This course deals with some important chemical poisons. Topics to be covered include those poisonings that either present frequently enough to merit attention or present infrequently but with serious consequences. Because exposure to chemicals can occur via a variety of routes decontamination decisions can be more complex than when dealing with pharmaceuticals. For some poisons envenomations a specific antidote is available. The selection of the appropriate antidote, the optimal dose and the indications for administration are important decisions to be made.
This module aims to cover the toxicology of following common or important chemicals used in agriculture:
• Organophosphates
• Paraquat
• Agents causing methaemoglobinaemia
• Other insecticides and herbicides
At the end of this module, students should be able to:
• Do a risk assessment of acute organophosphate exposure.
• Understand treatment of organophosphate poisoning.
• Understand the issues underlying treatment failure.
• Understand the chronic sequelae organophosphate poisoning.
• Understand the mechanism of toxicity of paraquat.
• Understand how this explains the delayed pulmonary manifestations of moderate paraquat toxicity
• List the most common clinical manifestations of poisoning with paraquat.
• Recognise situations where interventions are most likely to be useful.
• Understand the difference between a frequentist and a Bayesian approach to clinical trial evidence and how this alters what interventions you institute.
• Understand the mechanisms of methaemoglobinaemia
• Understand the basis of treatment with methylene blue
• Understand the issues underlying treatment failure
• Understand the spectrum of intoxication with insecticides and herbicides, in particular that some pesticides appear to have no direct toxic effects at all.
• Understand that aspiration of the pesticide and its solvent may be much worse than absorbing the pesticide from the GI tract, and that this should be factored into the risk assessment of performing GI decontamination.
• Describe the initial evaluation, stabilisation and treatment of organochlorine induced status epilepticus.
While politicians raise concerns about weapons of mass destruction and threats of chemical attack, the reality is that at least 300 000 people die from deliberate self-poisoning with organophosphates each year in Asia. Most published guidelines on treatment are generated in developed countries by authors with limited direct experience of organophosphate toxicity. There does not seem to be a significant difference in case fatality rates between the developed and developing world. Within this class of compounds there is considerable pharmacokinetic and pharmacodynamic diversity which leads to a number of differences in the clinical course of poisoning for various compounds and response to treatment. Supportive care and atropine are established treatments; most other treatments engender some controversy.
If an organophosphate poisoning comes to your hospital, get apprehensive and get out of bed. Read on.
1. To be able to do a risk assessment of acute organophosphate exposure.
2. Consider variables which may affect the risk assessment.
3. Understand treatment of organophosphate poisoning.
4. Understand the issues underlying treatment failure.
5. Understand the chronic sequelae organophosphate poisoning.
Link to Problems for Discussion
Paraquat is widely used around the world as a low cost and effective herbicide. However, it has one of the highest fatality rates of any poisoning, with around 70% of ingestions being lethal. Paraquat is a good example of an agent that causes oxidative stress. Treatments aimed at combating this mechanism have had very limited success in animals, and human data are inconclusive or lacking. There have also been a large number of attempts to develop tests or algorithms that predict outcome but with moderate success.
Most cases of paraquat poisoning result from deliberate self-harm but unintentional poisoning can occur when it has been stored incorrectly. Death has also occurred following large dermal exposure and intravenous administration.
Diquat is, like paraquat, a dipyridyl herbicide. Some formulations contain a mixture of both compounds. Diquat and paraquat have similar toxicity. Unlike paraquat, diquat is not accumulated by the lungs and has a half-life in the lung 5 times shorter than paraquat. Therefore, diquat produces less pulmonary injury and fibrosis.
Link to Problems for Discussion
'Doctor, the patient is a curious blue.’
‘Ah, then we had better give them the curious blue medicine.’
Methaemoglobin is occasionally produced therapeutically and is probably seen more commonly from recreational amyl nitrate use. There is a wide range of drugs and chemicals that can cause the oxidative stress that transforms Fe+++ to Fe++, causing the patient to appear cyanosed, altering the oxygen carrying capacity and turning blood to a chocolate-brown colour.
Link to Problems for Discussion
There are an estimated 300,000 deaths annually from pesticide self-poisoning in the Asia-Pacific region. The great majority of deaths are caused by three classes of pesticide: organophosphorus compounds, paraquat, and aluminium phosphide. Organochlorine pesticides were once important causes of fatal poisoning but their replacement by organophosphorus insecticides in agricultural practice has reduced the number of deaths they cause. There are numerous other pesticides in use globally – many of them appear to be relatively harmless after overdose.
Organophosphorus pesticides, propanil and paraquat are covered separately; this section looks at poisoning with other insecticides and herbicides.
• Organophosphorus compounds
• Carbamates
• Organochlorines (cyclodienes [eg. endosulfan] and cycloalkanes [eg. lindane])
• Pyrethroids (eg. permethrin)
• Neonicotinoids (eg. imidacloprid)
• N-phenylpyrazole insecticides (eg. fipronil)
• N,N-Diethyl-m-toluamide (DEET)
• Dipyridyl compounds (paraquat, diquat)
• Glyphosate
• Chlorphenoxy compounds (eg 2,4-D, MCPA)
• Propanil
There are several other relatively new classes of pesticides for which we currently have very little human toxicity data. Many of them are likely to be relatively harmless to humans in self-poisoning.
Significant acute exposure to insecticides or herbicides usually results in one of several clinical syndromes:
1. Cholinergic over-activity or crisis (OPs, carbamates)
2. Seizures (organochlorines, N-phenylpyrazoles)
3. Multiorgan failure or lung fibrosis (dipyridyls)
4. Muscle damage producing renal damage (chlorphenoxy compounds)
5. Methaemoglobinaemia (propanil)
6. Effects of the surfactant (probably true for glyphosate, in particular)
7. Aspiration pneumonia
8. No effect (some newer classes of pesticides)
1. Understand the spectrum of intoxication with insecticides and herbicides, in particular that some pesticides appear to have no direct toxic effects at all.
2. Understand that aspiration of the pesticide and its solvent may be much worse than absorbing the pesticide from the GI tract, and that this should be factored into the risk assessment of performing GI decontamination.
3. Understand the value of careful observation.
4. Describe the initial evaluation, stabilisation and treatment of organochlorine induced status epilepticus.
Link to Problems for Discussion