Alcohols

Question 1

What are the two main systems for metabolizing ethanol?

Answer 1

• Alcohol dehydrogenase

- Microsomal ethanol oxidizing systems (MEOS)

Question 2

Describe ADH

Answer 2

• Found in cytosol of cells in liver and gut
• Active enzyme with NAD+
• Metabolizes low to moderate doses of ethanol
• NAD+ is limiting, reaction exhibits zero-order kinetics (7-10 g/h)

Question 3

Describe MEOS metabolism of alcohol.

Answer 3

• Cycochrome P450, 2E1, 1A2 and 3A4
• NADPH is cofactor
• MEOS system contributes when ADH system is saturated and NAD+ is limiting
• Chronic alcohol consumption induces the MEOS (it works quicker, inducing more consumption)

Question 4

Give four membrane protein interactions that ethanol has.

Answer 4

• Allosteric ligand for GABAa receptors
• Inhibits the activity of glutamate at NMDA glutamate receptors (responsible for blackouts)
• Enzymes such as ATPase and adenyl cyclases
• IOn chanels such as K channels

Question 5

Give legal limits for blood alcohol levels

Answer 5

Impaired drivers have blood alcohol levels of 80 mg/dL (Criminal code limit) or 50 mg/dL (provincial code)

Question 6

Give two acute effects of ethanol on the body

Answer 6

• Myocardial contraction depressed at blood alcohol level greater than 100 mg/dl
• Vasodilation may result from depression of the vasomotor centre in the CNS and direct actions on smooth muscle, which can lead to hypothermia.

Question 7

Give the effects of chronic alcohol consumption.

Answer 7

• Reduced liver function
• REduced gluconeogenesis (can put you in state of malnutrition, and prevent brain functioning)
• Hypoglycemia and fat accumulation in liver
• Hepatitis and cirrhosis
• Induction of cytochrome P450 (reduced drug efficacy)
• Tolerance and dependence
• Cross-tolerance between ethanol and other sedative hypnotics
• Abstinence syndrome

Pancreatitis, gastritis, bloos and plasma protein loss, anemia and malnutrition, malabsorption of water soluble vitamins (such as B1 (thiamine)

Question 8

Give two behavioural and two pharmacological treatments for alcoholism

Answer 8

• Management of withdrawal
• Behavioural modification (eg. AA)

Disulfiram: Extreme discomfort due to buildup of acetaldehyde (blocks aldehyde dehydrogenase)

Fomepizole: Blocks ADH

Naltrexone and acamprosate may reduce cravings

Question 9

Describe ADH pathway of ethanol metabolism

Answer 9

• ADH/NAD+ converts ethanol to acetaldehyde

- Aldehyde dehydrogenase uses NAD+ to convert acetaldehyde to acetate

Question 10

Describe methanol metabolism and poisoning

Answer 10

• ADH converts methanol to formaldehyde
• Formaldehyde converted to formate, which is converted to CO2 and water

Buildup of formaldehyde and formate can cause visual disturbances, brachycardia, coma, seizures and cessation of respiration

Severe acidosis and retinal damage

Question 11

Describe ethylene glycol poisoning

Answer 11

• Sweet taste
• Toxicity related to buildup of oxalate/oxalic acid and other metabolites from ADH
• Fomepizole or ethanol can be used as inhibitors of ADH

Acidosis and nephrotoxicity