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CLINICAL TOXICOLOGY



"Dosis sola facit venenum" [The dose alone makes a poison]

Paracelsus (1493-1541) is considered the father of toxicology. He stated:
All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.

Later Paracelsus more scientifically laid the groundwork for experimental toxicology stating:
  1. Experimentation is necessary to note responses to toxins.
  2. There must be a distinction between toxic and therapeutic properties.
  3. These properties may be indistinguishable except by dose.
  4. One can determine dose ranges and sites of action for therapeutic and toxic effects.

Despite the groundwork, it is clear that much of the practice of clinical toxicology is not based on an evidence base that is comparable to many other major specialities. You need to bear this in mind when you read any textbook or monograph, including material in this course.


Toxicology_Publications.jpg


Efforts are being made to address this deficit, in particular with systematic reviews and the planning of new trials.

In the sections about individual drugs we will attempt to give practical clinical information and also try to highlight areas of doubt and controversy. While we also try to give you a practical clinical approach to individual poisons you need to understand that the monographs represent a combination of evaluation of the evidence, and opinion based on clinical experience and extension of basic theory.

Finally any presentation of clinical toxicity represents an interplay between the toxic substance and a range of psychiatric, economic and social factors which also need to be assessed. We will initially be concentrating on the direct toxicology issues.

Assessment of patients


Following the ingestion of toxic amounts of a drug or poison it is often useful to think of the likely effects as a combination of an excess of the known therapeutic or pharmacological effects (eg antihypertensives lower your blood pressure) with the possible additional ‘surprise’ effects not normally seen in therapy (eg some antihypertensives cause seizures).

Risk Assessment of Patients

The severity of poisoning should be assessed in accordance to the following:
  • Drug
  • Dose
  • Time since ingestion
  • Signs and symptoms of toxicity
  • Co-morbidities

The extension of clinical effect has led to the concept of recognising patterns of symptoms as Toxidromes. For example:
  • Cholinergic
  • Anticholinergic
  • Sympathomimetic
  • Opioid
  • Serotonergic
  • Sedative Hypnotic

These Toxidromes generally address the signs seen with an excess of stimulation of a specific receptor. The limitation of the classic Toxidrome is that many drugs have effects on multiple receptors so that a ‘pure toxidrome’ is not always seen. More evolved clinical assessment includes elements of toxidromes combined with other information from the history, examination, investigations and local epidemiology.

There are also broader clinical toxidromes, for example the overdose who presents with a seizure or acidosis or delirium or cardiac arrest or hepatic failure.

Finally all presentations can be modified by a knowledge of your own local epidemiology, for example in Newcastle, Australia, a sympathomimetic poisoning with ischaemic ECG changes is more likely to be amphetamines than cocaine where as the opposite is true in New York.

Most decisions in Clinical Toxicology are driven by relatively basic clinical information, which is gathered from the history, physical examination and simple investigations. The clinical information can be assisted by using pre-formatted charts that prompt the admitting doctor for certain information.

The major endpoints in clinical examination are:
  • Neurological: Level of consciousness, presence of delirium , seizures
  • Cardiovascular: pulse, blood pressure, abnormal ECG findings
  • Adequacy of Respiration and protection of airway
  • Acid/base disturbance: Arterial blood gases.
  • Detection of complications: eg pulmonary aspiration, rhabdomyolysis, compartment syndrome, hypoxic brain injury

Organ specific toxicity is rare at presentation.

Given these clinical concerns it follows that the majority of clinical care relates to the ABC of airway, breathing and circulation. This supportive care cannot be overemphasised nor can the need for frequent reassessment when drugs are still in the absorptive phase.

Specific antidotes have a place and will be dealt with in individual sections.



Readings:

  • Buckley NA, Whyte IM, Dawson AH. Diagnostic data in clinical toxicology Should we use a Bayesian approach? Clinical Toxicology 2002;40(3):213-222.

  • Albertson TE, Dawson A, de Latorre F, Hoffman RS, Hollander JE, Jaeger A, et al. TOX-ACLS: toxicologic-orientated advanced cardiac life support. Ann Emerg Med Apr 2001;37:S78-S90.