The Quizzes about Autonomic and Somatic Nervous System Pharmacology – Part 1

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The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology- Part 1

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Question 1

Anatomic, neurochemical, and pharmacologic studies of nerves a, c, e, f, and h indicate that they share one common Which statement below correctly summarizes what that i s?

A	Are cholinergic, activate postsynaptic muscarinic receptors
B	Are cholinergic, activate postsynaptic nicotinic receptors
C	Cannot release their neurotransmitter(s) in the presence of atropine
D	Have the ability to activate all the adrenergic and all the cholinergic nerves
E	Recycle their neurotransmitter after each action potential, rather than synthesizing new transmitter de novo

Question 1 Explanation: 

Here’s a simple rule: in the peripheral nervous systems—that is, the somatic nervous system and both branches of the autonomic nervous system—“the first nerve ‘out’ of the CNS (in this diagram, a, c, e, f, and h) is always cholinergic and the ACh released from those nerves always activates the nicotinic subtype of cholinergic receptor on the postsynaptic target cell(s).”

Question 2

Multidisciplinary assessments of nerve d, a “typical” postganglionic sympathetic nerve, indicate that i t i s quite different from all the other nerves shown in the peripheral nervous system Which statement describes that difference?

A	Atropine selectively blocks activation of receptors by the neurotransmitter released from nerve d
B	It causes bronchodilation (airway smooth muscle relaxation) when i t i s activated
C	It i s adrenergic (or noradrenergic i f you wish to use that term instead)
D	The primary neurotransmitter synthesized by nerve d i s epinephrine
E	When nerve d i s physiologically activated by an action potential, actions of i ts released neurotransmitter are terminated mainly by hydrolysis in the synaptic cleft

Question 2 Explanation: 

Another rule, with one important exception: “all the efferents in the peripheral nervous systems are cholinergic except postganglionic sympathetics going to structures other than sweat glands” (and the arrector pili muscles too). There are eight nerves in the schematic. Seven of them—all except the majority of postganglionic sympathetics (nerve d)—are cholinergic (synthesize andrelease ACh as their neurotransmitter). The main postganglionic sympathetic fibers (except those innervating sweat glands) synthesize and release NE (not epinephrine; answer d) as their neurotransmitter, and so are adrenergic (or noradrenergic if you prefer) nerves. What else can you call nerve d? A postganglionic sympathetic nerve to certain smooth muscles, to cardiac muscle, and certain exocrine glands except sweat glands. (Be sure to see the explanation for Questions 38 and 40.) Atropine (a) is incorrect. It selectively and competitively blocks the effects of ACh (and other muscarinic agonists) on muscarinic receptors. In the diagram above, those receptors are found on structures innervated by nerves b and g. Answer b is incorrect. NE, nerve d’s neurotransmitter, is an effective agonist for α-adrenergic receptors (α1 and α2) and for β1 receptors. Bronchodilation caused by sympathetic activation requires activation of β2 receptors; NE cannot do that but EPI, released from the adrenal (suprarenal) medulla, certainly can. And once NE has been released from its neurons and activates its postsynaptic receptors, its actions are promptly terminated by reuptake (via an “amine pump” that can be blocked by cocaine or tricyclic antidepressants). Hydrolysis in the synaptic cleft (e) is the mechanism by which the actions of ACh, released from cholinergic nerves, is terminated.

Question 3

Reuptake (into the nerve) i s the main physiologic process for terminating the postsynaptic activity of a peripheral nervous system neurotransmitter. To which nerve does this process apply?

A	Nerve a
B	Nerve a
C	Nerve b
D	Nerve c
E	Nerved
F	Nerve e
G	Nerve f
H	Nerve g
I	Nerve h

Question 3 Explanation: 

The actions of norepinephrine (NE), released from adrenergic nerves, are terminated by neuronal reuptake. (Don’t forget that this reuptake process is inhibited by cocaine and tricyclic antidepressants, and the outcome is increased and more prolonged adrenergic effects of NE because NE lingers longer and accumulates in the synapse, exposed to its postsynaptic targets.) All the other nerves shown in the diagram are cholinergic; the actions of the ACh they release are terminated promptly by hydrolysis (via acetylcholinesterase)

Question 4

Nerve d, the more typical postganglionic sympathetic nerve, i s activated by a normally generated action potential followed by neurotransmitter release into the On which receptor type does the neurotransmitter i t releases act? Remember: You can select only one answer.

A	α1 adrenergic
B	α2 adrenergic
C	β1 adrenergic
D	β2 adrenergic
E	Muscarinic
F	Nicotinic
G	It depends on the target ti ssue (effector) type

Question 4 Explanation: 

The neurotransmitter released from nerve d, the postganglionic sympathetic fibers (to structures other than sweat glands and arrector pili muscles), is norepinephrine. NE can activate α-adrenergic receptors (both α1 and α2), and β1 receptors (not β2). Of course, different structures have different subtypes of these receptors: structures such as arterioles and the iris dilator muscle have α 1 receptors; β1 receptors are found in the heart and in the juxtaglomerular apparatus (kidneys; they help regulate renin release there), while β2 receptors (not activated by NE) are found on various smooth muscles, mainly in the airways. So, the only correct response to the question “which receptors are activated?” really depends on which structure is being innervated. As a final note, NE cannot activate cholinergic receptors, and so answers e and f are definitely incorrect.

Question 5

Which statement correctly describes what i s rather unique about nerve g, the postganglionic fibers that innervate eccrine sweat glands, compared with vi rtually all other postganglionic sympathetic nerves?

A	Cocaine blocks release of i ts neurotransmitter
B	Is cholinergic
C	Is stimulated by preganglionic adrenergic nerves (nerve f)
D	Its released neurotransmitter acts on nicotinic receptors
E	Uses epinephrine as i ts neurotransmitter

Question 5 Explanation: 

The postganglionic sympathetic fibers innervating sweat glands and arrector pili muscles are cholinergic. That is the exception to the rule that “all postganglionic sympathetic fibers are adrenergic.” How do you know it’s cholinergic? A variety of biochemical and histochemical methods can prove that ACh is the neurotransmitter. They also show that there is abundant acetylcholinesterase (AChE), which hydrolyzes ACh, in the synaptic cleft. But we’re going to make the assessment pharmacologically: We can prevent release of neurotransmitter from nerve g with botulinum toxin, which affects only (and all) cholinergic nerves; and we can prevent the response of the sweat glands innervated by nerve g with atropine, the prototype muscarinic receptor antagonist—a drug that has no effects on nicotinic (or other) receptors (eg, answer d) at usual doses. Likewise, nicotinic receptor blockers (or nicotine itself) have no effect at this site— another reason why answer d is incorrect. And how you do know it’s part of the SNS? Sweat glands are activated (secretions are increased) and arrector pili muscles contract (the hair on our skin “stands on end”) when the entire SNS is activated, such as in the “fight or flight response;” and if you trace the origins of the preganglionic nerves that activate the postganglionic ones, they emanate from the same regions of the spinal cord from which all other sympathetic preganglionic fibers arise—the thoracic and lumbar regions. Cocaine (a) is incorrect. It, and tricyclic antidepressants (eg, amitriptyline, imipramine, etc), block neuronal reuptake of NE. That is, its site of action is at the neuroeffector junction of postganglionic sympathetic neurons (nerve d)—all of them except those that innervate most sweat glands and arrector pili muscles, of course.

Question 6

Nerve g, the postganglionic nerve innervating eccrine sweat glands and arrector pili muscles, i s activated by a normally generated action potential and subsequent release of neurotransmitter from nerve f. On which receptor type does the neurotransmitter released by nerve g act?

A	α1 adrenergic
B	α2 adrenergic
C	Muscarinic
D	Nicotinic
E	β1 adrenergic
F	β2 adrenergic

Question 6 Explanation: 

The nerve is cholinergic, so the neurotransmitter it acts on, postsynaptically, must be either nicotinic or muscarinic. Nicotinic receptors are found on cell bodies of all postganglionic nerves (in both SNS and PNS; NN receptors), on the adrenal medulla (also NN), and on skeletal muscle (somatic nervous system, NM)—at the “first synapses out of the CNS.” Cholinergic receptors at all other sites are muscarinic, “defined” by the fact that those receptors are competitively blocked by atropine. Be sure to see the explanation for Question 37, above.

Question 7

Assume that all the efferent autonomic pathways in the schematic are tonically active (a reasonable assumption), even i f at low and quantitatively different We add vecuronium (or any of several related drugs) to the system and, as expected, i t blocks neurotransmitter activation of certain structures. Which nerve innervates those structures and normally would activate them in the absence of pancuronium or i ts related drugs?

A	Nerve a
B	Nerve b
C	Nerve c
D	Nerve d
E	Nerve e
F	Nerve f
G	Nerve g
H	Nerve h

Question 7 Explanation: 

Vecuronium and several related drugs (all of which have “curonium” or, at least, “cur” in their generic names) are nondepolarizing skeletal neuromuscular blockers (quite different, mechanistically, from succinylcho-line, the depolarizing blocker). They specifically and competitively block activation of nicotinic receptors (NM) on skeletal muscle by ACh, thereby preventing skeletal muscle depolarization and subsequent contraction; and have no effect on muscarinic receptors or any of the adrenergic receptor subtypes. Remember something about the natives of the Amazon obtaining a poisonous substance from the skin of certain species of frogs, putting it on the tips of their darts, and using that to kill their dinner with a blow-gun? That was curare, d-tubocurarine, the very old prototype nondepolarizing skeletal neuromuscular blocker, as we’ve come to know it

Question 8

Nearly every structure that i s influenced by sympathetic nervous system activity has postganglionic sympathetic (adrenergic) nerves innervating  i t. Which one of the following structures i s most definitely affected by sympathetic nervous system influences, and responds to epinephrine, but lacks innervation by postganglionic adrenergic fibers and so i s not affected by norepinephrine released from adrenergic nerves?

A	Airway (eg, bronchiolar) smooth muscle
B	Arteriolar smooth muscle
C	Iri s dilator muscles of the eyes
D	Sinoatrial cells (pacemaker) of the heart
E	Ventricular myocytes

Question 8 Explanation: 

The neurotransmitter of postganglionic sympathetic nerves is norepinephrine (unless the target cells are sweat glands or arrector pili muscles, in which case the final neurotransmitter is acetylcholine). Norepinephrine is a “good” agonist for α- and β1-adrenergic receptors, but not for β2. Airway smooth muscle cells are not innervated by the sympathetic nervous system. In terms of sympathetic influences, bronchodilation (airway smooth muscle relaxation) is caused only by epinephrine released from the adrenal (suprarenal) medulla. Here again is the diagram to which Questions 45 to 49 referred

Question 9

The figure below shows some of the main elements of norepinephrine (NE) synthesis, release, actions, and other steps in adrenergic neurotransmission. You do not need the diagram to answer this series of questions, but seeing i t may aid your answering or reviewing. Note that the effector (target) cell on the far right has either an α-adrenergic receptor or a β-adrenergic receptor. Mitochondria in the terminus of adrenergic nerve “endings” contain an abundance of monoamine oxidase (MAO). What best summarizes the biological role of the MAO in these adrenergic nerves?

A	Drives storage vesicles that contain norepinephrine to the nerve “ending” so that exocytotic norepinephrine release can occur in response to an action potential
B	Metabolically degrades NE that i s free (not stored in vesicles) in the nerve terminal
C	Metabolizes dopamine to norepinephrine
D	Provides metabolic energy for nonexocytotic release of norepinephrine in response to amphetamines and other catecholamine-releasing drugs
E	Synthesizes ATP that i s required to transport free intraneuronal norepinephrine into the storage granules/vesicles

Question 9 Explanation: 

While mitochondria in virtually all cells in which they are found are important for oxidative phosphorylation and ATP synthesis, I asked about the mitochondrial MAO that is rich in adrenergic neurons. There MAO will degrade NE that is free (ie, not safely stored away) in the storage vesicles. If that intravesicular uptake is inhibited, NE stores will be depleted. None of the structures or processes shown in the diagram are responsible for intraneuronal movement of NE-containing storage vesicles to, and ultimate fusion with, the nerve “ending” (a). Metabolism of dopamine to NE (c) occurs in the storage vesicles via the enzyme, dopamine β- hydroxylase. MAO does not provide “energy” for nonexocytotic NE release (d), and plays no role in ATP synthesis (e).

Question 10

Many studies have shown that a large fraction of norepinephrine (NE) in the normal resting adrenergic neuron i s stored in membrane-bound vesicles or We administer a drug that, over time, depletes this supply of neurotransmitter and decreases the intensity of responses to sympathetic nerve activation. In vi tro studies reveal that the drug acts by inhibiting uptake of intraneuronal NE into the vesicles; i t has no direct effect on catecholamine synthesis, release, or interactions with i ts receptors. Which drug fi ts this description best?

A	Pargyline
B	Prazosin
C	Propranolol
D	Reserpine
E	Tyramine

Question 10 Explanation: 

Reserpine blocks intraneuronal synthesis and storage of norepinephrine (NE), and the ability of the reuptake process to re-store norepinephrine that has already been released from an activated adrenergic nerve (seeQuestion 39), thereby exposing the free intraneuronal NE to degradation by intraneuronal MAO. This is important for other reasons: the final synthesis of NE from its precursor, dopamine, occurs in the vesicles. If dopamine entry is blocked, as it is by reserpine, NE synthesis is decreased. Reserpine also blocks vesicular uptake of dopamine in parts of the CNS. Pargyline (a) is a nonselective MAO inhibitor. Note that unlike reserpine, MAO inhibitors do not inhibit intraneuronal storage of NE. Rather, they inhibit metabolic inactivation of NE in adrenergic nerve endings (or, at other sites, other monoamines). This leads to a “build-up” of norepinephrine in adrenergic nerve endings. Prazosin (b) and propranolol (c) are adrenergic receptor blockers (α1 and β1-2, respectively) and have no direct effect on NE storage. Tyramine (e) is an indirect-acting sympathomimetic that displaces and releases neuronal NE via a process that does not involve exocytosis.

Question 11

A substance abuser self-administers cocaine and experiences a variety of s ignificant changes in cardiovascular function, in addition to the CNS-stimulating effects for which the drug was What statement describes the mechanism by which the cocaine caused i ts main peripheral and CNS effects?

A	Activates α2-adrenergic receptors leading to increased NE release
B	Blocks NE (and dopamine, in the CNS) reuptake via the amine pump
C	Directly activates postsynaptic α- and β-adrenergic receptors, leading to sym-pathomimetic (adrenomimetic) responses
D	Inhibits MAO, leading to increased intraneuronal NE levels
E	Prevents NE exocytosis

Question 11 Explanation: 

Cocaine (and tricyclic antidepressants such as imipramine) are classic examples of drugs that inhibit catecholamine reuptake by the “amine pump,” which is the main process by which released NE (or dopamine) reenters the neuron and its receptor-mediated effects are terminated physiologically. In the presence of cocaine or a tricyclic, released neurotransmitter lingers and accumulates in the synapse (neuroeffector junction), and so pertinent adrenergic responses appear heightened or more intense, and prolonged. The pump is also important for the neuronal uptake, and ultimate effects, of such catecholamine-releasing drugs as ephedrine, pseudo-ephedrine, amphetamines, methylphenidate, and tyramine. As long as an adrenergic synapse is present (as it is in the diagram) and exposed to cocaine or a tricyclic antidepressant, the drugs’ effects are not dependent on whether the effector (target) is smooth muscle, cardiac muscle, or an exocrine gland of any sort. Cocaine has no direct effect on α2-adrenergic receptors (a), nor on any of the postsynaptic adrenergic receptors (c). Likewise, the drug has no effect on MAO (d) nor on the exocytotic release of NE in response to an action potential (e). There is no direct functional link between the amine pump and such processes as NE release (exocytotically or otherwise) or activation of presynaptic (α2) adrenergic receptors.

Question 12

We administer a drug that i s a selective antagonist at the presynaptic α-receptors (α₂) in the peripheral nervous It has no effect on α₁ receptors, β receptors, or any other l igand receptors that are important in peripheral  nervous  system function. What i s  the  main response that i s l ikely to occur following administration of the α₂ -blocker?

A	Activation of the amine pump, stimulation of norepinephrine reuptake
B	Inhibition of dopamine β-hydroxylase, the enzyme that converts intraneuronal dopamine to norepinephrine
C	Increased norepinephrine release in response to each action potential
D	Inhibition of norepinephrine exocytosis
E	Stimulation of intraneuronal monoamine oxidase activity

Question 12 Explanation: 

The adrenergic neuronal α2 (presynaptic) receptor, like all other adrenergic receptors, is G-protein-coupled. When the receptor is activated by a suitable agonist, it signals the neuron to stop further NE release following an action potential. Norepinephrine itself is one such agonist; its activation of the presynaptic α2 receptor, which occurs concomitant with activation of postsynaptic (α1 or β1) adrenergic receptors (depending on what the distal target cell is), provides a physiologic “feedback” signal that halts further NE release. That is, released NE regulates the release of more NE from the very neuron from which the neurotransmitter came. Although activation of both the presynaptic α2 receptors and NE reup-take by the amine pump/transporter occurs almost simultaneously, there is no direct functional or biochemical linkage between the two. That is, blocking (or stimulating) the α2 receptor will not directly affect NE reuptake (a), nor will drugs that affect the amine pump necessarily have any direct effect on the α2 receptors and the function they serve. There is no effect on norepinephrine synthesis (b, whether by dopamine β-hydroxylase or other enzymes involved in neurotransmitter synthesis), nor on MAO (d). Note: Clonidine, which you typically (and correctly) think of as a centrally acting antihypertensive drug, acts as an α2 agonist in the periphery. It’s “turning off” of NE release, then, can contribute to reduced vasoconstriction (and other adrenergic processes mediated by NE), which in turn helps lower blood pressure. However, clonidine is a very lipophilic drug. When it is given in usual doses, by the usual route (oral or transdermal), the drug enters the CNS well, and rather promptly, and it acts there (in the cardiovascular control center of the brain’s medulla) to inhibit sympathetic outflow. It is that central effect that accounts for the drug’s main antihypertensive mechanism.

Question 13

Not shown in the diagram i s an enzyme that has the ability to metabolically inactivate NE that has diffused away from the It i s also present in the l iver (as i s MAO) and in the intestinal walls. Among other things, the rapidity with which this enzyme catabolizes i ts substrates accounts for why norepinephrine, dopamine, and dobutamine have extraordinarily short half-lives, must be given intravenously in order to cause meaningful effects, have negligible effects when given by other parenteral routes, and are ineffective when given by mouth. An inhibitor of this drug i s used therapeutically, but not for i ts autonomic effects. What i s the name of this enzyme?

A	Aromatic L-amino acid decarboxylase
B	Catechol O-methyltransferase (COMT)
C	Dopamine β-hydroxylase
D	Phenylethanolamine N-methyltransferase
E	Tyrosine hydroxylase

Question 13 Explanation: 

Only COMT has the properties noted in the question. Entacapone is an example of a COMT inhibitor that is used therapeutically. It is given mainly to manage Parkinson disease, in conjunction with levodopa. It inhibits the peripheral (eg, intestinal) conversion of levodopa to dopamine (recall that dopamine itself does not cross the blood-brain barrier), and is an alternative to carbidopa (which inhibits carboxylases). (See Questions 113, 114, 147, 166, and 174-176, in the CNS chapter, for more information on these and other dopaminergic drugs for parkinsonism.) The other enzymes listed in the question are involved in catecholamine synthesis. Aromatic L-amino acid decarboxylase (a) converts DOPA to dopamine, which is then converted to norepinephrine by dopamine β-hydroxylase (c). In the adrenal medulla, phenylethanolamine Nmethyltransferase (d) converts some norepinephrine to epinephrine. Tyrosine hydroxylase (e) converts tyrosine to DOPA.

Question 14

We administer a therapeutic dose of a drug that selectively and competitively blocks the postsynaptic α-adrenergic (α₁) It has no effects on presynaptic α-adrenergic receptors (α₂) or β-adrenergic receptors found anywhere in the periphery, whether as an agonist or antagonist. What i s the most l ikely drug?

A	Clonidine
B	Phentolamine
C	Phenoxybenzamine
D	Phenylephrine
E	Prazosin

Question 14 Explanation: 

Prazosin selectively and competitively blocks α1 adrenergic receptors and, unlike many other α-blockers (phentolamine, phenoxybenzamine), has virtually no presynaptic (α2) effects at usual doses. None of the other drugs fit the bill: Clonidine (a) is a centrally acting α-adrenergic agonist used mainly as an antihypertensive drug. The main consequence of that effect is a reduction of “sympathetic outflow” that reduces all of the three main determinants of blood pressure: heart rate, stroke volume, and total peripheral resistance. Phentolamine is a competitive α-blocker, but it blocks both presynaptic (α2) and postsynaptic (α1) receptors more or less equally well. Phenoxybenzamine (c) is similar to phentolamine in terms of its receptor targets. However, phenoxybenzamine’s actions last far longer than those of phentolamine, and they arise from noncompetitive/irreversable α-blockade. (Rather than merely occupying the receptors, as is the case with most antagonists, phenoxybenzamine alkylates the receptors, “permanently” impairing their ability to interact with suitable agonists). Phenylephrine (d) is a strong agonist for all the α-adrenergic receptors, has no α-antagonist activity, and exerts no direct effects of any type on β-receptors.

Question 15

Festoterodine i s a relatively new drug that was heavily marketed to prescribers  and directly to  consumers. It i s  indicated for the  treatment of an overactive urinary bladder, reducing the symptoms of urge  incontinence, urinary urgency, and urinary frequency. It prevents  physiologic activation of the bladder’s detrusor and s imultaneously prevents relaxation of the sphincter. Side effects include constipation, dry mouth, blurred vis ion, photophobia, urinary retention, and s l ight increases in heart rate. Another advisory for the drug: “Heat stroke and fever due to decreased sweating in hot temperatures have been reported.” Festoterodine has no direct effects on blood vessels that might change blood pressure. Based on this information, what prototype drug i s most l ike festoterodine?

A	Atropine
B	β-adrenergic blockers (eg, propranolol)
C	Isoproterenol
D	Neostigmine
E	Phentolamine

Question 15 Explanation: 

You probably never learned or read about festoterodine (it’s still relatively new), but that makes no difference in terms of being able to answer this question. The description of this drug is, in reality, also an excellent description of many of the properties of atropine, the prototype muscarinic receptor blocking drug, and of nearly a dozen other antimuscarinics marketed for “overactive bladder.” In terms of bladder function, parasympathetic influences tend to promote urine flow; antimuscarinics, then, tend to suppress that effect. (Conversely, sympathetic influences, via α-adrenergic receptor activation, tend to suppress urine flow and α-adrenergic blockers cause the opposite.) You should be able to eliminate incorrect answers by a simple process of elimination. For example, do β-blockers (b) cause the visual, urinary tract, sweat gland, or cardiovascular responses noted in the question? Not at all, nor do isoproterenol (c; β1/2 agonist), neostigmine (d; cholinesterase inhibitor, which produces precisely the opposite responses that atropine, festoterodine, and all the other antimuscarinics used for bladder overactivity do), or phentolamine (e; nonselective α-blocker). Note: The mechanism of action of festoterodine, its indications, side effects, and adverse responses—and just about any other relevant property you can imagine, including the dose—are exactly the same as those of an older and widely advertised brand name drug, its sole active generic ingredient being tolterodine. Coincidental? Not at all. Both drugs have the same active metabolite

Question 16

A morbidly obese person vis i ts the local bariatric (weight loss) cl inic seeking a pill that will help shed The physician prescribes dextroamphetamine. In addition to causing i ts expected centrally mediated anorexigenic (appetite-suppressant) and cortical-stimulating effects i t causes a host of peripheral adrenergic effects that, for some patients, can prove fatal. What best summarizes the main mechanism by which dextroamphetamine, or amphetamines in general, cause their peripheral autonomic effects?

A	Activates MAO
B	Blocks NE reuptake via the amine pump/transporter
C	Displaces, releases, intraneuronal NE
D	Enhances NE synthesis, leading to massive neurotransmitter overproduction
E	Stabilizes the adrenergic nerve ending by directly activating α2 receptors

Question 16 Explanation: 

Amphetamines (dextroamphetamine, methamphetamine, amphetamine, and several related drugs) can be classified as indirect-acting sympathomimetics (adrenomimetics). They are transported into the adrenergic nerve ending by the amine pump, displace NE from its storage vesicles (via processes that are not dependent on an action potential), and cause the stored neurotransmitter to be released into the synaptic space. At that point, all the expected effects of NE on its receptors and effectors occur. These drugs have no direct effects, whether as an agonist or antagonist, on the adrenergic receptors. Their actions are wholly dependent on intraneuronal catecholamine stores. Amphetamines and related drugs have no ability to directly activate (or inhibit) MAO (a); to affect intraneuronal NE stores (c); or stimulate (or inhibit) intraneuronal NE synthesis (d). The amine pump upon which cocaine and related drugs mainly act is located on the presynaptic adrenergic nerve “ending,” as are the main populations of α2 receptors; however, these drugs do not directly affect, either by stimulating or blocking, those α2 receptors (e).

Question 17

We administer a pharmacologic dose of epinephrine and observe (among other responses) a direct increase of cardiac rate, contractility, and electrical impulse conduction Which adrenergic receptor was responsible for these direct cardiac effects?

A	α1
B	α2
C	β1
D	β2
E	β3a

Question 17 Explanation: 

The inotropic (contractility), chronotropic (rate), and dromotropic (conduction velocity-related) effects of epinephrine on the heart are mediated through activation of β1-adrenergic receptors. These receptor sites mediate an epinephrine-induced increased firing rate of the SA node (spontaneous, or Phase 4, depolarization), increased conduction velocity through the AV node and the His-Purkinje system, and increased contractility and conduction velocity of atrial and ventricular muscle. Epinephrine activation of α adrenoceptors does not affect cardiac function in any physiologically or therapeutically important way—except for the crucial role of α adrenoceptors as mediators of coronary artery vasoconstriction (clearly a vascular smooth muscle, not cardiac muscle, phenomenon). The β2- adrenergic receptors play virtually no direct role in cardiac stimulation. They are more important in the relaxation of tracheobronchial smooth muscle, dilation of arterioles that serve skeletal muscles, increased secretion of insulin by the pancreas, and to a lesser degree relaxation of the detrusor of the urinary bladder. (Lipolysis in fat cells and melatonin secretion by the pineal gland appear to involve stimulation of β3-adrenergic receptors. However, we do not have any clinically useful drugs that selectively activate or block the β3 receptors, and so you might want to question how much you learn about the β3s.)

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Part 1 | Part 2 | Part 3 | Part 4 

II. Preview all questions below

Acetylcholine synthesis, fates, and actions

Acetylcholinesterase and i ts inhibitors

Adrenergic agonists and antagonists

Adrenergic receptor  subtypes

Catecholamine synthesis, fates, and actions

Cholinergic receptor subtypes

Cholinergic agonists and antagonists

Ganglionic stimulants and blockers

Peripheral nervous system structure and function

Skeletal muscle relaxants (centrally acting)

Skeletal neuromuscular blockers

Questions

Note: The fi rst several questions in this chapter are based on a schematic diagram of the peripheral nervous system. I think this i s a suitable and efficient way to help you assess, or clarify, some fundamental (and essential) aspects of peripheral nervous system anatomy, (neuro)physiology, and pharmacology based on a few main “rules” and key exceptions to them. I hope this approach will be beneficial.

The diagram below shows the main efferent pathways in the peripheral nervous  systems—the autonomic (parasympathetic and sympathetic; PNS, SNS, respectively) and somatic nervous systems—from the CNS/spinal cord (at the far left, not labeled) out to the peripheral target (effectors). The sweat glands shown in the figure represent eccrine sweat glands. The innervation of arrector pili muscles i s basically the same.

Those nerves (and answer choices) are:

1. Preganglionic parasympathetic
2. Postganglionic parasympathetic
3. Preganglionic sympathetic
4. Postganglionic sympathetic to structures other than sweat glands
5. “Preganglionic” (functional equivalence) sympathetic to the adrenal (suprarenal) medulla
6. Preganglionic sympathetic, sweat gland (eccrine) innervation
7. Postganglionic sympathetic to eccrine sweat glands
8. Motor nerve, somatic nervous system

1. Anatomic, neurochemical, and pharmacologic studies of nerves a, c, e, f, and h indicate that they share one common Which statement below correctly summarizes what that i s?

1. Are cholinergic, activate postsynaptic muscarinic receptors
2. Are cholinergic, activate postsynaptic nicotinic receptors
3. Cannot release their neurotransmitter(s) in the presence of atropine
4. Have the ability to activate all the adrenergic and all the cholinergic nerves
5. Recycle their neurotransmitter after each action potential, rather than synthesizing new transmitter de novo

2. Multidisciplinary assessments of nerve d, a “typical” postganglionic sympathetic nerve, indicate that i t i s quite different from all the other nerves shown in the peripheral nervous system Which statement describes that difference?

1. Atropine selectively blocks activation of receptors by the neurotransmitter released from nerve d
2. It causes bronchodilation (airway smooth muscle relaxation) when i t i s activated
3. It i s adrenergic (or noradrenergic i f you wish to use that term instead)
4. The primary neurotransmitter synthesized by nerve d i s epinephrine
5. When nerve d i s physiologically activated by an action potential, actions of i ts released neurotransmitter are terminated mainly by hydrolysis in the synaptic cleft

3. Reuptake (into the nerve) i s the main physiologic process for terminating the postsynaptic activity of a peripheral nervous system neurotransmitter. To which nerve does this process apply?

1. Nerve a
2. Nerve b
3. Nerve c
4. Nerve d
5. Nerve e
6. Nerve f
7. Nerve g
8. Nerve h

4. Nerve d, the more typical postganglionic sympathetic nerve, i s activated by a normally generated action potential followed by neurotransmitter release into the On which receptor type does the neurotransmitter i t releases act? Remember: You can select only one answer.

1. α₁ adrenergic
2. α₂ adrenergic
3. β₁ adrenergic
4. β₂ adrenergic
5. Muscarinic
6. Nicotinic
7. It depends on the target ti ssue (effector) type

5. Which statement correctly describes what i s rather unique about nerve g, the postganglionic fibers that innervate eccrine sweat glands, compared with vi rtually all other postganglionic sympathetic nerves?

1. Cocaine blocks release of i ts neurotransmitter
2. Is cholinergic
3. Is stimulated by preganglionic adrenergic nerves (nerve f)
4. Its released neurotransmitter acts on nicotinic receptors
5. Uses epinephrine as i ts neurotransmitter

6. Nerve g, the postganglionic nerve innervating eccrine sweat glands and arrector pili muscles, i s activated by a normally generated action potential and subsequent release of neurotransmitter from nerve f. On which receptor type does the neurotransmitter released by nerve g act?

1. α₁ adrenergic
2. α₂ adrenergic
3. Muscarinic
4. Nicotinic
5. β₁ adrenergic
6. β₂ adrenergic

7. Assume that all the efferent autonomic pathways in the schematic are tonically active (a reasonable assumption), even i f at low and quantitatively different We add vecuronium (or any of several related drugs) to the system and, as expected, i t blocks neurotransmitter activation of certain structures. Which nerve innervates those structures and normally would activate them in the absence of pancuronium or i ts related drugs?

1. Nerve a
2. Nerve b
3. Nerve c
4. Nerve d
5. Nerve e
6. Nerve f
7. Nerve g
8. Nerve h

8. Nearly every structure that i s influenced by sympathetic nervous system activity has postganglionic sympathetic (adrenergic) nerves innervating  i t. Which one of the following structures i s most definitely affected by sympathetic nervous system influences, and responds to epinephrine, but lacks innervation by postganglionic adrenergic fibers and so i s not affected by norepinephrine released from adrenergic nerves?

1. Airway (eg, bronchiolar) smooth muscle
2. Arteriolar smooth muscle
3. Iri s dilator muscles of the eyes
4. Sinoatrial cells (pacemaker) of the heart Ventricular myocytes

Questions 9 to 13

The figure below shows some of the main elements of norepinephrine (NE) synthesis, release, actions, and other steps in adrenergic neurotransmission. You do not need the diagram to answer this series of questions, but seeing i t may aid your answering or reviewing. Note that the effector (target) cell on the far right has either an α-adrenergic receptor or a β-adrenergic receptor.

9. Mitochondria in the terminus of adrenergic nerve “endings” contain an abundance of monoamine oxidase (MAO). What best summarizes the biological role of the MAO in these adrenergic nerves?

1. Drives storage vesicles that contain norepinephrine to the nerve “ending” so that exocytotic norepinephrine release can occur in response to an action potential
2. Metabolically degrades NE that i s free (not stored in vesicles) in the nerve terminal
3. Metabolizes dopamine to norepinephrine
4. Provides metabolic energy for nonexocytotic release of norepinephrine in response to amphetamines and other catecholamine-releasing drugs
5. Synthesizes ATP that i s required to transport free intraneuronal norepinephrine into the storage granules/vesicles

10. Many studies have shown that a large fraction of norepinephrine (NE) in the normal resting adrenergic neuron i s stored in membrane-bound vesicles or We administer a drug that, over time, depletes this supply of neurotransmitter and decreases the intensity of responses to sympathetic nerve activation. In vi tro studies reveal that the drug acts by inhibiting uptake of intraneuronal NE into the vesicles; i t has no direct effect on catecholamine synthesis, release, or interactions with i ts receptors. Which drug fi ts this description best?

1. Pargyline
2. Prazosin
3. Propranolol
4. Reserpine
5. Tyramine

11. A substance abuser self-administers cocaine and experiences a variety of s ignificant changes in cardiovascular function, in addition to the CNS-stimulating effects for which the drug was What statement describes the mechanism by which the cocaine caused i ts main peripheral and CNS effects?

1. Activates α₂-adrenergic receptors leading to increased NE release
2. Blocks NE (and dopamine, in the CNS) reuptake via the amine pump
3. Directly activates postsynaptic α- and β-adrenergic receptors, leading to sym-pathomimetic (adrenomimetic) responses
4. Inhibits MAO, leading to increased intraneuronal NE levels
5. Prevents NE exocytosis

12, We administer a drug that i s a selective antagonist at the presynaptic α-receptors (α₂) in the peripheral nervous It has no effect on α₁ receptors, β receptors, or any other l igand receptors that are important in peripheral  nervous  system function. What i s  the  main response that i s l ikely to occur following administration of the α₂ -blocker?

1. Activation of the amine pump, stimulation of norepinephrine reuptake
2. Inhibition of dopamine β-hydroxylase, the enzyme that converts intraneuronal dopamine to norepinephrine
3. Increased norepinephrine release in response to each action potential
4. Inhibition of norepinephrine exocytosis
5. Stimulation of intraneuronal monoamine oxidase activity

13. Not shown in the diagram i s an enzyme that has the ability to metabolically inactivate NE that has diffused away from the It i s also present in the l iver (as i s MAO) and in the intestinal walls. Among other things, the rapidity with which this enzyme catabolizes i ts substrates accounts for why norepinephrine, dopamine, and dobutamine have extraordinarily short half-lives, must be given intravenously in order to cause meaningful effects, have negligible effects when given by other parenteral routes, and are ineffective when given by mouth. An inhibitor of this drug i s used therapeutically, but not for i ts autonomic effects. What i s the name of this enzyme?

1. Aromatic L-amino acid decarboxylase
2. Catechol O-methyltransferase (COMT)
3. Dopamine β-hydroxylase
4. Phenylethanolamine N-methyltransferase
5. Tyrosine hydroxylase

14. We administer a therapeutic dose of a drug that selectively and competitively blocks the postsynaptic α-adrenergic (α₁) It has no effects on presynaptic α-adrenergic receptors (α₂) or β-adrenergic receptors found anywhere in the periphery, whether as an agonist or antagonist. What i s the most l ikely drug?

1. Clonidine
2. Phentolamine
3. Phenoxybenzamine
4. Phenylephrine
5. Prazosin

15. Festoterodine i s a relatively new drug that was heavily marketed to prescribers and directly to  It i s  indicated for the  treatment of an overactive urinary bladder, reducing the symptoms of urge  incontinence, urinary urgency, and urinary frequency. It prevents  physiologic activation of the bladder’s detrusor and s imultaneously prevents relaxation of the sphincter. Side effects include constipation, dry mouth, blurred vis ion, photophobia, urinary retention, and s l ight increases in heart rate. Another advisory for the drug: “Heat stroke and fever due to decreased sweating in hot temperatures have been reported.” Festoterodine has no direct effects on blood vessels that might change blood pressure. Based on this information, what prototype drug i s most l ike festoterodine?

1. Atropine
2. β-adrenergic blockers (eg, propranolol)
3. Isoproterenol
4. Neostigmine
5. Phentolamine

16. A morbidly obese person vis i ts the local bariatric (weight loss) cl inic seeking a pill that will help shed The physician prescribes dextroamphetamine. In addition to causing i ts expected centrally mediated anorexigenic (appetite-suppressant) and cortical-stimulating effects i t causes a host of peripheral adrenergic effects that, for some patients, can prove fatal. What best summarizes the main mechanism by which dextroamphetamine, or amphetamines in general, cause their peripheral autonomic effects?

1. Activates MAO
2. Blocks NE reuptake via the amine pump/transporter
3. Displaces, releases, intraneuronal NE
4. Enhances NE synthesis, leading to massive neurotransmitter overproduction
5. Stabilizes the adrenergic nerve ending by directly activating α₂ receptors

17. We administer a pharmacologic dose of epinephrine and observe (among other responses) a direct increase of cardiac rate, contractility, and electrical impulse conduction Which adrenergic receptor was responsible for these direct cardiac effects?

1. α1
2. α2
3. β1
4. β2
5. β3a