maintained at a level low enough to
allow the person to function
- 2. Or is withdrawn gradually
Drugs to Help Maintain
Abstinence
Alcohol-sensitizing drugs (including:
disulfiram & calcium carbimide) :
- Used to prevent the patient from
drinking by producing an aversive
reaction when consuming alcohol
- The drug alters the metabolism of
alcohol
Drugs to Help Maintain
Abstinence – Cont.
- Allows acetaldehyde to accumulate
which in turn causes acetaldehyde
syndrome (characterized by throbbing
headache, nausea, vomiting, chest pain
ect.)
Drugs to Help Maintain
Abstinence – Cont.
Opioid Antagonist including:
Naltrexone, Nalmefene, Acamprosate
are used in European Countries
Naltrexone:
- Used to reduce craving for alcohol
- The hypothesis is that the reinforcing
properties of alcohol involve the opioid
system
Drugs to Help Maintain
Abstinence – Cont.
- The blockade of the system by use of
naltrexone should reduce cravings by
reducing the positive reinforcement
associated w/ alcohol use
Drugs to Help Maintain
Abstinence – Cont.
Dopaminergic drugs: use in
maintaining abstinence
- Positive reinforcement associated w/
alcohol attractiveness appears to
involve the dopaminergic reward
system
- Withdrawal may be accompanied by
hypofunction of this reward system
Drugs to Help Maintain
Abstinence – Cont.
- Depression is often comorbid
(<coexisting) w/ alcohol dependency &
some dopaminergic drugs have
antidepressant results.
Drugs to Help Maintain
Abstinence – Cont.
Serotoninergic Drugs (used to treat
alcohol dependence)
- Serotonin-specific reuptake inhibitors (SSRIs)
(e.g. fluoxetine) : used for treating
depression & anxiety.
- Serotonin 5-HT1a agonist (e.g. buspirone):
used for treating anxiety. Effective in treating
comorbid anxiety in alcoholics but less
effective at reducing alcohol consumption.
Drugs to Help Maintain
Abstinence – Cont.
- Serotonin 5-HT3 antagonist (e.g.
ondansetron) : used for treating
nausea.