Alcohols: Pharmacology & Toxicology Flashcards
Kinetics
Organic solvent
As amphiphillic: absporption both via ‘gaps’ in between
cells and via aquaporin (alls passage of small organic
molecules)
Elimination
Significant 1st pass metabolism
Metabolised by alcohol dehydrogenase (96%)
ethanol–> acetaldehyde–>acetate
NAD dep–> NAD is rate limiting and causes
saturation
–> 0 order kinetics
Induction enzymes: CYP system
Excreted renally and via lungs (4%)
Mechanism of Action
Acute Exposure: Increases effect of serotonin on 5HT3R as well as ACh on Nicotinic R–> both activate cation channels–> stimulation –> ‘Thrilled state’
Increase alcohol amount: CNS depressant effects dominate. Inhibition of glutamate action on NMDA. Increase effect of GABA A R–> hyperpolarisation
Chronic Consumption: slight decrease on GABA A R. Prolif of Ca channels + NMDA
Overall effect
Depression of CNS
Disinhibition in dopaminergic mesolimbic reward pathway–> addictive
Effects of Ethanol
Euphoria
Decreased inhibition and articulation of speech
Feeling of warmth due to stimulation of nerve endings
Vertigo
Ataxia
Aggression
Anxiolytic
Increased urination
Gastric irritation–> acute alcoholic gastritis
Pathological Drunkenness: small amounts of alcohol inducing deep personality changes
Legal Regulations
Lethal Blood Alcohol
Hungary: 0 tolerance when driving
>0.5g/l–> crime
>0.8g/l–> 5x increased probability of an accident
Lethal (due to respiratory depression) blood alcohol can be as high as 5g/l; varies.
Acute Intoxication
Increased risk of trauma
Most severe case: central resp depression (level of medulla)
Th: artifical respiration; gastric lavage
Therapy: Methanol Poisoning
Fomepizole:
Inhibits alcohol dehydrogenase–> decreases production of acetaldehyde
(Methanol–> formaldehyde TOXIC)
Chronic Alcoholism
Peripheral Neuropathy Demyelination of fibers in CNS Wernicke Encaphalopathy Korsakoff: psychosis, confabulation Dementia Pellagra (vit B6 def.) Short term memory loss
Effect of Ethanol on:
CV System
Moderate amounts may be beneficial: French Paradox
J formed curve; at 1 unit per day–> prev. atherosclerosis
Increase HDL
Higher amounts
Alcoholic CMP; degeneration of cardiac muscle
Increase probability of stroke
Effect of Ethanol on:
GIT
Increase HCl and enzyme secretion–> ulceration, GERD
GI cc
Pancreatitis
Effect of Ethanol on:
Liver
Inhibition of beta oxidation–> steatosis + oxidative stress–> cirrhosis
Decrease of urea cycle function–> hepatic encephalopathy
Treatment of Hepatic Encephalopathy
Lactulose
Effect of Ethanol on:
Hormonal System
Vitamins
Hormonal System:
Feminisation, Anovulatory cycle
Vitamins: deficiency
Esp B6 –> anaemia u.A.
Fetal Alcohol Syndrome
No statistical correlation under 2 stand glasses/day
Recommendation: 0
Craniofacial malformations
Mental retardation
Growth retardation
Increased susceptibility to infections
Spontaneous abortions
Premature labour
Fetus may be born drunk:
Resp depression
Withdrawal Symp
Tolerance
Genetic Factors (asians have lower alcohol dehydrogenase system)
Acquired: Induction of enzymatic system
Dependence
Physical: Basis of withdrawal
Physiological: dopaminergic reward pathway
