Modern Medical Toxicology VV Pillay
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1General Principles
2

Introduction1

 
EPIDEMIOLOGY OF POISONING
It has been estimated that some form of poison directly or indirectly is responsible for more than 1 million illnesses worldwide annually, and this figure could be just the tip of the iceberg since most cases of poisoning actually go unreported, especially in Third World countries. The incidence of poisoning in India is among the highest in the world: it is estimated that more than 50,000 people die every year from toxic exposure.
The causes of poisoning are many—civilian and industrial, accidental and deliberate. The problem is getting worse with time as newer drugs and chemicals are developed in vast numbers. The commonest agents in India appear to be pesticides (organophosphates, carbamates, chlorinated hydrocarbons, pyrethroids and aluminium/zinc phosphide), sedative drugs, chemicals (corrosive acids and copper sulfate), alcohol, plant toxins (datura, oleander, strychnos, and gastrointestinal irritants such as castor, croton, calotropis, etc.), and household poisons (mostly cleaning agents). Among children the common culprits include kerosene, household chemicals, drugs, pesticides, and garden plants.
 
HISTORICAL OVERVIEW
The history of poisons and poisoning dates back several thousand years. Early poisons were almost exclusively plant and animal toxins, and some minerals. They were used mainly for hunting. Some were used as “ordeal poisons*,” for e.g. physostigmine from Physostigma venenosum (Calabar bean), and amygdalin from peach pits. Arrow and dart poisons were very popular for hunting animals (and sometimes fellow humans). In fact it is said that the term “toxicology” is derived from toxicon, a Greek word which when translated reads, “poison into which arrowheads are dipped”. Common arrow poisons included strophanthin, aconitine, and extracts from Helleborus (a cardiotoxic plant), and snake venom.
One of the earliest classifications of poisons was done by the Greek physician Dioscorides (AD 40–80) who categorised poisons into 3 groups—animal, vegetable, and mineral. Experimental toxicology perhaps began with Nicander (204–135 BC), another Greek physician who experimented with animal poisons using condemned criminals as subjects. An early treatise on plant poisons is De Historia Plantarum, by Theophrastus (370–286 BC). The ancient Indian text Rig Veda (12th century BC) also describes several plant poisons. The Greeks used some plant toxins as poisons of execution. Socrates (470–399 BC) was executed by the administration of hemlock.
Among mineral poisons, one of the earliest known elements was lead which was discovered as early as 3500 BC. Apart from its extensive use in plumbing, lead was also employed in the production of vessels and containers, which led to widespread chronic health problems. During the Roman period, lead acetate was widely used as a sweetening agent for wine resulting in a high incidence of plumbism, particularly among members of the aristocracy. In fact, the fall of the Roman empire is attributed to the debilitating effects of this scourge.
Homicidal poisoning has also had a hoary past. One of the earliest laws against the murderous use of poisons was the Lex Cornelia passed in Rome in 81 BC. After the fall of the Roman empire, there was a lull in the development of Toxicology until 1198, when Moses Maimonides published his classic work Treatise on Poisons and Their Antidotes. Then came the Renaissance toxicologists—Paracelsus (1493–1541), Ambroise Pare (1510–1590), and William Piso (1611–1678). Paracelsus’ study on the dose-response relationship is generally considered as the first time that a scientific approach was made in the field of toxicology.
Development of toxicology as a distinct speciality began in earnest in the 18th and 19th centuries with the pioneering work of Bonaventure Orfila (1787–1853), who is generally regarded as the father of modern toxicology. He advocated the practice of autopsy followed by chemical analysis of viscera to prove that poisoning had taken place. His treatise Traite des Poisons published in 1814 laid the foundations of forensic toxicology. In 1829, one of his students, Robert Christison (1797-1882) published a simplified English version titled A Treatise on Poisons.
The first published work on clinical toxicology was A Practical Treatise on Poisons written by O Costill, and published in 1848.
Subsequent to World War II, the role of Poison Control Centres began to be increasingly recognised in the prevention and treatment of poisoning, as well as in disseminating accurate information on toxicological matters to medical professionals and the general public.
 
POISON CONTROL CENTRES
Arising out of a growing concern over the rising incidence of poisoning worldwide, coupled with a lack of public awareness about its seriousness, Poisons Information Services made their first appearance in the Netherlands in 1949. In 1961, a telephone answering service was introduced in Leeds, England, which gave information to medical practitioners and others about the poisonous properties of a variety of household, agricultural, and therapeutic substances. On 2 September 1963, a National Poisons Information Service was established at Guy's Hospital, London. The same year, the Illinois Chapter of the American Academy of Pediatrics opened an Information Centre in Chicago, USA. Since then, all around the world similar Centres have sprung up, performing the invaluable functions of generating public awareness on poisoning, and imparting much needed toxicological diagnostic and therapeutic assistance to doctors.
India made a belated foray with the establishment of the National Poisons Information Centre at the All India Institute of Medical Sciences, New Delhi in December, 1994. A second Centre was subsequently opened at the National Institute of Occupational Health, Ahmedabad. Some more Regional Centres have come up in cities such as Chennai, and efforts are under way to establish similar Centres in other parts of the country. The author has established a full-fledged Centre at Cochin (in Amrita Institute of Medical Sciences, a multispecialty teaching hospital) with poison information and analytical services (Box 1.1). The Centre subscribes to POISINDEX, while the WHO has provided INTOX free of cost. An Analytical Laboratory attached to the Centre tests for common poisons or drugs in body fluids, as well as in water and medicinal preparations, and other commercial products.
Poison Centres provide immediate, round the clock toxicity assessment and treatment recommendation over the telephone for all kinds of poisoning situations affecting people of all ages, including ingestion of household products, overdose of therapeutic medication, illegal foreign and veterinary drugs, chemical exposures on the job or elsewhere, hazardous material spills, bites of snakes, spiders and other venomous creatures, and plant and mushroom poisoning. When a call about a poisoning is received, the poison information specialist obtains a history from the caller, assesses the severity of the poisoning, provides treatment recommendations, and refers the patient for further medical attention when necessary.
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Referrals to health care facilities when made are later followed up with phone calls to assess progress, and provide additional recommendations until any medical problems related to the poisoning are resolved. Information from the beginning of the call to the final outcome are noted on preformatted case sheets, and quantifiable data is filled in by darkening respective bubbles on the sheet. The data generated is periodically analysed by the Centre and is also monitored for quality assurance of the information specialists. Upto 75% of poisonings reported to Poison Centres are managed entirely by telephone consultations without further necessity of additional costs for the health care system.
 
MORTALITY FROM POISONING
This varies from country to country depending on the kind of poisons encountered, the extent of awareness about poisoning, the availability of treatment facilities, and presence or absence of qualified personnel. While in developed countries the rate of mortality from poisoning is as low as 1 to 2%, in India it varies from a shocking 15 to 35%. Children under 15 years of age account for most cases of accidental poisoning, but fortunately they are associated with relatively low mortality. On the other hand, most suicidal exposures are seen in individuals over 15 years of age but are associated with high mortality.
Table 1.1   Toxicity Rating
Usual Fatal Dose
Rating
Less than 5 mg/kg
6 (Super Toxic)
5 to 50 mg/kg
5 (Extremely Toxic)
51 to 500 mg/kg
4 (Very Toxic)
501 mg/kg – 5 gm/kg
3 (Moderately Toxic)
5.1 gm/kg – 15 gm/kg
2 (Slightly Toxic)
More than 15 gm/kg
1 (Practically Non-Toxic)
In poisoning cases, the attending physician is often asked to comment on the prognosis of the victim's condition. Unfortunately in cases of serious poisoning, it is very difficult to predict the outcome. There are many reasons for this. In a substantial number of cases, the doctor is unaware of the exact nature of the poison consumed; in others, the victim may have ingested several kinds of drugs simultaneously. Even in those cases where the exact identity and dose of a single ingested poison is known, the doctor may not have a clear idea as to its toxicity. In order to ameliorate the situation to some extent and help physicians have some idea as to the hazardous nature of various poisons, a system of “toxicity rating” has been evolved for common poisons. The higher the toxicity rating for a particular substance (over a range from 1 to 6), the greater its potency (Table 1.1). The rating is based on mortality, and is applicable only to the acute toxicity of a single dose taken orally. In the case of commercial products where various combinations of poisonous substances may have been used, one has to derive an estimate of the toxicity rating in totality, taking into consideration all the components put together, with particular reference to individual concentrations.
To assess and rate the toxicity of a drug, the Usual Fatal Dose (UFD) is taken into consideration which is derived from animal experimental data and statistics of human poisoning. The UFD is based on the Minimum Lethal Dose (MLD) which is usually indicative of the lethal dose that is fatal to 50% of animals (LD 50). While the UFD of virtually every poison/drug finds mention in this book under the relevant section, Table 1.2 serves as a quick reference source for common agents.
 
POISONING SEVERITY SCORE
The European Association of Clinical Poison Centres and Clinical Toxicologists has proposed a guide for scoring poisoning severity, applicable to cases of acute poisoning in both adults and children.
Table 1.2   Usual Fatal Dose of Common Toxic Agents
Acetyl salicylic acid (Aspirin) : 15 to 20 gm
Cyanide (salt) : 200 to 300 mg
Methanol : 60 to 250 ml
Acids (Mineral) : 10 to 15 ml
Datura : 50 to 75 seeds
Morphine : 200 mg
Aconite (Root) : 1 gm
DDT : 15 to 30 gm
Nicotine : 60 mg
Aluminium phosphide : 500 mg
Diazinon : 1 gm
Oleander : 5 to 15 leaves or 15 gm root
Arsenic trioxide : 250 mg
Ethanol : 5 to 8 gm/ kg
Opium : 500 mg
Atropine : 10 mg
Ethylene glycol : 100 ml
Organochlorines (except Lindane and DDT) : 2 to 6 gm
Long-acting Barbiturate : 3 gm
Formaldehyde : 30 to 60 ml
Oxalic acid : 15 to 20 gm
Short-acting Barbiturate : 1 to 2 gm
Heroin : 50 mg
Paracetamol : 12 to 20 gm
Benzene : 15 to 20 ml
Iron : 200 mg/kg
Parathion : 100 mg
Carbolic acid (Phenol) : 20 ml
Isopropanol : 200 to 250 ml
Phosphorus : 60 to 120 mg
Castor : 5 to 10 seeds
Lead acetate : 20 gm
Strychnine : 50 to 100 mg
Cocaine : 1 to 2 gm
Lindane : 15 to 30 gm
TEPP : 100 mg
Copper sulfate : 30 gm
Malathion : 1 gm
Thallium (salt) : 1 gm
Curare : 60 mg
Mercuric chloride : 1 to 2 gm
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As per this system, there are basically 4 grades of severity:
None (0)—Nil/Minimal signs or symptoms
Minor (1)—Mild, transient and spontaneously resolving symptoms
Moderate (2)—Pronounced or prolonged symptoms
Severe (3)—Severe or life-threatening symptoms
In minor poisoning, symptomatic and supportive treatment is generally not required, whereas this normally is the case for moderate poisoning. In severe poisoning, advanced symptomatic and supportive treatment is always necessary.
FURTHER READING
  1. Arun M, Palimar V, Mohanty MK. Epidemiology of poisoning fatalities in Manipal. J Indian Soc Toxicol 2006: 2: 36–9.
  1. Batra AK, Keoliya AN, Jadhav GU. Poisoning: An unnatural cause of morbidity and mortality in rural India. J Assoc Physicians India 2003; 51: 955–9.
  1. Cyriac Job. A regional study of poisoning in children. J Indian Soc Toxicol 2005; 1: 13–7.
  1. Dash SK, Mohanty MK, Mohanty S. Sociodemographic profile of poisoning cases. J Indian Acad Forensic Medicine 2005; 27: 133–8.
  1. Gargi J, Tejpal HR, Chanana A, Rai G, Chaudhary R. A retrospective autopsy study of poisoning in the northern region of Punjab. J Punjab Acad Forensic Med Toxicol 2008; 8: 17–9.
  1. Gupta BD, Vaghela PC. Profile of fatal poisoning in and around Jamnagar, Gujarat, India. J Indian Soc Toxicol 2006: 1: 12.
  1. Multani AS, Bal BS, Singh SP, et al. Spectrum of acute poisoning in medical emergencies – A prospective study. (Abstract). J Assoc Physicians India 2003; 51: 1199–1200.
  1. Naik RS, Tirpude BH, Sarwey GN, et al. Importance of toxicology laboratory in Forensic Medicine department of medical colleges. J Forensic Med Toxicol 1999; 16: 70–1.
  1. Pillay VV. Comprehensive Medical Toxicology. 2nd edn, 2008. Paras Medical Publisher,  Hyderabad,  India.
  1. Pillay VV. The need for a poison information center in every major hospital. J Karnataka Medico-Legal Soc 1999; 8: 6–9.
  1. Sharma BR, Harish D, Sharma V, et al. The epidemiology of poisoning: An Indian viewpoint. J Forensic Med Toxicol 2002; 19: 5–11.
  1. Sharma D, Bhullar DS. Profile of poisoning cases reported by state chemical laboratory, Punjab. J Indian Soc Toxicol 2006: 1: 17.
  1. Shetty SK, Menezes RG, Kamath G, et al. Analysis of poisoning deaths in Mangalore, coastal Karnataka. J Indian Soc Toxicol 2006: 1: 19.
  1. Singh LR, Momonchand A, Singh PI. Pattern of accidental poisoning in children. J Indian Acad Forensic Med 2001; 23: 69–71.