Cholinergic Transmission and Depolarizing Block
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Questions and Answers

What is the primary mechanism of action of succinylcholine?

  • It causes direct stimulation of muscle contraction.
  • It is hydrolyzed faster than acetylcholine in the plasma.
  • It inhibits acetylcholinesterase.
  • It competes with acetylcholine at the neuromuscular junction. (correct)

    • Which of the following is a characteristic of the neuromuscular blockade caused by succinylcholine?

  • It can be reversed by acetylcholinesterase inhibitors. (correct)
  • It typically lasts more than 30 minutes.
  • It is associated with significant respiratory muscle paralysis. (correct)
  • It causes prolonged muscle contractions before paralysis.

    • What is the primary reason for post-operative muscle pain associated with succinylcholine use?

  • Increased pressure in the muscle tissue.
  • Direct damage to the muscles during surgery.
  • Initial muscle contraction and fasciculations. (correct)
  • Formation of antibodies against muscle fibers.

    • What serious condition can result from a mutation of the ryanodine receptor when succinylcholine is administered?

    <p>Malignant hyperthermia presenting with muscle spasms.</p> Signup and view all the answers

    What is the typical duration of neuromuscular block caused by succinylcholine?

    <p>Less than 10 minutes.</p> Signup and view all the answers

    Which of the following effects is associated with succinylcholine administration?

    <p>Bradycardia due to increased myocardial stimulation.</p> Signup and view all the answers

    What is the treatment for malignant hyperthermia?

    <p>Dantrolene to inhibit Ca2+ release.</p> Signup and view all the answers

    Which statement regarding potassium release during succinylcholine administration is accurate?

    <p>It leads to hyperkalemia from muscle fasciculations.</p> Signup and view all the answers

    What initiates an action potential in a skeletal muscle fiber?

    <p>Endplate potential reaching threshold</p> Signup and view all the answers

    What role does Ca2+ play in the depolarization of the postsynaptic membrane at a neuromuscular synapse?

    <p>It causes a lesser depolarization compared to Na+ and K+</p> Signup and view all the answers

    What occurs during a depolarizing block?

    <p>Persistent activation of nAChRs leads to decreased excitability</p> Signup and view all the answers

    What is primarily responsible for the secondary block known as phase II block?

    <p>Receptor desensitization</p> Signup and view all the answers

    What must occur for an excitatory postsynaptic potential (EPSP) to lead to an action potential at the axon hillock?

    <p>EPSP must be large enough to depolarize the region</p> Signup and view all the answers

    What happens to the electrical excitability of a cell after prolonged exposure to nicotine?

    <p>It partially recovers but remains blocked</p> Signup and view all the answers

    Which of the following ions is primarily responsible for causing depolarization in the postsynaptic membrane when ACh acts on nAChRs?

    <p>Sodium (Na+)</p> Signup and view all the answers

    What determines the threshold for initiating an action potential at the skeletal muscle fiber?

    <p>Amplitude of the endplate potential</p> Signup and view all the answers

    Which of the following is a potential sign of cholinergic toxicity related to muscarinic effects?

    <p>Salivation</p> Signup and view all the answers

    What is a common CNS effect of cholinergic toxicity?

    <p>Restlessness</p> Signup and view all the answers

    Which management step is essential immediately after exposure to cholinergic agents?

    <p>Administer activated charcoal</p> Signup and view all the answers

    What role does atropine play in managing cholinergic toxicity?

    <p>It binds to muscarinic receptors</p> Signup and view all the answers

    Which of the following symptoms is associated with nicotinic effects of cholinergic toxicity?

    <p>Fasciculations</p> Signup and view all the answers

    What is the primary action of cholinesterase reactivators in the context of toxicity?

    <p>To restore function of cholinesterase</p> Signup and view all the answers

    Which of these is NOT a treatment step for cholinergic toxicity?

    <p>Administer intravenous fluids</p> Signup and view all the answers

    Which muscarinic effect can lead to respiratory complications?

    <p>Bronchoconstriction</p> Signup and view all the answers

    What is a potential cardiovascular effect of acetylcholinesterase inhibitors?

    <p>May cause tachycardia and hypertension</p> Signup and view all the answers

    Which class of drugs directly prevents the breakdown of acetylcholine?

    <p>Irreversible cholinesterase inhibitors</p> Signup and view all the answers

    What are the effects of acetylcholinesterase inhibitors on cholinergic receptors?

    <p>They increase binding to nicotinic and muscarinic receptors</p> Signup and view all the answers

    What defines reversible cholinesterase inhibitors compared to irreversible ones?

    <p>They have a weaker binding to the cholinesterase enzyme</p> Signup and view all the answers

    Which organ system effects are induced by acetylcholinesterase inhibitors?

    <p>Parasympathomimetic effects across multiple organ systems</p> Signup and view all the answers

    What is the main mechanism by which acetylcholinesterase inhibitors exert their effects?

    <p>By preventing acetylcholine breakdown</p> Signup and view all the answers

    How do acetylcholinesterase inhibitors affect cardiovascular function?

    <p>They can result in both bradycardia and hypertension</p> Signup and view all the answers

    Which of the following is NOT a characteristic of irreversible cholinesterase inhibitors?

    <p>They can be reversed with antidotes</p> Signup and view all the answers

    What is the criterion for adequate therapy with atropine?

    <p>Control of bronchial and oral secretions</p> Signup and view all the answers

    What must be done as the patient's condition improves while on atropine?

    <p>Reduce the dose slowly over 24 hours or longer</p> Signup and view all the answers

    What is the mechanism of action of pralidoxime and obidoxime?

    <p>They reactivate AChE by luring the phosphate group away from the serine hydroxyl group</p> Signup and view all the answers

    How soon must pralidoxime and obidoxime be administered following exposure to organophosphates?

    <p>Within 24 hours</p> Signup and view all the answers

    What type of receptor does atropine primarily affect?

    <p>Muscarinic receptors</p> Signup and view all the answers

    What is a common use of acetylcholine esterase inhibitors?

    <p>To enhance cholinergic transmission</p> Signup and view all the answers

    What characterizes a neuromuscular blocking drug (NMB)?

    <p>They inhibit acetylcholine release at the neuromuscular junction</p> Signup and view all the answers

    Which of the following is NOT a sign of organophosphate poisoning?

    <p>Increased muscle strength</p> Signup and view all the answers

    What is a common clinical effect of ganglion-blocking drugs?

    <p>Hypotension</p> Signup and view all the answers

    Which of the following mechanisms describes how nicotine can block ganglia?

    <p>By prolonged depolarization</p> Signup and view all the answers

    What major effect occurs when both sympathetic and parasympathetic divisions are inhibited by ganglion blockers?

    <p>Impaired micturition</p> Signup and view all the answers

    What is the primary use of neuromuscular blocking drugs (NMBs)?

    <p>To cause skeletal muscle paralysis</p> Signup and view all the answers

    What effect is commonly associated with the use of ganglion-blocking drugs historically?

    <p>Reduction in circulating catecholamines</p> Signup and view all the answers

    What is a significant drawback of using ganglion-blocking drugs in clinical settings?

    <p>Broad range of undesirable effects</p> Signup and view all the answers

    Which receptors do neuromuscular blocking drugs primarily act upon?

    <p>Nm receptors at the neuromuscular junction</p> Signup and view all the answers

    Why are ganglion-blocking drugs no longer used clinically?

    <p>Their broad range of effects can be undesirable.</p> Signup and view all the answers

    What is the primary effect of ganglionic blockers on the autonomic nervous system?

    <p>Inhibit both sympathetic and parasympathetic pathways</p> Signup and view all the answers

    Which of the following describes the action of neuromuscular blockers?

    <p>Induce muscle paralysis by acting on somatic nicotinic receptors</p> Signup and view all the answers

    What are the clinical uses of acetylcholinesterase inhibitors?

    <p>To treat organophosphate poisoning and myasthenia gravis</p> Signup and view all the answers

    What results from the inhibition of acetylcholinesterase in the body?

    <p>Prolonged action of acetylcholine at the neuromuscular junction</p> Signup and view all the answers

    Which statement accurately reflects the physiological effects of organophosphate poisoning?

    <p>Excessive stimulation of muscarinic and nicotinic receptors</p> Signup and view all the answers

    What are the primary sites of action for cholinergic antagonists?

    <p>At both sympathetic and parasympathetic pathways</p> Signup and view all the answers

    What distinguishes neuromuscular blockers from ganglionic blockers?

    <p>NMBs only block nicotinic receptors in the somatic nervous system</p> Signup and view all the answers

    Which class of drugs is primarily used to reverse the effects of acetylcholinesterase inhibitors?

    <p>Cholinesterase reactivators</p> Signup and view all the answers

    In which circumstance can succinylcholine's duration of action be significantly prolonged?

    <p>Presence of genetic variants of plasma cholinesterase</p> Signup and view all the answers

    What effect does acetylcholinesterase inhibitors have on succinylcholine's action?

    <p>It prolongs succinylcholine's duration of action</p> Signup and view all the answers

    Which of the following neuromuscular blocking agents has the shortest duration of action?

    <p>Succinylcholine</p> Signup and view all the answers

    What is the primary route of elimination for succinylcholine?

    <p>Plasma cholinesterase hydrolysis</p> Signup and view all the answers

    In which population might you expect decreased plasma cholinesterase activity, affecting succinylcholine duration?

    <p>Neonates</p> Signup and view all the answers

    Which of the following neuromuscular blockers is eliminated through spontaneous chemical degradation?

    <p>Cisatracurium</p> Signup and view all the answers

    Which neuromuscular blocking agent is primarily removed through renal excretion?

    <p>Vecuronium</p> Signup and view all the answers

    What happens to the duration of action of succinylcholine in individuals with severe deficiency of plasma cholinesterase?

    <p>Increases to more than 2 hours</p> Signup and view all the answers

    What is the main effect of competitive antagonists at Nm receptors in neuromuscular blocking?

    <p>Prevent acetylcholine binding</p> Signup and view all the answers

    Which of the following non-depolarizing neuromuscular blockers is derived from plants used by native South Americans?

    <p>Tubocurarine</p> Signup and view all the answers

    What is the primary reason why neuromuscular blockers are administered intravenously?

    <p>To achieve faster onset of action</p> Signup and view all the answers

    How do increasing concentrations of acetylcholine affect neuromuscular blockade?

    <p>They displace neuromuscular blockers, restoring muscle contraction</p> Signup and view all the answers

    Which of the following statements about curariform drugs is accurate?

    <p>They are competitive antagonists at nicotinic receptors</p> Signup and view all the answers

    What complication arises at high doses of neuromuscular blockers?

    <p>Physical blocking of ion channel pores</p> Signup and view all the answers

    What role do acetylcholinesterase inhibitors play after surgery when neuromuscular blockers are used?

    <p>They help reverse neuromuscular blockade</p> Signup and view all the answers

    Which of the following is an effect of curare and its derivatives?

    <p>They cause paralysis by blocking Nm receptors</p> Signup and view all the answers

    What effect does increased acetylcholine have on the iris sphincter muscle?

    <p>Produces pupil constriction (miosis)</p> Signup and view all the answers

    What is the role of the ciliary muscle when acetylcholine is increased?

    <p>It contracts to focus on close objects</p> Signup and view all the answers

    Which phenomenon occurs due to the enhanced outflow of aqueous humor?

    <p>Decreased intraocular pressure</p> Signup and view all the answers

    What is one therapeutic use of organophosphate compounds in humans?

    <p>For the treatment of glaucoma</p> Signup and view all the answers

    What is a common toxic effect of organophosphate exposure?

    <p>Neurological symptoms due to CNS involvement</p> Signup and view all the answers

    What counteracts the effects of pilocarpine in the eye?

    <p>Atropine</p> Signup and view all the answers

    What is a primary characteristic of organophosphate compounds?

    <p>High lipid solubility, enabling rapid absorption</p> Signup and view all the answers

    Which is a consequence of cholinesterase inhibition by organophosphates?

    <p>Prolonged action of acetylcholine at receptors</p> Signup and view all the answers

    Study Notes

    Cholinergic Transmission

    • Acetylcholine (ACh) acts on nicotinic receptors at neuromuscular junctions and ganglionic synapses.
    • ACh binding causes an influx of cations (sodium, potassium, and calcium), leading to depolarization of the postsynaptic membrane.
    • At the neuromuscular junction, this depolarization initiates an action potential, which propagates along the muscle fiber, causing contraction
    • At ganglionic synapses, depolarization triggers action potentials, initiating nerve impulses.

    Depolarizing Block

    • Results from persistent activation of nicotinic acetylcholine receptors (nAChRs).
    • This leads to a decrease in electrical excitability of the postsynaptic cell.
    • As voltage–sensitive sodium channels become inactivated, the cell is unable to respond to subsequent stimuli.
    • Desensitization of nAChRs also contributes to the block.
    • This is similar to a non-depolarizing block and may be reversed by acetylcholinesterase inhibitors.

    Succinylcholine

    • A depolarizing neuromuscular blocking agent.
    • Hydrolyzed by plasma and liver cholinesterase.
    • Metabolism occurs faster than non-depolarizing neuromuscular blocking agents.
    • Typically lasts less than 10 minutes.
    • Paralysis occurs in a specific order, starting with the chest and abdomen, followed by arms, neck, legs, and finally respiratory muscles.

    Adverse Effects of Succinylcholine

    • Post-operative muscle pain: Due to initial muscle contraction and fasciculations.
    • Bradycardia: Can be caused by direct myocardial effects, increased muscarinic stimulation, and ganglionic stimulation.
    • Potassium release: During administration, potassium is released from muscles, likely due to fasciculations.
    • Increased intraocular pressure: Caused by tonic contraction of myofibrils or transient dilation of ocular choroidal blood vessels.
    • Malignant hyperthermia: A rare inherited condition caused by a mutation of the ryanodine receptor.

    Acetylcholinesterase Inhibitors

    • Indirect-acting ACh receptor agonists.
    • Do not directly bind to muscarinic or nicotinic receptors.
    • Inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
    • This increases ACh levels at cholinergic synapses.

    Effects Of Cholinesterase Inhibition

    • Increase in ACh levels leads to interaction with both N and M receptors.
    • This results in increased cholinergic/parasympathetic effects.
    • Effects mimic those of direct-acting cholinomimetic agents, affecting the ocular, cardiovascular, respiratory, gastrointestinal, and urinary systems.

    Toxicity

    • Muscarinic effects include salivation, lacrimation, miosis, accomodative spasm, bronchoconstriction, bradycardia, hypotension, emesis, intestinal cramps, and diarrhea.
    • Nicotinic effects include depolarizing neuromuscular blockade, resulting in muscle weakness, respiratory muscle weakness, fasciculations.
    • Central nervous system effects include anxiety, restlessness, headaches, seizures, respiratory depression, and coma.

    Management of Toxicity

    • Remove contaminated clothing and wash the patient with soap and water.
    • Administer activated charcoal if within 1-2 hours of exposure.
    • Atropine: An antimuscarinic drug that blocks muscarinic receptors to reduce muscarinic effects of toxicity.
    • Pralidoxime or obidoxime: Reactivates AChE by removing the phosphate group from the enzyme.

    Key Points:

    • Cholinergic transmission is mediated by ACh and its interaction with nicotinic and muscarinic receptors.
    • Depolarizing neuromuscular blockers act by persistently activating nAChRs, leading to a block of transmission.
    • Acetylcholinesterase inhibitors increase ACh levels at cholinergic synapses, leading to exaggerated cholinergic effects.
    • Organophosphate poisoning can be life-threatening and requires immediate medical intervention.

    Nicotinic Receptors

    • Nicotinic receptors are found in autonomic ganglia and skeletal muscles.
    • There are two main subtypes: Nn (neuronal) and Nm (muscle).
    • Both subtypes are inhibited by the following:
      • Ganglion Blockers
      • Neuromuscular Blockers

    Ganglion Blockers

    • Ganglion blockers are obsolete for therapeutic use.
    • The clinical use of ganglion blockers is currently limited to research purposes.
    • They are used to study the autonomic nervous system.
    • They work by blocking the transmission of nerve impulses in autonomic ganglia, which results in a decrease in both sympathetic and parasympathetic activity.
    • Ganglion blockers can cause a wide range of effects including hypotension and loss of cardiovascular reflexes, inhibition of secretions, gastrointestinal paralysis, and impaired micturition.

    Neuromuscular Blocking Drugs (NMBs)

    • NMBs primarily cause skeletal muscle paralysis.
    • NMBs are used as adjuncts during general anesthesia.
    • NMBs facilitate endotracheal intubation and optimize surgical conditions.
    • NMBs lack CNS activity.

    Non-Depolarising Neuromuscular Blockers

    • Non-depolarising NMBs are competitive antagonists at NM receptors.
    • They block ACh binding, which prevents skeletal muscle contraction.
    • Increasing ACh concentrations can displace NMBs from the receptor, which can restore muscle contraction.
    • Acetylcholinesterase inhibitors (AChE-I’s) are used to reverse neuromuscular blockade after surgery, by increasing ACh concentration at the NMJ.

    Depolarising Neuromuscular Blockers

    • Succinylcholine is the only clinically relevant depolarizing neuromuscular blocking drug.
    • Succinylcholine acts as an agonist at the nicotinic acetylcholine receptor on skeletal muscle, causing depolarization and a brief period of fasciculations.
    • Succinylcholine is hydrolysed by cholinesterase in the plasma, resulting in a short duration of action (2-6 minutes).
    • AChE-I’s can prolong the action of succinylcholine.

    Acetylcholinesterase Inhibitors (AChE-I’s)

    • AChE-I’s prolong the action of ACh, by inhibiting the breakdown of acetylcholine at the synaptic cleft.
    • Increased ACh levels can reverse neuromuscular blockade induced by non-depolarising NMBs.
    • AChE-I’s are also used in the treatment of myasthenia gravis, Alzheimer's disease, and glaucoma

    Organophosphate Poisoning

    • Organophosphates are used as pesticides, insecticides, and chemical warfare agents.
    • They are highly lipid soluble and are effectively absorbed from all sites in the body, including the skin, mucous membranes, and gut.
    • They can cause accidental or intentional poisoning.
    • They inhibit acetylcholinesterase, leading to an accumulation of acetylcholine at cholinergic synapses.
    • The accumulation of acetylcholine leads to a variety of clinical manifestations, including:
      • Muscarinic effects:
        • Salivation
        • Lacrimation
        • Urination
        • Defecation
        • Gastrointestinal distress
        • Bronchoconstriction
        • Bradycardia
        • Pupil constriction
      • Nicotinic effects:
        • Muscle fasciculations
        • Weakness
        • Paralysis
        • Hypertension
      • CNS effects:
        • Headache
        • Drowsiness
        • Confusion
        • Seizures
        • Coma
    • Organophosphate poisoning is a medical emergency requiring immediate treatment.
    • Atropine is used to block the effects of acetylcholine on muscarinic receptors.
    • Pralidoxime is an antidote that reactivates acetylcholinesterase.

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    Description

    This quiz covers the fundamentals of cholinergic transmission, exploring the role of acetylcholine at neuromuscular junctions and ganglionic synapses. Additionally, it examines the mechanisms of depolarizing blocks and the effects of succinylcholine on nicotinic acetylcholine receptors. Test your understanding of these critical concepts in neurophysiology.

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