Chapter 23. Toxicology Principles in the Management of Acute Poisonings

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2 Chapter 23 Toxicology Principles in the Management of Acute Poisonings

3 Toxicology Principles in the Management of Acute Poisonings The basic principles of toxicology come into play in the rational management of individuals that have become ill from chemicals through either intentional or unintentional exposures.

4 Toxicology Principles in the Management of Acute Poisonings Among the important toxicological principles that are applied in evaluating the poisoned individual are: Exposure and aspects related to reducing absorption Dose response considerations Target tissue and systemic effects Chemical interactions Chemical antagonism as a management approach Acute versus chronic effects

5 Did You Know? In 2011, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.7%), cosmetics/personal care products (8.0%), household cleaning substances (7.0%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%).

6 Management of Acute Poisoning In the management of an individual who may have been acutely poisoned, the medical staff must: Make a rapid assessment of the patient with respect to the level of consciousness, ventilation, blood pressure, and other physiological assessments as deemed necessary Consider the need for a clinical chemistry assessment for determining blood levels of certain drugs or illicit substances

7 Management of Acute Poisoning, cont. Consider whether it is possible or necessary to limit further absorption of the chemical or attempt to increase its elimination Consider whether an antidote is available, appropriate, or necessary Consider contacting their regional poison information center for additional advice

8 Management of Acute Poisoning: Clinical Assessment for Known Chemicals Clinical assessment is made to determine the need for specific treatments when the chemical has been identified. Examples include: Salicylates: to assess the severity of poisoning and the need for alkaline diuresis or hemodialysis Acetaminophen: to assess the severity of poisoning and the need for administration of N- acetylcysteine

9 Management of Acute Poisoning: Clinical Assessment for Known Chemicals Iron: to assess the severity of poisoning and the need for administration of deferoxamine Theophylline: to assess the severity of poisoning and the need for charcoal hemoperfusion Lithium: to assess the severity and the need for hemodialysis Barbiturates: to assess the need for charcoal hemoperfusion

10 Management of Acute Poisoning: Clinical Assessment for Known Chemicals Methanol: to assess the severity of poisoning and the need for administration of ethanol or hemodialysis Ethylene glycol: to assess the severity of poisoning and the need for administration of ethanol or hemodialysis Ethanol: to facilitate the monitoring of treatment of ethylene glycol and methanol poisonings

11 Reducing Toxicant Absorption Absorption is a requirement for systemic toxicity. For respiratory exposures, the only ways to reduce absorption is by eliminating the chemical from the breathing zone or shortening the exposure time. The absorption of chemicals that have been spilled onto the skin can often be reduced, the extent of which depends on the nature of the chemical (e.g., lipid vs. water solubility), its concentration, and the duration of contact time.

12 Reducing Toxicant Absorption Example: The washing of skin with soap and water as quickly as possible after a spill of a residential use organophosphate pesticide formulation further reduces skin absorption. This is especially important for undiluted liquids from the product container and for solid preparations as well.

13 Reducing Toxicant Absorption, cont. Shortened exposure time coupled with dilution reduces the amount absorbed. This is commonly referred to as decontamination.

14 Reducing Toxicant Absorption- Oral Consumption For oral consumption, reduction of absorption may be accomplished (depending on the chemical) through gastric lavage and activated charcoal. For chemicals already absorbed into the blood and in severe cases of intoxication, charcoal hemoperfusion may be a clinical option. Gastric lavage is used when a patient has ingested life-threatening amounts of a toxic agent up to 1 2 hours previously.

15 Reducing Toxicant Absorption- Oral Consumption cont. It is not used for corrosive substances because of increased risk of esophageal and gastric perforations or petroleum compounds because of risk of chemical pneumonitis. Activated charcoal is often used to limit further absorption because it adsorbs a wide variety of drugs and toxic agents, if given within and hour or two of ingestion.

16 Reducing Toxicant Absorption- Oral Consumption cont. It has been shown to be effective for many pharmaceuticals (e.g., aspirin, paracetamol, digoxin, phenobarbitone, and theophylline) as well as many nonpharmaceutical chemicals.

17 Reducing Toxicity by the Use of an Antidote An antidote can simply be defined as a clinical treatment using a chemical(s) to counteract the effects of another. An antidote for any chemical can only be developed upon a thorough understanding of the toxicokinetics and toxicodynamics of the offending agent. Because a potential antidote may have additional risks associated with its use, the toxicological properties must be determined as well.

18 Reducing Toxicity by the Use of an Antidote The ultimate therapeutic goal is to reduce toxicity by interacting with the toxicant in ways that: Directly inhibit its effect through modification of its chemical properties Inhibit its effect by altering its physical properties Reduce effects at its sites of action Facilitate its elimination Provide for replacement of endogenous protective (e.g., glutathione) or required (e.g., oxygen) chemicals

19 Table 23-1 Examples of Common Poisonings and Their Antidotes

20 Table 23-1 Examples of Common Poisonings and Their Antidotes

21 Route of Exposure Influences Toxicity: An Example Using Cocaine When cocaine is injected, the entire dose is delivered systemically in seconds and a peak plasma level is obtained so rapidly that the individual experiences a rush or flash that produces increased feelings of alertness, euphoria, well-being, energy, confidence, and sexuality. The user becomes more restless and irritable and visual, tactile, and auditory hallucinations may occur.

22 Route of Exposure Influences Toxicity: An Example Using Cocaine Cocaine hydrochloride (the water-soluble form of cocaine) is snorted or injected intravenously, whereas crack cocaine is smoked. The route of exposure can profoundly influence the level of toxicity for the same dose.

23 Cocaine Example, cont. Topical application onto the nasal mucosa results in a much slower absorption due to local vasoconstriction and a lower peak plasma level. Smoking crack cocaine delivers the substance directly to the pulmonary circulation, where it is delivered to the heart and into the brain. Not all the cocaine that is smoked is available for delivery, so the delivered dose is less than that for intravenous use.

24 Route of Exposure Influences Toxicity: An Example Using Cocaine Cocaine, like amphetamines, is sympathomimetic: it produces behavioral effects it increases heart rate it increases blood pressure it increases muscle tension it increases core body temperature These effects are associated with its toxicity.

25 Cocaine Example, cont. The resulting tachycardia and hypertension may result in: myocardial infarction cerebrovascular hemorrhage coronary vasospasms cardiac arrhythmias Many individuals have the signs and symptoms of a myocardial infarction.

26 Cocaine Example, cont. The most potentially serious toxicity results from intravenous use, then respiratory and then nasal exposures. Overdose of cocaine is usually rapidly fatal, with victims dying within minutes from arrhythmias, seizures, and respiratory depression. In 2004 approximately 40,000 cases of illicit stimulant and other street drug use resulted in 214 fatalities. The management of individuals with severe cocaine intoxication includes measures to antagonize the sympathetic effects of this substance

27 Intentional and Unintentional Exposures in the American Population In 2004 approximately 84% of reported poisonings (2 million cases) resulted from unintentional exposures to chemicals, with approximately 200 deaths as outcomes. This category of exposures includes therapeutic error, misuse, animal bites and stings, food poisonings, occupational and environmental exposures, adverse reactions and unspecified

28 Intentional and Unintentional Exposures in the American Population Intentional exposures resulted in less than 20% of reported poisonings, however over 900 deaths occurred. Intentional exposure to nonclinically important chemicals for the purpose of obtaining a high continues to be a problem of enormous public health concern.

29 Intentional and Unintentional Exposures in the American Population Marijuana is the most commonly used illicit drug and is used by approximately 15 million Americans. Approximately 2 million persons currently use cocaine, and there are 200,000 current heroin users.

30 Intentional and Unintentional Exposures in the American Population Among youngsters aged years, inhalant use is higher than the use of cocaine. Current illicit drug use is highest among young adults 18 to 25 years old, with over 20% using drugs.

31 Intentional and Unintentional Exposures in the American Population, cont. The costs of illicit substance use, from the suppliers to the users, through law enforcement and the court system and the associated medical costs for treatment of acute poisonings and rehabilitation programs are staggering. Intentional exposures may very well represent the number one preventable public health problem in the country.

32 Inhalant Use Volatile organics contained in such products as lacquer thinners, gasoline, typing correction fluid, lighter fluids, and glues that may be collected in a common paper bag so that the vapors can be concentrated and inhaled.

33 Inhalant Use Aerosols with fluorocarbons and other propellants that can be release along with other chemicals such as alcohols, ketones, and n-hexane (found in such common products as cans of spray paint) when inhaled directly have the potential to produce significant neurological, cardiovascular, and liver toxicity.

34 Inhalent use, cont. Anesthetic agents such as chloroform, methyl trichloroethylene, and ether that may be present in common products (e.g., special cleaners, grease dissolvers). Nitrites such as isobutyl, butyl, and amyl nitrite that are found in many commonly available household products and have similar effects to nitrites that are used clinically as vasodilators.

35 Toxicities Associated with Street Drugs The most common toxicities associated with street drugs result from stimulants, depressants, hallucinogens, and narcotics.

36 Common Stimulants Methamphetamine ( speed, crystal, ICE ) Methylenedioxymetamphetamine (ecstasy, MDMA, XTC) Methylenedioxyamphetamine (MDA) Methylphenidate (Ritalin, used to treat attention deficit and hyperactivity disorders, especially in children) Phenmetrazine (used to treat obesity) Cocaine (in all its forms)

37 Depressants Depressants (sedative hypnotics) include: barbiturates such as pentobarbital (yellow jackets) phenobarbital (purple hearts) amobarbital (blue angels) secobarbital (red devils)

38 Depressents, cont. The benzodiazepines include: flurazepam (sleeping pills) flunitrazepam ( date rape drug ) diazepam (Valium ) alprazolam (Xanax ) chlordiazepoxide (Librium ) clonazepam (anticonvulsant) methaqualone (Quaalude or downers )

39 Flunitrazepam (Rohypnol ) An example of a clinical drug (a benzodiazepine) that has become a popular street drug, especially among teenagers and young adults. Clinically, it is used in the short-term management of insomnia and as a sedative hypnotic and preanesthetic medication. It is 10 times more potent than Valium. Its effects begin within 30 minutes, peak within 1 2 hours, and, depending on the dose, may persist for 8 hours or longer.

40 Flunitrazepam (Rohypnol ), cont. It produces a marked decrease of blood pressure, urinary retention, visual disturbances, gastrointestinal disturbances, memory impairment, dizziness, confusion, and excitability or aggressive behavior in some users. Intoxications can result in death from respiratory failure and cardiovascular collapse, especially in combination with alcohol. On the street, the drug is referred to as rophy, circles, Mexican Valium, roofies, etc. Being under its influence is referred to as being roached out.

41 Gamma-hydroxybutyrate (GHB) The drug gamma-hydroxybutyrate (GHB) is an increasingly abused and potentially lethal drug. GHB is a CNS depressant most often abused for the purpose of feeling euphoric and uninhibited. In the United States GHB can be prescribed in a very low dose as an experimental treatment for narcolepsy.

42 Gamma-hydroxybutyrate (GHB), cont. Those who abuse GHB (also known as G or liquid ecstasy ) may require emergency medical attention when they overdose or experience withdrawal symptoms. GHB and other club drugs are often abused by young people at all-night parties and raves. In some European countries GHB is prescribed as a treatment for alcoholism, although the medical evidence to support its use is wanting.

43 Gamma-hydroxybutyrate (GHB), cont. GHB, usually in combination with alcohol, has been linked to more than 60 deaths, mostly among young adults. The number of reported GHB-related deaths may be an underestimate because GHB does not remain in the body very long and is usually not tested for at autopsy.

44 Depressants The general progression of effects from depressants are: relief from anxiety sedation hypnosis confusion, ataxia and delirium surgical anesthesia depression of vasomotor and respiratory centers in the brainstem coma death

45 Depressants, cont. Treatment of overdose of benzodiazepines includes flumazenil, a benzodiazepine receptor blocker. A number of hallucinogens are illegally used, and although these drugs differ in mechanisms of action, chemical similarities, CNS target receptors, and seriousness of toxic effects, they are often considered together because of the common form of intoxication that includes hallucinations, delusions, and illusions that occasionally result in death due to dangerous behaviors.

46 Common Hallucinogens Cannabis: marijuana, delta-9-thc Anticholinergics: atropine, scopolamine, mandrake root, jimson weed Indolamines: lysergic acid diethylamide (LSD), morning glory seed (LSM), psilocybin, psilocin, ibogaine, dimethyltryptamine (DMT) Phenylethylamines: mescaline, bufotenin, dimethoxymethyl-amphetamine (DOM) Dissociative anesthetics: ketamine, phencyclidine (PCP)

47 Websites Agency for Toxic Substances and Disease Registry (ATSDR): American Association of Poison Control Centers: American College of Medical Toxicology: Centers for Disease Control and Prevention (CDC):

48 Websites Food and Drug Administration (FDA): MEDLINEplus: Medwatch Homepage: National Institute on Drug Abuse: tml

49 Websites National Institute of Environmental Health Sciences (NIEHS): National Institutes of Health (NIH): Poisonous Plants Informational Database: U.S. Department of Health and Human Services: 05.html World Health Organization: