14.10 Alcohol Flashcards
Relative chemical principals
- The use of the unqualified term ‘alcohol’ means Ethyl alcohol = Ethanol = C2H5OH.
- Colourless. Clear. Volatile. Flammable liquid at room temperature
- Ethanol is odourless. (NB!) -> other chemicals in liquor you smell
- It is the congeners that gives liquor its characteristic smell.
- It is thus more correct to speak of the odour of liquor rather than the odour of alcohol.
- SG=0,79.i,e,1mlofethanol=0,79gor1lofethanol=790g
- Boiling point 78°C.
- Hydrophilic – dilutes well in water.
Synthesis of ethanol
- natural fermentation (fungus) -> converts glucose -> piruvate -> acetylocoa -> ethhanol
➡️ Saccharomyces cerevisiae - synthetic ethanol production (ethenine + water)
Distillation
- These are the processes by which the alcohol concentration can be dramatically increased by actively displacing water.
- Fractional distillation can have an alcohol concentration of up to 95% = Rectified Spirit.
- Special distillation processes can achieve a concentration of nearly 100% = Absolute or dehydrated alcohol.
Methylated spirits (diverse alcohols)
- Known by this name because the ethyl alcohol/ethanol, which it contains, was first denatured by the addition of methyl alcohol/methanol
- In SA, this practice has been discontinued due to the toxicity of methyl alcohol.
Current formula:
- Ethyl alcohol 95%
- Butyl alcohol 4%
- Pyridine base 1%
- Methyl violet (“Blue Train”) as a colouring agent
- Bitrex to denature it. (To make it bitter)
Toxicalcohols - Methanol (wood alcohol)
Toxicity:
- highly toxic to humans when ingested, inhaled, or absorbed through the skin.
- can cause severe health effects, including blindness, organ damage, and death.
- Even small amounts of methanol can be lethal.
Symptoms of Methanol Poisoning:
- headache, dizziness, nausea, vomiting, abdominal pain, and respiratory distress.
- most distinctive signs is visual impairment, including blurred vision and, in severe cases, blindness.
- visual impairment is due to the conversion of methanol to formaldehyde and formic acid in the body.
- direct CNS depression and mitochondrial cytochrome c oxidase inhibition
Metabolism and Toxic Byproducts:
- Methanol is metabolized in the body primarily by alcohol dehydrogenase enzyme, forming formaldehyde and then further metabolizing to formic acid.
- These byproducts are highly toxic and can lead to acidosis and organ damage.
Ethanol as a Treatment:
- Ethanol, or ethyl alcohol, can be used as an antidote in cases of methanol poisoning.
- Ethanol competes with methanol for the same metabolic pathways, delaying the conversion of methanol to its toxic byproducts.
- Ethanol administration can be life- saving in methanol poisoning cases.
Sources of ethanol
FOOD:
- Minimal due to fermentation processes (e.g. ginger beer) or as a solvent for in colouring agents (16 loaves of bread contain the same amount of alcohol as one metric tot of brandy).
MEDICINES:
- Alcohol is often used in the preparation of medicines in wide variations of concentration e.g. Lennon’s Balsem Vita (85% v/v), Liver Tonic (45% v/v), Bioplus (10% v/v). The concentration appears on the label.
ENDOGENOUS ALCOHOL PRODUCTION:
- Alcohol is formed in the human body as a by-product of metabolic processes
- 0,003g% blood
- But it is broken down and eliminated as quickly as it was formed.
- It is thus not reflected in normal blood tests.
NB Pharmacokinetics - Absorption
- Alcohol is absorbed directly and unchanged by means of diffusion:
GIT:
- By far the most important route of absorption.
- Alcohol is absorbed via a mucous membrane to the capillary bed and systemic circulation.
LUNGS:
- Can be breathed in as vapour or mist.
- Is absorbed quickly and completely. It is however an irritating material and a maximum level of alcohol in the blood of 0,01g% can be expected.
SKIN:
- Ethyl alcohol is not absorbed through intact skin intact.
- Theoretically, absorption through wounds is possible.
INTRAVENOUS, SUBCUTANEOUS:
- Theoretically possible.
- Subcutaneous injection will cause pain, anaesthesia and vasospasm (with weak absorption due to vasospasm).
- Intravenous ethanol infusion is used as an antidote to intubated patients with methanol poisoning.
Absorption in GIT
- the longer content stays in stomach, t
- the quicker the stomach empties, the quicker it will be absorbed
Absorption is influenced by various factors
SURFACE OF THE MUCOUS MEMBRANE:
- The small intestine has a far greater mucous membrane surface than the stomach, and alcohol will thus be absorbed much faster here than in stomach ⬆️
- If the mucous membrane is covered by mucus or food this will delay the absorption.⬇️
ABSORPTION CAPACITY OF THE MUCOUS MEMBRANES:
- The mucous membrane of the small intestine has a better supply of blood vessels than the stomach, hence absorption in the small intestine is greater than in the stomach. ⬆️
- Increases mucous membrane blood supply (warm food, gastritis, congestion) will increase uptake.⬆️
- Diffusion is dependent on the concentration gradient between the alcohol in the stomach and the BAC (Fick’s Law).⬆️
MOTILITY OF THE INTESTINE, AND FUNCTIONAL STATUS OF THE PYLORIC SPHINCTER OF THE STOMACH:
- Greater gastric motility relates to quick passage of gastric content through the pyloric sphincter with more rapid movement and absorption of alcohol in the small intestine.⬆️
- Gastric motility is increased by greater volumes of food and liquids.⬆️
- Gastric emptying is increased with gastritis and ulceration, due to irritation.⬆️
- Gastric motility is slowed down by medications (sympathomimetics), high concentration of alcohol (with paralysis of stomach muscle wall) nausea and shock.⬇️
ABSORPTION CAPACITY OF THE MUCOUS MEMBRANES:
- Surgical procedures of the stomach or duodenum (e.g. gastrectomy, gastrojejenostomy) may lead to increased emptying of content into the small intestine. ⬆️
- Irritating substances in stomach may lead to pyloric sphincter spasm, with delayed passage of contents.⬇️
- Psychological factors may influence pyloric sphincter function by either increasing or decreasing function.
NATURE, COMPOSITION, AMOUNT AND STRENGTH OF ALCOHOL:
- Greater volumes of liquor makes contact with larger mucous membrane surface and also increases stomach emptying.
- Drinks containing gas are absorbed faster ( increased surface area and mucosal irritation) – Champagne.
- Warm drinks are absorbed faster than cold drinks – Irish Whiskey.
- Maximum absorption at 10 – 20 % alcohol.
- Higher concentration delay due to excessive mucous secretion, pyloric sphincter spasm and suppression of motility.
- Absorption of beer is delayed due to the lower concentration of alcohol and due to the amount of carbohydrates in beer.
CONTENTS OF THE ALIMENTARY CANAL:
• Food dilutes alcohol and reduces contact with the mucous membranes.
• Certain foods, especially fats, lead to a delay in the passage of contents to the small
intestine and thus a delay in absorption.
MEDICINES/CHEMICALS:
• Parasympathetic agents will increase the intestinal peristalsis and relax the pyloric sphincter
• Sympathomimetics slow down intestinal peristalsis and cause contraction of the pyloric sphincter.
• Intake of large quantities of nicotine and caffeine delay alcohol absorption
How fast is alcohol absorbed?
- On an empty stomach, with an optimal alcohol concentration (10-20%), the following can be expected:
- 60% of alcohol is absorbed in 60 minutes.
- 90% of the alcohol is absorbed in 90 minutes.
- Total absorption takes 2 hours.
Pharmacokinetics - Distribution
Influenced by Cardiac Output
- Alcohol is absorbed in the intestinal tract, diffused into the circulation and is distributed to the rest of the body.
- The following factors influence the distribution:
CARDIAC OUTPUT:
- Any psychological or physical factor that increases cardiac output will improve the distribution of alcohol.
WATER CONTENT OF TISSUES OR ORGANS:
- Alcohol is water-soluble: A direct relation exists between the water content of an organ and its ability to accommodate alcohol.
- The water content of blood and brain tissue is more or less the same. If blood sampling were done at a peripheral vein, the result would be a true reflection of the brain alcohol concentration
- The alcohol concentrations of bone, fat, brain and blood differ.
BLOOD PERFUSION:
- Impaired perfusion due to the narrowing of a blood vessel will have a slowing effect on the distribution.
DIFFUSION RATE:
- Alcohol never accumulates or is stored in any organ.
- Diffusion across the blood-brain-barrier is fast and neurological symptoms appear quickly.
Pharmacokinetics - Metabolism
- 85-90% of alcohol is metabolised by the hepatocytes.
METABOLISM TAKES PLACE AT A CONSTANT RATE
- 0,01 - 0,02 g/dL/hour = called ß60.
- Average ß60 = 0,015 g/dL/hour (legal: 0.015)
Slide 41 NB
Pharmacokinetics - Excretion
Influences
ALCOHOL ELIMINATION POSSIBLY ACCELERATED BY (controversy exists surrounding this):
- Very high blood alcohol level.
- Chronic use of alcohol.
- Older people.
- High doses of fructose.
- A protein meal.
- Insulin and glucose.
ALCOHOL ELIMINATION IS POSSIBLY DECELERATED BY (controversy exists surrounding this):
- Severe liver disease, with liver dysfunction.
ALCOHOL ELIMINATION IS DEFINITELY DECELERATED:
- An inherited deficiency in aldehyde dehydrogenase. (“Asian flushing syndrome”)
- Asian population. Not in Africans or Caucasians.
- Ethanol is metabolized to acetaldehyde, which builds up due to the mutation in the ALH2 gene. Slower acetaldehyde clearance. Drunk longer. Hang over stronger.
ALCOHOL ELIMINATION IS NOT INFLUENCED BY:
- Exposure to heat/cold.
- Physical activity
- Diabetes
- Trauma
- Sleep
- Liver cirrhosis
- Hyperthyroidism
- Medicines
- Blood alcohol concentration
• Chronic alcohol intake leads to increased tolerance, possibly due to increased receptor binding loci or increased elimination.
Pharmacokinetics - Excretion
- 10-15% is excreted unchanged in the urine.
BAC - Breath alcohol concentration
Excretion:
- Lungs: 0,5-3% Breath DOES correlate with BAC.
- Kidneys: 0,3-5% DOES NOT correlate with BAC.
- Skin: 0,5% does not correlate with BAC.
- Salivary glands.
- Mammary glands.
- The smell of alcohol has no relation to the level of intoxication.
NB Pharmacodynamics - CNS
- Continuous suppressive narcotic effect.
- Inhibits the normal inhibitory control mechanisms, with a false feeling of stimulation (0,01-0,10 g%):
- Excessive self-confidence, loss of judgment, and clouding of insight.
- The cortical neurons for highly developed functions are affected earlier than the lower centers in the basal ganglia and brainstem.
- Forebrain before hindbrain. (Your reputation goes before your life goes)
- Your reputation goes before your life goes.
- Affects frontal brain first (helps to interact with environment around us)
Later follows:
- Mobility/Speech affection (0,10-0,20 g/dL)
- Visual impairment (0,20-0,30 g/dL)
- Cerebellar impairment (0,15-0,35 g/dL)
- Diencephalic impairment (0,25-0,40 g/dL)
- Medullary impairment (0,40-0,50 g/dL)
Slide 50-52
The mellanby-effect
- A person “appears drunker while he is busy getting drunk, then when he is sobering up, at the same BAC”.
