Pesticides Poisoning (Organophosphorus Compounds & Carbamates) Lecture Notes PDF

It College of Medicine – ‫كلية الطب‬ Dr. Asmaa F. Sharif Ph D., JMHPE, MSc., MBBCh – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 1...

It College of Medicine – ‫كلية الطب‬ Dr. Asmaa F. Sharif Ph D., JMHPE, MSc., MBBCh – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 1 No.  By the end of the lecture, the student should know:  Circumstances of Organophosphorus compounds (OPC) College of Medicine – ‫كلية الطب‬ poisoning.  Toxicokinetics, mechanism of toxicity, clinical picture of OPC poisoning.  Treatment of OPC cases.  Comparison between OPC and carbamate poisoning.  Pearls and pitfalls in OPC poisoning cases. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 2 No.  1. Accidental: During dealing with insecticides (manufacturing, spraying). College of Medicine – ‫كلية الطب‬ 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 – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 3 No.  Absorption: co  Rapidly absorbed by all routes; respiratory (the fastest), gastrointestinal, conjunctival, dermal & via the mucous membranes.  Increased absorption via the broken skin, dermatitis and high College of Medicine – ‫كلية الطب‬ environmental temperature. TtemperatureTPabsTtion Distribution: PassB.B 13  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 metabolized mainly in the liver by hepatic cytochrome P-450 c system. Excretion: through urine & stool – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 4 No.   Inhibition of cholinesterase enzyme: ◦ Normally, Acetylcholine is hydrolyzed immediately to acetic acid and choline in the presence of cholinesterase.Act College of Medicine – ‫كلية الطب‬ It ◦ 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. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 5 No. College of Medicine – ‫كلية الطب‬ – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 6 No.  Parasympathetic  1) Muscarinic effects (DUMBELLS): classic cholinergic syndrome College of Medicine – ‫كلية الطب‬ ◦ Diarrhea, Nausea, vomiting and colic. DUMBELLS ◦ ◦ Urination and defecation. Miosis and blurred vision. Diarrhea tied Eadcardia ◦ Bradycardia and hypotension. ◦ Bronchospasm, wheezing and cyanosis. ◦ Lacrimation. ◦ All secretions are increased (sweating, salivation, …). – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 7 No. College of Medicine – ‫كلية الطب‬ – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 8 No.   2) Nicotinic effects: ◦ Sympathetic ganglia: College of Medicine – ‫كلية الطب‬ O  Prolonged QTc, PVT (torsade's de pointes).  Diaphoresis due to stimulation of sweat glands.  Hypertension and tachycardia (accidentally seen) neuromuscularsunction on ◦ NM junction: Skeletal muscle fasciculations, weakness, paralysis and respiratory arrest. eht1f – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 9 No.   3) CNS effects: ◦ Stimulation then inhibition: Anxiety, insomnia, confusion, ataxia, College of Medicine – ‫كلية الطب‬ on coma ◦ Seizures: more often in children. ◦ Cheyne-stocks respiration and respiratory and circulatory depression.  Cause of death: ◦ Respiratory failure due to: (bronchospasm & bronchorrhea, respiratory muscle failure or respiratory center inhibition). ◦ Arrhythmia – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 10 No.   Rescuers & health care providers must take measures to prevent direct contact with skin or contaminated clothes to College of Medicine – ‫كلية الطب‬ e_0 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-dote therapy or intubation) ◦ Fluid therapy especially in children of – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 11 No.   Airway and breathing management with frequent suctioning of College of Medicine – ‫كلية الطب‬ secretions and respiratory support is the priority.  Intubation may be required to facilitate control of secretions and for ventilatory support if respiratory failure ensues.  Ventricular arrhythmia should be managed.  Fluid loss and other manifestations should be controlled as usual.  Seizures: IV diazepam, Éif failed, IV phenobarbital. For status epilepticus: general anesthesia.  IV fluids: to compensate fluid loss in secretions – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 12 No.  Gastrointestinal decontamination:  In the case of ingestion, GI decontamination procedures College of Medicine – ‫كلية الطب‬ 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 only in case of recent ingestion.  Activated charcoal is administered only in co- ingestion. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No. 9/23/2024 13  Dermal decontamination:  Rescuers should wear protective clothing and gloves. College of Medicine – ‫كلية الطب‬  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 (15 min), consult ophthalmogist. III) Enhancement of elimination: No rule – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No. 9/23/2024 14  Action: competitive antagonist of Ach at (muscarinic + CNS). College of Medicine – ‫كلية الطب‬ It reverses only the muscarinic & CNS effects, not the nicotinic manifestations. Duration of action: May last ≥ 24 hours. It is given, after the patient is well oxygenated as hypoxia sensitizes heart to arryhtmogenic effect of atropine (arrhythmia) Side/ Effects: 0  With high dose: peripheral anticholinergic toxicity (tachycardia, flushed skin, mydriasis, urine retention, hallucination) – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 15 No.  Dose: Loading: 1.2 0.05  Adult: 1-2 mg IV (mild to moderate toxicity), 3-5 mg IV (severe toxicity). O O College of Medicine – ‫كلية الطب‬  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. O Maintenance: Obtaining mild degree of atropinization by: 1-2mg/4-6 hours 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 o distress during acute cholinergic crisis. 9/23/2024 16 – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No.   Action: College of Medicine – ‫كلية الطب‬ ◦ They reactivate the cholinesterase enzyme ◦ Detoxify the organophosphate molecules ◦ Have 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 poisoning ◦ Any C/P of NM weakness ◦ Significant atropine requirement. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 17 No.   Obidoxime = toxogonin: the form used outside USA Dose: College of Medicine – ‫كلية الطب‬ 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 88  muscle rigidity – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No. 9/23/2024 18   Carbamate insecticides are another class of acetylcholinesterase inhibitors and are differentiated from the organophosphorus College of Medicine – ‫كلية الطب‬ 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. Similar to organophosphates except for:  Inhibition of cholinesterase is reversible within 24-48 hours, so manifestations are less severe and of shorter duration. off  Poor penetration of BBB leading to mild or no CNS manifestations. e – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 19 No.   Oximes are not indicated as: ◦ Action of carbamate is reversible. College of Medicine – ‫كلية الطب‬  Oximes are only allowed in the following cases: ◦ If the diagnosis is not definite weather organophosphates or carbamates. 0 ◦ If it is a case of mixed organophosphate and carbamate poisoning. a oximes – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 20 No.   Prognosis: ◦ If organophosphates insecticide poisoning is recognized College of Medicine – ‫كلية الطب‬ 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. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 21 No.   Patients should be kept under observation (12-24 hours) due to delayed onset of symptoms esp. (skin exposure, fat College of Medicine – ‫كلية الطب‬ soluble agents).  No return to work (farmers): if CHE < 75% of normal.  If intubation is needed succinylcholine & mivacurium are t C/I  as they are metabolized by pseudocholinesterase so paralysis will be prolonged > 24 hours. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 22 No. College of Medicine – ‫كلية الطب‬ – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 23 No.