Pesticides (Organophosphorus Compounds & Carbamates) Dr. Asmaa Fady Ph D., MSC., M.B, B.Ch اسم ورقم المقرر – Course Name and No. 7/4/2019

Learning objectives By the end of the lecture, the student should know: Circumstances of Organophosphorus compounds (OPC) poisoning. Toxicokinetics, mechanism of toxicity, clinical picture of OPC poisoning. Treatment of OPC cases. Comparison between OPC and carbamate poisonng. Pearls and pitfalls in OPC poisoning cases. اسم ورقم المقرر – Course Name and No. 7/4/2019

Circumstances of poisoning: 1. Accidental: During dealing with insecticides (manufacturing, spraying). Drinking from polluted bottles or ingestion of contaminated food. some cocaine abusers co-ingest OPCs to prolong effect of cocaine. 2. Suicidal: Common (easily obtained and known to cause rapid death). 3. Homicidal: Rare due to garlic odor اسم ورقم المقرر – Course Name and No. 7/4/2019

Toxico-kinetics of OPC: Absorption: Rapidly absorbed by all routes; respiratory (the fastest), gastrointestinal, conjunctival and dermal & mm. increase by broken skin, dermatitis, high environmental temperature. Distribution: They are distributed all over the body and can pass blood brain barrier. They are highly lipid-soluble so Some organophosphates are stored in fat tissue, which may lead to persistent toxicity lasting several days after exposure. Metabolism: They are metabolite mainly in the liver by hepatic cytochrome P-450 system. Excretion: through urine & stool اسم ورقم المقرر – Course Name and No. 7/4/2019

Mechanism of OPC toxicity Inhibition of cholinesterase enzyme: Normally, Acetylcholine is hydrolyzed immediately to acetic acid and choline in the presence of cholinesterase. The toxicological effects of organophosphates are due to inhibition of cholinesterase in the nervous system resulting in accumulation of acetylcholine thus causing initial stimulation that is followed by depression of impulse transmission at the following sites: Postganglionic parasympathetic nerve endings (muscarinic). Autonomic ganglia and neuromuscular junctions (nicotinic). CNS. اسم ورقم المقرر – Course Name and No. 7/4/2019

Mechanism of toxicity اسم ورقم المقرر – Course Name and No. 7/4/2019

Clinical picture of OPC poisoning 1) Muscarinic effects (DUMBELLS): classic cholinergic syndrome Diarrhea, Nausea, vomiting and colic. Urination and defecation. Miosis and blurred vision. Bradycardia and hypotension. Bronchospasm, wheezing and cyanosis. Lacrimation. All secretions are increased (sweating, salivation, …). اسم ورقم المقرر – Course Name and No. 7/4/2019

اسم ورقم المقرر – Course Name and No. 7/4/2019

Clinical picture of OPC poisoning 2) Nicotinic effects: Sympathetic ganglia: Prolonged QTc, PVT (torsades de pointes). Diaphoresis due to stimulation of sweat glands. Hypertension and tachycardia (accidentally seen) NM junction: Skeletal muscle fasciculations, weakness, paralysis and respiratory arrest. اسم ورقم المقرر – Course Name and No. 7/4/2019

Clinical picture of OPC poisoning 3) CNS effects: Stimulation then inhibition: Anxiety, insomnia, confusion, ataxia, coma, Seizures: more often in children. Cheyne-stockes respiration and respiratory and circulatory depression. Cause of death: respiratory failure due to: (bronchospasm & bronchorrhea, Respiratory muscle failure or respiratory center inhibition). Arrhythmia اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: Rescuers & health care providers must take measures to prevent direct contact with skin or contaminated clothes to avoid 2ry contamination. Observe asymptomatic patients for at least 8-12 hours to rule out delayed onset symptoms with especially after skin exposure or highly lipophilic substances. Admission criteria: Suicidal Significant exposure requiring Anti-dotal therapy or intubation. Fluid therapy especially in children اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: I) Emergency and supportive measures: ABC Airway and breathing management with frequent suctioning of secretions and respiratory support is the first priority. Intubation may be required to facilitate control of secretions and for ventilatory support if respiratory failure ensues. Ventricular arrhythmia, fluid loss and other manifestations should be controlled as usual. Seizures: IV diazepam, if failed, IV phenobarbital. For status epilepticus: general anesthesia. IV fluids: to compensate fluid loss in secretions اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: II) Decontamination: Gastrointestinal decontamination: In the case of ingestion, GI decontamination procedures are of questionable benefit because of the rapid absorption of these compounds. Profuse vomiting and diarrhea are seen early in ingestion and may limit any beneficial effect of additional GI decontamination. It is better not to use ipecac. Gastric lavage in case of recent ingestion. Activated charcoal is administered (co-ingestion). اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: II) Decontamination: Dermal decontamination: Rescuers should wear protective clothing and gloves. Removal of clothes and shoes of the victims. Washing the patient’s skin and hair by soap and water then with ethyl alcohol & water to prevent further absorption. Shaving scalp hair if oily OPC difficult to be washed remember to wash creases, external auditory meatus, around umbilicus, genitalia, hair & under nail. Eye decontamination: with copious water or saline, consult ophthalmogist. III) Enhancement of elimination: No rule اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: IV) Physiological antidotes (Atropine) Action: competitive antagonist of Ach at (muscarinic + CNS). It reverses only the muscarinic & CNS effects. Duration of action: May last ≥ 24 hours . It is given, after the patient is well oxygenated as hypoxia sensitize heart to arryhtmogenic effect of atropine. Side/ Effects: With high dose: peripheral anticholinergic toxicity (tachycardia, flushed skin, mydriasis, urine retention, hallucination) اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: IV) Physiological antidotes (Atropine) Dose: Loading: Adult: 1-2 mg IV (mild to moderate toxicity), 3-5 mg IV (severe toxicity).   Then repeated /15 min until dryness of bronchial secretions or double dose / 5 min. Child: 0.05 mg /kg IV, then double the dose/ 5 min. Maintenance: obtaining mild degree of atropinization by: 1-2mg/4-6hours for 2 days then withdraw slowly & put patient under observation for 24 hours after last atropine dose More helpful than intubation, PEEP in treatment of respiratory distress during acute cholinergic crisis. اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: IV) Physiological antidotes (Oximes) Action: They reactivate the cholinesterase enzyme detoxify the organophosphate molecules An anticholinergic effect. Clinical effect most apparent at nicotinic receptors Correct nicotinic manifestations, less manifest at muscarinic receptors. Indications: nicotinic or respiratory distress Suspected or confirmed OPC or carbamate poisoning ANY C/P of NM weakness Significant atropine requirement. اسم ورقم المقرر – Course Name and No. 7/4/2019

Treatment of OPC poisoning: IV) Physiological antidotes (Oximes) Obidoxime = toxogonin: form used outside USA Dose: 1 ampoule (250mg) on 100 ml saline slowly IV (15-30 min)/4 or 8 or 12 according to severity. S/E: very low at therapeutic dose, rate related: Transient dizziness & blurred vision Rapid IV: sudden cardiac & resp. arrest laryngospasm muscle rigidity اسم ورقم المقرر – Course Name and No. 7/4/2019

Carbamate poisoning Similar to organophosphates except for: Inhibition of cholinesterase is reversible within 24-48 hours, so manifestations are less severe and of shorter duration. Poor penetration of BBB leading to mild or no CNS manifestations. اسم ورقم المقرر – Course Name and No. 7/4/2019

Carbamate poisoning Carbamate insecticides are another class of acetylcholinesterase inhibitors and are differentiated from the organophosphorus compounds by their relatively short duration of toxic effects. Carbamates inhibit acetylcholinesterase for minutes to 48 hours, and the carbamate-cholinesterase binding is reversible. Although the clinical picture of acute carbamate poisoning may be identical to that of organophosphate poisoning, اسم ورقم المقرر – Course Name and No. 7/4/2019

Carbamate poisoning treatment Oximes are not indicated as: Action of carbamate is reversible. Oximes are only allowed in the following cases: If the diagnosis is not definite weather organophosphates or carbamates. If it is a case of mixed organophosphate and carbamate poisoning. اسم ورقم المقرر – Course Name and No. 7/4/2019

Pearls & Pitfalls: Prognosis: If organophosphates insecticide poisoning is recognized and treated rapidly the outcome is good Untreated patient may die within 24 hr due to respiratory failure Unsuccessful ttt  death within 10 days or complicated. Significantly poisoned patient may require a large amount of atropine. اسم ورقم المقرر – Course Name and No. 7/4/2019

Pearls & Pitfalls: Patients should be kept under observation (12-24 hours) due to delayed onset of symptoms esp. (skin exposure, fat soluble agents). No return to work (farmers): if CHE < 75% of normal. If intubation is needed succinylcholine & mivacurium are C/I  as they are metabolized by pseudocholinesterase so paralysis will be prolonged > 24 hours. اسم ورقم المقرر – Course Name and No. 7/4/2019

اسم ورقم المقرر – Course Name and No. 7/4/2019