Phys Response to Alcohol Flashcards
(28 cards)
In what 3 forms is less than 10% of the consumed ethanol excreted?
Urine, Sweat, Breath
Where is most of the ethanol absorbed (specific)?
Proximal portion of small intestine (20% in stomach and large bowel)
What are the three main ethanol metabolism pathways? Which pathway does the bulk of the metabolism?
- Alcohol Dehydrogenase (ADH) pathway -> BULK of metabolism
- Microsomal Ethanol-Oxidizing System (MEOS) pathway
- Peroxisome pathway
In the ADH pathway, where does metabolism take place?
Cytosol of hepatocytes
In the ADH pathway, what is the limiting reagent?
NAD+
In the ADH pathway, what are the products of ethanol metabolism?
Acetalaldehyde and NADH
In the ADH pathway, where is the acetalaldehyde metabolized?
Mitochondria
In the ADH pathway, what metabolizes the acetalaldehyde? What is it broken down into?
- Acetalaldehyde dehydrogenase
- Acetate (and NAD+ -> NADH)
In the ADH pathway, does the rate of ethanol metabolism increase with a higher BAC?
No (zero-order kinetics)
Where does the MEOS pathway take place?
Liver Microsomes
Under what condition does the MEOS pathway initiate?
High BAC (common with chronic alcoholism)
What are the oxidizing factors involved in the MEOS pathway?
Cytochrome P450, Enzyme CYP2E1, NADPH (Not NAD+)
What is the enzyme used for ethanol metabolism in the peroxisome pathway?
Catalase (H2O2 -> H2O)
Does the peroxisome pathway play a major role in alcohol metabolism under normal physiological conditions?
No (b/c requires H2O2)
What metabolite ratio is increased in the liver through ethanol metabolism?
NADH/NAD+
How does the increased NADH/NAD+ ratio affect glycolysis?
Increase in glycolysis
-Pyruvate -> lactate (lactic acidosis)
How does the increased NADH/NAD+ ratio affect the TCA cycle?
Increase in TCA cycle
-Oxaloacetate -> Maleate
(prevents gluconeogenesis-“fasting hypoglycemia”)
-> Increases ketogenesis (ketoacidosis) and lipogenesis (hepatosteatosis)
How does the increased NADH/NAD+ ratio affect the posterior pituitary?
Inhibits ADH output (dehydration) and oxytocin output (can delay labor)
How does the increased NADH/NAD+ ratio affect the hypothalamus?
Increases corticotropin-releasing factor/hormone secretion
increases post-gang sympathetic nerve discharge
What are the two main inhibitors of ethanol metabolism?
Fomepizole - inhibits ADH
Disulfram - inhibits acetalaldehyde dehydrogenase (acetalaldehyde -> hangover symptoms; used to treat recovering alcoholics)
MOA for ethanol?
-CNS-depressing effects through GABA-A receptors
-GABA is an inhibitory neurotransmitter
A: increases Cl- conductance
B: increases K+ conductance
Adverse effects from excess acetalaldehyde?
(Hangover symptoms)
Nausea, vomiting, headaches, hypotension
Adverse effects of ethanol on CNS?
Acute: sedation, inhibition of ADH secretion, loss of inhibitions, impaired judgement, ataxia, resp. depression
Chronic: thiamine deficiency, Wernicke-Korsakoff syndrome (ataxia, confusion, extraoccular muscle paralysis)
Adverse effects of ethanol on cardiovascular system?
Acute: vasodilation, sometimes hypothermia
Chronic: dilated cardiomyopathy
