L2: Pesticides Flashcards
Def of Pesticides
- Any substance used for preventing, destroying or repelling any pest.
Classification of Pesticides
- Insecticides
- Rodenticides
- Herbicides
Examples of Insecticides
- Cholinesterase inhibitors (Organophosphates and Carbamates)
- Chlorinated Hydrocarbons (DDT, Toxaphene)
- Pyrothroids
Examples of Rodenticides
- Warfarine
- zinc phosphide
Examples of Herbicides
Paraquat.
Types of Insecticides
(Cholinesterase inhibitors)
Organophosphates:
- Diazinon
- Malathion
- Parathion.
Carbamates:
- Carbaryl
- Sevin
- Temik.
Toxic action of OPC & Carbamates
Inhibition of AChE
How do OPC & Carbamates inhibit AChE?
- Inhibition of AChE and plasma or butayrl cholinesterase (pseudocholinesterase or BuChE)
- This inhibition blocks conversion of acetylcholine to its degradation products → acetic acid and choline.
- Once AChE has been inactivated, acetylcholine accumulates in autonomic nervous system, somatic nervous system and brain,
- resulting in overstimulation of muscarinic and nicotinic receptors.
OPCs inactivate AChE (Permenantly/temporarily) giving rise to ………
- inactivate AChE permanently giving rise to cholinergic toxic syndrome and the syndrome persists until new enzyme is synthesized.
Cholinergic Transmission, OCP & Atropine
Carbamates inhibit AChE (Permenantly/Temporarily) leading to …..
Temporarily
- Leading to less severe intoxication with much shorter duration (‡ 24 hours).
- Carbamates also penetrate the blood-brain barrier poorly, producing fowor CNS offocts.
Routes of exposure to OPC
All Routes
- Most organophosphates are highly lipid soluble compounds and are well absorbed from intact skin, oral mucous membranes, conjunctiva, gastrointestinal & respiratory tracts.
CP of OPC Exposure
- Acute organophosphates poisoning
- Chronic organophosphates poisoning
Onset of Acute OPC Toxicity
- Immediate
- Delayed
Immediate onset of Acute OPC Toxicity
- Toxic manifestations appear within 30 minutes - 3 hours of exposure.
Delayed onset of Acute OPC Toxicity
- Symptoms may be delayed up to 8-12 hours especially after extensive skin exposure or indirect agent
e.g: malathion that require reactivation to active form
Examples of pesticides causing delayed onset of Acute OPC Toxicity
Malathion
Fatalities due to Pesticides Exposure
- Most fatalities occur within 24 hours.
Cause of Death in Acute OPC Toxicity
Respiratory failure
- It is a major cause of mortality in patients with acute cholinesterase inhibitor toxicity.
- All of acute clinical manifestations as muscarinic, nicotinic, and CNS effects can contribute to respiratory failure.
Acute lung injury, pulmonary edema, and chemical pneumonitis due to aspiration of hydrocarbon solvents may complicate multiple respiratory disturbances thaf characterize cholinesterase inhibitor poisoning.
..
Manifestations of Acute OPC Toxicity
- Muscarinic Manifestations
- Nicotinic Manifestations
- General Neurological Manifestations
Cause of muscarinic manifestations of Acute OPC Toxicity
Due to inhibition of cholinesterase at muscarinic receptors
Muscarinic manifestations of Acute OPC Toxicity
Cause of Nicotinic manifestations of Acute OPC Toxicity
- Due to inhibition of cholinesterase at nicotinic receptors
Nicotinic Manifestations of Acute OPC Toxicity
Cause of Neurologic Manifestations of Acute OPC Toxicity
- Due to inhibition of cholinesterase at central receptors in CNS
Neurologic Manifestations of Acute OPC Toxicity
what is DUMBBLLES a mnemonic for?
What is the most important sequale of OPC poisoning?
Specific Neurological Manifestations (Paralysis)
Types of Specific Neurological Manifestations due to Acute OPC Toxicity
- Type I paralysis (Acute paralysis)
- Type Il paralysis (Intermediate syndrome)
- Type Ill paralysis (OPIDN)
Onset of Type I Paralysis (Acute Paralysis) of Acute OPC Toxicity
- Within 24-48 h
Mechanism of Type I Paralysis (Acute Paralysis) of Acute OPC Toxicity
Persistent depolarization:
- At neuromuscular junction resulting from blockade of AChE.
Manifestations of Type I Paralysis (Acute Paralysis) of Acute OPC Toxicity
- Muscle Fasciculations
- Muscle Cramps
- Muscle Twitching
- Muscle Weakness—> It may involve respiratory muscles —->respiratory failure.
TTT of Type I Paralysis (Acute Paralysis) of Acute OPC Toxicity
Oxime therapy
Onset of Type II Paralysis (Intermediate Syndrome) of Acute OPC Toxicity
- 96 h: Alter resolution of acule cholinergic poisoning symptoms
Mechanism of Type II Paralysis (Intermediate Syndrome) of Acute OPC Toxicity
Unknown
The exact mechanism is not known but many theories exist as
- Release of lipophilis pesticide from fat stores
- Inadequate oxime therapy
- Complication of cholinergic myopathy
Manifestations of Type II Paralysis (Intermediate Syndrome) of Acute OPC Toxicity
Muscle Weakness
- Weakness of neck flexors (Patient complains from inability to lift his head from pillow)
- Weakness in proximal groups of muscle with relative sparing of distal groups.
Cranial Nerve Palsies
TTT of Type II Paralysis (Intermediate Syndrome) of Acute OPC Toxicity
Supportive measures:
- It does not respond to oximes or atropine
Onset of Type III Paralysis (OPIDN) of Acute OPC Toxicity
- 1-3 weeks: After exposure to large doses of certain OPCs
Mechanism of Type III Paralysis (OPIDN) of Acute OPC Toxicity
Esterose lnhibition:
- Inhibition of neuropathy larget esterase (NTE) via phosphorylation
Manifestations of Type III Paralysis (OPIDN) of Acute OPC Toxicity
Muscle Weakness:
- Initially complains of symmetric lower extremity weakness.
- Glove & stocking paresthesia
- Leg cramping & calf pain.
Muscle Atrophy:
- Atrophy and paralysis of peroneal muscles → foot drop and eventually ataxia.
- Steppage gait develops with loss of reflexes
progression of Type III Paralysis (OPIDN) of Acute OPC Toxicity
- This progresses to upper extremities.
Recovery of Type III Paralysis (OPIDN) of Acute OPC Toxicity
- Sensory symptoms resolve over
1-2 months, but paralysis remains
TTT of Type III Paralysis (OPIDN) of Acute OPC Toxicity
Supportive measure: It does not respond to oximes or atropine
What is OPIDN?
Organophosphate-induced delayed polyneuropathy
Criteria of Chronic Organophosphate Posioning
- It refers to the effects of long-term or repeated low-level exposures to a toxic substance and may take years to produce signs and symptoms.
Effects of Chronic Organophosphate Posioning
- Carcinogenicity, Mutagenicity, Teratogenicity & Oncogenicity,
- Hepatic damage: Jaundice, Fibrosis & Cirrhosis.
- Reproductive disorders: Sperm Count, Sterility & Miscarriage.
Investigations to diagnose of Acute OPC Toxicity
Cholinestrase Level
- Decrease in Levels up. to 30-50% ofnormal value indicates exposure
Where is RBC (True) Cholinestrase found? and its characters
lt is found in
- CNS gray matter
- RBCs
- Motor end plate
It is considered more accurate
“indicator of neurological toxicity”
Where is Plasma (Pseudo) Cholinestrase found? and its characters
It is found in
- CNS white matter
- Plasma
- Liver
- Pancreas
- Heart.
Easier to assay and generally more readily available.
TTT Aspects of Acute OPC Toxicity
- Observation
- Emergency & supportive measures
- Decontamination
- Antidotes
observation in cases of Acute OPC Toxicity
- Observe asymptomatic patients for at least 8-12 hours to rule out delayed onset symptoms.
Emergency & Supportive measures for Acute OPC Toxicity
Skin & Eye Decontamination after Acute OPC Toxicity
- Remove contaminated clothes and give shower to patient with water and soap.
- Flush eyes with copious water for 10-15 minutes.
- Clean skin folds and under fingernails.
- Avoid contact with contaminated clothing and body fluids by wearing rubber gloves.
Gastric Decontamination after Acute OPC Toxicity
Gastric Lavage:
- Not useful due to early onset of symptoms including vomiting.
Activated charcoal:
- One dose if mixed ingestions reported
What are antidotes for Acute OPC Toxicity?
- Atropine sulphate (Anti-cholinergic)
- Oxime therapy (Cholinesterase reactivators)
MOA of Atropine Sulphate
It antagonizes muscarinic effects only of organophosphates on CNS, CVS and gastrointestinal tract.
Doses of Atropine Sulphate
Starting, Reassessment & Loading
Starting dose of Atropine Sulphate
0.5-2 mg IV (0.05-0.2 mg/kg in children) With repeating dose every 5-10 min.
Reassessment in dosing of Atropine Sulphate
- Initially, reassess patient’s secretions, oxygen saturation, and respiratory rate every 5-10 minutes.
- The most important indication for redosing atropine is → Persistent wheezing or bronchorrhea.
- Tachycardia is not necessarily a contraindication to additional atropine in the context of severe respiratory secretions.
what is the most important indication for redosing of Atropine Sulphate?
Persistent wheezing or bronchorrhea.
Is tachycardia a contraindication for Atropine Sulphate?
- Tachycardia is not necessarily a contraindication to additional atropine in the context of severe respiratory secretions.
Mantainence dose of Atropine Sulphate
- Once respiratory secretions have boon initially controlled,
- Continuous infusions of atropine may be useful in selected cases (0.02-0.05 mg/kg/hr.),
- Clinical cautious is required lo provent over-atropinization.
End point of therapy by Atropine Sulphate
- Clearing up of the secretions from tracheobronchial tree and drying up of most secretions.
- On the opposite side: Mydriasis is not a therapeutic end point.
Indication for Oxime Therapy (Cholinestrase reactivation
- Oxime therapy should be started as early as possible in cases of acute OP poisoning,
- To prevent permanent binding of organophosphate to acetyl-cholinesterase and allow receptor regeneration.
MOA of Oxime Therapy (Cholinestrase reactivation
- A direct conversion of organophosphate to a harmless compound
- Transient protection of enzyme from further inhibition.
- Reactivation of the inhibited enzyme.
Examples of Oxime Therapy (Cholinestrase reactivation
- Pralidoxime
- Obidoxime
Doses of Pralidoxime
- Loading dose
- Maintenance dose
Maintenance dose of Pralidoxieme
continuous infusion of 8-20 mg/kg/h (up to 650 mg/h).
Loading dose of pralidoxieme
(30-50 mg/kg, total of 1-2 g in adults) over 30 minutes
Maintenance dose of Obidoxime
intravenous infusion of 750 mg over 24 h
End point of therapy of Oxime Therapy (Cholinestrase reactivation
24 hours after patient becomes asymptomatic (stoppage of atropine).
Loading dose of Obidoxime
250 mg (4 mg/kg) by slow intravenous injection.
AE of Oxime Therapy (Cholinestrase reactivation
Drowsiness, visual disturbances, nausea, tachycardia and muscle weakness.
CI of Oxime Therapy (Cholinestrase reactivation
In some carbamates poisoning due to formation of toxic compounds.
Toxic action of Pyrethroids Toxicity
- Allergenic.
- Neurotoxic
CP of Pyrethroids Toxicity
- Allergic reaction.
- Bronchospasm.
- Anaphylaxis.
- Tremors
- Convulsions
Dx of Pyrethroids Toxicity
No specific test
TTT of Pyrethroids Toxicity
- Adrenaline.
- Antihistamines
- Activated charcoal.
- Diazepam
Toxic action of Warfarin Toxicity
- It is an anticoagulant.
- It inhibits hepatic synthesis of vitamin K-dependent
coagulation factors II, VIl, IX and X.
CP of Warfarin Toxicity
- Onset 48 hours after exposure
- Bleeding, Massive occhymoses, Brain, hemorrhage & Shock.
Dx of Warfarin Toxicity
- Elevated INR
- Blood in urine and feces
TTT of Warfarin Toxicity
- Vitamin K. Fresh
- Frozen plasma.
- Iron.
- Activated Charcoal.
Toxic Action of Zinc Phosphide Toxicity
- Toxicity is mediated by release of phosphine gas.
CP of Zinc Phosphide Toxicity
- Tachypnea.
- Hypotension.
- Pulmonary edema.
- Convulsion, coma
Dx of Zinc Phosphide Toxicity
History of exposure.
TTT of Zinc Phosphide Toxicity
Cardio-respiratory support
Decontamination:
- Gastric aspiration and use of 3-5% sodium bicarbonate in lavage fluid has been proposed
- To reduce stomach acid and resulting production of phosphine → but is not of proven benefit.
