Alcohol

3 types of alcohol

methanol

ethanol

ispropanol

methanol

toxic

freezes

coma and death

ethanol

“dirty drug”—varied mechanisms

alcohol like we know it

fermentation of sugar and yeast

calories; no nutritional values

chornic alcohol users can suffer from malnutrition

isopropanol

toxic

rubbing alcohol

blood alcohol concentration (BAC)

influence behavioral effects rather than the amount ingested

• a 12 oz beer, 5 oz glass of wine, 1.5 oz of spirits, or 12 oz of wine cooler will each raise your BAC by the same amount

low risk drinking (women)

no more than 3 drinks in a day, 2 in a week

low risk drinking (men)

no more than 4 drinks in a day, 14 in a week

symtoms of alcohol poisoning

unconsciousness

vomiting

slow ad irregular breathing

cold, clammy, bluish skin

alcohol metabolism

Some people have genes that code for an inactive form of ALDH. Drinking alcohol results in a build-up of toxic acetaldehyde, causing flushing, nausea, and vomiting, tachycardia, headache, dizziness, etc.

GABA

agonist

CNS depressant effects

Glutamate

antagonist (post-synaptic)

release of glutamate (pre-synaptic)

CNA depressant effects

Dopamine

increased transmission of DA in the limbic system

rewarding effects

opioid

increase in endogenous opioid synthesis

rewarding effects

ethanol is …

a GABA (a) receptor noncompetitive agonist

a GABA (a) receptor noncompetitive agonist…

• increases Cl- conductance

• hyperpolarizes the membrane—less excitable

  • widespread inhibition

• binds at a different site from GABA and from benzodiazepines, etc.

  • dangerous to combine alcohol and similar drugs

• responsible for anxiolysis (reduced anxiety), loss of inhibitions, loss of coordination, sedation (drowsiness)

ethanol is an…

NMDA receptor noncompetitive antagonist (at high doses)

NMDA receptor noncompetitive antagonist (at high doses)

• redudces Na+ and Ca2+ conductance

• hyperpolarizes the membrane—-less excitable

• responsible for some cognitive effects of alcohol

  • imapried learbing and memory

  • psychotomimetic effects 

ethanol increases … release by inhibiting GABA neurons in the VTA

dopamine

glutamate

receptor antagonism and reduces release

memory loss

GABA

acutely enhances GABA-induced Cl- influx to hyperpolarize

sedative effects: anxiety reduction, sedation, incoordination, memory impairment

dopamine

acute increase in transmission in mesolimbic tract

reinforcement

opioids

acute increase in endogenous opioid synthesis and release

reinforcement

brain areas affected by alcohol

prefrontal cortex

amygdala

VTA

cerebellum

hypothalamus & pituitary gland 

hippocampus

prefrontal cortex

judgement, decision making, motivation (glutamate, GABA, dopamine)

amygdala

stess and emotional response

VTA

attention deficits, substance abuse (dopamine)

cerebellum

motor coordination (GABA)

hypothalamus & pituitary gland

changes in sexual desires and performance; temperature regulation

hippocampus

learning and memory deficits, seizures depression

physical dependence

intensity and duration of withdrawal are dependent on the amount and duration of drug taking

hangover may be ebidence of 

withdrawal or a sign of acute toxicity

withdrawal symtoms:

• tremors

• anxiety

• high blood pressure

• rapid heart rate

• sweating

• rapid breathing

• nausea

• vomiting

• delirium tremens

delirium tremens

convulsions, unstable blood pressure, hallucinations, disorientation, panic attacks

long term of heavy alcohol use brain damage

direct damage from the alcohol itself

elevated acetaldehyde 

insufficient liver function, inadequate nutrition

Korsokoff’s syndrome

progressive permanent loss of memory function

anterograde amnesia

inability to form new memories

retrograde amnesia

inability to retrieve old memories

• caused by damage to the thalamus from chronic vitamin B1 deficiency

liver disease

Liver triglycerides accumulate in liver cells

alcohol is metabolized first, leaving fats for storage

Coffee has been shown to help fight liver disease

alcoholic hepatitis

liver cell damage caused by the accumulation acetaldehyde

alcoholic cirrhosis

The death of liver cells stimulates scar formation

• eventually, the blood supply is cut off

fetal alcohol syndrome

• Alcohol readily passes through the placental barrier and fetus quickly reaches the same BAC as the mother

• Fetal alcohol syndrome (FAS) refers to the damaging developmental effects of prenatal alcohol exposure

• effects

  • Intellectual disability and cognitive/behavioral developmental delays

  • Low birthweight

  • Distinctive craniofacial malformations

  • Other physical abnormalities: cardiac, kidneys, testes, skeletal in fingers and toes

pharmacokinetic treatment of alcohol

• Reducing withdrawal symptoms

  • Use alternative GABA(a) agonists, including benzodiazepines such as diazepam (Valium)

  • Used with Detox programs

Disulfiram

inhibits ALDH (converts ALDH to acetic acid in the normal metabolism of alcohol)

Naltrexone (Vivitrol)

an opioid receptor antagonist; it reduces alcohol consumption and craving and improves abstinence rates

CRF1 antagonists

repeated episodes of intoxication and withdrawal lead to increased CRF1 receptors in the amygdala, sensitization of the reactivity to stressors, and significantly elevated rates of alcohol consumption

Ketamine

NMDA glutamate receptor antagonist: could reverse the hyperexcitable state in withdrawal

Glucocorticoid receptor (GR) antagonist

reduced alcohol self-administration and craving