Nervous System Introduction
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Questions and Answers

What is the main function of afferent neurons in the peripheral nervous system?

  • Carry signals away from the brain and spinal cord to peripheral tissues
  • Bring information from the periphery to the CNS (correct)
  • Regulate digestion and cardiac output
  • Control the contraction of skeletal muscles

    • Which part of the nervous system is composed of the brain and spinal cord?

  • Afferent division
  • Peripheral nervous system
  • Central nervous system (CNS) (correct)
  • Efferent division

    • What is the other name for the Autonomic Nervous System (ANS)?

  • Visceral nervous system (correct)
  • Peripheral nervous system
  • Central nervous system
  • Somatic nervous system

    • What type of muscles are innervated by the ANS?

    <p>Both b and c</p> Signup and view all the answers

    Which type of neurons carry signals away from the brain and spinal cord to peripheral tissues?

    <p>Efferent neurons</p> Signup and view all the answers

    What is the function of the somatic efferent neurons?

    <p>Voluntary control of skeletal muscles</p> Signup and view all the answers

    What are the two types of efferent neurons in the ANS?

    <p>Preganglionic and postganglionic neurons</p> Signup and view all the answers

    Where is the cell body of a preganglionic neuron located?

    <p>Within the CNS</p> Signup and view all the answers

    Where do the preganglionic neurons emerge from?

    <p>Brainstem and spinal cord</p> Signup and view all the answers

    What type of neurons are responsible for reflex regulation of the ANS?

    <p>Afferent neurons</p> Signup and view all the answers

    Where do the preganglionic neurons of the sympathetic system originate from?

    <p>Thoracic and lumbar regions of the spinal cord</p> Signup and view all the answers

    What is the function of the adrenal medulla?

    <p>To secrete epinephrine and norepinephrine into the blood</p> Signup and view all the answers

    What is the main difference between the sympathetic and parasympathetic nervous systems?

    <p>Length of preganglionic and postganglionic neurons</p> Signup and view all the answers

    What is the function of the enteric nervous system?

    <p>To control the motility, exocrine and endocrine secretions, and microcirculation of the GI tract</p> Signup and view all the answers

    What is the sympathetic nervous system responsible for?

    <p>All of the above</p> Signup and view all the answers

    Where do the postganglionic neurons originate from?

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

    What is the vagus nerve responsible for?

    <p>Innervating most of the organs in the thoracic and abdominal cavity</p> Signup and view all the answers

    What is the characteristic of the sympathetic nervous system that allows it to activate numerous effector organs at the same time?

    <p>Highly branched preganglionic nerve endings</p> Signup and view all the answers

    What is a common characteristic of neurotransmitters and most hormones and local mediators?

    <p>They are hydrophilic</p> Signup and view all the answers

    What is the function of receptors on the cell surface of target organs?

    <p>To mediate the signal of neurotransmitters</p> Signup and view all the answers

    Which nerve is the predominant factor in controlling heart rate?

    <p>Vagus nerve</p> Signup and view all the answers

    Which of the following neurotransmitters is NOT commonly involved in the actions of therapeutically useful drugs?

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

    What type of antagonism is seen in the control of homeostatic organ functions?

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

    What type of neurotransmitter is released by autonomic nerve fibers in the parasympathetic nervous system?

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

    Which of the following organs receives only sympathetic innervation?

    <p>Adrenal medulla</p> Signup and view all the answers

    What is the term for a neuron that releases acetylcholine as a neurotransmitter?

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

    What is the main difference between the somatic nervous system and the ANS?

    <p>Voluntary control</p> Signup and view all the answers

    What is the characteristic of the sympathetic preganglionic fibers?

    <p>Broad distribution</p> Signup and view all the answers

    Which system is responsible for transmitting nerve impulses across autonomic ganglia?

    <p>Autonomic nervous system</p> Signup and view all the answers

    What is the characteristic of the parasympathetic division?

    <p>Limited distribution</p> Signup and view all the answers

    What is the term for a neuron that releases norepinephrine as a neurotransmitter?

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

    What is the function of the myelination of the motor nerves?

    <p>Enables a fast response</p> Signup and view all the answers

    In which system does transmission involve the release of acetylcholine from the autonomic postganglionic nerves to the effector organs?

    <p>Parasympathetic nervous system</p> Signup and view all the answers

    What is the main function of neurotransmitters?

    <p>To communicate between nerve cells</p> Signup and view all the answers

    What is the process by which neurotransmitters are released from the nerve terminals?

    <p>Fusion of synaptic vesicles with the presynaptic membrane</p> Signup and view all the answers

    What is the characteristic of local mediators?

    <p>Act locally on cells in the immediate environment</p> Signup and view all the answers

    What is the primary effect of sympathetic output on the heart?

    <p>Increase heart rate</p> Signup and view all the answers

    What is the 'fight-or-flight' response triggered by?

    <p>Direct sympathetic activation of the effector organs and stimulation of the adrenal medulla</p> Signup and view all the answers

    What is the primary function of the parasympathetic nervous system?

    <p>To maintain homeostasis within the body</p> Signup and view all the answers

    What is the role of the CNS in the control of autonomic functions?

    <p>To provide sensory input to the ANS</p> Signup and view all the answers

    What is the primary function of reflex arcs in the ANS?

    <p>To translate afferent impulses into reflex responses</p> Signup and view all the answers

    What is the result of increased sympathetic output to the heart and vasculature?

    <p>An increase in blood pressure and tachycardia</p> Signup and view all the answers

    What is the effect of sympathetic stimulation on the pupils?

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

    What is the effect of parasympathetic stimulation on the heart rate?

    <p>Decrease heart rate</p> Signup and view all the answers

    What is the characteristic of the parasympathetic nervous system?

    <p>It never discharges as a complete system</p> Signup and view all the answers

    What is the characteristic of most organs in the body?

    <p>They are innervated by both divisions of the ANS</p> Signup and view all the answers

    What is the role of voltage-sensitive calcium channels in the release of acetylcholine?

    <p>To increase the concentration of intracellular calcium, promoting the fusion of synaptic vesicles with the cell membrane</p> Signup and view all the answers

    What is the effect of botulinum toxin on the release of acetylcholine?

    <p>It blocks the release of ACh</p> Signup and view all the answers

    What is the function of postsynaptic cholinergic receptors on the surface of effector organs?

    <p>To bind to ACh and initiate a nerve impulse</p> Signup and view all the answers

    What is the role of acetylcholinesterase (AChE) in the synapse?

    <p>To break down ACh into choline and acetate</p> Signup and view all the answers

    What is the function of the sodium-coupled high-affinity uptake system in the neuron?

    <p>To transport choline back into the neuron and recycle it into ACh</p> Signup and view all the answers

    What is the effect of the toxin in black widow spider venom on the release of ACh?

    <p>It causes all the ACh stored in synaptic vesicles to empty into the synaptic gap</p> Signup and view all the answers

    What is the role of muscarinic and nicotinic receptors in the postsynaptic response?

    <p>To bind to ACh and initiate a biological response</p> Signup and view all the answers

    What is the function of butyrylcholinesterase (pseudocholinesterase) in the body?

    <p>To break down ACh into choline and acetate in the plasma</p> Signup and view all the answers

    What is the role of choline acetyltransferase in the synthesis of acetylcholine?

    <p>It catalyzes the reaction of choline with acetyl coenzyme A to form ACh</p> Signup and view all the answers

    What is the rate-limiting step in ACh synthesis?

    <p>The transport of choline into the cytoplasm of the cholinergic neuron</p> Signup and view all the answers

    What is the primary neurotransmitter in the postganglionic sympathetic division of sweat glands?

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

    What is the function of the presynaptic vesicles in cholinergic neurons?

    <p>To store and release acetylcholine</p> Signup and view all the answers

    What is the effect of hemicholinium on the synthesis of acetylcholine?

    <p>It inhibits the transport of choline into the cytoplasm</p> Signup and view all the answers

    What is the characteristic of the cholinergic neurons that innervate the muscles of the somatic system?

    <p>They use acetylcholine as a neurotransmitter</p> Signup and view all the answers

    What is the significance of the quaternary nitrogen in choline?

    <p>It gives choline a permanent positive charge</p> Signup and view all the answers

    What is the function of adenosine triphosphate and proteoglycan in the presynaptic vesicles?

    <p>They are packaged and stored in the presynaptic vesicles</p> Signup and view all the answers

    What is the effect of activating the M2 subtype on cardiac muscle?

    <p>Decrease in heart rate and force of contraction</p> Signup and view all the answers

    What is the function of protein kinase C?

    <p>To phosphorylate numerous proteins within the cell</p> Signup and view all the answers

    What is the effect of nicotine at low concentration on nicotinic receptors?

    <p>It stimulates the receptor</p> Signup and view all the answers

    What is the function of muscarinic agonists in clinical practice?

    <p>To treat xerostomia and glaucoma</p> Signup and view all the answers

    What is the characteristic of nicotinic receptors in the NMJ?

    <p>They are specifically blocked by atracurium</p> Signup and view all the answers

    What is the effect of activation of M1 receptor agonists?

    <p>Treatment of Alzheimer's disease</p> Signup and view all the answers

    What is the function of nicotinic receptors in the autonomic ganglia?

    <p>To regulate the transmission of nerve impulses</p> Signup and view all the answers

    What is the characteristic of M3 receptor antagonists?

    <p>They are being investigated for the treatment of chronic obstructive pulmonary disease</p> Signup and view all the answers

    What type of receptors are muscarinic receptors classified as?

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

    What is the primary mechanism of acetylcholine signal transduction in muscarinic receptors?

    <p>Interaction with G protein, leading to activation of phospholipase C</p> Signup and view all the answers

    Where are muscarinic receptors primarily found?

    <p>On the surface of ganglia of the peripheral nervous system and on autonomic effector organs</p> Signup and view all the answers

    What is the effect of IP3 on the cell?

    <p>It causes an increase in intracellular calcium</p> Signup and view all the answers

    What is the role of diacylglycerol (DAG) in muscarinic signal transduction?

    <p>It is a second messenger that can stimulate or inhibit enzymes</p> Signup and view all the answers

    Which of the following muscarinic receptors are also found on gastric parietal cells?

    <p>M1 receptors</p> Signup and view all the answers

    What is the characteristic of muscarinic receptors in terms of their affinity for nicotine?

    <p>They have a low affinity for nicotine</p> Signup and view all the answers

    What is the term for the substances that mimic the action of acetylcholine?

    <p>Cholinomimetic agents</p> Signup and view all the answers

    What is the result of ACh activating M3 receptors on endothelial cells?

    <p>Production of nitric oxide</p> Signup and view all the answers

    What is the effect of ACh on the detrusor muscle in the genitourinary tract?

    <p>Increases the tone of the detrusor muscle</p> Signup and view all the answers

    What is the function of ACh in the eye during ophthalmic surgery?

    <p>Constricts the pupil</p> Signup and view all the answers

    Why does atropine prevent ACh from producing vasodilation?

    <p>Atropine blocks muscarinic receptors</p> Signup and view all the answers

    What is the effect of ACh on intestinal secretions and motility?

    <p>Increases intestinal secretions and motility</p> Signup and view all the answers

    What is the reason why ACh is not released into the blood in significant quantities?

    <p>ACh has no known function in the vascular system</p> Signup and view all the answers

    Which of the following is a characteristic of direct-acting cholinergic agonists?

    <p>They have a longer duration of action than ACh.</p> Signup and view all the answers

    What is the effect of acetylcholine on the heart?

    <p>It decreases heart rate and cardiac output.</p> Signup and view all the answers

    Which of the following is a type of direct-acting cholinergic agonist?

    <p>Naturally occurring alkaloids</p> Signup and view all the answers

    What is the effect of acetylcholine on blood pressure?

    <p>It decreases blood pressure.</p> Signup and view all the answers

    Which of the following is a characteristic of pilocarpine and bethanechol?

    <p>They preferentially bind to muscarinic receptors.</p> Signup and view all the answers

    What is the main problem with the therapeutic use of direct-acting cholinergic agonists?

    <p>They show little specificity in their actions.</p> Signup and view all the answers

    What is the location of muscarinic receptors?

    <p>Primarily at the neuroeffector junction of the parasympathetic nervous system.</p> Signup and view all the answers

    What is the effect of acetylcholine on the sinoatrial (SA) node?

    <p>It decreases the rate of firing at the SA node.</p> Signup and view all the answers

    What is the effect of bethanechol on the detrusor muscle of the bladder?

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

    Why is bethanechol not hydrolyzed by AChE?

    <p>Due to the esterification of carbamic acid</p> Signup and view all the answers

    What is the duration of action of bethanechol?

    <p>1 hour</p> Signup and view all the answers

    What is the therapeutic application of bethanechol in urologic treatment?

    <p>All of the above</p> Signup and view all the answers

    What is the effect of carbachol on the cardiovascular and GI systems?

    <p>It first stimulates and then depresses both systems</p> Signup and view all the answers

    Why is carbachol biotransformed by other esterases?

    <p>Because it is a poor substrate for AChE</p> Signup and view all the answers

    What is the effect of carbachol on the release of epinephrine from the adrenal medulla?

    <p>It stimulates the release of epinephrine</p> Signup and view all the answers

    What is the treatment for severe cardiovascular or bronchoconstrictor responses to bethanechol?

    <p>Administration of atropine sulfate</p> Signup and view all the answers

    What is a common characteristic of neurotransmitters and most hormones and local mediators?

    <p>They can have both excitatory and inhibitory effects</p> Signup and view all the answers

    What is the primary effect of sympathetic output on the heart?

    <p>Increased heart rate</p> Signup and view all the answers

    What is the therapeutic use of echothiophate?

    <p>Treatment of open-angle glaucoma</p> Signup and view all the answers

    What is the result of increased sympathetic output to the heart and vasculature?

    <p>Vasoconstriction and increased blood pressure</p> Signup and view all the answers

    What is the effect of parasympathetic stimulation on the heart rate?

    <p>Decreased heart rate</p> Signup and view all the answers

    What is the primary function of reflex arcs in the ANS?

    <p>Regulation of autonomic functions</p> Signup and view all the answers

    What is the role of pralidoxime in treating organophosphate poisoning?

    <p>It reacts with the organophosphate to regenerate AChE</p> Signup and view all the answers

    What is the characteristic of the parasympathetic nervous system?

    <p>It has a shorter preganglionic fiber</p> Signup and view all the answers

    What is the effect of echothiophate on intraocular pressure?

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

    What is the primary use of anticholinesterase agents?

    <p>Treatment of Alzheimer's disease</p> Signup and view all the answers

    What is the primary action of edrophonium on the active center of AChE?

    <p>Reversible binding</p> Signup and view all the answers

    What is the duration of action of edrophonium?

    <p>10 to 20 minutes</p> Signup and view all the answers

    What is the primary therapeutic use of physostigmine?

    <p>Treatment of overdoses of drugs with anticholinergic actions</p> Signup and view all the answers

    What is the primary difference between physostigmine and neostigmine?

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

    What is the therapeutic use of neostigmine?

    <p>All of the above</p> Signup and view all the answers

    What is the characteristic of pyridostigmine and ambenonium?

    <p>Intermediate duration of action</p> Signup and view all the answers

    What is the primary adverse effect of neostigmine?

    <p>Generalized cholinergic stimulation</p> Signup and view all the answers

    What is the contraindication for neostigmine?

    <p>Both A and B</p> Signup and view all the answers

    What is the primary difference between edrophonium and neostigmine?

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

    What is the primary action of cholinesterase inhibitors?

    <p>Potentiation of cholinergic activity</p> Signup and view all the answers

    What is the effect of carbachol on the eye?

    <p>It causes miosis and a spasm of accommodation</p> Signup and view all the answers

    What is the advantage of pilocarpine compared to ACh and its derivatives?

    <p>It is uncharged and can penetrate the CNS at therapeutic doses</p> Signup and view all the answers

    What is the therapeutic use of pilocarpine in glaucoma?

    <p>To treat both open-angle and angle-closure glaucoma</p> Signup and view all the answers

    What is the effect of anticholinesterase agents?

    <p>They decrease the breakdown of ACh</p> Signup and view all the answers

    What is the characteristic of edrophonium?

    <p>It is a short-acting AChE inhibitor</p> Signup and view all the answers

    What is the result of using pilocarpine to treat glaucoma?

    <p>A decrease in intraocular pressure</p> Signup and view all the answers

    What is the effect of pilocarpine on salivation?

    <p>It increases salivation</p> Signup and view all the answers

    What is the advantage of carbachol compared to pilocarpine?

    <p>It is more potent and receptor non-selective</p> Signup and view all the answers

    What is the treatment for poisoning with pilocarpine?

    <p>Administering atropine</p> Signup and view all the answers

    What is the effect of anticholinesterase agents on the body?

    <p>They stimulate both muscarinic and nicotinic receptors</p> Signup and view all the answers

    What type of receptors do antimuscarinic agents block?

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

    What is the effect of antimuscarinic agents on sympathetic neurons?

    <p>They block only cholinergic sympathetic neurons</p> Signup and view all the answers

    What is the clinical use of neuromuscular-blocking agents?

    <p>As skeletal muscle relaxant adjuvants in anesthesia</p> Signup and view all the answers

    What is the term for agents that bind to cholinoceptors and prevent the effects of acetylcholine and other cholinergic agonists?

    <p>Cholinergic antagonists</p> Signup and view all the answers

    What is the other term for anticholinergic agents?

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

    What type of receptors do ganglionic blockers show a preference for?

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

    What is the effect of antimuscarinic agents on skeletal muscles?

    <p>They have no effect on skeletal muscles</p> Signup and view all the answers

    What is the clinical importance of cholinergic antagonists?

    <p>They are beneficial in a variety of clinical situations</p> Signup and view all the answers

    What is the primary action of atropine on muscarinic receptors?

    <p>It blocks the activity of ACh on muscarinic receptors</p> Signup and view all the answers

    What is the effect of atropine on heart rate at low doses?

    <p>It decreases heart rate</p> Signup and view all the answers

    What is the therapeutic use of atropine in ophthalmology?

    <p>To measure refractive errors</p> Signup and view all the answers

    What is the effect of atropine on salivary glands?

    <p>It decreases salivation</p> Signup and view all the answers

    What is the half-life of atropine?

    <p>About 4 hours</p> Signup and view all the answers

    What is the use of atropine as an antidote?

    <p>For the treatment of cholinergic agonist poisoning</p> Signup and view all the answers

    What is the effect of atropine on sweat glands?

    <p>It decreases sweat production</p> Signup and view all the answers

    What is the use of atropine as an antispasmodic agent?

    <p>To relax the GI tract</p> Signup and view all the answers

    What is the effect of atropine on the eye?

    <p>It causes mydriasis (dilation of the pupil)</p> Signup and view all the answers

    What is the route of administration of atropine in ophthalmology?

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

    What is the effect of nicotine on autonomic ganglia?

    <p>It first stimulates and then paralyzes all ganglia</p> Signup and view all the answers

    What is the mechanism of action of nondepolarizing neuromuscular blockers at low doses?

    <p>They competitively block ACh at the nicotinic receptors</p> Signup and view all the answers

    What is the therapeutic benefit of neuromuscular-blocking agents?

    <p>They facilitate tracheal intubation and provide complete muscle relaxation during surgery</p> Signup and view all the answers

    What is the effect of high doses of nondepolarizing neuromuscular blockers on the ion channels of the motor endplate?

    <p>They block the ion channels</p> Signup and view all the answers

    What is the result of ganglionic blockade by nicotine?

    <p>Decreased blood pressure and cardiac rate</p> Signup and view all the answers

    What is the effect of neuromuscular-blocking agents on the muscle cell membrane?

    <p>They prevent depolarization of the muscle cell membrane</p> Signup and view all the answers

    What is the characteristic of nondepolarizing neuromuscular blockers?

    <p>They act as antagonists at the nicotinic receptors</p> Signup and view all the answers

    What is the effect of cholines-terase inhibitors on the neuromuscular blockade?

    <p>They decrease the duration of neuromuscular blockade</p> Signup and view all the answers

    What is the therapeutic use of neuromuscular-blocking agents?

    <p>To facilitate tracheal intubation and provide complete muscle relaxation during surgery</p> Signup and view all the answers

    What is the effect of nicotine on the GI tract and bladder musculature at higher doses?

    <p>Complete cessation of activity</p> Signup and view all the answers

    What is the primary therapeutic use of scopolamine?

    <p>Prevention of motion sickness</p> Signup and view all the answers

    What is the effect of atropine on the CNS?

    <p>It produces restlessness, confusion, and hallucinations</p> Signup and view all the answers

    What is the characteristic of ipratropium and tiotropium?

    <p>They are quaternary derivatives of atropine</p> Signup and view all the answers

    What is the advantage of tiotropium over ipratropium?

    <p>It is administered once daily</p> Signup and view all the answers

    What is the effect of atropine on the urinary system?

    <p>It increases urinary retention</p> Signup and view all the answers

    What is the characteristic of tropicamide and cyclopentolate?

    <p>They are used as ophthalmic solutions for mydriasis and cycloplegia</p> Signup and view all the answers

    What is the effect of benztropine and trihexyphenidyl?

    <p>They are used as adjuncts with other antiparkinsonian agents</p> Signup and view all the answers

    What is the effect of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium chloride?

    <p>They are used to treat overactive bladder</p> Signup and view all the answers

    What is the advantage of oxybutynin transdermal system over oral formulations?

    <p>It causes less dry mouth</p> Signup and view all the answers

    What is the characteristic of ganglionic blockers?

    <p>They act on nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia</p> Signup and view all the answers

    What is the primary mechanism by which the action of succinylcholine is terminated?

    <p>Hydrolysis by plasma pseudocholinesterase</p> Signup and view all the answers

    What is the initial effect of succinylcholine on muscles?

    <p>Transient twitching</p> Signup and view all the answers

    Why is succinylcholine used during rapid endotracheal intubation?

    <p>Its rapid onset of action</p> Signup and view all the answers

    What is the consequence of succinylcholine administration in patients with electrolyte imbalances?

    <p>Prolonged apnea</p> Signup and view all the answers

    What is the effect of succinylcholine on potassium levels?

    <p>Increased potassium levels</p> Signup and view all the answers

    What is the consequence of succinylcholine administration in patients with atypical plasma cholinesterase?

    <p>Prolonged apnea</p> Signup and view all the answers

    What is the mechanism by which succinylcholine produces muscle paralysis?

    <p>Depolarization of the nicotinic receptors</p> Signup and view all the answers

    What is the therapeutic use of succinylcholine during electroconvulsive therapy?

    <p>To produce muscle relaxation</p> Signup and view all the answers

    What is the characteristic of succinylcholine's pharmacokinetics?

    <p>Rapid hydrolysis by plasma pseudocholinesterase</p> Signup and view all the answers

    What is the adverse effect of succinylcholine in susceptible patients?

    <p>Malignant hyperthermia</p> Signup and view all the answers

    What is the effect of cholinesterase inhibitors on nondepolarizing neuromuscular blockers?

    <p>They overcome the action of the blockers</p> Signup and view all the answers

    Which type of muscles are most susceptible to blockade by competitive agents?

    <p>Small, rapidly contracting muscles of the face and eye</p> Signup and view all the answers

    What is the mechanism of action of succinylcholine?

    <p>It attaches to the nicotinic receptor and acts like ACh to depolarize the junction</p> Signup and view all the answers

    Why are neuromuscular-blocking agents not effective orally?

    <p>They are not absorbed from the gut</p> Signup and view all the answers

    What is the effect of halogenated hydrocarbon anesthetics on neuromuscular blockade?

    <p>They exert a stabilizing action at the NMJ and enhance the blockade</p> Signup and view all the answers

    What is the effect of aminoglycoside antibiotics on neuromuscular blockade?

    <p>They synergize with pancuronium and other competitive blockers, enhancing the blockade</p> Signup and view all the answers

    What is the characteristic of the amino steroid drugs, such as vecuronium and rocuronium?

    <p>They are deacetylated in the liver and their clearance may be prolonged in patients with hepatic disease</p> Signup and view all the answers

    What is the effect of calcium channel blockers on neuromuscular blockade?

    <p>They increase the neuromuscular blockade of competitive blockers</p> Signup and view all the answers

    What is the characteristic of cisatracurium?

    <p>It is degraded spontaneously in plasma and by ester hydrolysis</p> Signup and view all the answers

    What is the effect of pancuronium on neuromuscular blockade?

    <p>It is excreted unchanged in the urine</p> Signup and view all the answers

    Study Notes

    Introduction to the Nervous System

    • The nervous system is divided into two anatomical divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
    • The CNS consists of the brain and spinal cord.
    • The PNS includes neurons located outside the brain and spinal cord.

    Functional Divisions within the Nervous System

    • The PNS is subdivided into the efferent and afferent divisions.
    • Efferent neurons carry signals away from the CNS to peripheral tissues.
    • Afferent neurons bring information from the periphery to the CNS.
    • The efferent portion of the PNS is further divided into the somatic and autonomic nervous systems (ANS).

    Autonomic Nervous System (ANS)

    • The ANS regulates vital bodily functions without conscious participation.
    • It is composed of efferent neurons that innervate smooth muscle, cardiac muscle, vasculature, and exocrine glands.
    • The ANS is divided into three divisions: sympathetic, parasympathetic, and enteric nervous systems.

    Sympathetic Nervous System

    • The sympathetic nervous system is involved in the "fight or flight" response.
    • It increases heart rate, blood pressure, and blood flow to skeletal muscles.
    • It also affects GI motility, bladder function, and sexual organs.

    Parasympathetic Nervous System

    • The parasympathetic nervous system is involved in maintaining homeostasis.
    • It is required for life and maintains essential bodily functions, such as digestion and elimination of waste.
    • It opposes or balances the actions of the sympathetic nervous system.

    Enteric Nervous System

    • The enteric nervous system is a collection of nerve fibers that innervate the GI tract, pancreas, and gallbladder.
    • It is often referred to as the "brain of the gut" and functions independently of the CNS.

    Central Nervous System (CNS) Control of Autonomic Functions

    • The ANS requires sensory input from peripheral structures to provide information on the current state of the body.
    • The CNS responds to the stimuli by sending out efferent reflex impulses via the ANS.
    • Reflex arcs are formed, which comprise a sensory (or afferent) arm and a motor (or efferent or effector) arm.

    Innervation by the ANS

    • Most organs are innervated by both divisions of the ANS.
    • The sympathetic and parasympathetic nervous systems have opposite effects on the same organ.

    Chemical Signaling Between Cells

    • Neurotransmission in the ANS is an example of chemical signaling between cells.
    • Other types of chemical signaling include hormone secretion and local mediator release.
    • Neurotransmitters, such as acetylcholine and norepinephrine, are released by nerve terminals and bind to specific receptors on target cells.

    Cholinergic Neurons

    • Preganglionic fibers terminating in the adrenal medulla, autonomic ganglia, and postganglionic fibers of the parasympathetic division use acetylcholine (ACh) as a neurotransmitter.
    • Postganglionic sympathetic division of sweat glands also use ACh.
    • Cholinergic neurons innervate muscles of the somatic system and play an important role in the central nervous system (CNS).

    Neurotransmission at Cholinergic Neurons

    • Neurotransmission involves six sequential steps: synthesis, storage, release, binding of ACh to a receptor, degradation of ACh, and recycling of choline and acetate.
    • Synthesis of ACh:
      • Choline is transported from the extracellular fluid into the cytoplasm of the cholinergic neuron by an energy-dependent carrier system.
      • Choline acetyltransferase catalyzes the reaction of choline with acetyl coenzyme A to form ACh.
    • Storage of ACh:
      • ACh is packaged and stored into presynaptic vesicles by an active transport process.
      • Vesicles contain ACh, ATP, and proteoglycan.
    • Release of ACh:
      • Voltage-sensitive calcium channels open, causing an increase in intracellular calcium, promoting fusion of synaptic vesicles with the cell membrane and release of their contents.
      • Release can be blocked by botulinum toxin.
    • Binding to the receptor:
      • ACh released from synaptic vesicles binds to postsynaptic receptors on the target cell, presynaptic receptors on the neuron, or other targeted presynaptic receptors.
      • Binding leads to a biologic response within the cell, such as initiation of a nerve impulse or activation of specific enzymes.
    • Degradation of ACh:
      • Acetylcholinesterase (AChE) cleaves ACh to choline and acetate in the synaptic cleft.
    • Recycling of choline:
      • Choline is recaptured by a sodium-coupled, high-affinity uptake system and transported back into the neuron.
      • Choline is acetylated into ACh, stored until released by a subsequent action potential.

    Cholinergic Receptors (Cholinoceptors)

    • Cholinergic receptors are divided into two families: muscarinic and nicotinic receptors, based on their affinity for cholinomimetic agents.

    Muscarinic Receptors

    • Muscarinic receptors belong to the class of G protein-coupled receptors (metabotropic receptors).
    • They recognize muscarine, an alkaloid found in certain poisonous mushrooms, and bind to ACh, but show only a weak affinity for nicotine.
    • There are five subtypes of muscarinic receptors, with M1, M2, and M3 receptors being functionally characterized.
    • Locations of muscarinic receptors:
      • Found on ganglia of the peripheral nervous system and autonomic effector organs, such as the heart, smooth muscle, brain, and exocrine glands.
      • M1 receptors are also found on gastric parietal cells, M2 receptors on cardiac cells and smooth muscle, and M3 receptors on the bladder, exocrine glands, and smooth muscle.
    • Mechanisms of acetylcholine signal transduction:
      • Activation of M1 or M3 receptors leads to a conformational change, interacting with Gq protein, which activates phospholipase C, producing IP3 and DAG.
      • IP3 increases intracellular Ca2+, while DAG activates protein kinase C.
    • Muscarinic agonists:
      • Pilocarpine is a nonselective muscarinic agonist used to treat xerostomia and glaucoma.
      • Research is ongoing to develop muscarinic agonists and antagonists that target specific receptor subtypes, such as M1 receptor agonists for Alzheimer's disease and M3 receptor antagonists for chronic obstructive pulmonary disease.

    Nicotinic Receptors

    • Nicotinic receptors recognize ACh and nicotine, but show only a weak affinity for muscarine.
    • Composed of five subunits, functioning as a ligand-gated ion channel.
    • Binding of two ACh molecules elicits a conformational change, allowing sodium ions to enter, resulting in depolarization of the effector cell.
    • Nicotinic receptors are located in:
      • CNS
      • Adrenal medulla
      • Autonomic ganglia
      • Neuromuscular junction (NMJ) in skeletal muscles
    • Nicotinic receptors in autonomic ganglia differ from those in the NMJ, with ganglionic receptors being selectively blocked by mecamylamine, and NMJ receptors being specifically blocked by atracurium.

    Direct-Acting Cholinergic Agonists

    • Direct-acting cholinergic agonists mimic the effects of ACh by binding directly to cholinoreceptors (muscarinic or nicotinic)
    • Classified into two groups: endogenous choline esters (ACh, carbachol, and bethanechol) and naturally occurring alkaloids (nicotine and pilocarpine)
    • All direct-acting cholinergic drugs have a longer duration of action than ACh

    Acetylcholine (ACh)

    • A quaternary ammonium compound that cannot penetrate membranes
    • Neurotransmitter of parasympathetic and somatic nerves as well as autonomic ganglia
    • Lacks therapeutic importance due to multiplicity of actions and rapid inactivation by cholinesterases
    • Has both muscarinic and nicotinic activity

    Actions of Acetylcholine

    • Decreases heart rate and cardiac output by mimicking vagal stimulation
    • Decreases blood pressure by causing vasodilation through M3 receptor activation and nitric oxide production
    • Increases salivary secretion and stimulates intestinal secretions and motility in the gastrointestinal tract
    • Enhances bronchiolar secretions
    • Increases tone of the detrusor muscle, causing urination in the genitourinary tract
    • Stimulates ciliary muscle contraction for near vision and constricts the pupillae sphincter muscle, causing miosis in the eye
    • Used in 1% solution to produce miosis during ophthalmic surgery

    Cholinergic Agonists

    • bethanechol:
      • An unsubstituted carbamoyl ester structurally related to ACh
      • Not hydrolyzed by AChE, has muscarinic activity, and no nicotinic actions
      • Major actions on smooth musculature of bladder and GI tract, with 1-hour duration of action
      • Used to stimulate the atonic bladder, particularly in post-partum or postoperative nonobstructive urinary retention
    • carbachol:
      • Has both muscarinic and nicotinic actions
      • Biobiotransformed by other esterases, but at a much slower rate
      • Profound effects on cardiovascular and GI systems due to ganglion-stimulating activity
      • Can cause release of epinephrine from the adrenal medulla by its nicotinic action
      • Rarely used therapeutically except in the eye as a miotic agent to treat glaucoma
    • pilocarpine:
      • A tertiary amine and a muscarinic agonist
      • Stable to hydrolysis by AChE and penetrates the CNS at therapeutic doses
      • Primarily used in ophthalmology
      • Actions include rapid miosis, contraction of the ciliary muscle, and spasm of accommodation
      • Used to treat glaucoma and xerostomia resulting from irradiation of the head and neck

    Indirect-Acting Cholinergic Agonists: Anticholinesterase Agents (Reversible)

    • AChE inhibitors:
      • Prevent the degradation of ACh, resulting in an accumulation of ACh in the synaptic space
      • Can provoke a response at all cholinoceptors in the body
      • Classified as short-acting or intermediate-acting agents
    • edrophonium:
      • Prototype short-acting AChE inhibitor
      • Rapidly absorbed and eliminated, with a short duration of action (10-20 minutes)
      • Used in the diagnosis of myasthenia gravis
    • physostigmine:
      • A tertiary amine and a substrate for AChE
      • Reversibly inactivates AChE, resulting in potentiation of cholinergic activity throughout the body
      • Stimulates not only the muscarinic and nicotinic sites of the ANS but also the nicotinic receptors of the NMJ
      • Duration of action is about 30 minutes to 2 hours
      • Used to increase intestinal and bladder motility, and to treat overdoses of drugs with anticholinergic actions
    • neostigmine:
      • A synthetic compound that reversibly inhibits AChE
      • More polar than physostigmine, poorly absorbed from the GI tract, and does not enter the CNS
      • Effect on skeletal muscle is greater than that of physostigmine
      • Used to stimulate the bladder and GI tract, and as an antidote for competitive neuromuscular-blocking agents
    • pyridostigmine and ambenonium:
      • Used in the chronic management of myasthenia gravis
      • Durations of action are intermediate (3-6 hours and 4-8 hours, respectively)
      • Adverse effects are similar to those of neostigmine
    • tacrine, donepezil, rivastigmine, and galantamine:
      • Used to treat Alzheimer's disease by inhibiting AChE in the CNS
      • GI distress is their primary adverse effect

    Indirect-Acting Cholinergic Agonists: Anticholinesterase Agents (Irreversible)

    • echothiophate:
      • An organophosphate that covalently binds to AChE
      • Resulting in a long-lasting increase in ACh at all sites where it is released
      • Used topically in the eye to treat open-angle glaucoma
      • Rarely used due to its side effect profile, which includes the risk of causing cataracts

    Toxicology of Anticholinesterase Agents

    • organophosphate toxicity:
      • Manifested as nicotinic and muscarinic signs and symptoms (cholinergic crisis)
      • Can be peripheral or affect the whole body
    • pralidoxime (2-PAM):
      • Reactivates inhibited AChE, but unable to penetrate into the CNS
      • Used to treat peripheral effects of organophosphates, but not the CNS effects
    • atropine and diazepam:
      • Used to treat muscarinic side effects and convulsions caused by organophosphates, respectively

    Cholinergic Antagonists

    • Cholinergic antagonists: agents that bind to cholinereceptors (muscarinic or nicotinic) and prevent the effects of acetylcholine (ACh) and other cholinergic agonists.
    • Three types of cholinergic antagonists:
      • Antimuscarinic agents (block muscarinic receptors)
      • Ganglionic blockers (block nicotinic receptors of sympathetic and parasympathetic ganglia)
      • Neuromuscular-blocking agents (block cholinergic transmission between motor nerve endings and skeletal muscle)

    Antimuscarinic Agents

    • Block muscarinic receptors, causing inhibition of muscarinic functions
    • Do not block nicotinic receptors, so no action at skeletal neuromuscular junctions or autonomic ganglia
    • Examples:
      • Atropine
      • Scopolamine
      • Ipratropium
      • Tiotropium

    Atropine

    • Tertiary amine belladonna alkaloid with high affinity for muscarinic receptors
    • Acts both centrally and peripherally
    • General actions last about 4 hours
    • Effects:
      • Eye: mydriasis (dilation of the pupil), unresponsiveness to light, and cycloplegia (inability to focus for near vision)
      • Gastrointestinal (GI): reduces activity of the GI tract, reduces spasms and secretions
      • Cardiovascular: produces divergent effects on the cardiovascular system, depending on the dose
      • Secretions: blocks muscarinic receptors in salivary glands, producing dryness of the mouth (xerostomia)
    • Therapeutic uses:
      • Ophthalmic: topical atropine exerts mydriatic and cycloplegic effects
      • Antispasmodic: relaxes the GI tract
      • Cardiovascular: treats bradycardia
      • Antisecretory: blocks secretions in the upper and lower respiratory tracts prior to surgery
      • Antidote: used to treat organophosphate poisoning and overdose of anticholinesterases

    Scopolamine

    • Tertiary amine plant alkaloid that produces peripheral effects similar to atropine
    • Greater action on the central nervous system (CNS) and longer duration of action compared to atropine
    • Effects:
      • Anti-motion sickness: one of the most effective anti-motion sickness drugs available
      • Blocks short-term memory
      • Produces sedation, but at higher doses, it can produce excitement
    • Therapeutic uses:
      • Prevention of motion sickness
      • Postoperative nausea and vomiting

    Ipratropium and Tiotropium

    • Quaternary derivatives of atropine, approved as bronchodilators for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD)
    • Delivered via inhalation
    • Do not enter the systemic circulation or the CNS, isolating their effects to the pulmonary system

    Ganglionic Blockers

    • Specifically act on the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia
    • Examples:
      • Nicotine
    • Mechanism of action:
      • Depolarize autonomic ganglia, resulting in stimulation and then paralysis of all ganglia
    • Responses:
      • Complex and mostly unpredictable
      • Stimulatory effects result from increased release of neurotransmitters

    Neuromuscular-Blocking Agents

    • Block cholinergic transmission between motor nerve endings and skeletal muscle
    • Examples:
      • Nondepolarizing (competitive) blockers
      • Depolarizing agents
    • Mechanism of action:
      • Nondepolarizing agents: competitively block ACh at the nicotinic receptors
      • Depolarizing agents: depolarize the plasma membrane of the muscle fiber, similar to the action of ACh
    • Examples:
      • Cisatracurium
      • Pancuronium
      • Rocuronium
      • Vecuronium
      • Succinylcholine

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    The nervous system is divided into two anatomical divisions: the central nervous system and the peripheral nervous system. Learn about the efferent and afferent divisions and how they function.

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