Organophosphates are a class of poisonous synthetic compounds originally made for chemical warfare from organic compounds. These were used in chemical warfare, now a days these compounds these are commonly used as pesticides. They work by inhibiting an important enzyme in the body, acetylcholinesterase. Due to their household use their toxicity may often be underestimated, however even in the low percentage in which the commercial pesticide is present it is still very potent.
Organophosphates are preferred for commercial use in agriculture because they do not contribute to biomagnification. Once sprayed they get broken down into a simpler compounds and are chemically decomposed. They are unlikely to end up on your dinner plate as per CDC.
We can classify the compounds into 3 classes based on type:
Pesticides, carbamates and nerve agents.
- Methyl Parathion
They are similar to OP, but they lack a phosphate group. Also, their action is reversed in a couple of hours. Examples are carbaryl, propoxur.
Common nerve gasses are classified into three groups, these are all poisons.
G series – German
V series– British
Novick- A group of Russian made nerve agents, highly toxic. It is not known if they last long in the environment or if they degrade, unlike pesticides mentioned above.
Mechanism: The above-mentioned agents work by inhibition of acetylcholine esterase enzyme, thus naturally affecting the cholinergic system. Based on the time length for which the binding occurs the inhibition may be reversible or irreversible.
In the case of irreversible inhibition, the organophosphate can be countered with a group of agents called OXIMES. These are compounds that due to their structure offer a better group for the OP to bind to, rather than the ACH-esterase enzyme. Thus, the OP agent releases the ACH esterase enzyme allowing it to function. In case oximes are not used the ACH-esterase enzyme bound to the OP ages and are removed and disposed of. Fresh ACH-esterase enzyme must be synthesised which may take hours to days, resulting in the death of the patient. The blockade of the enzyme ACH-esterase prevents the degradation of Acetyl Coenzyme-A which causes unregulated stimulation of the cholinergic system via nicotinic and muscarinic receptors.
Poisoning with OP is frequently seen in case of farmers or workers especially in south India, often intentional, generally by oral consumption. Sometimes exposure is accidental. In India, farmers will not adhere to all the safety guideline mentioned by the manufactures. Mask, gloves or apron will not be used, and self-exposure frequently occurs.
Other routes of accidental exposure may be via inhalation of a sprayed pesticide or direct contact to the poison. In a country like India, such agents may be overused due to lack of regulation and illiteracy.
Toxidrome: Symptoms of OP poisoning are those of cholinergic stimulation since the degradation of Ach is prevented. The mnemonic used to remember this toxidrome is SLUDGE or DUMBELS, which stands for, Salivation, Lacrimation. Urination, Diarrhoea, gastic upset, Emesis and Diarrhoea, Urination, Miosis, Bronchorrhea, Emesis, Lacrimation, Salivation respectively. These may be referred to as muscarinic effects.
Nicotinic effects include tachycardia, mydriasis, pallor(may not be seen in Indians), muscle fasciculations and cramping.
Gastric lavage sample testing or blood tests may help identify the presence of OP, but these tests take time. Patient party or reliable eyewitness account may help provide reliable evidence to confirm the presence of poisoning or type of poisoning if they have the compound with them.
Antidote: drugs used to counter the effects of OP poisoning are oximes such as pralidoxime, obidoxime. Optimal dosing of pralidoxime is a matter of debate in India. Other drugs such as atropine and glycopyrrolate may be combined. These two agents help counter the effect of acetylcholine. But the drawback is that this drug is required to be used at an extremely high dose that causes major limiting adverse effects. The US military has been working on potential antidotes for a while and has found the drug galantamine to be beneficial often reducing the doses of other antidotes needed.
It is always recommended that when a patient is brought in full body decontamination is done. Such as removing all clothing, wash the body, gastric lavage if required based on poison, wash eyes etc. check airway breathing, circulation etc.
Long-term effects: Chronic exposure to OP based on the class of agents can lead to nervous system damage. Often causing loss of motor function. The resulting damage is permanent effects are more severe with nerve agents, but pesticides can also cause the same levels of effects with long-term exposure.
SIMPLE CASE STUDY:
A 6-year-old boy is referred to a tertiary care hospital, he drank the contents of pesticide bottle stored in a farm shed. He has pinpoint pupils, heart rate of 130bpm, lacrimation and salivation and vomiting. On suspecting op poisoning he is referred immediately to a tertiary care hospital after basic decontamination.
Diagnosis is confirmed since the bottle of pesticide is available and contents claim the presence of op. The boy’s respiration begins to drop along with saturation and he has to be intubated and lungs had crepts. Patient status began to decline rapidly in the meanwhile and was minimally responsive. A drip of pralidoxime is administered along with atropine. An initial test dose was given, after which at 10-minute interval dose was increased of atropine, until sufficient atropinisation is seen, lung crepitations began to resolve, pinpoint pupils abolished. After a week the patient was more responsive and began to communicate again
For further reading:
Management of acute organophosphorus pesticide poisoning: