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Questions and Answers
Which type of nicotinic receptor is primarily involved in neuromuscular blocking?
Which type of nicotinic receptor is primarily involved in neuromuscular blocking?
What is one clinical use of acetylcholinesterase inhibitors?
What is one clinical use of acetylcholinesterase inhibitors?
Which of the following best describes the action of neuromuscular blockers?
Which of the following best describes the action of neuromuscular blockers?
Which organophosphate poisoning symptom is typically observed?
Which organophosphate poisoning symptom is typically observed?
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What mechanism do ganglionic blockers primarily utilize?
What mechanism do ganglionic blockers primarily utilize?
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Which type of cholinergic antagonists affects only the second half of the parasympathetic pathway?
Which type of cholinergic antagonists affects only the second half of the parasympathetic pathway?
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What is one potential adverse effect of neuromuscular blocking drugs?
What is one potential adverse effect of neuromuscular blocking drugs?
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Which of the following represents a physiological effect of acetylcholinesterase inhibitors?
Which of the following represents a physiological effect of acetylcholinesterase inhibitors?
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Which of the following neuromuscular blockers is known to be a competitive antagonist at Nm receptors?
Which of the following neuromuscular blockers is known to be a competitive antagonist at Nm receptors?
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What is the primary reason that curariform drugs are not well absorbed from the gut?
What is the primary reason that curariform drugs are not well absorbed from the gut?
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Which of the following neuromuscular blockers is derived from a plant source used historically by South American natives?
Which of the following neuromuscular blockers is derived from a plant source used historically by South American natives?
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What mechanism is employed by AChE inhibitors during the reversal of neuromuscular blockade?
What mechanism is employed by AChE inhibitors during the reversal of neuromuscular blockade?
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Which of the following statements is true regarding high doses of neuromuscular blockers?
Which of the following statements is true regarding high doses of neuromuscular blockers?
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What specific effect do competitive neuromuscular blockers have on skeletal muscle contraction?
What specific effect do competitive neuromuscular blockers have on skeletal muscle contraction?
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Which neuromuscular blocker is not traditionally used due to safety concerns and lack of clinical need?
Which neuromuscular blocker is not traditionally used due to safety concerns and lack of clinical need?
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Which of the following is a reason why neuromuscular blockers are administered via IV?
Which of the following is a reason why neuromuscular blockers are administered via IV?
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What is the primary ocular effect of increased acetylcholine (Ach) stimulating M3 receptors?
What is the primary ocular effect of increased acetylcholine (Ach) stimulating M3 receptors?
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Which muscle contraction is associated with accommodation of the lens to focus on close objects?
Which muscle contraction is associated with accommodation of the lens to focus on close objects?
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What therapeutic use of ecothiophate is mentioned?
What therapeutic use of ecothiophate is mentioned?
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How does atropine affect acetylcholine (ACh) at muscarinic cholinergic receptors?
How does atropine affect acetylcholine (ACh) at muscarinic cholinergic receptors?
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What is a consequence of organophosphate toxicity?
What is a consequence of organophosphate toxicity?
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What aspect of organophosphates contributes to their potential for causing widespread toxicity?
What aspect of organophosphates contributes to their potential for causing widespread toxicity?
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Which of the following is NOT a result of contraction of the iris sphincter muscle?
Which of the following is NOT a result of contraction of the iris sphincter muscle?
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Where can organophosphate toxicity occur?
Where can organophosphate toxicity occur?
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What effect does increased ACh have on cholinergic receptors?
What effect does increased ACh have on cholinergic receptors?
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Which of the following is a muscarinic effect of toxicity?
Which of the following is a muscarinic effect of toxicity?
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What is the primary treatment for cholinesterase inhibitor poisoning?
What is the primary treatment for cholinesterase inhibitor poisoning?
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What symptom is associated with nicotinic effects of cholinergic toxicity?
What symptom is associated with nicotinic effects of cholinergic toxicity?
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What should be done within 1-2 hours of exposure to cholinesterase inhibitors?
What should be done within 1-2 hours of exposure to cholinesterase inhibitors?
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What is a common CNS effect of cholinergic toxicity?
What is a common CNS effect of cholinergic toxicity?
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Which of the following statements about atropine is true?
Which of the following statements about atropine is true?
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Which symptom is most indicative of muscarinic receptor activation?
Which symptom is most indicative of muscarinic receptor activation?
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What is primarily responsible for the initiation of an action potential at a neuromuscular synapse?
What is primarily responsible for the initiation of an action potential at a neuromuscular synapse?
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What does the term 'depolarising block' refer to?
What does the term 'depolarising block' refer to?
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What happens to the voltage-sensitive sodium channels during the depolarising block?
What happens to the voltage-sensitive sodium channels during the depolarising block?
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What is the outcome of receptor desensitisation during prolonged nicotine exposure at a sympathetic ganglion?
What is the outcome of receptor desensitisation during prolonged nicotine exposure at a sympathetic ganglion?
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In the context of cholinergic transmission, what factor can partially restore electrical excitability after nicotine has acted for several minutes?
In the context of cholinergic transmission, what factor can partially restore electrical excitability after nicotine has acted for several minutes?
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What is the endplate potential (epp) in skeletal muscle fibres responsible for?
What is the endplate potential (epp) in skeletal muscle fibres responsible for?
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What characterizes the fast excitatory postsynaptic potential (fast epsp) at ganglionic synapses?
What characterizes the fast excitatory postsynaptic potential (fast epsp) at ganglionic synapses?
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Which ion influx is least significant in causing depolarisation at a postsynaptic membrane?
Which ion influx is least significant in causing depolarisation at a postsynaptic membrane?
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What type of transmission occurs at the skeletal neuromuscular junction?
What type of transmission occurs at the skeletal neuromuscular junction?
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Which neurotransmitter is mainly responsible for excitatory responses in both the skeletal neuromuscular junction and autonomic ganglia?
Which neurotransmitter is mainly responsible for excitatory responses in both the skeletal neuromuscular junction and autonomic ganglia?
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What is a characteristic effect of agonists acting on nicotinic receptors?
What is a characteristic effect of agonists acting on nicotinic receptors?
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Which of the following is a common antagonist at autonomic ganglia?
Which of the following is a common antagonist at autonomic ganglia?
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What effect does Varenicline have on nicotinic receptors?
What effect does Varenicline have on nicotinic receptors?
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Which cation is primarily involved in the increased permeability observed with nicotinic receptor activation?
Which cation is primarily involved in the increased permeability observed with nicotinic receptor activation?
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What is the primary excitatory response in many brain regions involving nicotinic receptors categorized as?
What is the primary excitatory response in many brain regions involving nicotinic receptors categorized as?
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What is the primary function of neuromuscular blockers?
What is the primary function of neuromuscular blockers?
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Which of the following drug classes specifically affects nicotinic receptors at the neuromuscular junction?
Which of the following drug classes specifically affects nicotinic receptors at the neuromuscular junction?
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What adverse effect is commonly associated with the use of neuromuscular blocking drugs?
What adverse effect is commonly associated with the use of neuromuscular blocking drugs?
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Which receptors are primarily targeted by organophosphate compounds?
Which receptors are primarily targeted by organophosphate compounds?
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What physiological effect can result from increased acetylcholine due to acetylcholinesterase inhibitors?
What physiological effect can result from increased acetylcholine due to acetylcholinesterase inhibitors?
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What is the primary mechanism of action for neuromuscular blocking agents?
What is the primary mechanism of action for neuromuscular blocking agents?
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In the context of cholinergic transmission, what happens to postsynaptic membrane potential following prolonged exposure to nicotine?
In the context of cholinergic transmission, what happens to postsynaptic membrane potential following prolonged exposure to nicotine?
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What is a significant clinical use of acetylcholinesterase inhibitors?
What is a significant clinical use of acetylcholinesterase inhibitors?
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What is the duration of action for Edrophonium?
What is the duration of action for Edrophonium?
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Which statement correctly describes the mechanism of carbamate esters?
Which statement correctly describes the mechanism of carbamate esters?
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Recovery from organophosphate poisoning depends on what process?
Recovery from organophosphate poisoning depends on what process?
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What is a typical clinical use for Edrophonium?
What is a typical clinical use for Edrophonium?
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Which of the following drugs is categorized as an organophosphate?
Which of the following drugs is categorized as an organophosphate?
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Which characteristic of Edrophonium limits its use for ongoing treatment?
Which characteristic of Edrophonium limits its use for ongoing treatment?
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Which type of bond is formed between organophosphates and acetylcholinesterase?
Which type of bond is formed between organophosphates and acetylcholinesterase?
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What is the expected duration of action for carbamate esters?
What is the expected duration of action for carbamate esters?
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What is the primary clinical use of pyridostigmine in the context of neuromuscular pharmacology?
What is the primary clinical use of pyridostigmine in the context of neuromuscular pharmacology?
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Which drug is used to reverse neuromuscular blockade after surgery?
Which drug is used to reverse neuromuscular blockade after surgery?
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What is the primary mechanism by which neostigmine reverses muscle paralysis?
What is the primary mechanism by which neostigmine reverses muscle paralysis?
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What is the duration of action for the drug ecothiophate when used topically?
What is the duration of action for the drug ecothiophate when used topically?
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What condition can malathion be used to treat?
What condition can malathion be used to treat?
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Which of the following is true regarding the action of non-depolarizing neuromuscular blocking agents (NMBAs)?
Which of the following is true regarding the action of non-depolarizing neuromuscular blocking agents (NMBAs)?
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Which of the following describes the role of acetylcholinesterase (AChE) in neuromuscular pharmacology?
Which of the following describes the role of acetylcholinesterase (AChE) in neuromuscular pharmacology?
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What type of toxicity is primarily associated with parathion?
What type of toxicity is primarily associated with parathion?
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What is the primary mechanism by which acetylcholinesterase inhibitors function?
What is the primary mechanism by which acetylcholinesterase inhibitors function?
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Which of the following effects is consistent with increased levels of acetylcholine due to acetylcholinesterase inhibitors?
Which of the following effects is consistent with increased levels of acetylcholine due to acetylcholinesterase inhibitors?
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How can cholinesterase inhibitors be classified based on their duration of action?
How can cholinesterase inhibitors be classified based on their duration of action?
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What are the potential cardiovascular effects of acetylcholinesterase inhibitors?
What are the potential cardiovascular effects of acetylcholinesterase inhibitors?
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At higher doses, what significant release becomes clinically relevant when administering acetylcholinesterase inhibitors?
At higher doses, what significant release becomes clinically relevant when administering acetylcholinesterase inhibitors?
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Which of the following best describes the interaction of acetylcholine with both nicotinic and muscarinic receptors?
Which of the following best describes the interaction of acetylcholine with both nicotinic and muscarinic receptors?
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Which of the following reactions could occur at the neuromuscular junction when acetylcholine levels are increased?
Which of the following reactions could occur at the neuromuscular junction when acetylcholine levels are increased?
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What effect do multiple doses of irreversible cholinesterase inhibitors typically lead to?
What effect do multiple doses of irreversible cholinesterase inhibitors typically lead to?
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Study Notes
Cholinergic Transmission
- Acetylcholine (ACh) acts on nicotinic (neuromuscular or ganglionic) synapses
- ACh causes influx of cations, particularly sodium (Na+) and potassium (K+), and calcium (Ca2+) to a lesser extent leading to depolarization of the postsynaptic membrane
- Depolarization of the postsynaptic membrane: leads to the endplate potential (epp) in a skeletal muscle fiber
- epp spreads along adjacent excitable parts of the muscle fiber
- Amplitude of the epp reaching the threshold for excitation initiates action potential, propagating contraction throughout the muscle
- Depolarization also causes a fast excitatory postsynaptic potential (fast epsp) at ganglionic synapses
- epsp's cause localized current flows, which may reach the axon hillock and trigger an action potential
Depolarizing Block
- Occurs when nicotinic acetylcholine receptors (nAChRs) are persistently activated
- Results in decreased electrical excitability of the postsynaptic cell
- Persistent activation of receptors by nicotine leads to initial depolarization and action potential firing, but eventually leads to cessation of firing and blockade of transmission
- Main reason for loss of electrical excitability is inactivation of voltage-sensitive sodium channels, preventing their opening upon stimulation
- Following prolonged nicotine exposure, the cell partially repolarizes, but transmission remains blocked, likely due to receptor desensitization.
Non Depolarizing Neuromuscular Blockers
- Examples include: Tubocurarine, Rocuronium, Pancuronium, Vecuronium, Cisatracurium, Atracurium
- Competitively antagonize nAChRs, blocking ACh binding and preventing muscle contraction
- Competitive nature allows for reversal of block with increased ACh concentrations at the neuromuscular junction
- This is why acetylcholinesterase inhibitors (AChEIs) are used to reverse neuromuscular blockade following surgery
- At high doses, non-depolarizing neuromuscular blockers cause physical blocking of the ion channel pore, leading to more intense motor blockade that is difficult to reverse with AChEIs
Acetylcholinesterase Inhibitors
- Increase ACh levels in the synapse and enhance cholinergic activity
- Ocular effects: can cause pupillary constriction (miosis) and contraction of the ciliary muscle
- Can enhance outflow of aqueous humor, making them potentially useful for treating glaucoma
- Organophosphates are examples of AChEIs, widely used as pesticides and insecticides
- Some organophosphates are chemical warfare agents
- Widely absorbed from skin, mucous membranes, and gut
- Lipophilicity leads to distribution throughout the body, including the CNS
- Organophosphate toxicity can occur after dermal, ocular, or oral exposure
Organophosphate Toxicity: Signs and Symptoms
- Increased ACh in the body activates both muscarinic and nicotinic receptors leading to a range of symptoms:
- Muscarinic Effects: Salivation, Lacrimation, Miosis, Accommodative spasm, Bronchoconstriction, Bradycardia, Hypotension, Emesis, Intestinal cramps, Diarrhoea, Urinary incontinence
- Nicotinic Effects: Depolarizing neuromuscular blockade, Muscle weakness, Respiratory muscle weakness, Fasciculations
- CNS Effects: Anxiety, Restlessness, Headaches, Seizures, Respiratory depression, Coma
Management of Organophosphate Toxicity
- Remove contaminated clothing and wash patient with soap and water
- Administer activated charcoal if within 1-2 hours of exposure
- Ensure adequate airway and intubate if necessary
- Administer Atropine: Antimuscarinic drug that binds to muscarinic receptors, acting as an antagonist
- Administer a cholinesterase reactivator: to restore cholinesterase enzyme activity
Nicotinic Receptors
- There are three types of Nicotinic receptors: muscle type, ganglion type, and CNS type
- The location for the muscle type is the skeletal neuromuscular junction, mainly postsynaptic
- The location for the ganglion type receptor is autonomic ganglia: mainly postsynaptic
- The location for the CNS type receptor is many brain regions: pre- and postsynaptic
- The membrane response for the muscle type is excitatory, increased cation permeability (mainly Na+, K+)
- The membrane response for the ganglion type is excitatory, increased cation permeability (mainly Na+, K+)
- The membrane response for the CNS type is pre- and postsynaptic excitation, increased cation permeability (mainly Na+, K+)
- Agonists for the Muscle type receptor are Acetylcholine, Carbachol, Succinylcholine
- Agonists for the Ganglion type receptor are Acetylcholine, Carbachol, Nicotine
- Agonists for the CNS type receptor are Nicotine, Epibatidine, Acetylcholine, Varenicline
- Antagonists for the Muscle type receptor are Tubocurarine, Pancuronium, Atracurium, Vecuronium
- Antagonists for the Ganglion type receptor are Mecamylamine, Trimetaphan, Hexamethonium
- Antagonists for the CNS type receptor are Mecamylamine, Methylaconitine
Acetylcholinesterase inhibitors
- AChE inhibitors are drugs that result in the activation of cholinergic receptors by not binding directly to muscarinic or nicotinic receptors
- These drugs increase acetylcholine (ACh) levels by inhibiting the breakdown of ACh by the enzyme acetylcholinesterase (AChE)
- These drugs increase the effects of ACh on both nicotinic and muscarinic receptors
- AChE inhibitors can be classified as reversible or irreversible depending on how strongly they bind to the enzyme
- Reversible cholinesterase inhibitors bind to the anionic site of AChE but do not form a covalent bond, allowing for easy reversibility
- Examples of reversible AChE inhibitors: Edrophonium, Neostigmine, Physostigmine, Pyridostigmine
- Irreversible cholinesterase inhibitors form a strong covalent bond with the catalytic site of AChE, making the bond very difficult to break
- Examples of irreversible AChE inhibitors: Ecothiophate, Parathion, Malathion, Isoflurophate
Clinical Uses of AChE inhibitors
- Edrophonium is mainly used to diagnose myasthenia gravis and can also be used to differentiate between a myasthenic crisis and a cholinergic crisis
- Neostigmine and Pyridostigmine are used to treat myasthenia gravis
- Neostigmine and Pyridostigmine can also be used to reverse the effects of neuromuscular blocking agents, which are used to cause paralysis during surgery
- Ecothiophate is used topically to treat glaucoma
- Parathion is an insecticide that can cause toxicity in humans
- Malathion is used topically to treat head lice
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Description
Explore the intricate mechanisms of cholinergic transmission involving acetylcholine and nicotinic receptors. Understand how depolarization affects postsynaptic membranes and the implications of persistent receptor activation leading to depolarizing block. This quiz covers key concepts essential for grasping neuromuscular and ganglionic synapse functions.
