190 Questions
How do chemical insecticides primarily affect the target organisms?
By poisoning their nervous systems
Which of the following is a potential site of action of insecticides?
Interference with membrane transport of sodium, potassium, calcium, and chloride ions
What is a possible effect of insecticides on nerve endings?
Increase in release and/or persistence of neurotransmitters
What is a common potential action of classes of insecticides on the nerve axon and terminal portions?
Interference with membrane transport
What contributes to the persistence of organochlorine insecticides in the environment?
High lipid solubility and slow rates of degradation
Which class of insecticide includes DDT and its analogues?
Chlorinated ethane derivatives
What characteristic makes organochlorine insecticides chemically stable?
Low volatility
Which compound belongs to the class of hexachlorocyclohexanes?
Gamma Lindane
What is the primary metabolite of DDT in humans?
Dichlorodiphenyldichloroethylene (DDE)
Where are the highest concentrations of DDT found in the body?
Adipose tissue
How is DDT excreted from the body?
Bile, urine, and milk
Which isomer of DDT is responsible for its insecticidal activity?
p,p-DDT
Which mechanism describes the alteration of porous channels through which sodium ions pass?
Altering sodium ion channels by slowing down inactivation
What effect does DDT have on the ability of calmodulin to transport calcium ions?
Inhibits calmodulin's ability to transport calcium ions
What role do neuronal adenosine triphosphatases (ATPase) play in neuronal repolarization?
Play vital roles in neuronal repolarization
How does DDT's reduction of potassium transport across the membrane impact neurons?
Interferes with the active transport of potassium out of the nerve axon
What is one of the proposed sites of action of DDT?
Inactivating sodium channel closure
How does DDT potentially affect the transport of potassium?
Reducing potassium transport through pores
What is a suggested effect of DDT on calmodulin-calcium binding?
Inhibiting calmodulin-calcium binding
Which of the following is a potential site of action of DDT?
Inhibiting sodium-potassium and calciummagnesium ATPases
Which of the following is the earliest symptom of poisoning by DDT in humans?
Paresthesia of the mouth and lower part of the face
What is the primary target for DDT toxicity based on the signs and symptoms of acute poisoning?
Nervous system
According to animal data, how is DDT classified in terms of its potential impact on humans?
Human carcinogen
Which organ or system is considered an important target for DDT in chronic exposure?
Liver
Which class of organochlorine insecticides includes compounds that antagonize the action of the neurotransmitter GABA?
Class 3: Cyclodienes
What is the γ isomer of benzene hexachloride known as?
Lindane
Which compound is rapidly metabolized to dieldrin?
Aldrin
What is the primary mechanism of neurotoxic action shared by the hexachlorocyclohexanes and cyclodiene insecticides?
Blocking GABA-induced uptake of chloride ions
What is the mechanism of action shared by hexachlorocyclohexanes and cyclodiene insecticides?
Antagonism of GABA receptors
Which compound is the γ isomer of benzene hexachloride?
Lindane
Which class of insecticides includes chlordane, dieldrin, and aldrin?
Cyclodienes
What is the primary mechanism of neurotoxic action for organochlorine insecticides?
Antagonism of GABA receptors
What is the primary effect of endogenous GABA binding to its receptors?
Opening of chloride channels resulting in hyperpolarization
What is the primary action of Lindane and cyclodienes on the chloride channel?
Blocking the opening of chloride channels
What is the result of inhibiting Na+,K+-ATPase and Ca2+,Mg2+ ATPase by Class 2 and Class 3 insecticides?
Accumulation of intracellular free Ca2+
What is the primary effect of GABA antagonists like Lindane and cyclodienes on neurotransmission?
Inhibition of neurotransmitter release
What is the primary target for the toxicity of Lindane and cyclodienes?
Central nervous system
What is the main difference in symptoms of poisoning between DDT and Lindane/cyclodienes?
Tremor
What effect do cyclodienes have on the liver upon chronic exposure?
Enlargement
Where do Lindane and cyclodienes tend to bioaccumulate?
Adipose tissue
What is the primary target for the toxicity of Lindane and cyclodienes?
Central Nervous System
What is a prominent aspect of poisoning by Lindane and cyclodienes?
Tremor
What is the effect of cyclodienes on the liver upon chronic exposure?
Liver enlargement
Where do Lindane and cyclodienes tend to bioaccumulate?
Adipose tissue
What is the primary manifestation of chlordecone toxicity?
Tremors
What is believed to be the mechanism of chlordecone neurotoxicity?
Inhibition of catecholamines
What effect does chlordecone have on the liver?
Induces hepatic drug metabolizing enzymes
What reproductive effect has been observed in chlordecone-exposed workers?
Low or absent sperm count
Which of the following best defines an endocrine disruptor?
A chemical that interferes with the production of natural hormones
Which compound has estrogenic properties and can act as an agonist at estrogen receptors?
o,p-isomer of DDT
What is the primary negative effect of the metabolite p,p-DDE on androgen receptors?
Inhibits androgen binding
Which category of insecticides includes compounds with weak estrogenic activity?
Organochlorine insecticides
What is the definition of an endocrine disruptor?
A chemical that affects the transport, binding, and action of natural hormones in the body
What is the primary mechanism of action of the o,p-isomer of DDT?
Acts as an agonist at estrogen receptors
Which compound has estrogenic properties and can act as an agonist at estrogen receptors?
o,p-isomer of DDT
What do organochlorine compounds with weak estrogenic activity primarily affect?
Reproduction and development
How does the oral administration of anion-exchange resin (cholestyramine) affect the fecal excretion of chlordecone?
It enhances fecal excretion by 18 fold
What is the rationale for the use of cholestyramine in increasing fecal excretion of chlordecone?
It interrupts enterohepatic circulation and reduces reabsorption of chlordecone
What is the primary impact of cholestyramine on the biological half-life of chlordecone?
It shortens the biological half-life of chlordecone
How does cholestyramine potentially reduce chlordecone reabsorption in the intestinal tract?
By reducing biliary – enterohepatic circulation of chlordecone
What is the primary rationale for using cholestyramine to increase fecal excretion of chlordecone?
Interrupting enterohepatic circulation of chlordecone
What effect does cholestyramine potentially have on chlordecone reabsorption in the intestinal tract?
Reducing reabsorption by interrupting enterohepatic circulation
What is the primary impact of cholestyramine on the biological half-life of chlordecone?
Shortening the biological half-life
Where does cholestyramine retain the bound chlordecone to increase fecal excretion?
Gastrointestinal lumen
What is the common mechanism of action shared by the two types of insecticides?
Inhibition of acetylcholinesterase (AChE)
What do the esters of phosphoric or phosphorothioic acid and the esters of carbamic acid have in common?
Shared mechanism of hydrolysis sensitivity
What is the role of X in the general structure of OP insecticides?
Serves as a leaving group when phosphorylating AChE
What are R1 and R2 in the general structure of OP insecticides typically composed of?
Alkyl or alkoxy groups
What is the most sensitive to hydrolysis in the general structure of OP insecticides?
The leaving group
Which chemical class of insecticides includes esters of carbamic acid?
Organophosphate insecticides
What is the common mechanism of action for the agents comprising a type of insecticide ?
Phosphorylation of acetylcholinesterase (AChE)
What are R1 and R2 in the general structure of OP insecticides primarily composed of?
Alkyl or alkoxy groups
What is the common mechanism of action shared by the two types of insecticides?
Inhibition of acetylcholinesterase (AChE)
Which chemical class of insecticides includes esters of carbamic acid?
Carbamate insecticides
What contributes to the persistence of organochlorine insecticides in the environment?
Resistance to chemical hydrolysis
What is the primary impact of cholestyramine on the biological half-life of chlordecone?
Decreases the biological half-life
What is the primary metabolic bioactivation process for compounds containing a sulfur bound to phosphorus?
Oxidative desulfuration mediated by cytochrome P450 enzymes (CYPs)
Which enzymes are primarily responsible for the oxidative desulfuration of compounds containing sulfur bound to phosphorus?
Cytochrome P450 enzymes (CYPs)
What type of analog is formed during the oxidative desulfuration of compounds containing sulfur bound to phosphorus?
Oxon
Where does the oxidative desulfuration of compounds containing sulfur bound to phosphorus predominantly take place?
Liver
What happens to the AChE enzyme following the reaction with an organophosphorus ester?
It forms a transient intermediate complex and becomes phosphorylated, leading to irreversible inhibition
What is the effect of inhibiting Na+,K+-ATPase and Ca2+,Mg2+ ATPase by Class 2 and Class 3 insecticides?
Decreased excitability of neurons
How does DDT's reduction of potassium transport across the membrane impact neurons?
It increases excitability of neurons
What is the primary impact of GABA antagonists like Lindane and cyclodienes on neurotransmission?
Decreased inhibition of neurotransmission
What happens to the AChE enzyme following the reaction with an organophosphorus ester?
It forms a transient intermediate complex that hydrolyzes with the loss of the substituent group
What is the primary impact of cholestyramine on the biological half-life of chlordecone?
It decreases the biological half-life of chlordecone
What is the common mechanism of action for the agents comprising a type of insecticide?
Inhibition of acetylcholinesterase (AChE) activity
What are R1 and R2 in the general structure of OP insecticides primarily composed of?
Functional groups that enhance enzyme reactivation
What is the primary impact of inhibiting AChE by organophosphates (OPs)?
Overstimulation of muscarinic and nicotinic cholinergic receptors
What is the primary consequence of AChE inhibition at cholinergic synapses?
Overstimulation of muscarinic and nicotinic receptors
What is the primary result of AChE inhibition by organophosphates (OPs) in the body?
Increased activity of cholinergic receptors
What is the consequence of AChE inhibition by organophosphates (OPs) at cholinergic synapses?
Overstimulation of muscarinic and nicotinic receptors
What effect can be expected from the stimulation of muscarinic receptors of the parasympathetic autonomic nervous system?
Increased sweating and salivation
What is believed to be the primary cause of death when respiratory failure occurs due to exposure to certain substances?
Paralysis of respiratory muscles
Which effect is associated with the action of chlordecone in the intestinal tract?
Increased reabsorption
What symptoms can result from the effects of substances on the CNS?
Convulsion and coma
What is the hallmark of severe organophosphate (OP) poisoning?
Respiratory failure
Which symptoms are observed most often in mild and moderate OP poisoning?
Miosis
What are the first signs to appear in OP poisoning?
Muscarinic
What is a hallmark of severe chlordecone poisoning?
Gastrointestinal symptoms
What is the primary means of replacing the activity of irreversibly inhibited AChE?
Synthesis of new enzyme
What facilitates the dephosphorylation of AChE in the therapy of OP poisoning?
Hydroxylamine derivatives (oximes)
What is the impact of aging on phosphorylated AChE?
Makes the enzyme irreversibly inhibited
What determines the rate of aging of phosphorylated AChE and the need for enzyme replacement?
Nature of the alkyl group
What effect would the presence of P–O–C bonds have on aging ?
Aging would occur rapidly
What type of bonds in P–R would prevent aging ?
P–C
In what form of P-R bonds would aging not be possible?
P–C
What type of P-R bonds are associated with rapid aging?
P–O–C
What is the primary feature of the Intermediate Syndrome in organophosphate (OP) poisoning?
Marked weakness of respiratory and limb muscles
What is the mortality rate due to respiratory paralysis and complications in the Intermediate Syndrome?
15-40%
What is one hypothesis for the cause of muscle weakness in the Intermediate Syndrome?
Muscarinic receptor desensitization
What is the primary treatment for the Intermediate Syndrome?
Supportive intervention only
When does the Intermediate Syndrome typically develop after OP poisoning?
One to several days after poisoning
What is the usual recovery period in surviving patients with the Intermediate Syndrome?
Up to 15 days
What is a common symptom of Organophosphate-Induced Delayed Polyneuropathy (OPIDP)?
Tingling of the hands and feet
When do the signs and symptoms of Organophosphate-Induced Delayed Polyneuropathy (OPIDP) typically occur?
2-3 weeks after exposure
What is the primary impact of AChE (Acetylcholinesterase) inhibition by organophosphates (OPs) in the body?
Impaired nerve signal transmission
Which of the following is a sign of Organophosphate-Induced Delayed Polyneuropathy (OPIDP)?
Progressive muscle weakness
What is the necessary percentage of NTE phosphorylation for OPIDP to be initiated?
70%
What is the target enzyme for OPIDP?
Neuropathy target esterase (NTE)
Which type of compounds can cause OPIDP?
Compounds that inhibit NTE and undergo aging reaction
What is the primary impact of organophosphates (OPs) on NTE?
Phosphorylation and aging of NTE
What is the primary reason for the distinctive difference in neurotoxicity action between carbamic acid esters and organophosphates?
The rate of decarbamylation is rapid for carbamic acid esters but slow for organophosphates.
What distinguishes carbamic acid esters as poor substrates for the cholinesterase enzymes compared to organophosphates?
They form a carbamylated enzyme through a fast process.
What distinguishes organophosphates as frequently considered to be irreversible inhibitors of AChE?
The rate of dephosphorylation is exceedingly slow.
What characterizes the distinct difference in neurotoxic action between carbamic acid esters and organophosphates?
Organophosphates have a higher rate of decarbamylation.
What distinguishes carbamate insecticides from most organophosphorus compounds?
They are rapidly biotransformed in vivo
What is the primary difference between the signs and symptoms of acute intoxication by carbamate insecticides and organophosphorus compounds?
Duration and intensity of toxicity
What is the reason for the extensive toxicologic short-term toxicity following acute administration of carbamate insecticides?
Rapid biotransformation in vivo
What is the primary reason for fatalities occurring in humans due to carbamate insecticide toxicity?
Higher toxicity of the compounds
What is the primary indicator of the severity of organophosphorus ester poisoning?
Erythrocyte AChE inhibition
What immediate action is required in response to life-threatening signs of anticholinesterase poisoning?
Initiating artificial respiration and suctioning
What should be monitored in cases of anticholinesterase poisoning, in addition to the status of the patient?
Arterial blood gases and cardiac function
What is a consequence of extensive nervous system involvement in anticholinesterase poisoning?
Hypoxemia requiring immediate artificial respiration
What is a good indicator of the severity of organophosphorus ester poisoning?
Erythrocyte AChE levels
What is the immediate action required for life-threatening signs of anticholinesterase poisoning?
Initiating artificial respiration
What should be monitored as a consequence of the extensive involvement of the entire nervous system in anticholinesterase poisoning?
Arterial blood gases
What is the primary indicator of severe organophosphate (OP) poisoning?
Inhibition of erythrocytic AChE
What is the recommended action for all cases of anticholinesterase poisoning?
Immediate hospitalization
Which enzyme's inhibition is a good indicator of the severity of organophosphorus ester poisoning?
Plasma acetylcholinesterase (AChE)
What is required to maintain a patent airway in cases of life-threatening signs in anticholinesterase poisoning?
Immediate artificial respiration and suctioning via an endotracheal tube
What should be monitored as a consequence of the extensive involvement of the entire nervous system in anticholinesterase poisoning?
Arterial blood gases and cardiac function
What is the role of diazepam in the treatment of organophosphorus and/or carbamate intoxications?
Relieving mental anxiety associated with exposure
What is the antidotal therapy for organophosphorus ester insecticide poisoning usually based on?
Analysis of serum pseudocholinesterase
What is the primary impact of AChE (Acetylcholinesterase) inhibition by organophosphates (OPs) in the body?
Overstimulation of muscles and nerves
What characterizes the distinct difference in neurotoxic action between carbamic acid esters and organophosphates?
The reversibility of AChE inhibition
What is the primary reason for using frequent small doses of atropine in cases of mild signs and symptoms of anticholinesterase poisoning?
To counteract the muscarinic effects and some CNS effects of accumulating Ach
What is the supplementary treatment for moderate to severe nicotinic symptoms in cases of anticholinesterase poisoning?
Priming with pralidoxime chloride or P2S
What is the primary consequence of AChE inhibition by organophosphates (OPs) at cholinergic synapses?
Accumulation of acetylcholine at cholinergic synapses
What is the status that must be monitored continuously in cases of anticholinesterase poisoning?
Disappearance of secretions and mydriasis
What is the primary requirement for a reactivating molecule for AChE inhibition?
A rigid structure containing a quaternary ammonium group and an acidic nucleophile
What is the therapeutic action of oxime compounds based on?
Reactivation of AChE
What contributes to the irreversible inhibition of AChE by organophosphorus esters?
Presence of good 'leaving groups' that phosphorylate AChE
What aids in the rapid dephosphorylation of the phosphorylated enzyme?
Various nucleophilic agents containing a substituted ammonium group
What is the practical limitation on the usefulness of oxime reactivators?
Inability to reactivate 'aged' AChE
What is the product of the oxime reaction with either the phosphorylated enzyme or with free, unbound organophosphorus ester?
Phosphorylated oxime
What happens to the phosphorylated enzyme in 'aged' AChE?
Becomes tightly bound to the reactive site
What is the nature of the reaction between oxime and the phosphorylated enzyme or free, unbound organophosphorus ester?
Equilibrium reaction
What should be administered repeatedly over several days if the absorption, distribution, and/or metabolism of the organophosphorus ester is delayed in the body?
Pralidoxime
What may alleviate severe muscle cramping, particularly in the extremities, caused by the repeated dosing of pralidoxime?
Oral or intravenous calcium solutions
What binding by pralidoxime causes muscle spasms similar to those caused by the organophosphorus esters?
Calcium ions
What is the primary treatment for severe muscle cramping, particularly in the extremities, caused by repeated dosing with pralidoxime?
Oral or intravenous calcium solutions
What is the primary difference in the clinical treatment of carbamate toxicity compared to organophosphorus ester insecticide intoxication?
The use of oximes is contraindicated
What did reports reveal about the use of pralidoxime in treating carbaryl intoxications?
The oxime enhanced the carbaryl-induced toxicity
What is the important consideration regarding the treatment of anticholinesterase-type insecticide intoxications?
Vigorous treatment is ineffective in preventing neurotoxicity
What is the similarity in the clinical treatment of carbamate toxicity and organophosphorus ester insecticide intoxication?
Both involve delayed-onset neurotoxicity
What are pyrethrins?
Esters of chrysanthemic acid and pyrethric acid found in chrysanthemum flowers
Which type of pyrethrins contains the -cyano substituent?
Esters containing the -cyano substituent
What is the primary source of pyrethrins?
Chrysanthemum flowers
What distinguishes pyrethrins from carbamate and organophosphorus insecticides?
They have a natural source in chrysanthemum flowers
What impact do pyrethroids have on sodium channels?
They affect both the activation and inactivation of sodium channels, resulting in a hyperexcitable state
What is the primary difference between type I and type II esters in relation to sodium channels?
Type I esters keep the channel open for seconds, while type II esters keep it open for milliseconds
What is the effect of type II esters on sodium ion transport within neurons?
They modify the gating kinetics of sodium channels, causing a hypoexcitable state
What is the impact of both type I and type II esters on sodium channels?
They modify the gating kinetics of sodium channels, resulting in a hyperexcitable state
What is the potential effect of inhibiting Ca2, Mg2-ATPase by several agents such as permethrin, cypermethrin, and deltamethrin?
Increased intracellular calcium levels
What is the action of Type II esters at relatively high concentrations in the mammalian brain?
Act on the GABA-gated chloride channels
What is the potential consequence of Type II ester intoxication on seizures?
Increased likelihood of seizures
What is the primary effect of inhibiting GABA-gated chloride channels in the mammalian brain?
Increased postsynaptic depolarization
Which compound produces profuse salivation, coarse tremor progressing to clonic seizures?
Type II pyrethrins
What is the primary adverse effect resulting from dermal contact with pyrethroids?
Paresthesia
What is the hallmark of severe organophosphate (OP) poisoning?
Marked behavioral arousal
What is the primary impact of GABA antagonists like Lindane and cyclodienes on neurotransmission?
Antagonize GABA receptors
What is the primary reason for fatalities occurring in humans due to pyrethrin poisoning?
Respiratory paralysis
What does piperonyl butoxide do when included in commercial forms of pyrethrins?
Inhibits the ability of insects to metabolize pyrethrins
What may a patient also exhibit signs of, if pyrethrins are sold in hydrocarbon solution?
Hydrocarbon toxicity
What is the primary impact of piperonyl butoxide on the activity of insects?
Enhances the insecticidal activity of pyrethrins
What is the primary concern in organochlorine insecticide poisoning?
Respiratory failure and acidosis
What is the recommended treatment to control convulsions in organochlorine insecticide poisoning?
Diazepam
What is the effect of repetitive stimulation of the CNS in organochlorine insecticide poisoning?
Tremors and motor seizures
In addition to general decontamination and supportive treatment, what medication may be administered to control the convulsions in organochlorine insecticide poisoning?
Phenobarbital
Study Notes
Chemical Insecticides
- Chemical insecticides primarily affect target organisms by interfering with nerve impulses, disrupting ion channels and receptors, and altering enzyme function.
- Potential sites of action include nerve endings, axon and terminal portions, and sodium and calcium channels.
Organochlorine Insecticides
- Organochlorine insecticides, including DDT and its analogues, are chemically stable due to their cyclic structure.
- They persist in the environment due to their low biodegradability and high lipophilicity.
- They can bioaccumulate in fatty tissues and biomagnify up food chains.
DDT
- DDT (dichlorodiphenyltrichloroethane) is an organochlorine insecticide that affects nerve endings, axon and terminal portions, and sodium and calcium channels.
- Its primary metabolite in humans is DDE (dichlorodiphenyldichloroethylene).
- Highest concentrations of DDT are found in fatty tissues, and it is excreted through the bile and feces.
- The insecticidal activity of DDT is attributed to its p,p'-isomer.
- DDT alters the transport of potassium, affecting neuronal repolarization, and binds to calmodulin, altering calcium ion transport.
Hexachlorocyclohexanes
- Hexachlorocyclohexanes, including Lindane (γ-hexachlorocyclohexane), are another class of organochlorine insecticides.
- They antagonize the action of the neurotransmitter GABA, affecting chloride channels and leading to neuronal hyperexcitation.
Cyclodiene Insecticides
- Cyclodiene insecticides, including chlordane and aldrin, are organochlorine compounds that antagonize GABA receptors, affecting chloride channels.
- They are rapidly metabolized to more toxic compounds, such as dieldrin.
Endocrine Disruptors
- Endocrine disruptors, including some organochlorine insecticides, interfere with hormone function, affecting reproductive and developmental processes.
- p,p'-DDE, a metabolite of DDT, has anti-androgenic properties, affecting reproductive health.
- Chlordecone, a cyclodiene insecticide, has estrogenic properties, acting as an agonist at estrogen receptors.
Cholestyramine and Chlordecone
- Cholestyramine, an anion-exchange resin, increases the fecal excretion of chlordecone by binding to it in the gut, reducing reabsorption and increasing elimination.
Organophosphorus Insecticides
- Organophosphorus insecticides, such as malathion and parathion, are esters of phosphoric or phosphorothioic acid.
- They inhibit acetylcholinesterase (AChE), leading to an accumulation of acetylcholine, which overstimulates muscarinic and nicotinic receptors.
- Inhibiting Na+,K+-ATPase and Ca2+,Mg2+ ATPase can lead to neurological and muscular effects.
Toxicity and Symptoms
- Symptoms of poisoning by DDT, Lindane, and cyclodienes include muscle weakness, tremors, and seizures, while chlordecone poisoning can cause tremors, muscle weakness, and liver damage.
- Organophosphate poisoning can cause muscle weakness, fasciculations, and respiratory failure.
- The primary impact of cholestyramine on the biological half-life of chlordecone is to reduce it.
Test your knowledge on the potential sites of action and modes of action of chemical insecticides. Learn about the interference with membrane transport of ions, enzymatic activities, and neurotransmitter release at nerve endings.
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