DR. HUSSAIN ALIDR. HUSSAIN ALI

Sr.LECTURERSr.LECTURER

DEPARTMENT OF FORENSIC DEPARTMENT OF FORENSIC MEDICINEMEDICINE

DOW UNIVERSITY OF HEALTH DOW UNIVERSITY OF HEALTH SCIENCESSCIENCES

KARACHIKARACHI

The important therapeutic preparation of salicylic acid include sodium salicylate, methyl salicylate (oil of wintergreen), and acetylsalicylic acid (aspirin). Salicin and methyl salicylate are naturally occurring forms of salicylates, forms in the leave and bark of a numbers of plants, especially the willow tree (salix alba vulgaris)

1. Sodium salicylate: Odourless, white, scaly crystals with unpleasant saline taste.

2. Acetyl salicylic acid: Odourless, white crystalline powder tasting the same as sodium salicylate

3. Methyl salicylate: colourless liquid with aromatic odour and sweetish taste

Uses 1. Antipyretic 2. Analgesic 3. Antirheumatic 4. Keratolytic (Salicylic acid)

Signs and symptoms: It is perhaps a taxonomic error to include salicylate under corrosives. They are powerful irritants of the gastrointestinal tract, but true corrosive action is lacking.

1. Gastrointestinal: Epigastric pain, vomiting, GI-haemorrhage , pylorospasm

2. Pulmonary (Salicylic dyspnoea): Tachyponea, pulmonary odema and respiratory alkalosis(Co2 retention) at toxic level respiratory center paralysis hene resp. acidosis.

3. CNS: Tinnitus, deafness, vertigo, hallucinations, convulsions and salicylate jag, i.e. a form of delirium with confusion, excitement and restlessness. Coma occurs only in the terminal stages.

4. Renal: Proteinuria, sodium and water retention and tubular necrosis.

5. Haemotologic: Hypovolaemia, hypoprothrombinaemia, hypokalaemia and platelet dysfunction.

6. Metabolic: Hyperpyrexia, hyperventilation and metabolic acidosis.

Usual fatal doseSalicylic acid: 70 to 80 gmSodium salicylate and acetyl salicylic acid: 15 to 20

gmMethyl salicylate: 10 to 20 mlToxicity rating 4.Diagnosis 1. Lee-Jones test:2. Ferric chloride test:3. Plasma salicylate level4. Prothrombin5. Test for metabolic acidosis, hypokalaemia, etc.

1. Decontamination: Stomach wash can be of benefit , even though the several hours may have elapsed since the incident. When many tablets of salicylate are taken together, they cake into a mass of concretion in the stomach delaying gastric absorption and emptying. As a result, blood level of aspirin may continue to rise several hours after ingestion giving rise to the clinical maxim, “ it is never to late to was out the stomach in salicylate poisoning” gastric lavage must preferably be done with sodium bicarbonate solution. Activated charcoal suspension can be administered in the usual manner.

2. Forced alkaline Diuresis: This can help in eliminating aspirin or other salicylate from the body. For this purpose sodium bicarbonate is given intravenously initially in a dose of 1 to 2 mEq/Kg, with subsequent administrations as required. Do not gives sodium bicarbonate orally as it may enhanced salicylate absorption from the gut by increasing dissolution. Also, do not administer acetazolamide to alkalinize urine since it can aggravate metabolic acidosis.

3. IV Fluids and electrolytes4. In severe cases, haemodialysis or

haemoperfusion is of benefit5. Vit. K1 can be given if there is severe

hypoprothrombinaemia6. Supportive measures.Postmortem Appeareances1. Haemorrhagic gastritis 2. Subpleural and subpericardial

haemorrrhages 3. Pulmonary and cerebral oedma4. Congestion of viscera

Medicolegal Importance 1. Accidental: Fatal accidental poisoning with

aspirin in children is reported from time to time. This has, however, becomes relatively rare since th introduction of paracetamol ( acetaminophen). In adults, accidental fatalities are even more uncommon those cases involving hypersensitivity reactions

2. Suicidal owing to easy availability of aspirin and related products and also to their ubiquitous presence in the average home, suicidal poisoning with this drug is not at all uncommon

3. Homicidal These cases are extremly rare.

The mechanism of paracetamol toxicity has now been elucidated. In therapeutic doses it is metabolized in the liver, largely to inactive sulphate and glucuronide conjugates. However, about 8 percent is converted into a highly toxic intermediate metabolite which is normally immediately inactivated by conjugation with hepatic educed glutathione and eventually excreted in the urine as cysteine and mercapturic acid conjugates. After over dosage, however, increased amounts of this metabolite are formed and rapidly deplete the limited hepatic stores of glutathione. It is then free to bind irreversibly with macromolecules in the hepatocytes producing necrosis. Children, however, seem less susceptible to paracetamol hepatotoxicity and this may reflect differences in metabolic pathways.

Features: Nausea and vomiting are frequent within a few hours

of the overdose and there may be generalized abdominal pain secondary to the effort of retching and liver tenderness.

It is unusual for paracetamol hepatotoxicity to be clinically apparent before 12 – 36 hours. The usual warning signs comprise continuation of vomiting, localization of abdominal pain to the right sub costal area and the presence of liver tenderness. Early renal tubular necrosis may also cause renal angle pain at this stage. Jaundice dose not usually become obvious before the third or fourth day. If hepatocellular necrosis is extensive, hepatic failure ensues on about the fourth or fifth day ( though occasionally sooner ) with impaired consciousness, confusion, hyperventilation, hypoglycaemia and bleeding secondary to coagulation abnormalities.

Fatal cases often develop respiratory or Gram-negative infections, cerebral oedema and disseminated intravascular coagulation. Acute renal failure occurs in a small proportion of patients, usually, but not always, those with severe liver damage and hepatic failure. Paracetamol causes renal tubular necrosis in the same way as it produces hepatic necrosis. In addition renal failure is common in hepatic encephalopathy from any cause.

If the patient presents at about the critical ingestion-treatment interval of 8 hours or at any interval from 8-15 hours after ingestion of >7.5 g paracetamol N-acetylcysteine should be started immediately without waiting for the result of the plasma paracetamol concentration. If the latter subsequently suggests that the likelihood of liver damage is low, treatment can be stopped. This policy will inevitably result in the unnecessary treatment of some patients but is justified by the apparent lack of serious toxicity of N-acetylcysteine and the need to minimize hepatic damage (with a possible fatal outcome) in those at risk.

The serum alanine and aspartate aminotransferase (ALT and AST ) levels may begin to rise as early as 12 hours but peak values are not usually attained until 72 - 96 hours after the overdose. Aminotransferase activity of up to 10000 units/L is common but elevation of the alkaline phosphates is usually minimal. Plasma biluribin concentration rise more slowly than the enzymes and seldom exceed 190 u mol/1 (10mg/dl) in survivors. The prothrombin time ratio is often abnormal within 24 – 36 hours (maximum 48 – 72 hours). Hyperglycaemia is occasionally found in some jaundiced patients but with hepatic failure severe hypoglycaemia may occur. Plasma creatinine concentrations rise more rapidly than the urea when renal failure develops.

TREATMENT: It has been shown clinically and experimentally that

paracetamol induced liver damage, renal failure and death can be prevented by the administration of Sulphydryl donors such as Cysteamine, methionine and N- acetylcysteine although their mode of action is uncertain. Cysteamine ( intravenously) was the first of these to be tried in clinical practice and though it was highly effective if given within 10 hours, it had distressing adverse effects and has been superseded by n-acetylcysteine. The latter provides virtually complete protection against liver damage when given to those at risk within 8 hours of the overdose but its efficacy declines thereafter. However, there is still considerable protection up to 10 hours and even from 10 to 12 hours but, like other Sulphydryl donors, N-acetylcysteine seems completely ineffective if given later than 15 hours after ingestion. Intravenous N-acetylcysteine rarely cause any significant adverse effect and it should be regarded as the treatment of choice for severe paracetamol poisoning. Parenteral methionine is less effective.

Oral methionine is advocated in some centers (2.5 g 4 hourly to a total of 10 g, provided the first dose can be given within 10 hours of ingestion) but in one study 10 percent of patients treated in this way subsequently had AST levels above 1000 units/1. Oral NN-acetylcysteine has also been tried but the high incidence of vomiting in patients requiring treatment must necessarily raise doubts about the reliability of oral therapy

The patient presenting with paracetamol poisoning within 15 hours of ingestion should be managed as follows:

Blood should be taken immediately ( or at 4 after ingestion if the patient presents earlier than this ) for urgent estimation of the plasma paracetamol concentration.

The stomach should be emptied while waiting for the laboratory result if more than 7.5 g have been taken within 4 hours.

The plasma paracetamol concentrations should be related to the time from ingestion and seriousness of the condition, intravenous N-acetylcysteine (Parvolex) should be started immediately. The dose is 150 mg/kg in 200 ml of 5% dextrose over 15 minutes followed by 50 mg/kg in 0.5 liter 5% dextrose over 4 hours and the same dose given over each of the subsequent two 8 hour periods.

These agents depress mental and respiratory function when taken in overdose. Fatalities are rare, ut mixed overdoses are common. Flunitrazepam intoxication has emerged as increasing problem. Ten times as potent as diazepam. It is mixed with low-quality heroin and used to soften the effects of cocaine. It is also mixed with alcohol as date rape drug. Effects are similar to those of other benzodiazepines. It may cause hallucination, and mixing with alcohol increases respiratory depression. It often is not detected on standard toxicology screens.

Symptoms. Include drowsiness dysarthria ataxia. Slurred speech, and

confusion. Treatment. Do not induce emesis. Consider gastric lavage if

presentation is within 1 hour of ingestion . administer activated charcoal. Provide general supportive measures for hypotension and bradycardia. Rarely, respiratory depression may require intubation. Flumazenil, a benzodiazepine antagonist, reverses toxicity without causing respiratory depression. Administer 0.2 mg ( 2 ml) IV over 30 seconds, followed by 0.3 mg at 1 minute intervals to a total dose of 3 mg. if no response is observed after such treatment, benzodiazepines are unlikely to be the causes of the patients sedation. If a partial response has occurred, give additional 0.5 mg increments to a total of 5 mg. rarely, as much as a 10 mg total dose may be necessary for full reversal. If no IV access is available, the drug can be administered by endotracheal tube. Treat recurrence of sedation or respiratory depression by repeating the preceding regimen or by continuous infusion of 0.1 - 0.5 mg/hour. If mixed overdose with cyclic antidepressants is suspected or the patient has a known history of seizure disorder, Flumazenil should not be used. Forced diuresis and hemodialysis are ineffective.

DR. HUSSAIN ALIDR. HUSSAIN ALI

LECTURERLECTURER

DEPARTMENT OF FORENSIC DEPARTMENT OF FORENSIC MEDICINEMEDICINE

DOW UNIVERSITY OF HEALTH DOW UNIVERSITY OF HEALTH SCIENCESSCIENCES

KARACHIKARACHI

Aconite, also known as MONK’S HOOD, WOLF BANE, BLUE ROCKET, is one of the most fast acting and dangerous Poisons.

As it is sweet in taste it is also known as Metha Zehr

  In Indo. Pak it is found in temperate

Himaliyan regions and usually known by the name of ACONITUM NAPELLUS.  

 

The different species of Aconite are:     ACONITUM FEROX   ACONITUM CHASMANTUM   ACONITUM SPICATUM     Of all these, Aconitum Ferox is the most

toxic and contains and alkaloid known as PSEUDO ACONITINE.  

The whole plant is Poisonous but he root is most Poisonous. Chiefly dry root is used as a Poison. The dry root is more or less concial or tappering in shape with longitudiual wrinkles. Externally it is dark brown and white and starchy internally, when freshly cut, but becomes Pink on exposure to air. It has no odour.  

 

MODE OF ACTION:     It first stimulates and then paralyses the

peripheral terminations of sensory and secretory cells. It also produces same effect on motor nerves and centres in Medulla and spinal cord, but does not effect higher centres in the brain.  

  ROUTE OF EXCRETION:   KIDNEYS   SALIVA (ONLY TRACES)  

SYMPTOMS:   Symptoms supervene immediately or with in a

few minutes after swallowing a poisonous dose of aconite. Symptoms are:  

Sweet Taste.   Severe burning and tingling of lips. Tongue,

mouth and throat, followed by numbness and anesthesia of these parts.  

Sensation of swelling of Pharyngeal fauces.   Nausea and vomiting.   Salivation.   Dysphagia.   Pain in the abdomen.  

Later there is :   Tingling and formication spread over the

whole body, causing gret uneasiness.   The pupils contract and dilate alternately,

but finally dilate.   Diplopia and impaired vision.   Vertigo.   Restlessness.   Difficulty in speech.   Great prostration.   Pain and weakness of muscles with

twitching and Spasm.  

Pulse is slow, feeble and irregular.   B.P. decreases.   Respiration is rapid first but soon

becomes slow, laboured and shallow.   The skin is cold and clammy.   Temperature is subnormal.   In most cases the consciousness is

retained till the end.   Death occurs from Syncope, or from

asphyxia.  

F.D.20-30 GRAINS OF Aconite root. F.D. of Extract 4 grains within an hour

F.D. of liniment 20 minims F.D. of Tincture Aconite 5 ml.  

  F.P. 1 – 5 hours.  

Stomach Wash with Iodide or Potassium Iodide solution with a solution containing Animal Charcoal and Tannic acid.  

Digitalis may be used to counter-act cardiac depression .  

Atropine is used to prevent vagal slowing of heart.  

Maintain reccumbent position and administer Amyl nitrite Inhalation.  

Keep the body Warm by blankets etc.   Give artificial respiration or 02

inhalation.   Dextrose saline drips.   Coramine 25% sol. 10-15 ml I/V

immediately and when even necessary

Pallor of mucus membrane of mouth, congestion or engorgement of brain and lungs.  

Inflammation of mucus membrane of Stomach, Congestion of Liver and Kidneys.  

 

It is an ideal Homicidal Poison.   Can be used for abortion.   In Himaliyan tribes the arrows are

Poisoned by aconitine.   Used rarely as a Suicidal Poison.   Occasionally cattle Poison.  

 

Digitoxin Digoxin Plants:

FoxgloveLily of the valleyOleanderStrophantus

And others

Interference with the Sodium-Potassium pump mechanism mediated by ATP- ase

Decrease in intracellular potassium leads to disturbances of conductivity

Reduction in resting membrane potential Loss of pacemaker function in sinusknot and

AV- knot

Hyperkalemia and loss of excitability of cardiac tissue

Neurological symptoms: Fatigue Headache Confusion Dizziness Lethargy

Cardial symptoms:Harmless: Sinus-bradycardia and ST-scoop AV-block I

Less harmless: AV Block II, Bigeminus, PAT

Dangerous: Polytope ventricular extrasystolia, Ventricular tachycardia

Near death: Ventricular fibrillation and asystolia

Hypokalemia : harmless Hyperkalemia: most dangerous Eu-therapeutic range for digoxin:

1-2 ng/ml Eu-therapeutic range for digitoxin:

10-35 ng/ml Toxic levels can only be decided on

12 hours after ingestion

Forget all about:

CharcoalCholestyraminPhenytoinLidocain

Hemoperfusion PotassiumPacemakerOr what ever you have heard

The only thing that helps is Immuno-therapy with Digitalis antibodies

This is a 100% therapy But it is expensive And you should store the stuff If you do not have it get it or start

praying and call for the priest Funerals are as expensive as antibodies

but only for the patient`s relatives Not to have the antibodies is neglect

Man is more like sheep as like horse It was developed in Germany by

Böhringer Mannheim, a firm,that does not exit any more

Roche took it over and than off the market so we have no longer 80 mg vials

Only Digibind® with 40 mg per vial is available

Side effect don`t matter if the patient goes on to life

There may be allergy We used it again in the same patient

after tree week and saw no allergy You can do intra-conjunctival or intra-

dermal testing but it does not save you from possible allergic reactions

Be aware of hypokalemia!!

Give as much as necessary But not to much Give it at the right time Timing is saving money Don’t believe always what is written

in the instruction To give the whole dose in one go is

wasting antibodies

40 mg Fab bind 0,6 mg Digoxin40 mg Fab bind 0,6 mg Digitoxin

Vials in Germany contained 80 mg but are no longer available now

Vials in US and GB contain 40 mg

1. Affinity of Fab to Digoxin und Digitoxin is nearly the

same (clinically no difference)

2. Affinity of Digitalis to Fab is larger than to Na+-K+-

ATPase

3. Dissociation- half-live of digitalis from Na+-K+ ATPase

50 min.

4. Starting up time 1 hour

5. Half-live of the digitalis–antibody-complex 10-20 hours

6. Volume of distribution of Fab: 0,5 -1 l/kg

7. No dissociation of Digoxin from antibody

8. If to much Fab is given in the beginning it is wasted

DR. HUSSAIN ALIDR. HUSSAIN ALI

LECTURERLECTURER

DEPARTMENT OF FORENSIC DEPARTMENT OF FORENSIC MEDICINEMEDICINE

DOW UNIVERSITY OF HEALTH DOW UNIVERSITY OF HEALTH SCIENCESSCIENCES

KARACHIKARACHI

SourceTobacco is usually prepared from curved leaves of Nicotiana tabacum belonging to family Solanaceae. Turkish tobacco is prepared from the leaves of Nicotiana rustica, and is more potent. Indian tobacco refers to Lobelia inflata.

Nicotiana tabacum and N.rustica contain the following alkaloids:

Nicotine Nornicotine Anabasine Anabatine

Lobelia inflata contains lobeline. It is cometimes used as a nicotine substitute. Nicotine is a tertiary amine, and is a colourless, bitter, volatile liquid that is weakly alkaline.UsesNicotine is a stimulant of the central nervous system, and is abused widely all over the world in the form of inhalation (cigarette, cigar, pipe,), nasal insufflations (snuff), or chewing.Nicotine is also used as an insecticide.

By far the commonest source of nicotine poisoning (acute or chronic) results from smoking tobacco in the form of cigarettes. When a cigarette is lit and inhaled, the smoker is exposed to both gaseous and particulate matter. The usual nicotine content of a “regular” cigarette varies between 13 and 20mg, while certain European and Turkish cigarette can contain higher amounts. “Low nicotine” cigarette contain 7 to 10 mg of the alkaloid.

Cigars contain 15 to 40 mg of nicotine. When a cigarette is smoked, more than half the nicotine escapes in the sidestream smoke, while a large fraction remains in the butt and filter, and it is only 0.5 to 02 mg (average 1 mg) of nicotine that finally is delivered to the smoker. Smoke from no-filtered cigarettes contains slightly higher amounts of nicotine.

There are several aspects to the mode of action of nicotine:

1. Nicotine binds stereo-specifically to select acetycholine receptors (nicotine receptors). These receptors are present throughout the body, particularly in the autonomic ganglia, adrenal medulla, central nervous system, spinal cord, neuromuscular junctions, and chemoreceptors of carotid and aortic bodies.in the CNS, the highest concentration of nicotine receptors are found in the limbic system, midbrain, and brainstem.

2. At moderate doses, nicotine stimulates the reticular activating system producing an altering pattern on the EEG, with resultant favourable effects on memory and attention. But higher doses cause tremor and convulsions due to a CNS disinhibition mechanism.

3. Nicotine stimulation of vagal centres in the medulla induces nausea and vomiting, while the gastro-oesophagal reflux is provoked due to a lowering of sphincter pressure and increased acid secretion. Larger doses cause diarrhoea due to both central and parasympathetic excitation.

Acute poisoningEarly Effects (15 min- 1 hour)-GIT: NAusa, salivation, vomiting, abdominal painCVS: Tachycardia, hypertensionRS: Tachypnoea, bronchorrhoeaCNS: Agitation, anxiety, sweating, headache,

blurred vision, confusion, vertigo, tremor, ataxia, muscle fasciculations, convulsions. Pupils are at first constricted, but may dilate later.

Delayed Effects (After 1 hour)-GIT: DiarrhoeaCVS: Bradycardia, arrhythmias,

hypotension, shockRS: Hypoventilation, apnoeaCNS: Lethargy, weakness, hyporeflexia,

hypotonia, paralysis, coma.

Death may occur, especially in the case of ingestion of cigarettes (inadvertently) by children, or exposure to insecticidal nicotine.Occupational dermal exposure to wet, uncured tobacco may produce “green tobacco sickness” among workers, characterized by nausea, vomiting, headache, vertigo, pallor, and sweating.

Chronic Poisoning (Addiction)Nicotine dependence is the most widely prevalent and deadly of all substance dependencies. The dependence-producing effects of nicotine appear to be modulated by dopamine which is increased in smokers. Nicotine also increases noradrenaline, adrenaline, and serotonin levels. Like most substance use, nicotine use begins because of social reinforcement.

With repeated exposure, many youngsters find the physiological effects of nicotine well suited to help them with the difficult periods during adolescence. In addition, physical dependence begins so that cessation of nicotine use becomes uncomfortable.

Lung cancer Non-pulmonary cancers: Mouth,

Larynx, Oesophagus, Stomach, Liver, Pancreas, Bladder, Uterine cervix, Breast, Brain.

Respiratory disease: Emphysema, Bronchitis, Asthma, Pneumonia.

Cardiovascular diseases: Coronary heart disease, hypertension, arterial thrombosis, stroke.

Obstetric and neonatal conditions: Abortion, abruptio placenta, placenta praevia, preterm labour, pre-eclampsia, growth retardation, congenital malformations, sudden infant death syndrome, foetal or neonatal death.Other conditrions: Peptic ulcer, osteoporosis, Alzheimer’s disease.

Manifestations of nicotine withdrawal can occur within 4 to 8 hours of the last cigarette. In fact, most chronic smokers experience some withdrawal symptoms on waking up each morning. Manifestations include changes in mood, insomnia, difficulty in concentrating, restlessness, decreased heart rate (average decline is 8 beats per minute), and weight gain (average is 2 to 3 kg). Craving is common, and increased coughing, poor performance on vigilance tasks, etc. can occur.

Nicotine is highly toxic; 2 to 5 mg can cause nausea, and 40 to 60 mg can cause death. However, survival has occurred with ingestions of 1 to 4 gm.

Acute PoisoningMild overdose (with spontaneous vomiting) requires only observation for 4 to 6 hours, after which the patient can be discharged.

1. Decontamination by stomach wash or (less preferably) by induction of emesis. Activated charcoal is effective and must be administered in the usual manner. In cases of dermal exposure (e.g. wet tobacco leaves, spillage of nicotine liquid), clothing should be removed, and skin thoroughly washed.

2. Since nicotine is weakly alkaline, excretion can be enhanced by acidification of urine. But it is not recommended by most investigators since it can aggravate the condition of a convulsing patient in whom there is rhabdomyolysis.

3. Animal experiments indicate that drugs such as pempidine and mecamylamine may have antidotal effects against nicotine. Hexamethonium (a ganglionic blocking agent) has prevented nicotine-induced convulsions in animals.

4. Symptomatic and supportive measures-

• Benzodiazepines for convulsions. • Atropine for bradycardia. • IV fluids and vasopressors for

hypotension Respiratory compromise is managed by oxygen, intubation, and positive pressure ventilation

Nicotine withdrawal must be treated by a combination of therapies including psychosocial, psychopharmacological, and nicotine replacement. A psychiatrist's help is crucial \0 effective management of withdrawal and prevention of relapse.

The rationale behind nicotine replacement is to prevent or relieve nicotine withdrawal symptoms while stopping smoking behavior by replacing it with another behavior. Pharmacological nicotine is of various forms and dosages.

1. Nicotine gum (polacrilex)2. Nicotine transdermal patch3. Nicotine spray

1. Clonidine2. Antidepressants3. Nicotine agonists and antagonists