Pharm Winter Exam 1 Ethanol

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Drugs for treatment of alcoholism

Back 1

1) Disulfram
2) Diazepam
3) Chlordiazepoxide
4) Naltrexone
5) Acamprosate
6) Fomepizole

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Ethanol

Mechanism

Back 2

Agonist GABAa
Inhibits NMDA
Long term ETOH use causes down regulation of GABAa and up regulation of NMDA

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Ethanol

Effects

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1) Low dose- inhibits inhibitory pathways: disinhibition
2) High dose-inhibits excitatory pathways:General CNS depressant
3) Impairment of intellectual and motor function
4) Anterograde amnesia

Front 4

Ethanol

Pharmacokinetics

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1) Absorbtion: Stomach, Small intestines, faster on empty stomach
2)Gastric metabolism of ETOH slower in women
3)Distributed in body water: crosses Blood brain barrier and placenta

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Ethanol

Metabolism

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1)Alcohol dehydrogenase-> acetaldehyde
2) Aldehyde dehydrogenase-> acetic acid
3)Zero Order kinetics
4)Induces CYP 2E1

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Ethanol

CNS Effects Low concentration

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1) Disinhibition
2) Decreased anxiety
3) Mild euphoria
4) Sedation

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Ethanol

CNS Effects high concentration

Back 7

1) Motor and Judgment impaired
2) Speech slurs
3) Ataxia

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Ethanol

Smooth Muscle effects

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1) Vasodialation (hypothermia)
2)Relax uterus (stop preterm labor)

Front 9

Ethanol

Kidney effect

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1) Reduce ADH = Diuresis

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Ethanol

Toxicity

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1) Emesis 6) Metabolic and
2) Stupor Electrolyte disturbance
3) Coma 7) Hypothermia
4) Respiratory depression
5)Death

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Ethanol Chronic Consumption

Malnutrition

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1) Alcohol has calories may displace food
2) Folate and thiamine

Front 12

Ethanol Chronic Consumption

Gastritis and Pancreatitis

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1) Direct Damage of pancreas
2) Erosive gastritis and malabsorption
3) Lesions of duodenum and esophagus

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Ethanol Chronic Consumption

Hepatotoxicity

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1) Heavy drinkers develop liver disease
2) Reduces glutathione =Oxidative stress
3) Acetaldehyde accumulates = mitochondrial membrane damage
4)Fatty liver, Fibrosis, Cirhosis
5) Combined with Hep B or C increased risk of liver cancer

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Ethanol Chronic Consumption

Cardiovascular effects

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1) Cardiomyopathy
2) Hypertention
3) Stroke

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Ethanol Chronic Consumption

Teratogenicity

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1) Mental retardation
2) Congenital malformations
3) Fetal alcohol syndrome

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Ethanol Chronic Consumption

Other effects

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1)Increased carcinogenicity: tobacco
2) Mild anemia
3) Sexual dysfunction
4) Decreased immune function
5) Wericke-Korsakoff
6) Peripheral Neuropathy
7) Skeletal muscle atrophy
8) Hypothermia

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Ethanol

Tolerance and Dependence

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1) Tolerance develops to effects because of increased metabolism.
2) Severe withdrawal syndrome
3) Cross tolerance with Barbituates, Benzodiazepines and general anesthetics
4) Lethal Dose not changed

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Ethanol

Withdrawal

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1) Anxiety,
2) Irritability,
3) Nightmares,
4) Nausea,
5) Tachycardia,
6) Palpitations

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Ethanol

Severe withdrawal

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1) Anxiety,
2) Fear,
3) Hallucinations,
4) Delirium,
5) Tremors,
6) Tonic-clonic seizures,
7) Arrythmias,
8) Increased blood pressure

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Ethanol

Withdrawal Treatment

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1) Prevent seizures, Delirium tremens, and arrythmias
2) Long acting benzodiazepine to taper withdrawal
3) Haloperidol to treat hallucinations

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Ethanol

Naltrexone

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1) Opioid Receptor antagonist
2) Blocks ability of alcohol to stimulate reward pathway.
3) Reduces craving

Front 22

Ethanol

Naltrexone Side effects

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1) Nausea
2) Liver damage
3) Contraindicated in Liver disease, hepatitis, or liver failure

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Ethanol

Acamprosate

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1) GABA analogue
2) Restores normal balance of GABA/ Glutamate transmission
3) No Liver Toxicity

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Ethanol

Disulfiram

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1) Blocks aldehyde dehydrogenase and inhibits P450
2) If person drinks EtOH: Flushing intense throbbing headache nausea and confusion
3) Has a long duration of action (3-4 days)
4) Dangerous not recommended

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Ethanol

Disulfiram like drugs

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1) Metronidazole
2) Some Cephalosporins
3)Oral Hypoglycemic agents

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Methanol toxicity

Back 26

Converted to formate by alcohol dehydrogenase

Visual disturbances

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Ethylene glycol toxicity

Back 27

Converted to Aldehydes and oxalate by alcohol dehydrogenase

Severe metabolic acidosis

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Treatment of Methanol and ethylene glycol toxicity

Back 28

Administer ethanol to compete with alcohol dehydrogenase

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Fomepizole

Back 29

Alcohol dehydrogenase inhibitor

Few side effects