Principles Of Clinical Toxicology

Thomas A Gossel

• Éditeur: CRC Press
• Année: 2018
• ISBN:
  9781351421966
• Édition: 3
• Sujet: Medicine
• Sous-sujet: Medical Theory, Practice & Reference

In this third edition, the editors have accounted for the numerous changes in protocols for managing poison ingestions and have again provided an indispensable resource for all students of pharmacy and the health sciences on the basic principles of clinical toxicology. The book's unique focus on the fundamentals helps the reader understand why events occur and why a particular treatment is selected. Each chapter presents pertinent information on classes of toxic agents, their common sources and usual methods of intoxication, incidence and frequency of poisoning, mechanisms of action, clinical signs and symptoms of poisoning and management guidance. The text includes illustrative case studies, carefully selected to reinforce the information covered. Each chapter concludes with review questions to further enhance comprehension.

Chemicals and Environmental Toxins

4

Alcohols, Glycols, and Aldehydes

Ethanol

Mechanism of Toxicity

Toxicokinetics of Ingestion

Estimation of Blood Alcohol Concentration (BAC)

Characteristics of Acute Toxicity

Management of Acute Toxicity

Methanol

Toxicokinetics of Ingestion

Mechanism of Toxicity

Characteristics of Acute Toxicity

Management of Toxicity

Isopropanol

Ethylene Glycol

Mechanism of Toxicity

Characteristics of Toxicity

Management of Toxicity

Propylene Glycol

Formaldehyde

Mechanism of Toxicity

Characteristics of Toxicity

Management of Toxicity

Acetaldehyde

Acetone

Summary

Case Study: Ethanol Intoxication

History

Discussion

Case Study: Intoxication with Mouthwash

History

Discussion

Case Study: Poisoning by Wine in a Child

History

Discussion

Case Studies: Methanol Intoxication

History: Case 1

History: Case 2

Discussion

Case Studies: Ethylene Glycol Poisoning

History: Case 1

History: Case 2

History: Case 3

Discussion

Case Study: Formaldehyde Poisoning

History

Discussion

Review Questions

References

Alcohols are hydroxy derivatives of straight or branched chain aliphatic hydrocarbons. The more common alcohols may include up to three hydroxyl groups with no more than one on each carbon. Lesser common alcohols may contain more than one hydroxyl group per carbon atom. Those alcohols that are the most common causes of toxicity include ethanol (ethyl alcohol; alcohol), methanol (methyl alcohol), and isopropanol (isopropyl alcohol). In general, the longer the carbon chain, the greater the toxicity. The exception to this rule is methanol, which is more toxic than ethanol.

Dihydroxy alcohols are called glycols (glyc- or glyco-from the Greek stem word meaning sweet), referring to their sweet taste. Dihydroxyethane is better known as ethylene glycol, the simplest glycol. It is commonly referred to as permanent antifreeze and is a fairly frequent cause of poisoning. Another glycol is dihydroxypropane (propylene glycol), a constituent of numerous pharmaceutical products. For the most part, propylene glycol is not toxic.

Alcohols and glycols are discussed together in this chapter for several reasons. First, they are chemically similar. They also share many common characteristics of acute poisoning, and their acute toxicities are treated similarly. However, each of the compounds in this chapter has its own specific characteristics.

ETHANOL

Ethanol is the only alcohol that has widespread intentional internal human use. Ethanol is one of the oldest drugs and is the primary alcohol present in fermented and distilled beverages. It is also the most commonly used psychoactive drug in the world (1).

Ethanol is a clear, colorless liquid that imparts a burning sensation to the mouth and throat when swallowed. Pure ethanol has a slightly pleasant odor. Ethanol is a powerful CNS depressant that acts primarily on the reticular activating system in the brain. In fact, its actions are qualitatively similar to those of general anesthetics. It has a relatively low or der of toxicity compared to methanol or isopropanol.

Ethanol is discussed first because it is the most frequently reported cause of alcohol toxicity and because an understanding of certain aspects of its metabolic pathway and toxic actions is necessary to understand the mechanism of toxicity and management of overdoses involving methanol and ethylene glycol. As with all alcohols and glycols discussed in this chapter, only acute toxicologic considerations will be presented.

Mechanism of Toxicity

The exact mechanisms by which ethanol produces its pharmacologic and toxicologic actions are not completely understood and have been investigated for many years. The CNS is selectively affected. Ethanol is thought to act directly on neuronal membranes and not on synapses. At the membrane, it may involve ion transport and biogenic amines.

The effect of ethanol on the CNS is directly proportional to its blood concentration (47). The first region affected is the reticular activating system, resulting in disruption of the motor and thought processes. Suppressing the cerebral cortex causes a variety of behavioral changes. Which specific behaviors will be suppressed and which will be released from inhibition depend on the individual. In general, complex, abstract, and poorly learned behaviors are disrupted at low alcohol concentrations.

Ethanol depresses the CNS in a descending order from the cortex to the medulla. Table 4.1 illustrates the correlation between blood alcohol concentration (BAC) and the area of the brain affected. Also, subjective feelings are noted based on blood alcohol concentration and the area of the brain where ethanol produces its effect.

Toxicokinetics of Ingestion

Absorption

The physicochemical properties of ethanol are such that it is slightly polar and has a weak electronic charge and low molecular weight. Ethanol is miscible in water and lipid soluble. Therefore, it is easily absorbed and can pass through cell membranes by simple diffusion.

TABLE 4.1. Range of toxicity of ethanol

Clinical description/symptoms	Blood alcohol concentration (w/v)	Part of brain
Mild Decreased inhibitions Slight visual impairment Slowing or reaction time Increased confidence	0.05–0.10%(50–100 mg/dL)	Frontal lobe
Moderate Ataxia Slurred speech Decreased motor skills	0.15–0.30% (150–300 mg/dL)	Parietal lobe
Decreased attention Diplopia		Occipital lobe
Altered perception Altered equilibrium		Cerebellum
Severe	0.3–0.5%(300–500 mg/dL)
Vision impairment		Occipital lobe
Equilibrium		Cerebellum
Stupor		Diencephalon
Coma
Respiratory failure	>0.5% (>500 mg/dL)	Medulla

The most common route of exposure to ethanol is ingestion, but it also can be absorbed by inhalation of vaporized ethanol or through the skin. Ethanol absorption after ingestion begins in the stomach, but only a small percentage of the amount ingested is absorbed directly into the blood through the stomach wall. The rate of absorption is much greater in the small intestine. Since absorption through the stomach wall is minimal and rapid absorption occurs in the small intestine, any factor that delays or enhances gastric emptying will influence the rate of absorption of alcohol into the blood.

Several factors govern gas...