Ethanol toxicity

Zaid S. Jumaah Collage of pharmacy University of Baghdad

INTRODUCTION

• Historical background 7000 B.C !

• Today 3.8% deaths 4.6% disabilities

What is ethanol• Amphipathic• Volatile, colorless

and flammable liquid

How it synthesize• Fermentation• Synthetic means

INTRODUCTION

PHARMACO-KINETICS/DYNAMICS

Absorption• Its absorbed mainly

through GIT bypassive diffusion

• Peak serum conc.30-60 min afteringestion

• Could be absorbed form other routs

20%

80%

Presence of food Delay the peak serum conc.

Up to 2-6 hrsbut not decrease

met

abol

ism

PHARMACO-KINETICS/DYNAMICS

Distribution & Elimination

• VD = 0.6 L/kg

• Rate of elimination8-35 mg/dl/hrwith average 20mg/dl/hr

Distribute through out

the bodyFast

Excretion5-7%

Breathalyzer

ALDH

PHARMACO-KINETICS/DYNAMICS

Metabolism:Ethanol

MEOSP450

MEOSP450

ADH

Peroximalcatalase

Peroximalcatalase

Acetaldehyde

NAD+ NADH

O2NADPH

H2O2NADP+

H2O2

H2O

Peripheral tissue AcetateH2O + CO2

Disulfiram

PyrazoleAminotriazole

PHARMACO-KINETICS/DYNAMICS

Mechanism of action

• Compilcated

• Modifying of neuronalmembranes

• Its thought to affect many receptors

GABA

Glutamate

Dopamine

PHARMACO-KINETICS/DYNAMICS

• Blood Alcohol Concentration (BAC)

• Alcohol Standard drink (alcohol unit):around 10gm or 10ml (UK)

Total amount of alcohol

Total body water BAC%

Regular beer can

0.5 Unit 1.4 UnitWine glass

4.2 UnitGin glass

PHARMACO-KINETICS/DYNAMICS

Body size

Gender

mood

Age

Tolerance

Drug use

Affecting factors

ACUTE TOXICITY

• Human Metabolizeone UK unit per hour

• When the metabolizingenzymes is saturated

TOXICITY OCCURE

consumption Metabolism

ALDH

ACUTE TOXICITY

EthanolMEOSP450

MEOSP450

ADH

Peroximalcatalase

Peroximalcatalase

Acetaldehyde

NAD+ NADH

O2NADPH

H2O2NADP+

H2O2

H2O

Peripheral tissue AcetateH2O + CO2

Metabolites

Flushing , Nausea, headach and general discomfort

Lactic acidosis, ketoacidosis and increase TG formation

ROS, and muscle weakness

ACUTE TOXICITY

CNS toxicity• It’s BAC dependent • Ranged from mild euphoria

to death

ACUTE TOXICITY

Other toxicities

GIT

Respiratory

Urinary Genitalia

Heart

ACUTE TOXICITY

Management• Correct any deterioration in Vital signs

• Increase ethanol clearance

• If the ingestion occurred within 1 hour of presentation

Airway IV fluid

Nasogastric

tube

No benefit from charcoal

Fructose Hemodialysis

CHRONIC TOXICITY

• ToleranceLow response to alcohol

• Withdrawal

Metabolic Functional Psychological

GABA Glutamate DopamineTremor

Insomnia

Hallucination

15% death if untreated

Ethanol Acetaldehydemetabolism

Acetate

Acetaldehyde dehydrogenase

Gultathione depletion

ROS &Free radicals

Altered membrane proteinsNeoantigens formation

Impaired cytoskeletal transportStimulation of HSC

Immunological injuryDamage to cell

membranes

Increase fatty acid synthesis

Decrease fatty acid oxidation

Down regulated inchronic alcohol use

Gut Permeability Endotoxaemia Kupfer cell activation

TNFα

CHRONIC TOXICITYLiver Toxicity

Increase NADH/NAD+

CHRONIC TOXICITY

Central Nervous System• Increased homocysteine :

withdrawal seizure, Brain atrophy and cognitive problems

• Disruption in memorylearning and sleep patterns

CHRONIC TOXICITY

Wernicke-Korsakoff syndrome• thiamine deficiency

• Korsakoff'sPsychosis

• Wernicke's encephalopathy

CHRONIC TOXICITY

Cardiovascular toxicity

• Acetaldehyde : protein, Ca+ andactin myocin

• Lipid peroxidation :ROS and others

Alcohol Induced Hypertension

CHRONIC TOXICITY

Gastrointestinal tract

• Irritation

• Pancreatitis : Acute and chronic

Pancreatic pain

CHRONIC TOXICITY

Cancer• Acetaldehyde

• defect in aldehyddehydrogenase

• GIT, liver cancer

CHRONIC TOXICITY

Alcohol and pregnancy (Fetal alcohol syndrome)

• physical, mental, and/or behavioural problems

• Mental retardation

Hormonal Imbalance

Respiratory

Gouty arthritis

Genitalia

Immune

CHRONIC TOXICITY

Other toxicities

Skin

CHRONIC TOXICITY

Management of chronic alcoholism

• Psychosocial treatment• Long-term treatment of

alcohol-related diseases• Nutritional supplements• Antabuse (Disulfiram)

CHRONIC TOXICITY

Management of withdrawal symptoms

• Benzodiazepines

• Nitrous oxide

• Vitamins

ETHANOL TOXICITY

Dose beer truly give you a beer belly ?

The answer is

NO drinking beer ALONE dose not cause a beer belly