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Pharmacokinetics of Ethyl Alcohol
Dr.Nafeeya
Department of Forensic Medicine & Toxicology
overview
Why we want to learn about ethyl
alcohol ?
Pharmacokinetics of ethyl alcohol
Mechanism of action of ethyl
alcohol
Medicolegal importance.
Important definitions
› Pharmacodynamics-Pharmacodynamics is the study of the biochemical and
physiological effects of drugs and their mechanisms of action .
› Pharmacokinetics-How the body acts on the drug.It involves absorption, distribution
,metabolism & drug excretion.
› Pharmacogenetics-Pharmacogenetics is the study of the genetic basis for variation in
drug response.
› Zero-order kinetics-implies that a constant amount of drug is eliminated from the blood
or the entire body per unit time.
› First-order kinetics-implies that a constant proportion is eliminated from the blood or
the entire body per unit time.
First order kinetics is a
concentration-dependent
process (i.e. the higher the
concentration, the faster the
clearance),
Zero-order kinetics is when a
constant amount of drug is
eliminated per unit time but
the rate is independent of the
concentration of the drug.
ETHYL ALCOHOL
• The most commonly abused drug in the world
• 75% of adults drink alcohol regularly
• In India, 11% of adults are classified as heavy drinkers
• Cost attributed to alcohol abuse exceed 200 billion dollars annually
• Traffic fatalities, homicides, rapes and suicides are all alcohol related
• Moderate alcohol use protect against cardiovascular diseases in individuals
Absorption
Simple passive
Diffusion
30 sec-blood,brain
5 minutes-stomach
20 minutes-kick start
First pass metabolism
Gastric & Liver ADH
First pass metabolism-lower blood alcohol
Absorption –elimination
Cemetidine
Rantac
Aspirin
Vd=0.5-0.7 L/kg
Factors affectingabsorption
• A Fatty meal
• Full Stomach
• Gender ,
• Body fat ,
• Drug interaction
• Alcohol Concentration
• Carbonated Drinks
• Habituation – before noon
Distribution
•Blood brain
barrier
•Insoluble in
fat
•Lungs- lost
by diffusion
•A=V-1 hr
•RBC-
METABOLISM
excretion
LIVER
KIDNEY
LUNG
SWEAT
ELIMINATION RATE =( BAC 1 – BAC 2)/ time difference
90%- oxidative
metabolism
10 % -
unchanged by
excretion via
lungs,kidney
,skin.
Factors modifying alcohol elimination rate
› Sex
› Age
› Race – B3 Class 1 ADH
› Food
› Biologic rhythms
› Alcoholism
› Drugs –Disulfiram
› AT ORGAN LEVEL
• Frontal lobes - most sensitive to
alcohol
• This results in mood changes
• Occipital lobe – visual disturbances
• Cerebellum – loss of coordination and
death from cardio-respiratory failure
› AT MOLECULAR LEVEL
› GABA RECEPTORS- sedative effects
› NMDA RECEPTORS –
› Glycine receptor
› Nicotinic Ach receptor
› G-protein –Coupled receptors
› 5HT3-receptor
› Voltage gated ca2+ channels
› Voltage activated K+ channels
MECHANISMOF ACTION
Compensatory
up regulation
of NMDAR
function
Causes of alcohol toxicity
Acetaldehyde formation
Mitochondrial damage
Oxidative stress
Hypoxia
Immune actions
Cytokine formation (TNF-alpha)
Kupffer cell activation
AUTOPSY FINDINGS
Hepatic necrosis Denk bodies
Cloudy swelling of parenchyma
CPM
Alcoholic CM
GD-PCT
Collection of specimens
•Blood
•Urine
•Saliva
•Breath
Laboratory test-chemical oxidation
Gas chromatography
Osmolol gap
Cavett ‘s test
Kozelka & hine test
Fresh –blood
Brain
CSF
Lung ,urine,
vitreous
Decomposed-Pleural fluid
Skeletal muscles
Embalmed
bodies-Sk-butt,
Blood ,urine
,vitreous,
viscera
Medicolegal importance
Alcohol &
traffic
accidents
Sudden
death
Manner of
poisoning
Alcohol
trauma &
delayed
death
Alcohol &
criminal
behaviour Ethanol
Sec 185 (a)
Sec 185 (b)
Sec 202
Sec 203
Sec 204
Alcohol is converted
generating a current
that is proportional to
the quantity of alcohol
present
Widmark’s formula
› 1.Amount of alcohol ingested by a suspect if his blood alcohol level is
known .
a=cpr
1. Alcohol ingestion in gram
2. Concentration of alcohol in the
blood
3. Weight of the body in kg
4. Widmark constant
Question?
› What is amount of alcohol ingested by a 70 kg male if his blood level to
30 mg%?
› Step 1-blood level must be converted from mg% to decigrams% by
dividing by 100.
› Step 2-application of formula
30mg % -0.3 decigram %
a=0.3x70x0.68
14.28 g
Male-0.68
Female-
0.55
› Step 3-conversion into c.c-divided by SG
› Step 4 – conversion into amount of liquor
Beer-8-12%
Wine-10-20%
Whisky ,gin,brandy-
40-60%
Rum,liquor-50-60%
14.28/0.79=18 cc of 100%
alcohol
Specific
gravity-
0.79
18x100/45=40 cc
Reference
› Goodnman& gilmans phamacologicalbasisof therapeutics13 thedition
› K.DTripathi–Essentialof pharmacology-6th edition
› Anil Aggrawal textbookof forensicmedicineandtoxicology
› Narayanareddy textbookof forensicmedicineandtoxicology
› Principlesof ForensicMedicine&ToxicologyRajeshBardalae
› KnightsForensicPathology-3rd edition
› V.VPillayForensicmedicinebook-4th edition

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Pharmcokinetics of ETHYL ALCOHOL IN FORENSIC VIEW

  • 1. Pharmacokinetics of Ethyl Alcohol Dr.Nafeeya Department of Forensic Medicine & Toxicology
  • 2. overview Why we want to learn about ethyl alcohol ? Pharmacokinetics of ethyl alcohol Mechanism of action of ethyl alcohol Medicolegal importance.
  • 3. Important definitions › Pharmacodynamics-Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanisms of action . › Pharmacokinetics-How the body acts on the drug.It involves absorption, distribution ,metabolism & drug excretion. › Pharmacogenetics-Pharmacogenetics is the study of the genetic basis for variation in drug response. › Zero-order kinetics-implies that a constant amount of drug is eliminated from the blood or the entire body per unit time. › First-order kinetics-implies that a constant proportion is eliminated from the blood or the entire body per unit time.
  • 4. First order kinetics is a concentration-dependent process (i.e. the higher the concentration, the faster the clearance), Zero-order kinetics is when a constant amount of drug is eliminated per unit time but the rate is independent of the concentration of the drug.
  • 5. ETHYL ALCOHOL • The most commonly abused drug in the world • 75% of adults drink alcohol regularly • In India, 11% of adults are classified as heavy drinkers • Cost attributed to alcohol abuse exceed 200 billion dollars annually • Traffic fatalities, homicides, rapes and suicides are all alcohol related • Moderate alcohol use protect against cardiovascular diseases in individuals
  • 6. Absorption Simple passive Diffusion 30 sec-blood,brain 5 minutes-stomach 20 minutes-kick start
  • 7. First pass metabolism Gastric & Liver ADH First pass metabolism-lower blood alcohol Absorption –elimination Cemetidine Rantac Aspirin Vd=0.5-0.7 L/kg
  • 8. Factors affectingabsorption • A Fatty meal • Full Stomach • Gender , • Body fat , • Drug interaction • Alcohol Concentration • Carbonated Drinks • Habituation – before noon
  • 11. excretion LIVER KIDNEY LUNG SWEAT ELIMINATION RATE =( BAC 1 – BAC 2)/ time difference 90%- oxidative metabolism 10 % - unchanged by excretion via lungs,kidney ,skin.
  • 12. Factors modifying alcohol elimination rate › Sex › Age › Race – B3 Class 1 ADH › Food › Biologic rhythms › Alcoholism › Drugs –Disulfiram
  • 13. › AT ORGAN LEVEL • Frontal lobes - most sensitive to alcohol • This results in mood changes • Occipital lobe – visual disturbances • Cerebellum – loss of coordination and death from cardio-respiratory failure › AT MOLECULAR LEVEL › GABA RECEPTORS- sedative effects › NMDA RECEPTORS – › Glycine receptor › Nicotinic Ach receptor › G-protein –Coupled receptors › 5HT3-receptor › Voltage gated ca2+ channels › Voltage activated K+ channels MECHANISMOF ACTION Compensatory up regulation of NMDAR function
  • 14. Causes of alcohol toxicity Acetaldehyde formation Mitochondrial damage Oxidative stress Hypoxia Immune actions Cytokine formation (TNF-alpha) Kupffer cell activation
  • 16. Cloudy swelling of parenchyma CPM Alcoholic CM GD-PCT
  • 17. Collection of specimens •Blood •Urine •Saliva •Breath Laboratory test-chemical oxidation Gas chromatography Osmolol gap Cavett ‘s test Kozelka & hine test
  • 18. Fresh –blood Brain CSF Lung ,urine, vitreous Decomposed-Pleural fluid Skeletal muscles Embalmed bodies-Sk-butt, Blood ,urine ,vitreous, viscera
  • 19. Medicolegal importance Alcohol & traffic accidents Sudden death Manner of poisoning Alcohol trauma & delayed death Alcohol & criminal behaviour Ethanol
  • 20. Sec 185 (a) Sec 185 (b) Sec 202 Sec 203 Sec 204 Alcohol is converted generating a current that is proportional to the quantity of alcohol present
  • 21. Widmark’s formula › 1.Amount of alcohol ingested by a suspect if his blood alcohol level is known . a=cpr 1. Alcohol ingestion in gram 2. Concentration of alcohol in the blood 3. Weight of the body in kg 4. Widmark constant
  • 22. Question? › What is amount of alcohol ingested by a 70 kg male if his blood level to 30 mg%? › Step 1-blood level must be converted from mg% to decigrams% by dividing by 100. › Step 2-application of formula 30mg % -0.3 decigram % a=0.3x70x0.68 14.28 g Male-0.68 Female- 0.55
  • 23. › Step 3-conversion into c.c-divided by SG › Step 4 – conversion into amount of liquor Beer-8-12% Wine-10-20% Whisky ,gin,brandy- 40-60% Rum,liquor-50-60% 14.28/0.79=18 cc of 100% alcohol Specific gravity- 0.79 18x100/45=40 cc
  • 24. Reference › Goodnman& gilmans phamacologicalbasisof therapeutics13 thedition › K.DTripathi–Essentialof pharmacology-6th edition › Anil Aggrawal textbookof forensicmedicineandtoxicology › Narayanareddy textbookof forensicmedicineandtoxicology › Principlesof ForensicMedicine&ToxicologyRajeshBardalae › KnightsForensicPathology-3rd edition › V.VPillayForensicmedicinebook-4th edition