L2: Pesticides Flashcards
1
Q
Def of Pesticides
A
- Any substance used for preventing, destroying or repelling any pest.
2
Q
Classification of Pesticides
A
- Insecticides
- Rodenticides
- Herbicides
3
Q
Examples of Insecticides
A
- Cholinesterase inhibitors (Organophosphates and Carbamates)
- Chlorinated Hydrocarbons (DDT, Toxaphene)
- Pyrothroids
4
Q
Examples of Rodenticides
A
- Warfarine
- zinc phosphide
5
Q
Examples of Herbicides
A
Paraquat.
6
Q
Types of Insecticides
(Cholinesterase inhibitors)
A
Organophosphates:
- Diazinon
- Malathion
- Parathion.
Carbamates:
- Carbaryl
- Sevin
- Temik.
7
Q
Toxic action of OPC & Carbamates
A
Inhibition of AChE
8
Q
How do OPC & Carbamates inhibit AChE?
A
- 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.
9
Q
OPCs inactivate AChE (Permenantly/temporarily) giving rise to ………
A
- inactivate AChE permanently giving rise to cholinergic toxic syndrome and the syndrome persists until new enzyme is synthesized.
10
Q
Cholinergic Transmission, OCP & Atropine
A
11
Q
Carbamates inhibit AChE (Permenantly/Temporarily) leading to …..
A
Temporarily
- Leading to less severe intoxication with much shorter duration (‡ 24 hours).
- Carbamates also penetrate the blood-brain barrier poorly, producing fowor CNS offocts.
12
Q
Routes of exposure to OPC
A
All Routes
- Most organophosphates are highly lipid soluble compounds and are well absorbed from intact skin, oral mucous membranes, conjunctiva, gastrointestinal & respiratory tracts.
13
Q
CP of OPC Exposure
A
- Acute organophosphates poisoning
- Chronic organophosphates poisoning
14
Q
Onset of Acute OPC Toxicity
A
- Immediate
- Delayed
15
Q
Immediate onset of Acute OPC Toxicity
A
- Toxic manifestations appear within 30 minutes - 3 hours of exposure.
15
Q
Delayed onset of Acute OPC Toxicity
A
- 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
16
Q
Examples of pesticides causing delayed onset of Acute OPC Toxicity
A
Malathion
17
Q
Fatalities due to Pesticides Exposure
A
- Most fatalities occur within 24 hours.
18
Q
Cause of Death in Acute OPC Toxicity
A
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.
19
Q
Acute lung injury, pulmonary edema, and chemical pneumonitis due to aspiration of hydrocarbon solvents may complicate multiple respiratory disturbances thaf characterize cholinesterase inhibitor poisoning.
A
..
20
Q
Manifestations of Acute OPC Toxicity
A
- Muscarinic Manifestations
- Nicotinic Manifestations
- General Neurological Manifestations
21
Q
Cause of muscarinic manifestations of Acute OPC Toxicity
A
Due to inhibition of cholinesterase at muscarinic receptors
22
Q
Muscarinic manifestations of Acute OPC Toxicity
A
23
Q
Cause of Nicotinic manifestations of Acute OPC Toxicity
A
- Due to inhibition of cholinesterase at nicotinic receptors
24
Nicotinic Manifestations of **Acute OPC Toxicity**
25
Cause of Neurologic Manifestations of **Acute OPC Toxicity**
- Due to inhibition of cholinesterase at central receptors in CNS
26
Neurologic Manifestations of **Acute OPC Toxicity**
27
what is **DUMBBLLES** a mnemonic for?
28
What is the most important sequale of OPC poisoning?
Specific Neurological Manifestations (Paralysis)
29
Types of **Specific Neurological Manifestations** due to **Acute OPC Toxicity**
- Type I paralysis (Acute paralysis)
- Type Il paralysis (Intermediate syndrome)
- Type Ill paralysis (OPIDN)
30
Onset of **Type I Paralysis (Acute Paralysis)** of **Acute OPC Toxicity**
- Within 24-48 h
31
Mechanism of **Type I Paralysis (Acute Paralysis)** of **Acute OPC Toxicity**
**Persistent depolarization:**
- At neuromuscular junction resulting from blockade of AChE.
32
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.
33
TTT of **Type I Paralysis (Acute Paralysis)** of **Acute OPC Toxicity**
Oxime therapy
34
Onset of **Type II Paralysis (Intermediate Syndrome)** of **Acute OPC Toxicity**
- 96 h: Alter resolution of acule cholinergic poisoning symptoms
35
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
36
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**
37
TTT of **Type II Paralysis (Intermediate Syndrome)** of **Acute OPC Toxicity**
**Supportive measures:**
- It does not respond to oximes or atropine
38
Onset of **Type III Paralysis (OPIDN)** of **Acute OPC Toxicity**
- 1-3 weeks: After exposure to large doses of certain OPCs
39
Mechanism of **Type III Paralysis (OPIDN)** of **Acute OPC Toxicity**
**Esterose lnhibition:**
- Inhibition of neuropathy larget esterase (NTE) via phosphorylation
40
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
41
progression of **Type III Paralysis (OPIDN)** of **Acute OPC Toxicity**
- This progresses to upper extremities.
42
Recovery of **Type III Paralysis (OPIDN)** of **Acute OPC Toxicity**
- Sensory symptoms resolve over
1-2 months, but paralysis remains
43
TTT of **Type III Paralysis (OPIDN)** of **Acute OPC Toxicity**
**Supportive measure:** It does not respond to oximes or atropine
44
What is **OPIDN**?
Organophosphate-induced delayed polyneuropathy
45
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.
46
Effects of **Chronic Organophosphate Posioning**
- Carcinogenicity, Mutagenicity, Teratogenicity & Oncogenicity,
- **Hepatic damage:** Jaundice, Fibrosis & Cirrhosis.
- **Reproductive disorders:** Sperm Count, Sterility & Miscarriage.
47
Investigations to diagnose of **Acute OPC Toxicity**
**Cholinestrase Level**
- Decrease in Levels up. to 30-50% ofnormal value indicates exposure
48
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"**
49
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.**
50
TTT Aspects of **Acute OPC Toxicity**
- Observation
- Emergency & supportive measures
- Decontamination
- Antidotes
51
observation in cases of **Acute OPC Toxicity**
- Observe asymptomatic patients for at least 8-12 hours to rule out delayed onset symptoms.
52
Emergency & Supportive measures for **Acute OPC Toxicity**
53
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.
54
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
55
What are antidotes for **Acute OPC Toxicity**?
- Atropine sulphate (Anti-cholinergic)
- Oxime therapy (Cholinesterase reactivators)
55
MOA of **Atropine Sulphate**
It antagonizes muscarinic effects only of organophosphates on CNS, CVS and gastrointestinal tract.
56
Doses of **Atropine Sulphate**
Starting, Reassessment & Loading
57
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.
58
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.
59
what is the most important indication for redosing of **Atropine Sulphate**?
Persistent wheezing or bronchorrhea.
59
Is tachycardia a contraindication for **Atropine Sulphate**?
- Tachycardia is not necessarily a contraindication to additional atropine in the context of severe respiratory secretions.
60
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.
61
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.
62
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.
63
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.
64
Examples of **Oxime Therapy (Cholinestrase reactivation**
- Pralidoxime
- Obidoxime
65
Doses of Pralidoxime
- Loading dose
- Maintenance dose
66
Maintenance dose of Pralidoxieme
continuous infusion of 8-20 mg/kg/h (up to 650 mg/h).
66
Loading dose of pralidoxieme
(30-50 mg/kg, total of 1-2 g in adults) over 30 minutes
67
Maintenance dose of Obidoxime
intravenous infusion of 750 mg over 24 h
68
End point of therapy of **Oxime Therapy (Cholinestrase reactivation**
24 hours after patient becomes asymptomatic (stoppage of atropine).
68
Loading dose of Obidoxime
250 mg (4 mg/kg) by slow intravenous injection.
69
AE of **Oxime Therapy (Cholinestrase reactivation**
Drowsiness, visual disturbances, nausea, tachycardia and muscle weakness.
70
CI of **Oxime Therapy (Cholinestrase reactivation**
In some carbamates poisoning due to formation of toxic compounds.
71
Toxic action of **Pyrethroids Toxicity**
- Allergenic.
- Neurotoxic
72
CP of **Pyrethroids Toxicity**
- Allergic reaction.
- Bronchospasm.
- Anaphylaxis.
- Tremors
- Convulsions
73
Dx of **Pyrethroids Toxicity**
No specific test
74
TTT of **Pyrethroids Toxicity**
- Adrenaline.
- Antihistamines
- Activated charcoal.
- Diazepam
74
Toxic action of **Warfarin Toxicity**
- It is an anticoagulant.
- It inhibits hepatic synthesis of vitamin K-dependent
coagulation factors II, VIl, IX and X.
75
CP of **Warfarin Toxicity**
- Onset 48 hours after exposure
- Bleeding, Massive occhymoses, Brain, hemorrhage & Shock.
76
Dx of **Warfarin Toxicity**
- Elevated INR
- Blood in urine and feces
77
TTT of **Warfarin Toxicity**
- Vitamin K. Fresh
- Frozen plasma.
- Iron.
- Activated Charcoal.
78
Toxic Action of **Zinc Phosphide Toxicity**
- Toxicity is mediated by release of phosphine gas.
79
CP of **Zinc Phosphide Toxicity**
- Tachypnea.
- Hypotension.
- Pulmonary edema.
- Convulsion, coma
80
Dx of **Zinc Phosphide Toxicity**
History of exposure.
81
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.
