NEUROTICS
1) CEREBRAL :
a) CNS DEPRESSANTS - e.g., Alcohol, GA,
Opioid analgesics, Sedatives, Hypnotics.
b) CNS STIMULANTS – e.g., CAD, Caffeine,
Amphetamine, Methylphenidate.
c) DELIRIANTS – Dhatura, Cannabis, Cocaine,
Atropa belladona, Hyocyamus.
2) SPINAL :
e.g. Strychnos nux vomica,
Gelsemium.
3) PERIPHERAL :
e.g. Conium , Curare.
ALCOHOL
•ETHYL ALCOHOL
•METHYL ALCOHOL
•ETHYLENE GLYCOL
•ISOPROPYL ALCOHOL
INEBRIANTS
• Inebriant –produces Intoxication
• Light headedness, confusion, disorientation,
drowsiness.
• Prolonged sleep
recovery
Hangover
(headache, irritability, lethargy, nausea & abdominal
discomfort).
ETHYL ALCOHOL
• C2H5OH
• Transparent , colourless, volatile liquid with spirituous
odor and burning taste.
• Absolute Alcohol = 99.95%
• Rectified Spirit = 90%
• Industrial Methylated Spirit = 95%+Wood Neptha = 5%
(Methyl alcohol)
• Fermentation of sugar by yeast -- till (15% vol)
• Beverages = Alc + Water + Congeners (0.5%)
add flavour
• “Proof spirit” – at 10.5˚C weighs exactly 12/13
part of an equal measure of D.W.
• “Underproof” and “Overproof”
• % of Alc content x 2 = Proof
• One unit = 8 gms
Percentage by Volume
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Vodka
Rum, Liquors
Whisky , Gin, Brandy
Port, Sherry
Wine , Champagne
Beers
: 60- 65%
: 50-60%
: 40-45%
: 20%
: 10 – 15%
: 5- 8%
• Consumption = 1-2 drinks per day
• Safe Limits of Alcohol =210g in men
&
140g in women
per
week
• Arrack : Liquor distilled from - palm, rice,
sugar or jaggery etc. (40-50%) and may be
mixed with Chloral hydrate and KBr for
greater kick.
ABSORPTION
• Requires no digestion
• Immediately by Simple diffusion
• 20% from Stomach , 80% from Small intestine.
• 60% absorbed in 30-60 min, 90% in 60-90 min.
• Detected in blood within 2-3min.
• Max.conc.in blood within 45-90min. (mainly1hr).
Factors Increasing Absorption
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Carbonated drinks
Warm
Conc. = 10-20%
Absence of congeners
Without food
Gastrectomy
Drugs (which increase gastric emptying )
eg. Cimetidine, ranitidine, etc.
Factors Decreasing Absorption
• Cold
• Conc. ‹ 10% (Dilution e.g. Beer)- takes double
time
› 40% - Pyloric Spasm
- Reduced gastric motility
- Irritation of mucosa & mucus
secretion
• Food (Fat and Protein)
- Fatty meal - delays by many hours
.
Mixed meal -reduces max conc. by ½
• Diseases : Achlorhydria , Chronic gastritis
• Drugs: (which reduce gastric emptying)
eg. Aspirin, Atropine, etc.
Distribution
• More : Alveolar air (diffusion)
: Water content
• Less : RBC
: Fat (Adipose tissue, Obese, Females)
: Venous (10% less than Arterial)
• Equilibrium :
- Capillary = Arterial =Brain (1-3min)
- Venous ( 1 hr)
• Females have 25% higher blood alcohol conc. for
the same amount consumed d/t :- small volume of distribution
- small aqueous compartment
- more variable absorption from gut
- lower activity of gastric ADH enzyme
- faster hepatic clearance
- higher conc. of acetaldehyde
- poor solubility in body fat
EXCRETION
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All routes.
10% is excreted.
5% - Breath
5% - Urine
Traces- Sweat , saliva, milk, tear and feaces.
Skin glands
Odour
METABOLISM
• 90% is Metabolised
- 90% of which is oxidised in Liver.
- 10% is metabolised by Cytochrome P4502E1 .
Alcohol
Acetaldehyde
dehydrogenase (ADH)
Alcohol
dehydrogenase
Acetaldehyde
NAD
Acetic acid (or
Acetyl CoA)
By- Fructose
- Enzymes (Chronic alcoholic)
By – Liver damage
Kreb’s
cycle
CO2 + H2O
Acetate can form – glycogen , protein ,fats and cholesterol.
A Diabetic who is Ketogenic will produce fat .
• Disappears from blood at 10-15 ml/hr
(15mg/100ml/hr)
• Elimination varies: 12-27mg/100ml/hr (Av=18mg)
• Fast - With large dose
- Chronic alcoholics (30-40mg/100ml/hr)
• Slow - Liver damage
• 10% of metabolized is deposited in tissues as lipids
(cholesterol and neutral fat)
ACTIONS
• Endogenous (Metabolism or bacterial activity in GIT)
• Stimulant and selective depressant (Primarily RAS
• Effects - Frontal lobes (mood changes)
- Occipital lobes (visual disturbances)
- Cerebellum
(loss of coordination)
• Like hypoxia on neural cells ( reduces activity)
• Depresses cells of Conduct , Judgement &
Self – criticism with release of inhibitory tone
(unrestrained behavior).
• ↓Brain function
↓Vitals
• Generalized vasodilatation (Skin)
Hemorrhage
• Hypnotic.
• Diaphoretic
Sensation of warmth
Heat
loss.
• Tachycardia
Bradycardia
(at lower conc.)
(at higher conc. ›300mg%)
• Toxic to every organ, d/t acetaldehyde or change
in redox potential.
• Blocks metabolism and increases levels of some
drugs.
• Moderate consumption → HDL & LDL
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↑ Appetite (↑salivary & gastric juice)
Carminative (Brandy)
Diuresis (d/t ↓ADH)
Spirituous liquor
Heamorrhagic gastritis
Mixing of drinks
↑Gastric emptying
Fasting blood Alcohol= 0.001mg%
• IN VINO VERITAS
Causes of Death
• CNS Depression (respiratory centre)
• Aspiration of vomit
• Chronic effects of Alcohol.
ACUTE POISONING
• 1) STAGE OF EXCITEMENT (50-100mg%) :
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Feeling of well being & slight excitation.
Action , emotion & speech are less restrained.
Lowering of inhibitions.
Inc. confidence and lack of self control.
Forgets good manners and is careless.
At 30mg% - impaired cognitive function ,
motor coordination & sensory perception.
• At 50mg% - slurring of speech, unsteadiness,
drowsiness, impaired reasoning & memory,
decreased perception & concentration .
• ↓Visual acuity at conc. 20mg% in abstainers
20-33mg% in moderate drinkers
40-70mg% in heavy drinkers.
• Judgment & motor control :
affected at 25-50mg%.
• Altered time & space perception.
• Pupils = Dilated.
• 40-100mg% = “ALCOHOL GAZE NYSTAGMUS”.
• 50-100mg% = loss of inhibitions & laughter.
• 100-150mg% = slurred speech, unsteadiness &
nausea.
• Mental concentration is poor & judgment is
impaired.
• ↓ Attention & Recall memory.
• ↓ Sensitivity to pain (at 80mg%).
• ↑ Reaction time (at 50mg%).
• ↑ Sexual desire & impaired performance
(prolonged intercourse without ejaculation).
2)STAGE OF INCOORDINATION (150-250MG%)
• Sense perception & skilled movements are
affected.
• Alteration in conduct.
• Carefree, cheerful, ill-tempered, irritable, excitable,
quarrelsome , sleepy, etc.
• In coordination in fine & skilled movements
( altered speech and fine finger movements)
• Nausea and Vomiting.
• Alcoholic smell (in breath).
• Face = flushed , Pulse = rapid, Temp = Subnormal.
• ↓ Sense of touch, taste, smell & hearing.
3) STAGE OF COMA
• Motor & sensory cells affected deeply
• Speech = thick and slurring
• Coordination is affected – giddy, stagger &
falls.
• Pulse = rapid,
• Temp =Subnormal
• Pupils = contracted, Dilate on pinching or
slapping, with slow return (Mc Ewan Sign).
Micturition Syncope :
• At night
• Loses consciousness d/t upright posture
Munich Beer Heart :
• Cardiac dilation and hypertrophy
Hang over :
• Recovers from deep sleep in 8 – 10 hrs
• Wakes with acute depression nausea,
abd. discomfort, irritability, lethargy and
headache.
• Death - at 400mg%
- below 400mg% in
chr. debilitating disease
severe arteriosclerotic heart disease
pulmonary emphysema
chronic lung disease with hypoxia.
• Low blood alc. levels seen in –
- Prolong coma causing hypoxic brain damage
- Prolong survival after heavy drinking.
• Fatal Dose :
150 – 250 ml of Absolute alc. consumed in 1 hr
• Fatal period :
12-24 hrs
• Tolerance :
is acquired, lost by out of practice
d/t- tissue sensitivity or rate of absorption
restricted by liver damage
Treatment
1) Evacuation of stomach & bowel with Gastric
Lavage.
2) Keep warm
3) 1 ltr. N.S. with 10% Glucose, 100 mg
Thiamine and 15 units of insulin
4) Nerve stimulants (Caffeine and Strychnine)
5) Oxygen
6) Dialysis – Hemo or Peritoneal
Post mortem appearance
• Alcoholic odour in cavities
• Stomach - Acute inflammation with coating of
mucus
• Brain, Liver & Lungs = congested with smell of
alc.
• Blood= fluid and dark
• Brain & Meninges = Oedematous & congested
• Cloudy swelling in parenchymatous organs
Chronic poisoning
• Addicts are the people who cannot stop drinking for
long or develops withdrawal symptoms if they stop
drinking.
• It results in impaired social or occupational
functioning.
• They suffer from nausea, vomiting, anorexia ,
diarrhoea , jaundice, tremors of the tongue and
hands, loss of memory, impairment of judgment,
coma, death.
Post mortem appearance
• Sign of malnutrition present.
• The GI mucosa is reddish brown and congested.
• Liver is congested and enlarged with weight
approximately 2kg . The surface is pale and greasy .
• Later cirrhosis develops and liver becomes smaller
and contracted with weight 800-1200gm.
• Kidneys show granular degeneration
• Heart shows fatty degeneration and patchy fibrosis.
Treatment
1. Disulfiram 250mg OD .
• It inhibits aldehyde dehydrogenase.
• It causes accumulation of aldehyde in blood and
tissues .
• Aldehyde causes unpleasant symptoms such as
flushing , palpitation , anxiety ,sweating , nausea ,
vomiting ,abdominal cramps ,due to which patient
dislikes alcohol.
• Disulfiram like reaction is caused by metronidazole.
• 2. Citrated calcium carbamide -50 mg OD
• 3. Chlorpromazine -25-50 mg 6 hourly
• 4. Clonidine : 60-180 mg/hr iv
• 5. Chlormethiazole
Drunkenness
• The state of an individual whose mind is affected by
the consumption of alcohol.
• Drunkenness is a consequence of drinking
intoxicating liquors to such an extent as to alter the
normal condition of an individual and significantly
reduce his capacity for rational action and conduct. It
can be asserted as a defence in civil and criminal
actions in which the state of mind of the defendant is
an essential element to be established in order to
obtain legal relief.
Medical examination of Drunkenness
A. Exclusion of injuries and pathological state
1.Severe head injury
2.Metabolic disorder
3.Neurological condition
4.Drugs like insulin, barbiturate, morphine
5.Pre-existing psychological disorder like hypomania
6.High fever
7.Exposure to CO
Medical examination of Drunkenness
B. History
C. General behaviour1.general manner
2.state of dress
3.speech
4.self control
D. Memory and mental alertness
E. Hand writing
F. Pulse - usually rapid, full and bounding
G. Temperature-raised
H. Skin-dry
I. Mouth
J. Eyes1.General appearance-lid swollen and red
2.Visual activity-reduced
3.Intrinsic muscle-pupil (equal or unequal dilate
or contracted, reaction to light (may be
unequal, brisk slow and absent)
4.Extrinsic muscle- test for convergence,
strabismus, and nystagmus.
K. Ears - examine for any impairment
L. Gait-examine for manner of walking, reaction time
to a direction to turn, manner of turning,
M. Stance-whether the examinee can understand
with his eye closed and heel together (Romberg's
sign)
N. Muscle incordination-finger nose test
O. Reflexes-test for knee and ankle reflex
P. Pulmonary, cardiac and alimentary system-general
examinations for presence or absence of any
disease.
Laboratory InvestigationA. Urine
• Conc. of alcohol is 25% higher than in blood
collected in same time.
• First sample should be taken as soon as possible
while second sample should be taken 25 to 30
minutes later.
• Multiplication of alcohol concentration in the
second urine specimen by 0.75 gives an
approximate value of blood alcohol level, during
the time that this specimen was being secreted.
B. Collection of blood
• Spirit must not be used for cleaning the skin, and
syringe must be free from any traces of alcohol.
• Skin should be cleaned with a solution of 1:1000
mercuric chloride or washed with soap and water.
• Blood sample should be preserved by addition of 100
mg. of sodium fluoride and 30 mg. potassium oxalate
for 10ml.followed by shaking. this prevent loss of
alcohol by glycolysis and bacterial action.
• Collection of post-mortem sample-the best place to
obtain blood is from femoral or iliac veins or axillary
veins.
• In embalmed bodies alcohol can be estimated either in
muscle or vitreous.
Widmark’s formula
a = prc
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a=weight of alcohol in gm.in the body
p=body wt in kg
r=constant (0.68 for men and 0.55 for women)
c= concentration of alcohol in blood (in mg. per kg.)
For urine analysis the formula is –
a = 3/4 prq
• q is alcohol concentration ( mg. per kg.) in urine
Methods of determining
blood alcohol
• Kozelka and Hine – Macro-method
• Cavett test – Micro test
Other techniques :
• Direct injection gas chromatography
• Enzyme- spectrophotometric assay
• Oxidation techniques
C.Breath
• Breath analyser machines operate on the
principle that alcohol absorbs radiation in the
infrared region.
• Concentration of alcohol in deep lung air
dependent on concentration in arterial
blood.2100-2300ml of alveolar air contains
same amount of alcohol as one ml. of blood
(Henry’s law)
• 60 – 100 ml of breath
• Drunkotester, drunkometer, intoximeter,
alcometer, alcotest, or breathalyser.
• Residual alcohol disappears from mouth in 20
minutes.
• Test should be repeated after 20 minutes.
D.Saliva
Mouth should be thoroughly washed with
water and about 5 ml of saliva collected in a
test tube containing 10 mg. of sodium
fluoride.
E. Vitreous
At equilibrium for every unit of alcohol in
blood there are 1.2 unit of alcohol in vitreous,
as it has high water content
Medical terminology
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Below 10 mg : Sober
10 to 70 mg % : Drinking
80 to 150 mg %:Under the influence
150 to 300 mg %:Drunk or intoxicated
300 to 400 mg%: Stupor
400mg% and above :Coma and death
Hazards of alcohol
• Alcohol is associated with domestic violence, child
abuse and suicide.
• Personal risk are:
1.He may die of exposure
2.On inhalation may cause pneumonia
3.Inhale his vomit or dentures
4.May fall and sustain a head injury
5.May fall into water and drowned
Alcohol palimpsests (alcoholic blackout)
• it is a condition seen among alcoholics, and
rarely in non addictive drinker, after drinking a
moderate amount of alcohols. this behaviour
resembles the blackouts in anoxaemia. this
may results in loss of memory of a period of
drinking spell, or in some cases, the inability
to recall what happened over a period of days.
Alcohol and traffic accident
• Safe driving is interfere due to:
1.increase in reaction time
2.creates false confidence
• Impairs concentration, dulls judgement and degrades
muscle coordination
• It decreases visual and auditory acuity
Below 50mg%-in majority driving not affected
At 60 mg%-risk of accident double in compare to sober
driver
80-100mg%-risk of accident increase 12 fold
Over 150mg%-risk become 20 times]
• Statutory limit in India is 30 mg% (S.185,
MOTOR VEHICLE ACT,1988).the punishment
for offences fine up to 2000rs or 6 month
imprisonment or both, and for subsequent
offence fine up to 3000 or imprisonment up to
2 years or both.
Alcohol withdrawal
• Symptoms appear 12 to 48 hrs after reduction in alcohols intake.
most common symptoms is tremor and shakes. the essential
feature is coarse tremors in hand tongue and eyelid in association
with at least one of the followinga)nausea and vomiting
b)malaise and weakness
c)hypertension ,tachycardia and sweating
d)anxiety, depressed mood and irritability
e)transient hallucination and illusion
f)headache and insomnia.
• Withdrawal seizures are typically single and generalised and usually
develop 6 to 48 hrs after last drink. About 1/3 rd of these patient
will develop delirium tremens unless preventive measures are
taken.
PathologyDelirium Tremens
• Results from long continued action of poison on the brain. it occurs
in chronic alcoholics due to
1)temporary excess
2)sudden withdrawal of alcohol
3)Shock after receiving an injury such as fracture of a bone
4)Acute infection, such as pneumonia, influenza, erysipelas,etc.
• Typically begin 72 to 96 hour the last drink.
Main symptoms
• are coarse muscular tremors,insomnia,restlessness,loss
ofmemory,psychomotoragitation,confusion,disorientation,f
ear,tendency to commit suicide. other symptoms are
diarrhoea, dilated pupil,tachypnoea and hypertension.
• Death occurs in 5 to 15% cases due to cerebral oedema,
cardiac failure and shock.
• Treatment-20 mg of chlordiazepoxide, or 100 mg of
diazepam are given 4 times a day.anticraving agent like
acamprostate,naltrexone and fluoxetine.
Alcoholic polyneuritis and korsakoff’s
syndrome
• Symptoms are weakness and pain in the
extremities, wrist and foot drop, loss of deep
reflex, tenderness of muscle.
• Alcoholic Paranoia-there are fixed delusion
but not hallucinations.
• Acute alcoholic hallucinosis -persistent
hallucination develop with in 48 hrs after
cessation of alcohols
• Alcoholic epilepsy -seizures occurs after a day
or more after termination of drinking session.
Wernicke’s encephalopathy
• Results from a hypothalamus, cerebellum
& midbrain lesion due to heavy drinking.
• Vit-B1 deficiency occurs
• Cardiac dysrhythmias- tachyarrhythmia's are
common because of high adrenergic activity.
• Marchiafava’s syndrome -degeneration of
corpus callosum may occur.
• Mallory-Weiss syndrome -ruptured
oesophagus with mediastinitis
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Malnutrition
Gastric and Peptic Ulcer
Cirrhosis
Myocarditis
Pancreatitis
Mental illness
Disturbance in tryptophan metabolism
• Holiday Heart Syndrome
• Wet Berri-berri- Inc. H.R. ,Raised JVP, Vasodilation,
peripheral edema & PND.
• Boer Haeve Syndrome – Spontneous transmural
rupture of esophagus (typically in forceful emesis).
• Zieve Syndrome :
-Occurs after withdrawl of alcohol from prolong
alcohol abuse.
-Hemolytic anemia, spur cells and acanthocytes,
hyperlypoproteinemia jaundice.
Alcohol and Criminal behaviour:
• S.510,IPC:
Misconduct in public by a drunken person is
punishable with imprisonment up to 24 hrs.
Alcohol and Sudden death
• Sudden death may occur due to cardiac
dysarrhythmias and cardiopulmonary arrest.
Alcohol after death
1. If death occur due to trauma- A post-mortem
alcohol estimation in Subdural blood clot will
give true picture.
2.No appreciable loss by evaporation or any
other means
3. With advance putrefaction, the entire content
of the vascular system including alcohol is
destroyed. Analysis of brain gives best results.
4.Ethanol and other alcohol can be produced
during putrefaction by fermentation of
carbohydrate and proteins of the body
(usually 20 to 30 mg/100ml).this may occur
due to enzyme, bacteria, yeast, fungi
• The commonest organism is E. coli.
5.The longer the interval after death and higher
the temperature, the more is produced.
6.Alcohol conc. in excess of 0.2% would indicate
alcohol consumption prior to death.
Methyl alcohol
• Also known as wood alcohol
• It is present in antifreeze , paint removers , dyes,
adhesives and varnish .
• Absorption : absorbed from stomach, intestine ,
lungs and skin.
• Rate of oxidation is 1/5th of that of ethanol.
• Accumulates in blood with repeated small doses
and remains in blood for 3 -4 days.
• 80mg/100ml of blood is dangerous level.
• Methanol → Formaldehyde → Formic acid
Liver
(x 33 )
(x6)
Metabolic Acidosis
Retinal Toxicity
• Formate may inhibit cytrochrome oxidase, inc lactate.
It is distributed according to water content, and conc in
vitreous body & optic nerve.
• Signs and symptoms :
Same as ethyl alcohol but inebriation is not
prominent.
• Symptoms are N/V , severe cramps in
abdomen, headache , dizziness , neck stiffness
,
• The effect on CNS is more intense and
prolonged – Delirium and Coma (for 2-3 days)
• Toxic effect on liver and kidney (acute tubular
necrosis).
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Metabolic acidosis (d/t lactic & other acids )
Anionic acidosis
Pupils are dilated and fixed
Visual disturbances like photophobia , blurred or
misty vision (snowfield vision), central and
peripheral scotoma , decreased light perception ,
concentric diminution of visual field for color and
form.
• Sudden failure of vision or complete blindness is
due to optic neuritis and atrophy.
• Fatal dose : 60-200ml
• Fatal period : 24-36 hrs
• Elimination :3-5% through lungs
12% through kidneys
• Cause of death : Acidosis
Treatment
• 1. G.Lavage. with 5% bicarbonate soln.
• 2. Activated charcoal
• 3. Antidote – Ethanol , 10% 100 ml as iv infusion ,
level of 100-150 mg% is maintained at all times.
• 4. Alternatively 60ml Ethyl alcohol in 200 ml fruit
juice is given per orally.
• 5.Haemodialysis is treatment of choice in severe
poisoning.
• 6. Methyl pyrazole (4MP or fomepizole) : It is
competitive inhibitor of alcohol dehydrogenase.
15mg/kg f/b 10mg/kg after 12 hours for 4 doses
• 7. Folinic or folic acid : 50-75mg every 4 hourly
• 8. Sodabicarb to treat the metabolic acidosis
• 9. Place the patient in left lateral position and
head down to avoid aspiration of vomitus
• PM appearances : Cyanosis is marked
• Absence of PM clotting of blood
• Pyridine may give the skin a purple colour
• The mucous membrane of stomach and
duodenum is congested and inflamed
• Small or large intestine or both are contracted
and resemble thick pipe with narrow lumen
• Lungs brain bladder are congested.
• Liver shows fatty changes
• Kidneys show tubular degeneration
• MLI: poisoning is mostly accidental
Questions
1.Widmark’s formula are used for estimation of
• Cyanides
• Alcohol
• D.D.T
• Teeth
2.Optic atrophy can be caused by.....poisoning
• Phosphrous
• Ethyl alcohol
• Methyl alcohol
• Lead
3.Fetal dose of methanol
• 15ml
• 30-60 ml
• 60-250ml
• 500ml
4.Morbid jealousy is diagnostic of
• Cocaine
• Cannabis
• Alcoholism
• Barbiturate
5.Macewan sign is seen in
• Alcohol
• Organophosphorus
• Dhatura
• Barbiturate
6.Best method of treatment of methyl alcohol
• Calcium gluconate
• Ethyl alcohol
• Amphetamine
• 1% ammonia
7.In chronic alcoholism which of the following is
seen
• Delirium tremens
• Wernike’s syndrome
• Korsakoff psychosis
• All of the above
8.The fatal dose of absolute alcohol
• 30 ml
• 60 ml
• 90 ml
• 150 ml
9.Which of the following is not useful in methyl
alcohol poisoning
• Gastric lavage
• Dialysis
• Ethyl alcohol
• High dose of Vit. B12
10. Wernicke’s encephalopathy is due to-
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Vitamin B1 deficiency
Vitamin B2 deficiency
Vitamin B6 deficiency
Vitamin B12 deficiency