aliphatic alcohol.. about ethyl alcohol, acute alcoholism, chronic alcoholism, methyl alcohol poisoning, ethylene glycol poisoning

1. Aliphatic alcohols
Dr K. Preethi

2. ....................................................
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 Alcohols are derivatives of aliphatic
hydrocarbons
 Alcohol is manufactured by
fermentation of sugars
 Major source of commercial alcohol is
mollases, a byproduct of sugar
industry

3. Alcoholic beverages
Malted liquors
• Fermentation of
germinating
cereals
• Alcohol content
is low 3-6%
• Eg: beers
wines
• Fermentation of
natural sugars
as in grapes
and fruits
• Light wines –
cider 9-12%
• Fortified wines
– port, sherry
16-22%
• Effervescent
wines –
champagne 12-
16%
spirits
• Distilled after
fermentation
• Eg: rum, gin,
vodka, whiskey,
brandy,
• 40 – 55%

4. Other forms of alcohol
 Absolute alcohol – 99% w/w ethanol
 Rectified spirit – 90% w/w ethyl
alcohol
 Proof spirit – 100% proof spirit is
49.29% w/w or 57.1% v/v alcohol
 Methylated spirit – denatured spirit by
adding 5 parts of wood naphtha to 95
parts of rectified spirit. It can be
applied on skin for antiseptic, cleaning
and astringent purposes

5. Pharmacological actions
Local actions:
 Mild rubefacient and counterirritant
 By evoparation it produces cooling
 On delicate skin produces irritation
and burning sensation
 Injected subcutaneously it causes
pain, inflammation, necrosis and
fibrosis
 Injected around a nerve it produces
permanent damage

6.  Applied to the surface – acts as
astringent, precipitate surface proteins
and hardens the skin
 As antiseptic – precipitate bacterial
proteins
 Alcohol does not kill bacterial spores

7. CNS:
 Alcohol is neuronal suppresant
 Any measurable concentration –
lowing of reflexes
 Performance is impaired, fine
discrimination, precise movements are
obliterated

8. Concentration in blood Effect
30 – 60mg/dl excitation, euphoria
Hesitation, caution, self
criticism are lost
80 – 150 mg/dl mental clouding,
disorganization of thought,
impairment of attention,
alteration of gait and
perception, drowsiness
150-200mg/dl sloppy, ataxic, drunk;
blackouts
200 – 300 mg/dl – stupor, unconciousness,
death

9.  Alcohol can induce sleep- poor quality
of sleep, repeated awakening,
hangover
 Alcohol raises the pain threshold
 Exerts anticonvulsant action but
followed by lowering of seizure
threshold
 Chronic alcohol abuse damages the
brain neurons, causes shrinkage of
brain

10. Mechanism of action
 Alcohol produce CNS depression by
altering the membrane lipid status
 Specific affect on voltage gated ion
channels and receptor operated
channels
 Enhance GABA release at GABAA
sites
 Inhibits NMDA and kainate type of
excitatory amino acid receptors
 Increase action at 5HT at 5HT3

11.  Inhibit voltage sensitive neuronal Ca
channels
 Activates specific K channels
 Release and turnover of dopamine in
brain is enhanced through beta
endorphin release – important for
pleasurable reinforcing effects of
alcohol and in the genesis of alcohol
dependence

12. CVS:
 Small dose: cutaneous and gastric
vasodilatation, skin is warm and flushed
 Moderate doses: tachycardia and mild
rise in BP due to increased muscular
activity and sympathetic stimulation
 Large doses: direct myocardial as well
as vasomotor centre depression, fall in
BP
 Chronic alcoholism – hypertension,
cardiomyopathy, atrial fibrillation, cardiac
arrhythmias

13. Blood:
 Regular intake of small amounts –
raise HDL cholesterol level and
decrease LDL oxidation
 Mild anaemia – megaloblastic
anaemia

14. Body temperature:
 Sense of warmth due to cutaneous
and gastric vasodilatation
 Heat loss in cold surroundings
 High doses depress the temperature
regulating centre

15. Respiration:
 Brandy and whisky are respiratory
stimulants in collapse
 Irritate buccal and pharyngeal mucosa
which transiently stimulate respiration
reflexly
 Direct action of alcohol on respiration
centre is only depressant

16. GIT:
 Dilute alcohol is a strong stimulant for
gastric secretion
 Higher concentration inhibits gastric
secretion, cause vomiting, mucosal
congestion and gastritis
 Lower esophageal sphincter tone is
reduced, increase the gastric reflux
 Acute pancreatitis is a complication of
heavy drinking

17. Liver:
 If adequate nutrition is maintained – no
significant liver damage
 Mobilize peripheral fat and increases fat
synthesis in liver
 Proteins may also accumulate in liver
due to decreased liver secretion
 Chronic alcoholism exposes liver to
oxidative stress and causes cellular
necrosis followed by fibrosis

18.  Acetaldehyde – damage to
hepatocytes and induce inflammation
 Increased lipid peroxidation and
glutathione depletion occures
 Combined with vitamin and other
nutritional deficiences
 Regular alcohol intake induces
microsomal enzymes

19. Skeletal muscle:
 Fatigue
 Weakness and myopathy occures in
chronic alcoholism

20. kidney:
 Diuresis due to alcoholinduced
inhibition of ADH secretion
 It does not impair renal function

21. Sex:
 Aggressive sexual behaviour is due to
loss of restrain and inhibition
 Chronic alcoholism produce
impotence, testicular atrophy,
gynaecomastia and infertility in men
and women

22. Endocrine effects:
 Moderate amounts of alcohol increase
ADR release – hyperglycemia and
other sympathetic effects
 Acute intoxication – hypoglycemia and
depletion of hepatic glycogen
 Gluconeogenesis is inhibited
 Uterine contractions are suppressed

23. pharmacokinetics
 Absorption from stomach is slow, from
intestine is fast
 Absorption from skin is significant in
infants
 Distributed widely in body, crosses
blood brain barrier and placenta freely
 Peak levels attained after 30 mins
 Limited first pass metabolism occurs
in stomach and liver

24.  Alcohol is oxidised in liver to the
extent of 98%
 In addition to alcohol dehydrogenase,
small amount of alcohol are oxidised
by hepatic microsomal enzymes
 Metabolism follows zero order kinetics
 Excretion occurs through kidneys and
lungs – but not significant

26. Interactions
 Synergises with anxiolytics,
antidepressants, antihistaminics,
hypnotics, opioids – CNS depression
 Sulfonylurea, cefoperazone,
metronidazole – disulfiram like
reaction. Supportive treatment
 Acute alcohol ingestion inhibits but
chronic intake induces CYP enzymes.
Metabolism of paracetamol,
tolbutamide, phenytoin are effected

27.  Hypoglycemic action of insulin and
sulfonylureas is enhanced by alcohol
ingestion
 Aspirin and other NSAIDS cause more
gastric bleeding when taken with
alcohol

28. Food value
 Alcohol requires no digestion and
metabolized rapidly
 Energy yielding substrate; 7 cal/g but
these cannot be stored
 It spares carbohydrates and fats as
energy source, so that regular intake
can contribute to obesity
 Do not have any nutritional effect

29. Contraindications
 Peptic ulcer, hyperacidity, GERD
 Epileptics
 Severe liver disease
 Unstable personalities
 Pregnant women – fetal alcohol
syndrome

30. Toxicity
Side effects of moderate drinking:
 Nausea
 Vomitings
 Flushing
 Hangover
 Traffic accidents

31. Acute alcoholic intoxication
 Unawareness,
 Unresposiveness
 Stupor
 Hypotension
 Gastritis
 Hypoglycemia
 Respiratory depression
 Collapse, coma and death

32. Treatment
 Gastric lavage
 Maintain airway
 Trachea intubation and positive pressure
respiration
 Supportive treatment
 Fluid and electrolyte balance
 Correction of hypoglycemia
 Thiamine
 Haemodialysis
 Insulin + fructose drip

33. Chronic alcoholism
 On chronic intake tolerance develops to
subjective and behavioural effects of
alcohol.
 It is both pharmacokinetic and cellular
tolerance
 Psychic dependence
 Physical dependence
 Heavy drinking associated with
nutritional deficiencies
 Impaired mental and physical
performance

34.  Neurological afflictions – polyneuritis,
pellagra, tremors, seizures, loss of brain
mass, Wernicke’s encephalopathy,
Korsakoff’s psychosis, megaloblastic
anaemia
 Alcoholic cirrhosis of liver, hypertension,
cardiomyopathy, CHF, arrhythmias,
stroke, acute pancreatitis, impotence,
gynaecomastia, infertility, skeletal
myopathy
 Oropharyngeal, esophageal, hepatic
malignancy and respiratory infections

35. Withdrawal syndrome
 Appears within a day
 Severity depends on duration and
quantity of alcohol consumed
 Anxiety, sweating, tachycardia, tremor,
impairment of sleep, confusion,
hallucinations, delirium, convulsions
and collapse

36. Treatment
 Psychological and medical supportive
measures
 Substitution therapy – CNS
depressants like barbiturates,
phenothiazines, chloral hydrate
 Benzodiazepines are preferred
 Ondansetron – 5 – HT3 antagonist
 Topiramate -antiepileptic

37.  Naltrexone:
- does not experience the pleasurable
effect on taking alcohol.
- Prevent relapse of alcoholism
- reduces alcohol craving, no of
drinking day
- approved for adjuvant in
comprehensive treatment
programmes for alcohol dependent
subjects

38.  Acamprosate:
- weak NMDA antagonist with modest
GABA A agonistic activity
- used for maintainace therapy of
alcohol abtinence
- reduce relapse of drinking behaviour
- Started soon after withdrawing alcohol
and given continuously at a dose of
666mg 2-3 times a day
- loose motions, nausea, abdominal
pain and itching are side effects

39. Clinical uses
 As antiseptic
 Rubefacient and counterirritant for
sprains, jointpains
 Rubbed into the skin to prevent
bedsores
 Astringent action of alcohol is used in
antiperspirant and aftershave lotions
 Alcoholic sponges to reduce body
temperature in fever

40.  Neuralgias and cancer pain - Injection
of alcohol round the nerve causes
permanent loss of transmission
 To ward off cold due to vasodilatation
 As appetite stimulant and carminative
 Reflex stimulation in fainting/hysteria –
one drop in nose
 To treat methanol poisoning

41. Disulfiram
 Inhibits aldehyde dehydrogenase
 Concentration of acetaldehyde increases
in tissues and blood and cause
distressing symptoms like flushing,
burning sensation, throbbing headache,
perspiration, uneasiness, tightness in
chest, diziness, vomiting, visual
disturbances, mental confusion, postural
fainting and collapse
 Duration of the syndrome depends on
the amount of alcohol consumed

42.  Disulfiram aversion therapy is
indicated in abstinent subjects
 After making sure that the subject has
not taken alcohol in the past 12 hrs
disulfiram is given at a dose of
500mg/day for 1 wk followed by
250mg daily
 Sensitization of alcohol develops after
2-3 hrs of first dose, reaches peak at
12 hrs and lasts for 7-14 days after

43.  The subject’s resolve not to drink is
reinforced by the distressing symptoms
that occur if he drinks a little bit
 Disulfiram should not be used in persons
who are physically dependent on alcohol
 Side effects – rashes, metalic taste,
nervousness, malaise and abdominal
upset
 Inhibits alcohol dehydrogenase,
dopamine beta hydrroxylase and several
cytochrome P450 enzymes – prolong
t1/2 of many drugs

44. Methyl alcohol
 Wood alcohol
 Mixing of methylated spirit with
alcoholic beverages by bootlegers or
its inadvertent ingestion results in
methanol poisoning
 Methanol metabolised to
formaldehyde and formic acid
 Follows zero order kinetics
 T1/2 – 20-60hrs

46.  Methanol also is a CNS depresants
 Toxic effects are largly due to formic
acid
 Blood level of >50mg/dl associated
with severe poisoning
 Even 15ml of methanol caused
blindness and 30 ml has caused death
 Fatal dose is 75-100ml

47. Manifestations of methanol
poisoning
 Vomiting,headache,epigastric pain,
uneasiness, drunkenness,
disorientation, tachypnoea, dyspnoea,
bradycardia, hypertension
 Delirium, seizures and coma
 Acidosis is prominent
 Retinal damage
 Blurring of vision, congestion of optic
disc followed by blindness always
precede death which is due to
respiratory failure

48. Treatment
 Keep the patient in quiet and dark
room
 Protect eyes from light
 Gastric lavage with sod. Bicarbonate
 Supportive measures to maintain
ventilation and BP
 Combat acidosis by i. v. Sod.
Bicarbonate infusion. It prevents the
retinal damage
 Potassium chloride infusion if
hypokalemia present

49.  Ethanol:
- 100mg/dl in blood saturates alcohol
dehydrogenase and retards methanol
metabolism
- reduce the generation of
formaldehyde and formic acid
- loading dose of 0.7 ml/kg followed
by 0.15 ml/kg/hr

50. - alcohol blood level needs to be
repeatedly measured
- enzyme saturating concentration of
ethanol itself produces intoxication
and cause hypoglycemia
- treatment has to be continued for
several days because the sojourn of
methanol in body is long

51.  Haemodialysis:
 Fomepizole: inhibitor of alcohol
dehydrogenase
- retards metabolism of methanol
- a loading dose of 15 mg/kg i.v.
followed by 10 mg/kg every 12 hrs
- effective and safe
- longer halflife

52.  Folate therapy: calcium leucovorin 50
mg injected 6hrly to reduce formate
levels by enhancing its oxidation

53. Ethylene glycol poisoning
 Occur sporadically, specially in
children
 Industrial solvent, coolant, antifreeze
 Oxidized in body to glycoaldehyde
then glycolic acid, glyoxylic acid,
oxalic acid in steps
 Acidosis, cardiopulmonary
complications and renal tubular
necrosis
 Fomepizole is the drug of choice
 Alternative is ethanol

54. Thank you