NEUROTICS 1 CEREBRAL a CNS DEPRESSANTS e g

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 • C 2 H 5 OH • 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 • • • 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 =210 g in men & 140 g 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 -3 min. • Max. conc. in blood within 45 -90 min. (mainly 1 hr).

Factors Increasing Absorption • • 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 -3 min) - 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 • • • 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 P 4502 E 1. Alcohol Acetaldehyde dehydrogenase (ADH) Alcohol dehydrogenase Acetaldehyde NAD Acetic acid (or Acetyl Co. A) By- Fructose - Enzymes (Chronic alcoholic) By – Liver damage Kreb’s cycle CO 2 + H 2 O Acetate can form – glycogen , protein , fats and cholesterol. A Diabetic who is Ketogenic will produce fat.

• Disappears from blood at 10 -15 ml/hr (15 mg/100 ml/hr) • Elimination varies: 12 -27 mg/100 ml/hr (Av=18 mg) • Fast - With large dose - Chronic alcoholics (30 -40 mg/100 ml/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. › 300 mg%) • Toxic to every organ, d/t acetaldehyde or change in redox potential. • Blocks metabolism and increases levels of some drugs. • Moderate consumption → HDL & LDL

• • • ↑ Appetite (↑salivary & gastric juice) Carminative (Brandy) Diuresis (d/t ↓ADH) Spirituous liquor Heamorrhagic gastritis Mixing of drinks ↑Gastric emptying Fasting blood Alcohol= 0. 001 mg% • IN VINO VERITAS

Causes of Death • CNS Depression (respiratory centre) • Aspiration of vomit • Chronic effects of Alcohol.

ACUTE POISONING • 1) STAGE OF EXCITEMENT (50 -100 mg%) : 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 30 mg% - impaired cognitive function , motor coordination & sensory perception. • At 50 mg% - slurring of speech, unsteadiness, drowsiness, impaired reasoning & memory, decreased perception & concentration. • • •

• ↓Visual acuity at conc. 20 mg% in abstainers 20 -33 mg% in moderate drinkers 40 -70 mg% in heavy drinkers. • Judgment & motor control : affected at 25 -50 mg%. • Altered time & space perception. • Pupils = Dilated. • 40 -100 mg% = “ALCOHOL GAZE NYSTAGMUS”. • 50 -100 mg% = loss of inhibitions & laughter. • 100 -150 mg% = slurred speech, unsteadiness & nausea.

• Mental concentration is poor & judgment is impaired. • ↓ Attention & Recall memory. • ↓ Sensitivity to pain (at 80 mg%). • ↑ Reaction time (at 50 mg%). • ↑ Sexual desire & impaired performance (prolonged intercourse without ejaculation).

2)STAGE OF INCOORDINATION (150 -250 MG%) • 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 400 mg% - below 400 mg% 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 2 kg. The surface is pale and greasy. • Later cirrhosis develops and liver becomes smaller and contracted with weight 800 -1200 gm. • Kidneys show granular degeneration • Heart shows fatty degeneration and patchy fibrosis.

Treatment 1. Disulfiram 250 mg 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 behaviour 1. 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. Eyes 1. 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 systemgeneral examinations for presence or absence of any disease.

Laboratory Investigation. A. 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 10 ml. 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 • • 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 -2300 ml of alveolar air contains same amount of alcohol as one ml. of blood (Henry’s law)

• 60 – 100 ml of breath • Drunkotester, drunkometer, intoximeter, 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 • • • 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 400 mg% 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 50 mg%-in majority driving not affected At 60 mg%-risk of accident double in compare to sober driver 80 -100 mg%-risk of accident increase 12 fold Over 150 mg%-risk become 20 times]

• Statutory limit in India is 30 mg% (S. 185, MOTOR VEHICLE ACT, 1988). the punishment for offences fine up to 2000 rs 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.

Pathology. Delirium 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-B 1 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

• • 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/100 ml). 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 1/5 th of that of ethanol. • Accumulates in blood with repeated small doses and remains in blood for 3 -4 days. • 80 mg/100 ml of blood is dangerous level.

• Methanol → Formaldehyde → Formic acid Liver (x 33 ) (x 6) 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).

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 -200 ml • 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 60 ml Ethyl alcohol in 200 ml fruit juice is given per orally. • 5. Haemodialysis is treatment of choice in severe poisoning.

• 6. Methyl pyrazole (4 MP or fomepizole) : It is competitive inhibitor of alcohol dehydrogenase. 15 mg/kg f/b 10 mg/kg after 12 hours for 4 doses • 7. Folinic or folic acid : 50 -75 mg 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