Title 7. PESTICIDE POISONING, ORGANOPHOSPHOROUS COMPOUNDS, CARBAMATES, ORGANOCHLORINES, PYRETHROIDS..pdf ✅

PHARMD GURU Page 1 Pesticides are compounds that are used to kill pests which may be insects, rodents, fungi, nematodes, mites, ticks, molluscs, and unwanted weeds or herbs. 1. Insecticides 2. Rodenticides 3. Fungicides 4. Nematicides 5. Acaricides 6. Molluscicides 7. Herbicides 8. Miscellaneous Pesticides. INSECTICIDES: These are compounds which kill or repel insects and related species. For example, organophosphates, carbamates, organochlorines, pyrethrum and its derivatives (pyrethroids). ORGANOPHOSPHOROUS COMPOUNDS  It is true that calling these compounds ―organophosphates‖ is not correct, and they should be referred to as ―organophosphorus compounds‖.  But, ―organophosphates‖ is such an irresistibly compact expression. So, with apologies to the purists, this term will be used for the sake of convenience in this book, even if it raises some hackles.  Organophosphates are among the most popular and most widely used insecticides in India. PESTICIDE POISONING: ORGANOPHOSPHOROUS COMPOUNDS, CARBAMATES, ORGANOCHLORINES, PYRETHROIDS.
PHARMD GURU Page 2 PHYSICAL APPEARANCE: These compounds are available as dusts, granules, or liquids. Some products need to be diluted with water before use, and some are burnt to make smoke that kills insects. USUAL FATAL DOSE:  Toxicity Rating: The following compounds are extremely toxic (LD50: 1 to 50 mg/kg), or highly toxic (LD50: 51 to 500 mg/kg) - Chlorfenvinphos, Chlorpyriphos, Demeton, Diazinon, Dichlorvos, Dimethoate, Disulfoton, Ediphenphos, Ethion, Fenitrothion, Fensulfothion, Fenthion, Fonophos, Formothion, Methyl Parathion, Mevinphos, Monocrotophos, Oxydemeton Methyl, Phenthoate, Phorate, Phosphamidon, Quinalphos, TEPP, and Thiometon.  The following compounds are moderately toxic (LD50: 501 to 5000 mg/kg), or slightly toxic (LD50: more than 5000 mg/kg) - Abate, Acephate, Coumaphos, Crufomate, Famphur, Glyphosate, Malathion, Phenthoate, Primiphos Methyl, Ronnel, Temephos, Triazophos, and Trichlorphon.  Even in cases where treatment was begun early with atropine and oximes, mortality in organophosphate poisoning is generally to the extent of 7 to 12%. MODE OF ACTION:  Organophosphates are powerful inhibitors of acetylcholinesterase which is responsible for hydrolysing acetylcholine to choline and acetic acid after its release and completion of function (i.e. propagation of action potential). As a result, there is accumulation of acetylcholine with continued stimulation of local receptors and eventual paralysis of nerve or muscle.  Although organophosphates differ structurally from acetylcholine, they can bind to the acetylcholinesterase molecule at the active site and phosphorylate the serine moiety. When this occurs, the resultant conjugate is infinitely more stable than the acetylcholine-acetylcholinesterase conjugate, although endogenous hydrolysis does occur. Depending on the amount of stability and charge distribution, the time to hydrolysis is increased. Phosphorylated enzymes degrade very slowly over days to weeks, making the acetylcholinesterase essentially inactive.
PHARMD GURU Page 3  Once the acetylcholinesterase is phosphorylated, over the next 24 to 48 hours an alkyl group is eventually lost from the conjugate, further exacerbating the situation. As this occurs, the enzyme can no longer spontaneously hydrolyse and becomes permanently inactivated.  Apart from acetylcholinesterase, organophosphates exert powerful inhibitory action over other carboxylic ester hydrolases such as chymotrypsin, butyrlcholinesterase (pseudocholinesterase), plasma and hepatic carboxylesterases, paraoxonases, and other non-specific proteases.  It has been proposed that delayed peripheral neuropathy caused by organophosphates is due to phosphorylation of some esterase(s) other than acetylcholinesterase, such as neurotoxic esterase, also known as neuropathy target esterase (NTE). Neuropathy caused by inhibition of NTE may develop 2 to 5 weeks after an acute poisoning. TOXICOKINETICS:  Organophosphates can be absorbed by any route including transdermal, transconjunctival, inhalational, across the GI and GU mucosa, and through direct injection.  Manifestations usually begin within a few minutes to few hours, but may be delayed upto 12 hours or more in the case of certain compounds (e.g. fenthion, parathion). CLINICAL (TOXIC) FEATURES 1. ACUTE POISONING: A) CHOLINERGIC EXCESS:  Musscarinic Effects (hollow organ parasympathetic manifestations): Common manifestations include bronchoconstriction with wheezing and dyspnoea, cough, pulmonary oedema, vomiting, diarrhoea, abdominal cramps, increased salivation, lacrimation, and sweating, bradycardia, hypotension, miosis, and urinary incontinence. Some of these can be remembered by the acronym SLUDGE —Salivation, Lacrimation, Urination, Diarrhoea, Gastrointestinal distress and Emesis. Excessive