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Pharmacology of Alcohol
Dr. Dawn-Elise Snipes
~ Explore the impact of alcohol on neurotransmitters and major bodily systems
~ Heavy drinking worsens morbidity from chronic disease as it exacerbates the effects of hypertension, diabetes mellitus, and hepatitis, and interferes with the metabolism and therapeutic actions of various medications
~ According to the “Dietary Guidelines for Americans 2015-2020,” U.S. Department of Health and Human Services and U.S. Department of Agriculture, moderate drinking is up to 1 drink per day for women and up to 2 drinks per day for men.
Alcohol and Nutrition
~ Deficiencies in folate, thiamine, B6, omega–3, folic acid, zinc, choline, iron, copper, selenium may play critical roles
~ Increased susceptibility to inflammation and damage from alcohol use.
~ Altered neurotransmitter levels

Wernicke’s Encephalopathy
~ WE is an acute neuropsychiatric disorder caused by thiamine (vitamin B1) deficiency, symptoms include altered mental status, ataxia, and ophthalmoplegia.
~ Repeated bouts of thiamine deficiency cause severe and permanent deficits in spatial memory and increased perseverative behavior.
~ thiamine deficiency, together with binge or chronic ethanol exposures, causes progressive cognitive dysfunction and loss of neural plasticity due to reduced GABAergic inhibition and increased glutamatergic excitation.

Alcohol and Sleep Disorders
~ Heavy alcohol use may be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep-related movement disorder
~ Alcohol acts as a sedative that causes presynaptic release of GABA in the brainstem and interacts with several other neurotransmitter systems (serotonin and glutamate) important in the regulation of sleep
~ Alcohol abuse and dependence are associated with
~ down regulation of brainstem GABAergic systems following development of alcohol dependence
~ chronic sleep disturbance and disrupted melatonin rhythms

Alcohol and the Endocrine System (HPA-Axis)
~ Acute exposure to alcohol activates the HPA axis, leading to a dose-related increase in circulating ACTH and cortisol and inducing anxiolytic-like responses
~ Chronic use leads to blunted HPA-Axis response and the inhibitory control of the HPA axis was impaired in heavy drinkers (flat and the furious)
~ Chronic alcohol exposure causes a decrease in testosterone, and progesterone and an increase in estrogen
~ Chronic alcohol exposure reduces the response to TSH insufficient T4 to be converted to T3
~ Interestingly there is a significant positive correlation between free T3 and alcohol-seeking behaviors in alcohol-dependent individuals

Alcohol and the Intestinal Microbiota
~ Alcohol-induced changes in the gut and intestinal microbiota composition contribute to the link between alcohol-induced oxidative stress and intestinal hyperpermeability to bacteria and toxins and systemic inflammation, and tissue damage/organ pathologies including the development of alcoholic liver disease (ALD)
~ Dysbiosis can be caused diet, disruption of circadian rhythms, illness, stress and alcoholic beverage consumption

~ Alcohol impacts nearly every system of the body and alters levels of most neurotransmitters
~ Chronic alcohol use can lead to HPA-Axis dysregulation
~ Increases in GABA and stimulation of mu-opioid receptors caused by alcohol can have dangerous additive effects when combined with benzodiazepines or opioids.
~ Alcohol may also potentiate SSRIs
~ Alcohol causes excitotoxicity in the brain resulting in reductions of both white and gray matter
~ Inhibition of thiamine absorption can cause a life-threatening condition called Wernicke-Korsakoff’s syndrome and should be a consideration when people present with sudden onset cognitive symptoms.

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