Forensic Medicine & Applied Toxicology-4

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A presentation to senior medical students of Moi Universy Schol of Medicine


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Forensic Classification of Poisons (1,2,3) :

Forensic Classification of Poisons (1,2,3) By Dr. Willis Ochieng Toxicologist 07/08/2014 1

Forensic Classification Of Poisons-1 Introduction:

Different criteria have been used to classify chemicals or substances, which may cause poisoning. None is ideal and the usefulness of the classification only depends on the purpose Substances are classified simply as being poisonous or non-poisonous if it is the only information needed Are classified as solids, gases or liquids based on their physical properties This classification may be useful if the exposure pattern is the information required Can be classified as either of plant or animal origin. Can be classified as acid , base or neutral If corrosive characteristics are needed In therapeutics, one may be interested only in knowing whether a substance in question is a drug or a conventional poison Since poisons include a wide spectrum of substances, the best criterion of classification must be laboratory based Laboratory based classification found useful is that based on symptomatology , the time of serious onset of symptoms of poisoning, occupational history and geographical location of the victim Based on this criterion, we are able to come up with six major classes for convenience Forensic Classification Of Poisons-1 Introduction 07/08/2014 2

Forensic Classification Of Poisons-1 Major Classes:

  Poisonous Gases, e.g. Carbon Monoxide, Carbon Dioxide, Hydrogen Cyanide Volatile Poisons, e.g. Ethanol, Methanol Therapeutic Drugs, e.g . Analgesics, Psychostimulants Irritant Poisons, e.g. Metals, Pesticides, e.g. Organophosphates Corrosive Poisons, e.g. Household products, acids and alkalis Natural Poisons and Miscellaneous Substances, e.g. Zootoxins, phytotoxins , food poisons Forensic Classification Of Poisons-1 Major Classes 07/08/2014 3

Forensic Classification Of Poisons-1 Poisonous Gases :

Most produce toxic signs or death within a very short period of time May observe presence of apnoea , asphyxia , dyspnoea , vomiting , or skin colouration Gather as much information at the scene as possible For example- Victim found in the hospital or in theatre, anaesthetic gases may be suspected. Victims found in bathrooms, cars, fires, kitchens, carbon monoxide may be suspected Non-biological evidence like presence of fire extinguishers, gas cylinders are pointers D ocument the occupation of the victim Occupations which have a risk to toxic gaseous exposures among many are- Chemical industry, electroplating, fumigation, furnaces, glue factories, mines, photography, sewers and tanneries Organoleptic manifestation- Carbon monoxide is odourless and cyanide may not be sensed by all due to genetic polymorphism. The commonest poisons in this category are carbon monoxide, carbon dioxide and hydrogen cyanide Death by these gases is due to asphyxia No trace of the gas in post-mortem tissues unless autopsy is done immediately after death Survivors should be moved to an environment with sufficient oxygen Forensic Classification Of Poisons-1 Poisonous Gases 07/08/2014 4

Forensic Classification Of Poisons-1 Carbon Dioxide (CO2) :

The presence (3%) in the atmosphere within the breathing zone produces- Headache , drowsiness, giddiness, loss of muscle power, and respiratory effects Initially , the effect is stimulation followed by depression of the respiratory system Minimal fatal concentration is between 17% and 20 % Concentrations of between 60-80% cause instant collapse and death due to tissue anoxia Deaths due to CO 2 are commonly observed in enclosed places and are by asphyxia Forensic Classification Of Poisons-1 Carbon Dioxide (CO 2 ) 07/08/2014 5

Forensic Classification Of Poisons-1 Carbon Monoxide (CO):

Carbon monoxide (CO) is an asphyxiant gas About 30 % in the air is characterised by dizziness, headache and malaise About 40% causes incoordination , staggering and confusion About 50 % contamination causes drunken gait, slurred speech, exhaustion, flushing and vomiting About 60 % causes unconsciousness About 70% causes death CO poisoning produces both immediate and delayed neuronal injury in selective regions of the brain not easily explained on the basis of hypoxia One possible explanation is that cellular injury during and after CO poisoning is related to the production of reactive oxygen species by the brain Extent of the reactive oxygen species generation in the brain may be greater after CO acute exposure than after hypoxic hypoxia due to intracellular uptake of CO Cardiovascular toxicity is believed to involve nitric oxide derived oxidants as a result of acute CO exposure Deaths related to this gas in Kenya are mainly accidental due to charcoal stoves or poorly ventilated huts CO related deaths due to combustion involve other toxic hydrocarbon materials and other gases like hydrogen cyanide from burning materials Forensic Classification Of Poisons-1 Carbon Monoxide (CO) 07/08/2014 6

Forensic Classification Of Poisons-1 Cyanide Poisoning :

Industrial intoxication occurs due to extensive use of cyanide compounds Eating foods with cyanide Cyanogenic compounds may produce acute or subacute toxicity. Signs of cyanide poisoning include headache, vertigo, agitation, confusion, coma, convulsions and death Smoke inhalation, a polyintoxication , is most often responsible for domestic cyanide poisonings Suicidal poisonings are rare Clinical diagnosis of cyanide poisoning is complicated by the lack of an easy, convenient assay for cyanide concentration in blood Elevated plasma lactate associated with cardiovascular collapse, should suggest cyanide intoxication Treatment includes 100% oxygen and assisted ventilation, decontamination, correction of acidosis and blood pressure support Autopsy prosectors examining individuals with cyanide poisoning are at risk for occupational cyanide exposure Forensic Classification Of Poisons-1 Cyanide Poisoning 07/08/2014 7

Forensic Classification Of Poisons-2 Volatile Poisons:

Exposure is either by inhalation or ingestion depending on the physical state of the poison Symptomatic indications may present as abdominal pain (especially with phenols), convulsions (especially with glycols), delirium , drowsiness , ataxia, speech and vision disturbance, jaundice (aniline, nitrobenzene), tremors, and vomiting The onset of toxic response , illness or death is rapid when inhaled and slower if taken orally Scene of exposure or death likely to implicate these chemicals are domestic locations, hospitals and research laboratories, industrial locations Presence of liquor, spirits, glues or polishes and other domestic products serve as strong evidence of intoxication by this class Occupation of the victim is important and useful in the investigation Persons handling dry cleaners, dyes, paints, petroleum products, plastics, polishes, perfumes, rubber industries are in a high risk group All the bottles or containers found near the victim even if empty, clothing if stained or if smelly should be collected With death following clinical intervention , request for ante-mortem examination of blood or urine samples if available At autopsy , a thorough examination of the lungs and brain specimens is emphasised If the body is badly decomposed, then sampling of vitreous humour may serve as a reasonable material for toxicological analysis Forensic Classification Of Poisons-2 Volatile Poisons 07/08/2014 8

Forensic Classification Of Poisons-2 Alcohol Toxicogenesis :

Ethanol and other short-chain alcohols toxicity results from cellular responses that are potentially cytotoxic and independent of cell type Aberration in phospholipid and fatty acid metabolism changes in the cellular redox state, disruption of the energy state, and increased production of reactive oxygen metabolites is implicated in cellular damage resulting from acute or chronic exposure to short-chain alcohols. Intracellular disruption of signalling cascades through interference with the synthesis of phosphatidic acid , decrease in phosphorylation potential and lipid peroxidation are mechanisms by which solvent alcohols can affect the rate of cell proliferation and, consequently, cell number Nonoxidative metabolism of short-chain alcohols, including phospholipase D-mediated synthesis of alcohol phospholipids, and the synthesis of fatty acid alcohol esters are additional mechanisms by which alcohols can affect membrane structure and compromise cell function Forensic Classification Of Poisons-2 Alcohol Toxicogenesis 07/08/2014 9

Forensic Classification Of Poisons-2 Alcohol (Ethanol)-1 :

The term alcohol generally refers to ethanol. It exists in different types of beverages- Common brands are whisky (40%), brandy (45%), rum (50-60%), gin (40%), sherry (15-20%), wines (10-15%) and beers (2-6 %) Poisoning occurs with inappropriate ingestion of alcohol . Acute (fatal) alcoholic poisoning occurs when a large amount is ingested within a short period of time Respiratory centre is initially stimulated followed by paralysis . Death often may be accelerated as a result of choking due to inhalation of vomit or suffocation of the face by bedding. Blood alcohol level between 400 - 500 mg/100mls is fatal for most people Novice drinkers may succumb to very low blood levels Addicted individuals may tolerate very high blood levels without showing major visible signs of intoxication Manifestations of toxic effects of alcohol depend upon the rapidity of its gastrointestinal absorption, presence and type of food Oily or fatty foods tend to delay the process of absorption A warm alcoholic drink which dilates the gastric mucosal capillary, accelerates absorption with a rapid onset of toxic symptoms People who habitually drink alcohol regularly may complain of gastritis, producing a mucus barrier Forensic Classification Of Poisons-2 Alcohol (Ethanol)-1 07/08/2014 10

Forensic Classification Of Poisons-2 Alcohol (Ethanol)-2 :

Ingestion of alcoholic brands with high alcohol concentrations initially accelerates absorption till a constant rate is attained. For this reason, punch (mixture of different brands and strength) may lead to a rapid onset of intoxication. Under normal circumstances, the body metabolises about 10-20cc of absolute alcohol every hour and can eliminate blood alcohol at the rate of 12-15mg per hour Stage of intoxication of a person can be assessed by analysing behaviour- Excitement stage is characterised by- longuacity , vivacity, a sense of well-being, a tendency to lose emotional restraint, forgetting of animosity and improved conversational ability. Confusional stage characterised by- Incoordination of pronunciation, slurred speech, fine control of fingers, visual concentration, blurring of sight, confusion of mind The person may be more proud or boastful than usual Should the drinking process be continued, the person will enter into stuperous stage Forensic Classification Of Poisons-2 Alcohol (Ethanol)-2 07/08/2014 11

Forensic Classification Of Poisons Drunkenness Medical Role Of the Doctor. :

A doctor examining someone suspected to be drunk cannot prove drunkenness. This is not his responsibility Main role is to assess whether or not the person is unfit to function In some cases, a person may have an insignificant alcohol blood level and yet behave as if he is drunk It is the responsibility of the doctor and the toxicologist to establish the truth of the matter by taking the victim’s blood for analysis Forensically, the doctor supported by laboratory should observe the following- Record accused own medical history , story of his drinks and subsequent events Rule out the presence of natural disease, fits, injury, and other drugs which may be contributing to the condition Judge in his view, at the time of examination, the ability of the accused to function well The time the examination took place must be noted, as well as the time elapsing between the alleged offence and the examination. Forensic Classification Of Poisons Drunkenness Medical Role Of the Doctor . 07/08/2014 12

Forensic Classification Of Poisons Chronic ingestion of alcohol:

No alcoholic is expected to live a full life expectation .The mortality rate from alcoholism and related co-morbidities is high Consumption of alcohol is associated with criminal activities like suicide and homicide . It also has a close correlation with all forms of accidents Restrictive use of alcohol is seen to reduce suicide rates by a big margin Deaths can be avoided by enforcement of a policy which does not allow for easy access to alcohol like increasing prices of alcoholic beverages One of the indications of chronic alcohol abuse is cirrhosis of the liver resulting from hepatic injury and scarring, or fibrosis Hepatic fibrosis represents the liver's wound healing response and is characterised by accumulation of interstitial matrix , or scar. Fibrosis in the liver results from the activation of stellate cells , or resident mesenchymal cells Stellate cell activation is a dramatic phenotype transition whose net effect is the replacement of normal liver matrix by scar . Features of stellate cell activation include, increased cell accumulation from proliferation and directed migration, increased matrix production, enhanced contractility, accelerated degradation of the normal liver matrix, release of profibrogenic cytokines, and loss of cellular vitamin A Alcohol may enhance fibrogenesis through stimulation of stellate cells by hypoxia, generation of lipid peroxides from damaged hepatocytes , production of acetaldehyde that may have direct fibrogenic activity, and through activation of Kupffer cells Forensic Classification Of Poisons Chronic ingestion of alcohol 07/08/2014 13

Forensic Classification Of Poisons Methanol :

Highly toxic. It has been used also as a homicidal agent. A component of many solvents and its involvement in poisoning is usually a long with other solvents Intoxication with methylated spirit or brews laced with methanol is increasingly causing a sizeable number of deaths Initial symptoms Blurred vision , elongated anion gap and metabolic acidosis are typically delayed and may not at first be recognised as methanol toxicity Treatment must be prompt and definitive General supportive care, ethanol infusion, dialysis and alkalisation form the mainstays of treatment Acute methanol ingestion can cause characteristic ocular damage, severe metabolic acidosis, serious neurological sequelae , together with widespread electrophysiological dysfunction Methanol affects the photoreceptors, Muller cells and the retrolaminar portion of the optic nerve. Optic neuropathy and putamal necrosis, are considered the most common sequels . All this can lead to severe vision loss In most cases, the mechanism causing death in methanol intoxication is as a result of combined effects of the anaesthetic action of methanol itself and metabolic acidosis by formic acid Forensic Classification Of Poisons Methanol 07/08/2014 14

Forensic Classification Of Poisons-3 Therapeutic Drugs Drug toxicity-1 :

All drugs are poisons Most drugs and other chemicals undergo metabolism in the animal body which may lead to- Formation of reactive intermediates which may be responsible for many adverse toxic reactions Formation of intermediates which are proximate carcinogens initiating a process of carcinogenesis However , well-nourished tissues have a highly effective chemical defence system which protects against the toxicity of oxygen radicals and other chemicals Toxic injury is likely to result only from major overdose, or prolonged exposure at lower dosage, or from nutritional deficiency Toxicity may be manifest in any different ways including- Acute effects that may lead to necrosis of the liver and kidney Subacute effects leading to gastrointestinal ulceration Chronic effects such as malignancy, effects on reproduction and on the unborn child and even on a mature adult through medication to the parent Forensic Classification Of Poisons-3 Therapeutic Drugs Drug toxicity-1 07/08/2014 15

Forensic Classification Of Poisons-3 Drug toxicity-2:

Drugs commonly implicated in poisoning in this group are solvent extractable . This knowledge is useful and narrows the field of investigation Pharmacological effects, indications or symptoms are variable and require further differentiation Analgesics are characterised by gastric irritation, haematuria , tinnitus, sweating, coma and convulsions Opiates , both natural and synthetic narcotics, are differentiated from others by their ability to contract pupils, muscle twitching, slow respiration, hypotension and coma Sedatives and hypnotics are identified by their ability to cause ataxia, slurred speech, drowsiness, stupor and coma Stimulants and antidepressants are characterised by the presence or absence of dilated pupils, dry mouth, headache, tachycardia, tremors and convulsions Time or duration of the onset of the symptoms . This depends on the route of exposure Relatively slow in oral ingestion and may appear approximately between 2 and 48 hours unless the exposure was by injection. Age of the victim is important as most of these drugs are abused mainly by the younger generation. Critical age group serving as a pointer is considered to be between 16 and 30 . The elders are suspects, as they are the single group of people using the biggest fraction of the prescription drugs particularly the analgesics . The scene of crime or death should be investigated in linkage with the age of the victim. For example, death or intoxication in the high school or college where the youth is found, points at the possible linkage with these drugs Forensic Classification Of Poisons-3 Drug toxicity-2 07/08/2014 16

Forensic Classification Of Poisons-3 Investigation Of Drug Poisoning :

  This must be approached with the possibility of co-ingestion- For example, accidental or suicidal poisonings due to benzodiazepines concoction containing a mixture of benzodiazepines, antipyretic analgesics and beer Cocaine and other stimulating drugs are more often used to increase physical fitness and are all likely to be used where physical strength is necessary By direct or indirect interference with vigilance these compounds may provoke accidents A lot of drugs is abused. This presents a lot of problems to the police and courts charged with the responsibility of fighting crime related or connected with drugs, particularly the opiates . Suspects detained at police stations for questioning may be under influence of drugs- This affects the reliability of confessions made under the influence of drugs or when experiencing withdrawal symptoms Court attendance in such state is absolutely incorrect and unfair to all They must be assessed for fitness to record valid and uninfluenced evidence. The framework for the assessment of fitness for interview must address the question of reliability Forensic Classification Of Poisons-3 Investigation Of Drug Poisoning 07/08/2014 17

Forensic Classification Of Poisons-3 Analgesics Salicylates (Aspirin) :

Acute intoxications with salicylates are common. In a dosage of 150-300 mg/kg they are severe, and above 500 mg/kg potentially fatal The presenting signs of salicylate poisoning, especially chronic (repeated or excessive doses for longer than 12 hours), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits These signs are also common in severe malaria in African children Beware that salicylate poisoning may cause, contribute or exacerbate the development of metabolic acidosis and hypoglycaemia, which are complications of severe malaria Beware that there is an increased sensitivity of the foetus to aspirin poisoning Consideration should be given to emergent delivery of term or near-term in aspirin-poisoned expectant mothers. Aspirin is a common drug and yet there are only a few cases reported where it was used for suicidal reason. Symptoms commonly seen with toxic exposure are dizziness, faintness, pallor, sweating, air hunger, irregular pulse, and vomiting . There may be disturbed acid-base balance, hyperventilation, cyanosis, delirium, coma, gastric erosion, and bleeding in severe poisoning . Depending on the condition of the patient, intervention by gastric lavage , sodium lactate intravenous infusion, vitamin K, and assisted respiration are useful Forensic Classification Of Poisons-3 Analgesics Salicylates (Aspirin) 07/08/2014 18

Forensic Classification Of Poisons-3 Anti-inflammatory Drugs :

  Several drugs in this category are in the market The most common likely to cause problems in the developing countries are paracetamol , ibuprofen and indomethacine . Toxic idiosyncratic response is common and is characterised by rashes, circulatory collapse, fainting, air-hunger, oliguria , agranulocytosis and leukemia . Forensic Classification Of Poisons-3 Anti-inflammatory Drugs 07/08/2014 19

Forensic Classification Of Poisons-3 Hypnotics :

The use of barbiturates as tranquillisers is now discouraged because there are relatively safer drugs now in the market Poisoning involves liver damage, marrow depression, brain damage e.g., hypomania . Opium Alkaloids and Narcotics- Generally, poisoning is characterised by narcosis, stupor, cyanotic coma, sweating, pin-point pupils, pulse changes, body temperature and respiratory abnormalities. Forensic Classification Of Poisons-3 Hypnotics 07/08/2014 20

Forensic Classification Of Poisons-3 Central Nervous System Stimulants :

Endogenous active substances and their receptors include acetylcholine, nicotinic receptor for nicotine , anandamide and CB 1 for delta 9-THC , endomorphins and the mµ opioid receptor for morphine In general, these drugs cause poisoning by manifestation of excitation, restlessness, mental excitement, incoherence, mania, flushing, dry skin, dry mouth, pupils dilated, respiratory problems, elevated pulse rate, coma and respiratory failure . Members of the group include amphetamines, atropine and their synthetic congeners Cocaine is common among the Kenyan rich youth. Cocaine poisoning, if present, is characterised by sudden collapse with pallor, dilated and fixed pupils, convulsions, elevated pulse rate, respiratory failure, mental confusion, motor spasms, tingling and numbness (of limbs) and irregular heart beat Forensic Classification Of Poisons-3 Central Nervous System Stimulants 07/08/2014 21

Forensic Classification Of Poisons-3 Naturally Occurring Stimulants :

Many naturally occurring alkaloids have pychostimulant properties and may lead to psychosis when ingested without control While cocaine has since been banned in all the nations of the world as a social drug, caffeine, nicotine and cathinone ( khat  ) still are uncontrolled and virtually accessible to all Several herbs enjoy their popularity among many peoples of the world in many concoctions like teas Due to the world's unmet demand of pychostimulants from natural resources, it was felt necessary for these drugs to be supplemented by synthetic ones to overcome the foreseen shortage This was the beginning of the proliferation of synthetic drugs This led to the production of amphetamines and methamphetamines with a greater abuse potential as a result of its affordability Forensic Classification Of Poisons-3 Naturally Occurring Stimulants 07/08/2014 22

Forensic Classification Of Poisons-3 Convulsant Poisons :

Poisoning is manifested by, twitching of muscle, intermittent arrest of respiration and stiffening of whole body . Most central nervous system drugs can cause convulsive poisoning Common members of this group existing in different forms and preparations are strychnine, nicotine, parasympathetic, anticholinesterase and antihistamines   Nicotine . The biggest source of nicotine exposure is by smoking cigarettes. It is fatal in acute exposure but exacerbate a lot of cardiovascular medical conditions in a prolonged chronic exposure. Cigarette smoking is the single biggest preventable cause of death and is contributing to inequalities in health, exacerbating and causing poverty Cigarette smoking is known to be a strong risk factor for several cardiovascular diseases such as ischaemic heart disease, stroke, intermittent claudication and aortic aneurysm. Atherosclerosis, often with superimposed thrombosis, has been shown to be the underlying disease process in all of these diseases . This fact has led to the assumption that smoking accelerates the atherosclerotic process and thereby promotes premature cardiovascular disease . Forensic Classification Of Poisons-3 Convulsant Poisons 07/08/2014 23

Forensic Classification Of Poisons-3 Abortificients :

Ergot- Used illegally in the procurement of abortion Ergot alkaloids used in obstetrics and gynaecology are ergometrine ( ergonovine ), methylergometrine ( methergine ) and bromocriptine . The pharmaceutical properties of ergonovine and methergine are critical . Methergine and ergonovine are known for their strong uterotonic effect and, compared with other ergot alkaloids, for their relatively slight vasoconstrictive abilities. These drugs do have a place in the management of the third stage of labour as they are strong uterotonics . They act differently from oxytocin and prostaglandins, and have different adverse effects. Oxytocin should be used as prophylaxis or as the drug of first choice; next, methergine or ergonovine , and if none of these drugs produce the desired effects, then prostaglandins should be used to control bleeding . Ergot alkaloid use in gynaecology has been limited and today is discouraged even in essential menorrhagia . It is suggested that ergonovine and methergine be used ( parenterally ) only in first trimester abortion curettage, to reduce blood loss. Bromocriptine has been used for lactation suppression . However, alternatives such as cabergoline , which possess fewer adverse effects, are now available and therefore preferred for this indication . These drugs and their herbal concoctions are commonly abused in procuring abortions and hence are of forensic importance. In general, acute toxicosis by ergot alkaloids manifest as sensations in hands and feet, cramps in muscles, dizziness, feeling of coldness, vomiting, diarrhoea, gangrene of fingers and mental changes . Forensic Classification Of Poisons-3 Abortificients 07/08/2014 24

Forensic Classification Of Poisons-3 Quinine and Antimalarials :

Quinine may cause ringing in ears, dizziness, skin rashes, visual and speech disturbances, delirium and convulsions. Doses of 5-8 grams are likely before these symptoms ensue. Chloroquine , which for a long time has been the preferred drug against malaria, is now discouraged due to parasite resistance. It is equally toxic in co-administration with other drugs whose metabolism is governed by P-450 group of enzymes . Chloroquine has been shown to be capable of inhibiting the activity of these enzymes in humans The effect is however modest but suggests a potential for drug-drug interactions when co-administered with other drugs that are substrates for this enzyme . The clinical significance of such an interaction will depend on the therapeutic index of any drug involved. Halofantrine (HF), which is metabolised by P-450 group of enzymes, was used in the treatment of uncomplicated multidrug-resistant Plasmodium falciparum malaria. Severe cardiotoxicity has been reported to be correlated with high plasma concentrations of HF but not with that of its metabolite N- debutylhalofantrine . What would be the effect of co-administration of ketoconazole , a P-450 inhibitor, with HF or with other conventional antimalarials on HF metabolism by human liver microsomes . Antimalarial drug inhibitory effects is reported ranked as follows : primaquine > proguanil > mefloquine > quinine > quinidine > artemether > amodiaquine . Artemisine , doxycycline , sulfadoxine , and pyrimethamine show little or no inhibition of HF metabolism. Mefloquine , quinine, quinidine , and ketoconazole used at maximal plasma concentrations inhibit N- debutylhalofantrine formation noncompetitively in HF metabolism. It follows therefore that the commonly used quinine and quinidine coadministered with HF might inhibit its metabolism resulting in the potentiation of HF-induced cardiotoxicity in patients which may be fatal. Forensic Classification Of Poisons-3 Quinine and Antimalarials 07/08/2014 25

Forensic Classification Of Poisons-3 Psychedelic Poisoning Psychedelic Substance Abuse-1 :

Typical psychopharmacological properties associated with these substances are pupillary dilation, strong agonistic and antagonistic serotonergic activity, loss of appetite during the experience; heightened arousal, sleep is often impossible They are usually not addictive, i.e., no withdrawal effects are experienced after discontinuing use and not associated with compulsive use. Toxic doses are essentially unknown, except with some phenethylamines . Drug-induced delirium is often seen in clinical practice. Delirium is strongly associated with anticholinergic activity ; drugs of different classes, including tricyclic antidepressants and traditional high-dose neuroleptics . These are high risk group of drugs A large number of drugs, including benzodiazepines, sedatives, dopamine-activating drugs, antiepileptics , histamine H 2 receptor blockers, digitalis and analgesics, are less frequently associated with delirious reactions and constitute a medium-high-risk group. The risk of inducing delirium in frail elderly and demented persons suggests that drugs which might induce delirium should be avoided. Forensic Classification Of Poisons-3 Psychedelic Poisoning Psychedelic Substance Abuse-1 07/08/2014 26

Forensic Classification Of Poisons Psychedelic Substance Abuse-2 :

Some of the typical features of persons with psychedelic influence are- Temporary loss of psychological ego Heightened awareness of sensory input Lucid and vivid recall of past events, especially from early childhood Modified perceptions and interpretation of reality Deep feelings of contentment, satisfaction, and familiarity Feeling of oneness, wholeness, and unity Conception of life as endless series of complex processes Ability to observe reality as if for the first time Personal insight and possible delusions Substances of abuse cause altered mental status by causing agitation, psychosis, hallucination, stupor, coma and in some cases death Crimes committed under the influence of these drugs may be pardoned by courts in special circumstance and hence of forensic importance. Forensic Classification Of Poisons Psychedelic Substance Abuse-2 07/08/2014 27

Forensic Classification Of Poisons-3 Effects Of Drugs In Accidents (Driving) :

Medicinal drugs are classified according to their effect on driving performance. Classes ranging from no effect, moderate to severe effects have been produced for estimation of effects on driving. Severe effects with sedative hypnotics, anticonvulsants, antidepressants, neuroleptics , narcotic analgesics and antitussives Present effects but negligible with antihistamines , beta blockers and central stimulants The effect on driving ability is dose-dependent and time-related , which makes the use of classification inadequate Antidiabetics have not been classified, as the danger lies in the risk of hypoglycaemia due to inadequate use The effect depends on co-ingestion of other medicines or alcohol, the development of tolerance and the condition of the subject Forensic Classification Of Poisons-3 Effects Of Drugs In Accidents (Driving) 07/08/2014 28

Forensic Classification Of Poisons-3 Behavioural Effects Of Drugs-1 :

Chronic exposure to psychostimulants , opiates, and alcohol may lead to the development of euphoria which may not be consistent with the legal and society expectation The pathophysiology of the disorder is explained by the neuroadaptation of the neurons within the mesolimic system particularly, the ventral tegmental area (VTA) and the nucleus accumbens ( NAc ) The endogenous bioamine responsible for this change is dopamine in mesolimbic brain region . Prolonged exposure to certain drugs may lead to increased release of dopamine in the NAc causing behaviourial changes, whereas withdrawal may lead to the reduction of dopamine. The reduction in this area is accompanied with feelings of dysphoria during the early withdrawal stage. Besides dopamine release, chronic exposure may increase the ability of the NAc to stimulate dopamine release. This is brought about by up-regulation of glutamate receptors on dopamine perikarya in VTA leading to the excitation of dopamine neurones with projections at the NAc region. Glutamatergic neurone stimulation is accompanied with elaboration of dopamine at NAc . Heightened activity may also be brought about by a decrease of the level of dopamine transporters at the nerve terminals within the NAc , prolonging the effect of dopamine. Activation of dopamine neurones via excitatory limbic projections to VTA due to stress and other factors may also give rise to increased dopamine levels at the NAc . Prolonged presence or diminution of dopamine at the NAc may also cause dopamine receptors (D1, D2) supersensitivity controlled by the levels of cAMP system. Up-regulation of cAMP system in NAc represents homeostatic compensation for the reduced dopamine levels during withdrawal with the resultant dysphoria . Forensic Classification Of Poisons-3 Behavioural Effects Of Drugs-1 07/08/2014 29

Forensic Classification Of Poisons-3 Behavioural Effects Of Drugs-2:

Mood and emotion is controlled by serotonin 5-HT in the brain circuitry within the limbic system . The endogenous ligand stimulates a wide spectrum of receptor subtypes Stimulation of 5-HT 1a causes membrane polarization and causes mood and emotional changes Serotonergic neurone cell bodies are found in the raphe nuclei in the brain stem with axons projected to all levels of neuraxis 5-HT 2 receptors are found at very high densities at specific layers of the cortex and are implicated in the mechanism of action of hallucinogenic drugs Any poison which blocks the removal of 5-HT from the synapse may lead to the stimulation of multiple populations of 5-HT receptors with undesirable consequences Since there is a rich innervations of hypothalamus responsible for the neuroendocrine control, serotonin must be responsible for a lot of behavioural disorders Hypothalamic stimulation mobilises factors which inhibit or stimulate anterior pituitary with the alteration of ACTH level in the systemic circulation affecting a wide spectrum of body physiological functions Forensic Classification Of Poisons-3 Behavioural Effects Of Drugs-2 07/08/2014 30

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