ALCOHOLS

CHRONIC EFFECTS
ETHANOL
 Withdrawal reactions of chronic alcohol use
 Sedative hypnotic o Insomnia
 Few medical applications o Hyperexcitation
 Abused as recreational drug o Delirium tremens
 Rapidly and completely absorbed (empty stomach)  NTAs that decrease in chronic alcohol use
 Distributed to most body tissues o Serotonin
 Volume of distribution is equivalent to total body water o Opioids craving
(0.5-0.7 L/kg) o Dopamine
Two enzyme systems that metabolize ethanol to acetaldehyde:
1. Tolerance
1. ALCOHOL DEHYDROGENASE (ADH)
o Occurs as a results of CNS adaptation
2. MICROSOMAL ETHANOL-OXIDIZING SYSTEM (MEOS)
o Partly by increase rate of ethanol metabolism
ALCOHOL DEHYDROGENASE (ADH) o Cross-tolerance to sedative-hypnotics that facilitate
GABA activity
 Cytosolic o Psychological dependence
 NAD-dependent o Physical dependence (abstinence syndrome)
 Found in the liver and gut
 Metabolism of low to moderate doses of ethanol 2. Liver
o Blood ethanol level of 100 mg/dl and below o Alcoholic hepatitis
 Zero-order kinetics reaction due to the limited supply of o Liver cirrhosis
NAD o Liver failure
 Fixed capacity metabolism of 7-10 g/h in the liver o Liver cancer
o Reduced gluconeogenesis
 At increase doses, it becomes independent of the
 Hypoglycemia
concentration of the drug
 Increase ketoacidosis  ”beer belly”
MICROSOMAL ETHANOL-OXIDIZING SYSTEM (MEOS)  Increase triglyceride synthesis
3. GIT
 Increases its activity with chronic exposureto ethanol or to
o Gut wall
inducing agents like barbiturates
 Irritation
 Partially responsible for the development of tolerance to
 Inflammation
ethanol
 Bleeding and scarring
 Ethanol induces the MEOS activity o Absorption defects
 One isoform of cytochrome P450 induced by ethanol converts  Decrease gastric and pancreatic secretion
acetaminophen to a hepatotoxic metabolite o Exacerbate nutritional deficiencies
 Malabsorption of vitamins in the small intestines
o Gastritis and pancreatitis
4. CNS
o Symmetrical peripheral neuropathy
 Damaged left = damaged right
o WERNICKE-KORSAKOFF syndrome
 Thiamine/vitamin D deficiency with ethanol
 Irreversible
 Ataxia
 This enzyme is inhibited by  Confusion
o Disulfiram  Paralysis of extraocular muscles
o Metronidazole o KORSAKOFF PSYCHOSIS
o Oral hypoglycemics  Memory loss
o Some cephalosporins  Prompt treatment with IV thiamineis essential to
prevent permanent brain damage
 Asians may have deficiency of the enzyme (ADH) and 5. Endocrine
experience nausea and flushing o Hypoglycemia, ketosis
o Derangement in steroid balance
FEMALES MALES
 Gynecomastia
Lower total body water Higher total body water
Fats do not have water Muscles have water  Testicular atrophy
Decrease ADH Increase ADH  Salt retention
Slower metabolism of ethanol Faster metabolism of ethanol 6. Cardiovascular
o Increased incidence
 HPN
ACUTE EFFECTS
 Anemia
1. CNS
 Dilated cardiomyopathy
o Chronic alcoholics
o “Binge” drinking can cause arrhythmias
 Tolerant and can function almost normally at much
o Mild to moderate drinking (10-15 g/day) may protect
higher blood levels than occasional drinkers
against coronary disease
o Additive depression with the use
o Raises serum levels of HDL and cholesterol
 Sedative-hypnotics
o Martini or red wine
 Opioid agonists
 1 glass for females
 Drugs that block muscarinic and H1 histamine
 1-2 glasses for males
receptors
7. Blood
o Facilitates the action of GABA at GABAA receptors
o Folic acid deficiency anemia
o Inhibits the ability of glutamate to activate NMDA (N-
o Iron deficiency anemia
methyl-D-aspartate)
8. Fetal alcohol syndrome
o “Blackouts” o Terratogenic
o Modifies the activities of  Mental retardation (most common)
 Adenyl cyclase
 Growth deficiencies
 Phospolipase C
 Microcephaly
 Ion channels  Midfacial hypoplasia
 Joint defects
 Heart defects
9. Neoplasia
o Increased incidence of neoplastic disease
 GIT
 Mouth
 Pharynx
 Larynx
2. Other organs
 Stomach
o Decrease contractility of the heart
 Liver
o Relaxes the vascular smooth muscles
 Breast
 Vasodilatation
10. Immune system
 Hypothermia
o Enhances inflammation in the liver and pancreas
o Relaxes the uterine muscles
o Inhibits immune function in other tissues
 o Predisposes to respiratory tract infection

TREATMENT OF ACUTE AND CHRONIC ALCOHOLISM

1. Excessive CNS depression
o Vital signs
o Prevention of aspiration
o IV dextrose
o Thiamine administration
o Correct electrolyte imbalance
2. Alcohol withdrawal syndrome
o Thiamine
o Sedative-hypnotic
 Diazepam and chlordiazepoxide
 Gradual dose tapering
o Clonidine, propranolol
3. Treatment of alcoholism
o High relapse rate
o Disulfiram
 Aldehyde dehydrogenase inhibitor
o Naltrexone
 Opioid receptor antagonist
 Targets CNS neurotransmitter system
o Acamprosate
 NMDA glutamate receptor antagonist
o Ondansetron
 5-HT3 serotonin receptor antagonist

ALCOHOL-DRUG INTERACTION
 Induction of smooth endoplasmic reticulum
 Chronic
o Enzyme inducer of liver
 Acute
o Inhibits metabolism of other drugs
o Additive
 Sedative effect with sedative-hypnotics
 Vasodilator effect with hypoglycemic agents
o Anti-platelet action with aspirin

OTHER ALCOHOLS
METHANOL
 Wood alcohol
 Substitute used by alcoholics
 Constituent of windshield cleaners
 Intoxication
o Visual dysfunction
o GI distress
o Shortness of breath
o Loss of consciousness
o Coma
 Metabolized to formaldehyde and formic acid
o Severe acidosis
o Retinal damage
o Blindness
 Retarded by IV ethanol
o Acts as preferred substrate for ADH
o Competitively inhibits the oxidation of methanol
 Industrial exposure
o Inhalation
o Skin absorption
o Self-administration
 Drinking antifreeze products

ETHYLENE GLYCOL
 Severe acidosis
 Renal damage
 Oxidized to oxalic acid
 Retarded by IV ethanol or fomepizole