ethanol its sources, blood alcohol level , ethanol and methanol toxicity

1. Ethanol and Methanol
Dr. Sumit Kumar

2. Introduction
Alcohols are hydroxy derivatives of aliphatic hydrocarbon
Alcohol is manufactured by fermentation of sugars:
• The major source of commercial alcohol is molasses
• Starchy cereals when soaked produce malt which is then fermented by
yeast to produce alcohol e.g. barley
C6H12O6 2CO2 + 2C2H5OH

3. Introduction…
Alcoholic beverages:
 Malted liquors: Obtained by fermentation of germinating cereals
e.g: Beers, Stout.
 Wines: Produced by fermentation of natural sugars present in grapes and
other fruits.
Light wines:
Alcohol content 9–12%,
never exceed 15%
Fortified wines:
Port, Sherry (16–22%)
Effervescent wines:
Champagne (12-16%):
Bottled before
fermentation is
complete

4. Spirits: These are distilled after fermentation
• Alcohol content vary from 40–55%, and are standardized to 42.8% v/v or
37% w/w.
• e.g. Rum, Gin, Whiskey, Brandy, Vodka, etc.
Absolute alcohol: 99% w/w ethanol
Rectified spirit: 90% w/w ethyl alcohol produced from fermented mollases
Proof spirit: If whiskey is poured on gun powder and ignited it explodes, labelled to be of
‘proof strength’. 100% proof spirit is 49.29% w/w or 57.1% v/v alcohol.

5. Pharmacological properties
Absorption, Distribution, and Metabolism:
• After oral administration, ethanol is absorbed from the stomach and small
intestine
• In empty stomach peaks blood level in 30 minutes. Food delays gastric
emptying & slows ethanol absorption.
• Crosses blood brain barrier, placenta, concentration in brain is very near
blood concentration.
• first-pass metabolism begins from stomach and in liver by alcohol
dehydrogenase (ADH),
Aspirin increases ethanol bioavailability by inhibiting gastric ADH.

6. Metabolism:
Metabolized by sequential hepatic oxidation, first to acetaldehyde by Alcohol
dehydrogenase and then to acetic acid by aldehyde dehydrogenase (ALDH)
NAD+ is required in each metabolic step, limiting ethanol metabolism to
about 8-10g or 10 mL/hr and shifts to zero-order kinetics
Small amount is also metabolized by hepatic cytochrome P450, CYP2E1
Excretion of alcohol occurs through kidney and lungs

7.  Ratio of ethanol in end-expiratory
alveolar air and blood is relatively
constant
 Blood ethanol levels (BELs) in
humans can be estimated readily
by the measurement of alcohol
levels in expired air
Legally allowed BELs is below 80 mg%
(80 mg /100 mL blood; 0.08% w/v)

8. INTERACTIONS
Synergistic effect with anxiolytics, antidepressants, antihistaminics, hypnotics,
opioids → marked CNS depression with motor impairment occurs
Disulfiram-like reactions is shown by sulfonylurea, cefoperazone, or
metronidazole when taken with alcohol
Acute alcohol ingestion inhibits, while chronic intake induces CYP enzymes
(especially CYP2E1)
Alcohol enhaces hypoglycaemic action of insulin and sulfonylureas
Alcohol when taken with aspirin and other nsaids cause more gastric bleeding

9. Effects Of Ethanol On Physiological Systems
• Local actions:
Irritant and counter irritant
Rubefacient
Astringent and antiseptic
Antiseptic of 20-70% , above 90%
antisepsis decreases

10. Effects Of Ethanol On Physiological Systems……..
CNS: Alcohol is a Neuronal Depressant
30–60 mg/dl :
Excitation and
Euphoria
80– 150 mg/dl:
Mental clouding,
altered thought,
impairment of
attention,
memory, gait
150–200 mg/dl:
Ataxic and
drunk
‘blackouts’
occurs
200–300 mg/dl:
Stupor and
medullary
centers are
paralyzed and
death may occur.

11. Neurohormonal mechanism of alcohol…

12. • Alcohol enhance GABA release at GABAA sites in the brain.
• It also inhibits NMDA and kainate type of excitatory amino acid receptors
(operating through cation channels).
• Action of 5-HT on 5-HT3 inhibitory autoreceptor (having an intrinsic ion
channel) is augmented.
• Release and turnover of DA in brain is enhanced through β endorphin
release in nucleus accumbens and an opioid receptor dependent
mechanism.
• Activity of membrane bound enzymes like Na+ K+ ATPase and adenylyl
cyclase is also altered.

13. CVS
Cardiac Arrhythmias:
Abnormal cardiac conduction, Increase QT interval,
Ventricular repolarization
Atrial arrhythmias:
Supraventricular tachycardia,
atrial fibrillation, and atrial flutter
Cardiomyopathy and strokes are also frequent
Alcohol reduces risk of CHD
• Increases in high-density lipoprotein (HDL)
• Elevates levels of tissue plasminogen activator tPA

14. Decreased muscle strength
• Heavy doses cause irreversible damage to muscle, reflected by
increase in creatine kinase activity in plasma.
• Muscle biopsies shows decreased glycogen stores
Body Temperature
• Ingestion of ethanol causes a feeling of warmth because alcohol
enhances cutaneous and gastric blood flow.
Diuresis
• Alcohol inhibits the release of vasopressin (antidiuretic hormone) from
the posterior pituitary gland, resulting in enhanced diuresis.

15. Respiration:
• They irritate buccal and pharyngeal mucosa which may transiently
stimulate respiration reflexly
Vitamins and Minerals:
Alcoholics often present with deficiencies owing to decreased intake, decreased
absorption, or impaired utilization of nutrients.
• Peripheral neuropathy
• Korsakoff’s psychosis
• Wernicke’s encephalopathy

16. Sexual Function:
• Both acute and chronic alcohol lead to impotence in men.
• Gynecomastia is associated with alcoholic liver disease
• female have menstrual cycle abnormalities, ovaries often are
small without follicular development
Blood:
• Mild anaemia is common in chronic alcoholics.
• Megaloblastic anaemia occurring in chronic alcoholism is due to
interference with folate metabolism.

17. GIT
 Esophageal reflux
 Barrett’s esophagus
 Traumatic rupture of the esophagus
 Mallory-weiss tears, and esophageal cancer
Heavy alcohol disrupt the gastric mucosal barrier
and cause acute and chronic gastritis.
The primary effects are fatty infiltration of the liver,
hepatitis, and cirrhosis.
most common cause of both acute and chronic
pancreatitis

18. Acute Ethanol Intoxication

19. Symptoms of acute acohol intoxication:
20-30 mg/dl : Increased reaction time, diminished fine motor control, impulsivity, and impaired
judgment
80 mg/dl: Slurred speech, incoordination, unsteady gait, and impairments of attention
80-200 mg/dl: Greater cognitive deficits, potentially accompanied by aggressiveness, and
anterograde amnesia
>200 mg/dl: Nystagmus and unwanted falling asleep
300 mg/dl: Depressed vital signs, coma, and death.
Symptoms are exacerbated and occur at a lower BEC when ethanol is taken along with other
CNS depressants

20. Treatment of acute alcohol intoxication
Treatment of acute alcohol intoxication is based on the severity of respiratory
and CNS depression
first priority is to maintain patent airway and prevent aspiration of vomitus.
Tracheal intubation and positive pressure respiration
Supportive treatment,
• Maintenance of fluid and electrolyte balance
• Correction of hypoglycaemia by glucose infusion
• Thiamine (100 mg in 500 ml glucose solution infused i.v.) Should be added.
Recovery can be hastened by haemodialysis.

21. Tolerance, Dependence, And Chronic Ethanol Use
Tolerance is defined as a reduced behavioral or physiological response to the same dose of
ethanol
Physical dependence is demonstrated by appearance of a withdrawal syndrome when alcohol
consumption is terminated.
Symptoms and severity are determined by the amount and duration of alcohol consumption
Include sleep disruption, autonomic nervous system (sympathetic) activation, tremors, and in
severe cases, seizures.
Delirium tremens: characterized by hallucinations, delirium, fever, and tachycardia.
Another aspect of dependence is craving and drug-seeking behavior, often termed
psychological dependence

22. Treatment
Psychological and medical supportive measures are needed during
withdrawal
Currently, three drugs are approved in the U.S. for treatment of alcoholism:
disulfiram (ANTABUSE), naltrexone (REVIA), and acamprosate
Naltrexone:
• Naltrexone blocks activation of dopaminergic pathways in the brain that are thought to be critical to reward.
• Naltrexone helps to maintain abstinence by reducing the urge to drink
• Nausea is the most common side effect, excessive dose causes liver damage, contraindicated in patient with liver failure
and acute hepatitis

23. Acamprosate:
• NMDA-receptor antagonist with modest GABAA receptor agonistic
activity
• Loose motion is a common side effect. Others are nausea,
abdominal pain and itching
Disulfiram:
• It inhibits ALDH activity and causes blood acetaldehyde
concentration to rise to 5-10 times
• Within 5-10 minutes, signs and symptoms of acetaldehyde
poisoning appears, face feels hot and flushed
• Intense throbbing and pulsating headache is seen

24. 5-HT3 antagonist ondansetron and the antiepileptic topiramate
have also shown some promise in treating alcoholism
Benzodiazepines (chlordiazepoxide and diazepam) are given to
prevent withdrawal.
Naltrexone is used to reduce alcohol craving.
Acamprosate used for maintenance therapy of alcohol abstinence

25. Clinical use of Ethanol
As antiseptic
Rubefacient and counterirritant for sprains, joint pains
Astringent action of alcohol is utilized in antiperspirant and aftershave lotions
Intractable neuralgias (trigeminal and others), severe cancer pain. Injection of
alcohol round the nerve causes permanent loss of transmission
To treat methanol poisoning

26. foetal alcohol syndrome:
 Intrauterine and postnatal
growth retardation
 Low IQ
 Microcephaly,
 Cranio-facial and other
abnormalities,
 Susceptibility to infections.
 Increases incidence of
miscarriage,
 Stillbirths
 Low
 Birth-weight babies

27. Methanol
One carbon alcohol, methanol (CH3
OH), is also known as methyl and
wood alcohol
• Paint removers,
• Shellac, and
• Antifreeze
• Added to industrial-use ethanol to mark it unsafe for human
consumption.
An important industrial reagent and solvent found in products such as

28. Methanol
 Methanol is a CNS depressant
 Toxic effects of methanol are
largely due to formic acid
 A blood level
 >50 mg/dl methanol is
associated with severe
poisoning
 15 ml of methanol causes
blindness
 fatal dose : 75–100 ml

29. Treatment of Methanol Poisoning
 Keep the patient in a quiet, dark room; protect the eyes from light
 Supportive measures to maintain ventilation and BP
 i.v. Sod. bicarbonate infusion to Combat acidosis
 Pot. chloride infusion to treat hypokalemia
 Ethanol (10% in water) is administered through a nasogastric tube, loading dose of
0.7 ml/kg is followed by 0.15 ml/kg/hour.
 Fomepizole a specific inhibitor of alcohol dehydrogenase and drug of choice for
methanol poisoning
 loading dose of 15 mg/kg i.v. followed by 10 mg/kg every 12 hours till serum
methanol falls below 20 mg/dl
 Folate therapy, leucovorin 50 mg injected 6 hourly

30. Thank you