The Quizzes about Autonomic and Somatic Nervous System Pharmacology – Part 3

I. Start the exam by click the “Start” button

The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology- Part 3

Start

Congratulations - you have completed The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology- Part 3. You scored %%SCORE%% out of %%TOTAL%%. Your performance has been rated as %%RATING%%

Your answers are highlighted below.

Question 1

A patient presents with an anaphylactic reaction following a wasp What i s the drug of choice for treating the multiple cardiovascular and pulmonary problems that, i f not promptly corrected, could lead to the patient’s death?

A	Atropine
B	Diphenhydramine
C	Epinephrine
D	Isoproterenol
E	Norepinephrine

Question 1 Explanation: 

Epi-nephrine, an excellent agonist for all the adrenergic receptors, is the drug of choice for managing the symptoms of an acute, systemic, immediate hypersensitivity reaction to an allergen (anaphylactic shock), all of which result from the release or production of various substances (eg, histamine, kinins) that contribute to cardiac, vascular, and pulmonary dysfunction. Death can occur because of several main adverse responses: profound hypotension and angioedema (which can be reversed by epinephrine’s α- agonist/vasoconstrictor effects); cardiac depression (reversed by epinephrine’s β1 actions); and laryngospasm and bronchospasm (reversed by the β2 effects of epinephrine). Atropine (a), the prototype muscarinic receptor blocker, will have modest effects to counteract airway smooth muscle contraction caused by acetylcholine, but no effect on the strong adverse cardiovascular or airway effects of histamine, kinins, and other mediators that play a critical role in anaphylaxis. Diphenhydramine (b) has strong histamine H1 and muscarinic receptor blocking actions, but it, too, cannot block all the adverse and potentially lethal cardiovascular and pulmonary effects of anaphylaxis-associated mediators. (Diphenhydramine clearly can alleviate bothersome urticaria and other cutaneous manifestations of allergic or anaphylactic reactions, but those actions are rather trivial compared with other life-threatening responses that it cannot beneficially affect.) No antihistamine can be considered a life-saving substitute for epinephrine. Isoproterenol (d), the prototype β1 and β2 agonist, will counteract airway smooth muscle contraction and help restore cardiac function, but because it lacks any vasoconstrictor (ie, α-agonist) activity it will not counteract widespread vasodilation and the hemodynamic consequences of it. Norepinephrine (e) has beneficial cardiac and peripheral vasoconstrictor activity, but since it lacks β2-bronchodilator activity it is not an acceptable alternative to epinephrine. Its bronchodilator effects are relatively weak, and it lacks any vasopressor effects that are needed to help restore blood pressure.

Question 2

Cardiac output improves when dobutamine i s given, by IV infusion, to a 60-year-old man with acute, symptomatic heart By what adrenergic receptor-mediated actions, and through which ultimate effects of i t, do therapeutic doses of dobutamine mainly raise cardiac output?

A	α-adrenergic agonist
B	α-adrenergic antagonist
C	β1-adrenergic agonist
D	β1-adrenergic antagonist.
E	Mixed α and β agonist
F	Mixed α and β antagonist

Question 2 Explanation: 

Dobutamine is mainly a β1-selective agonist that causes a positive inotropic effect and in turn raises stroke volume, leading to increased cardiac output. Dobutamine has some positive chronotropic activity (also β1- mediated) that also contributes to a rise of cardiac output, but the drug’s effects on the heart’s inotropic state predominate. Note: The best way to characterize the receptor-mediated effects of dobutamine is as a “selective β1 agonist,” but dobutamine’s actions (in the form available for therapeutic use) are a bit more complex. It is actually a racemic mixture of two isomers: the (+) isomer is the potent β1 agonist that causes the predominant cardiac and hemodynamic effects, but it also has some weak α1 antagonist (vasodilator) effects; the (–) isomer is an efficacious and potent α1 agonist (vasoconstrictor). The opposing vasoconstrictor effects of one isomer essentially cancel-out the vasodilator effects of the other. Regardless, it would not be correct to characterize the drug’s predominant cardiovascular actions as involving α-agonist or antagonist effects (a, b, e, f), and the drug certainly has no β-blocking actions (d).

Question 3

We are using novel in vi tro methods to investigate the fate and post-synaptic actions of norepinephrine, released upon an action potential generated in an adrenergic An action potential i s generated and the postsynaptic effector briefly responds. Almost instantaneously the response i s over. What process mainly accounted for the brevity of the response, and termination of the released NE’s actions?

A	Metabolism by enzyme(s) located near the postsynaptic receptor(s) and/or in the synaptic cleft
B	Reuptake into the nerve ending
C	Metabolism by catechol-O-methyltransferase (COMT)
D	Degradation by mitochondrial monoamine oxidase (MAO)
E	Conversion to a “false neurotransmitter” in the nerve ending

Question 3 Explanation: 

Norepinephrine (and other monoamine neurotransmitters such as dopa-mine) is removed from its receptors by an “amine pump” located in the neuronal membrane. Recall that this reuptake process can be blocked by (among other drugs) cocaine and tricyclic antidepressants. (You might ask “what about ‘stimulation’ of presynaptic α2 receptors?” Well, that answer might work, but it wasn’t one of the choices here. Moreover, presynaptic α2 receptor activation only inhibits release of additional NE; it does not stop the effects of NE that has already been released.) Monoamine oxidase (MAO; answer d), and to a lesser degree catechol-O-methyltransferase (COMT; answer c), are enzymes responsible for metabolic degradation of NE (the former intraneuronally as far as monoaminergic nerves go, the other extraneuronal). However, they are not important in terminating the immediate actions of released NE, which is a process dependent mainly on neuronal reuptake following each action potential and which is not affected by MAO or COMT inhibitors. Answer a, which cites metabolic inactivation of neurotransmitter in the synaptic cleft, is a good description of what happens to neuronally released ACh. Answer e, which mentions formation of a “false neurotransmitter”, does not explain the physiologic termination of released norepinephrine’s actions. That concept, however, has been mentioned as a potential mechanism by which monoamine oxidase inhibitors alter the adrenergic responses when MAO inhibitors are administered.

Question 4

We are contemplating administration of a nonselective β-adrenergic blocker to a In which of the following conditions i s this considered generally acceptable, appropriate, and safe?

A	Angina, vasospastic (“variant”; Prinzmetal)
B	Asthma
C	Bradycardia
D	Diabetes mellitus, insulin-dependent and poorly controlled
E	Heart block (second degree or greater)
F	Hyperthyroidism, symptomatic and acute
G	Severe congestive heart failure

Question 4 Explanation: 

The tachycardia associated with symptomatic hyperthyroidism reflects, to a great degree, thyroid hormone-related hyperreactivity of β-adrenergic receptors to drugs that have β-agonist activity. Of most concern in this situation is hyperreactivity of β1 receptors, which accounts for the untoward and potentially dangerous cardiac responses that usually occur. These can be managed, symptomatically, with a β-blocker. Indeed, during an acute and life-threatening episode of hyperthyroidism (thyrotoxicosis, or “thyroid storm”) a β-blocker is not only indicated but also may be lifesaving. Of all the conditions listed, this is the only indication for propranolol or virtually any other β-blocker; and the only one that is not likely to worsen some aspect of the current clinical presentation. β-Blockers are generally safe and effective for chronic-stable angina (chronic-stable or “stress-induced” angina), and they are often used prophylactically in that condition. However they may worsen, and so are generally contraindicated in patients with vasospastic (variant, or Prinzmetal) angina (a). In situations of coronary vasospasm, α-mediated vasoconstrictor/spasm-provoking influences tend to be opposed by β2- mediated vasodilator influences. Block the β2 effects and the constrictor or spasm-favoring α-influences are unmasked, leading to increased frequency and severity of angina and myocardial ischemia. Asthma (b) is an important and common condition that relatively or absolutely contraindicates the use of a β-blocker, regardless of its spectrum of activity or administration route. Even very small doses of a β-blocker—even a topical β-blocker that might be used for glaucoma, and even the so-called selective β1-blockers such as atenolol or metoprolol—can prove lethal for some asthmatics. That is because the airways of asthmatic individuals depend greatly on β2 activation (and other influences) to prevent bronchoconstriction or bronchospasm. Block those effects, and serious or even fatal consequences may arise. β-Adrenergic blockers lower heart rate and slow A-V nodal conduction velocity. Thus, pre-existing bradycardia (c) or heart (A-V nodal) block (e) tends to weigh against, if not contraindicate, safe use of any β-blocker. A working definition of heart block is, of course, an abnormally prolonged P-R interval, which can be detected easily on an electrocardiogram. If the patient has first-degree heart block (P-R intervals are prolonged, but all supraventricular electrical activity passes through the A-V node to activate the ventricles), a β-blocker may cause second-degree heart block (some supraventricular impulses are not conducted through the A-V node). If the patient has second-degree heart block, a β-blocker may cause complete (third degree) block, which can have dire consequences because the ventricular myocardium loses all control by impulses passing through the A-V node, and so ventricular activity is likely to fall to dangerous levels. β-Blockers may pose significant problems for some patients with severe, poorly controlled diabetes mellitus (d). These drugs can, for example, prevent tachycardia that is one signal to the patient that blood glucose levels are too low, and they can delay the recovery of blood glucose levels following an episode of hypoglycemia. However, for many patients with mild and well-controlled diabetes (especially type 2), in such conditions as mild-to-moderate heart failure (and others), the judicious use of a β-blocker probably provides more benefit than harm.

Question 5

A patient presents in the Emergency Department in great distress and with the following s igns and symptoms: Which drug most l ikely caused these s igns and symptoms?

A	AChE inhibitor
B	α-adrenergic blocker
C	Antimuscarinic
D	β-adrenergic blocker
E	Parasympathomimetic (muscarinic agonist)
F	Peripherally acting (neuronal) catecholamine depletor

Question 5 Explanation: 

These are among the classic signs and symptoms of atropine poisoning, which is also more generally known as the antimuscarinic or anticholinergic syndrome. The antimuscarinic drug-poisoned patient often can be described as: • red as a beet (characteristic facial flushing; a so-called “atropine flush”); • dry as a bone (no exocrine gland secretions, no fecal or urinary output because bowel and bladder motility are inhibited); • hot as a furnace (profound fever; a CNS “problem” compounded by a lack of body heat loss normally afforded by sweating); • blind as a bat (paralysis of accommodation and dilated pupils do not respond to even very bright light); • mad as a hatter (as in the Mad Hatter from Lewis Carroll’s Alice in Wonderland: CNS problems, including delirium and hallucinations). You may never see true atropine poisoning. As you know, that prototype antimuscarinic drug is not used clinically all that often, except in some particular specialties or situations. However, you should realize that many common groups of drugs (see Question 88), some of which are available over-the-counter (specifically, diphenhydramine), exert strong antimuscarinic effects. The signs and symptoms of “atropine poisoning” are an important component of their overdose syndromes, and you should be able to recognize them.

Question 6

Acebutolol and pindolol are classified as β-adrenergic blockers with intrinsic sympathomimetic activity (ISA). In a practical sense, what does ISA mean apropos the actions of these two drugs?

A	Are partial agonists (mixed agonist/antagonists)
B	Cause norepinephrine and epinephrine release
C	Induce catecholamine synthesis
D	Potentiate the actions of norepinephrine on α-adrenergic receptors
E	Useful when cardiac positive inotropic and chronotropic effects are wanted

Question 6 Explanation: 

The β-blockers with intrinsic sympathomimetic activity (ISA) are partial agonists—they act simultaneously as both β-agonists and competitive β-blockers. How can that be? At usual doses, and in the presence of low (eg, resting) sympathetic tone, they act as weak agonists for β-adrenergic receptors. Under these conditions, then, they may actually but slightly increase such β-mediated responses as heart rate. However, while these drugs are occupying the β-adrenergic receptors, they simultaneously block (antagonize)the effects of more efficacious (“stronger”) β agonists, eg, epinephrine and norepinephrine, or such exogenous agents (drugs) as isoproterenol. Thus, although they weakly increase resting heart rate, when catecholamine levels are high (as with stress, or exercise), such β-mediated responses as acceleration of heart rate and contractility are less intense than they would be had these drugs with ISA not been present. See Question 27 (in the General Principles chapter) for more information, because it was based on the effects of a β-blocker with ISA/partial agonist activity. Acebutolol and pindolol—indeed, all drugs classified as β-blockers—have no ability to cause release of norepinephrine (from adrenergic nerves) or epinephrine (from the adrenal medulla), and so answer b is incorrect. Likewise, these drugs do not induce (stimulate; nor inhibit) catecholamine synthesis (c); do not potentiate the actions of norepinephrine on α- (or on β-) adrenergic receptors (d); and cause negative inotropic and chronotropic effects (not positive; answer e).

Question 7

A 10-year-old boy i s diagnosed with Attention Deficit/Attention Deficit-Hyperactivity disorder (ADD/ADHD). Which drug i s most l ikely to prove effective for relieving the boy’s main symptoms?

A	Dobutamine
B	Methylphenidate
C	Pancuronium
D	Prazosin
E	Scopolamine
F	Terbutaline

Question 7 Explanation: 

Methylphenidate is pharmacologically similar to amphetamine. In the context of ADD/ADHD therapy it works as a CNS stimulant, with more pronounced effects on mental than on motor activities. It does so by releasing neuronal norepinephrine and dopamine via a nonexocytotic (not dependent on action potentials) mechanism. It is also used to treat narcolepsy. Dobutamine (a) is a β1-adrenergic agonist. Pancuronium (c) is a nondepolarizing skeletal neuromuscular blocker (nicotinic receptor competitive antagonist). Prazosin (d) is a competitive and selective α1-adrenergic blocker. Scopolamine (e) is an antimuscarinic (atropine-like) drug with greater efficacy for causing sedation and antimotion sickness effects. Terbutaline (f) is an agonist predominantly selective for β2- adrenergic receptors at “low” doses, but it can exert nonselective (isoproterenol-like) β1- and β2-agonist effects at high doses, including doses that may commonly be given therapeutically

Question 8

The table below shows the perioperative medication administration record (MAR) for an otherwise healthy 50-year-old woman. (To make things interesting—and write some additional questions—I’ll deviate from her actual MAR and ask a few questions about relevant but hypothetical scenarios.) She i s a nonsmoker, consumes no more than four glasses of wine per week, and has no personal or familial ri sk factors for heart disease or diabetes. She i s taking no other medications. This patient had two scheduled (nonemergent) laparoscopic abdominal surgeries done back-to-back in the OR. The fi rst was to remove  an adnexal (ovary and/or fallopian tube) mass that had been present for a  couple of years  and grew s lowly and i rregularly over a couple of years, and to get a pathology report to see whether i t i s cancerous. Her pathology affected one ovary. Once the ovary was removed a different surgeon performed a second procedure, through the same belly incisions, to alleviate some inconvenient urinary bladder problems. Her MAR i s very typical  of what you  would find for many otherwise healthy patients undergoing the  same or s imilar surgeries. The  fi rst drug l i sted, midazolam, was given in the preop area right before she was transported to the OR (and I will address i ts use in the CNS questions; the abbreviation IVP next to midazolam means “IV push,” that i s , a bolus injection). All the rest were given in the OR by a CRNA (certified registered nurse anesthetist). Use the table’s data, or what you should be able to infer from i t, to answer the next seven questions. Ephedrine was the fi rst drug administered after anesthesia premedication and induction with several parenteral What best describes ephedrine’s mechanism of action?

A	Directly, selectively, strongly stimulates α-adrenergic receptors in the peripheral vasculature
B	Enhances norepinephrine release by blocking presynaptic α-receptors
C	Increases norepinephrine synthesis
D	Inhibits norepinephrine’s intraneuronal metabolic inactivation
E	Releases intraneuronal norepinephrine into the synapse, also weakly but directly activates all adrenergic receptors

Question 8 Explanation: 

Ephedrine (and pseudoephedrine) are classified as mixed-acting sympathomimetics, meaning that their overall actions are a mixture or combination of two mechanisms. They mainly release intraneuronal norepinephrine, and so the predominant effects you see in the periphery are quite similar to those of NE itself (α- and β1 activation) because they are caused by NE. They also directly, but relatively very weakly, activate all the adrenergic receptors—alphas and the betas. Ephedrine and pseudoephedrine also exert similar effects in the CNS, leading to such effects as greater alertness (and difficulty falling asleep) and appetitesuppression (anorexigenic effect). The intensity of these effects is greater than those of typical direct-acting adrenergic agonists (EPI, NE, etc) but much weaker than those of indirect-acting sympathomimetics such as the amphetamines. Ephedrine’s actions are not at all selective for α-receptors on vascular smooth muscle, or anywhere else. So, answer a is incorrect. The mixedacting (and indirect-acting) sympathomimetics have no α- (or β- or cholinergic) blocking activity (b); do not enhance NE synthesis (c); and do not inhibit NE’s metabolism in any other way (d). Note: Some texts and lecturers “downplay” discussions of ephedrine. After all, it was commonly abused as a general CNS stimulant (to keep one awake) and as an anorexigenic (appetite suppressing/weight loss) drug. Such uses have largely been reduced by FDA mandate. It is also an outmoded drug for asthma, because it has bronchodilator activity, but that is very weak. Although the drug’s vasoconstrictor effects are also relatively weak (compared with, say, epinephrine, norepinephrine, or phenylephrine), it is “just enough” for many clinical situations, and the drug is used precisely for that purpose quite frequently intraoperatively, as shown in this patient’s operative drug administration chart.

Question 9

Ephedrine and drugs that act in s imilar ways or cause s imilar effects have a variety of therapeutic Given the background information provided for this patient, and the timing of ephedrine administration on the medication administration record, what i s the most l ikely reason why the ephedrine was given?

A	Cause bronchodilation so mechanical support of ventilation would be easier
B	Counteract CNS depression caused by the induction agents
C	Inhibit s inoatrial and atrioventricular nodal automaticity to terminate or prevent anesthesia-related cardiac arrhythmias
D	Lower heart rate that was raised excessively by the anesthetic drugs
E	Raise blood pressure that was lowered excessively by the induction agents

Question 9 Explanation: 

Ephedrine’s mechanisms of action were addressed in a previous answer. There I noted that ephedrine’s direct vasoconstrictor effects are “weak,” and they are not at all limited to α-adrenergic receptors (vascular or elsewhere). Nonetheless, the weak direct vasoconstrictor effect combined with the predominant NE-releasing action leads to clinically useful vasopressor effects. The preanesthetic and induction drugs given to this patient (and many others) are likely to produce some cardiodepressant effects (central, cardiac, and vascular), one manifestation of which is an excessive fall of blood pressure. Restoring blood pressure is the main purpose for which the ephedrine is given here. Ephedrine does cause CNS-stimulating effects (b), but it is generally weak and certainly insufficient to overcome (let alone affect) the CNS depression caused by several other drugs the patient received (midazolam, propofol, and morphine). Moreover, the patient is supposed to be anesthetized; why would we want to give a drug to counteract this so early into surgery? Ephedrine does not inhibit SA and AV nodal electrophysiology (c), nor heart rate (d) or contractility. If anything, through its indirect and NE-releasing effects it would be much more likely to stimulate the heart. Many years ago ephedrine was used as an oral bronchodilator, mainly for patients with asthma. Having no oral or inhaled “selective” β2 agonists as we have today, it was basically the “only game in town” for chronic management of airway smooth muscle constriction. Its bronchodilator effects were, at best, weak. The direct actions on β2 receptors are intrinsically weak; and since NE does not activate β2 receptors, NE release that occurs elsewhere does nothing in the way of causing bronchodilation. Again, there was nothing in the patient’s history of bronchoconstriction, nor did she receive any drugs that were likely to cause bronchoconstriction. (Yes, morphine can release histamine, which can cause bronchoconstriction, but this patient was described as otherwise healthy; and she was not a smoker, which might have put her at slightly greater risk of bronchoconstriction.)

Question 10

Assume, hypothetically, that the surgery had to be done The patient had been taking another drug—still in her ci rculation at usually effective concentrations—that weakened but did not completely eliminate all of ephedrine’s peripheral autonomic effects. Which drug(s) would be most l ikely to do that?

A	Atenolol (or metoprolol)
B	Cocaine or a tri cyclic antidepressant (eg, imipramine)
C	Trimethaphan (or hexamethonium)
D	Pargyline (or a s imilar nonselective MAO inhibitor)
E	Propranolol

Question 10 Explanation: 

In order for ephedrine to exert its predominant NE-releasing effects, it must be taken up from the synapse, into the adrenergic nerve “ending.” Cocaine and the tricyclic antidepressants inhibit ephedrine transport, just as they inhibit reuptake of NE that has been released from adrenergic nerves in response to an action potential (or in response to other NE-releasing drugs). Atenolol and metoprolol (a) relatively selectively block β1 receptors (at usual therapeutic doses; at high doses they also block β2 receptors— important if the patient has asthma, for example). They have no α-blocking activity at all. Thus, they don’t weaken all the effects of ephedrine. (If I had listed labetalol or carvedilol, which block all the α- and all the β-receptors, I’d give you your “two points” if you picked that answer.) Hexamethonium and trimethaphan (c) are autonomic (PNS and SNS) ganglionic (NN receptor) blocking drugs. They have no effect on ephedrine’s direct receptor-mediated actions, nor on ephedrine’s NE-releasing effects, both of which occur distal to the ganglia. (They would, of course, reduce or eliminate baroreceptor reflex responses that might arise if ephedrine suddenly and markedly raised blood pressure.) Pargyline (d), arguably the prototypic nonselective monoamine oxidase inhibitor, would intensify the responses to ephedrine or other sympathomimetics that work in part or in whole by releasing intraneuronal NE. Remember that MAO inhibitors cause a gradual but eventually dramatic rise in intraneuronal NE levels by inhibiting NE degradation by the enzyme; and although that NE is not released by a normal action potential, catecholamine-releasing sympathomimetics (ephedrine, pseudoephedrine, amphetamines, and even dietary tyramine) certainly, suddenly, and massively do so. Propranolol (e), of course, blocks all β-adrenergic receptors, but has no α-blocking activity and so does not affect any α-mediated responses to ephedrine.

Question 11

Shortly after the surgical wounds were closed and dressed, and right before the patient was transferred to the postanesthesia care unit (PACU), she received What was the reason for which i t was given?

A	Raise and support blood pressure during recovery
B	Raise or otherwise control bradycardia upon recovery from anesthesia
C	Restore normal neurotransmission in the brain, s ince i t had been suppressed by the induction and anesthetic agents
D	Reverse skeletal neuromuscular blockade/paralysis
E	Suppress urinary bladder function to reduce the ri sk of postoperative bladder incontinence

Question 11 Explanation: 

In the vast majority of situations in which we give a patient a nondepolarizing(curare-like) neuromuscular blocking drug (vecuronium in this case), we will also be giving the patient two other drugs. One, the focus of this question, is an acetylcholinesterase (AChE) inhibitor (neostigmine, listed here, is the most common one). It is given to reverse the competitive skeletal neuromuscular blockade: cause a build-up of ACh at the synapse by inhibiting its enzymatic hydrolysis by AChE), and the ACh can now overcome the blockade of the N M receptors on skeletal muscle. As explained more fully in other questions, the AChE inhibitor will cause build-up of ACh at all peripheral cholinergic synapses by inhibiting ACh’s metabolic inactivation. This leads to a variety of usually unwanted muscarinic effects. [Neostigmine does not enter the CNS, as does physostigmine (which is not at all appropriate for this indication), and so answer c is incorrect.] If the neostigmine (alone) does anything to blood pressure it will cause a fall (not a rise, a) due to the drug’s indirect (via increased ACh) negative chronotropic effect on the heart (thus, b is also incorrect). The secondary rise of ACh will also stimulate the bladder’s detrusor and trigone, and relax the sphincter, and so there will be no reduced risk or severity of urinary incontinence (e)

Question 12

The patient got her dose of glycopyrrolate mere seconds before the neostigmine was This i s done routinely in thousands of surgeries in which the drugs used are identical or at least very s imilar to those used here. To which pharmacologic class does glycopyrrolate most l ikely belong?

A	α-Adrenergic agonist
B	Antimuscarinic (atropine-like)
C	Cholinesterase inhibitor
D	Muscarinic receptor agonist
E	Nicotinic receptor (skeletal muscle; NM) agonist

Question 12 Explanation: 

The patient will receive neostigmine, and as explained in the previous question it will act at all cholinergic synapses in the peripheral nervous system—the NM receptors on skeletal muscle that we want to reactivate, and the muscarinic receptors that we don’t. If we didn’t block the muscarinic responses first, the patient is likely to experience ACh-mediated suppression of heart rate and nodal automaticity and conduction; stimulation of various gut and urinary tract muscles and relaxation of sphincters; bronchoconstriction; and increases in the secretory activity of a host of exocrine glands (salivary, lacrimal, mucous, gastric acid/parietal cell). As a result, and routinely, we give an antimuscarinic drug right before giving the stigmine, and that is what you need to know (and should have been able to deduce, even though you might not be familiar at all with glycopyrrolate.) Note: Glycopyrrolate is yet another drug that seems to get relegated to miscellaneous or unimportant status in texts and lectures (in which it might not be mentioned at all). However, it is used routinely in many hospitals as the go-to antimuscarinic in situations such as described here. Why not atropine, which you obviously know about? The effects of atropine tend to last much longer than what is needed here. Glycopyrrolate’s onset and duration of action are shorter than atropine’s—indeed, a rather close match to the pharmacokinetics of neostigmine, and so it is an excellent choice for this use.

Question 13

The patient in the case presented here was not facing any emergent or imminently l i fe-threatening problems, so skeletal muscle paralysis and intubation were relatively straightforward procedures, not at all Now assume, hypothetically, that emergency intubation was required, and succinylcholine (SuCh) was used because of i ts very rapid onset of action. Assume further that a s low infusion of SuCh was used to maintain paralysis throughout the procedure; blood levels of the drug were kept well in the therapeutic range; no curare-like (nondepolarizing) blocker was used; and the patient had no genetic or other factors that would affect the drug’s pharmacokinetics or action. When the surgery i s done, what drug would be given to reverse succinylcholine’s effects?

A	Atropine
B	Bethanechol
C	Neostigmine
D	Physostigmine
E	Nothing

Question 13 Explanation: 

At usual therapeutic (ie, nontoxic) doses succinylcholine (SuCh) causes rapid, brief (with a single dose), and noncompetitive depolarizing blockade of NM receptors on skeletal muscle. Even if skeletal muscle paralysis is maintained longer by continuous infusion of the drug (it is sometimes done), skeletal muscle function will return spontaneously—due to rapid metabolic inactivation of the drug by cholinesterases—without the need to administer any “reversal” drug. Indeed, for all practical purposes there is no clinically useful SuCh reversal drug (but see the note below). Succinylcholine has no effect on muscarinic receptors, and so atropine (a) or any other antimuscarinic drug will do nothing in terms of skeletal muscle function. Bethanechol (b) activates only muscarinic receptors (at all but extraordinarily high doses). Stigmines (neostigmine, physostigmine, or any other AChE inhibitors) will theoretically add to skeletal muscle paralysis, not reverse it. (I say theoretically because if skeletal muscle is now paralyzed by SuCh, it’s not likely that making more ACh available at the skeletal neuromuscular junction will intensify an already “maximum” response.) Note: You may have learned about so-called Phase-2 neuromuscular blockade caused by SuCh, and that it can be reversed with such drugs as atropine. This “Phase 2 block” is not a part of the “normal pharmacology” of SuCh unless a frank overdose occurs and toxicity develops. Phase 2 block can be partially reversed by administration of an anticholinergic drug (eg, glycopyrrolate or atropine itself), but adding yet another drug to a drug-overdosed patient isn’t the way to go. If Phase 2 block from succinylcholine does occur all one needs to do is keep the patient on mechanical ventilation for as long as necessary, simply wait for the drug to be eliminated (yes, it may take a while), and be as sure as possible before extubating the patient and/or stopping mechanical ventilation that spontaneous respiration is adequate and not likely to be compromised again.

Question 14

Now assume this patient received bethanechol several hours after her abdominal surgery, after effects of all the drugs used intraoperatively, except for morphine and ketorolac (analgesics) had worn Her heart rate fell s l ightly and she experienced some wheezing. Which word or phrase most l ikely accounts for or describes these cardiac and pulmonary responses?

A	Expected s ide effects
B	Idiosyncrasy
C	Parasympathetic ganglionic activation
D	Reflex (baroreceptor) suppression of cardiac rate
E	Undiagnosed asthma

Question 14 Explanation: 

These are expected side effects (not at all idiosyncratic, b) from bethanechol, a muscarinic agonist (parasympathomimetic drug). They occur even though the effects of the drug—the ones for which it is given—are “predominately” on the bladder musculature: contraction of the detrusor and relaxation of the sphincter to enable (if not cause) urination. The side effects noted in the question nonetheless are common and dose- (and patient-) dependent, and not at all idiosyncratic reactions. Moreover, although we could inhibit those side effects with an atropine-like (antimuscarinic) drug, doing so would simultaneously inhibit the drug’s intended effects on the bladder. Bethanechol has no sympathetic (or parasympathetic) ganglionic activating (c) or blocking actions at usual doses. The potential cardiac/cardiovascular effects of bethanechol used at usual doses are not so simple to explain, but certainly would not involve baroreceptor reflex-mediated suppression of cardiac rate (d). In order for the baroreceptors to reflexly suppress heart rate, blood pressure would have to go up quite a bit, and quite quickly. Bethanechol is a vasodilator, and so would lower BP (quickly, if injected too fast). The expected baroreceptor response to that would be increased sympathetic “outflow” from the CNS to the periphery, and that in turn would favor reflex tachycardia. However, bethanechol simultaneously will directly suppress spontaneous depolarization (Phase 4 of the action potential) of the S-A node, attempting to slow heart rate via direct muscarinic receptor agonist activity. So, what happens to heart rate? So the chronotropic effects depend on whether the direct bradycardic effect “wins out” or the reflex tachycardic influences do. If the patient had undiagnosed asthma (e; the presence of asthma would contraindicate use of the drug), the pulmonary response would be much more significant than “some wheezing.” Potentially fatal broncho-spasm could occur because the airway smooth muscles of asthmatic individuals are exquisitely (hyper)sensitive to muscarinic agonists, with even small doses of those drugs capable of causing a lethal outcome.

Question 15

Until recently the drug ri todrine has been used to suppress uterine contractions in some women who are in premature Side effects of the drug include ri ses of heart rate and increases in the force of contraction of the heart. High-output heart failure (caused by excessively increased cardiac output) and pulmonary edema have occurred, and in some cases the outcome has been fatal. Ritodrine also causes bronchodilation. It has no vasoconstrictor effects, nor any effects on the s i ze of the pupil(s) of the eye(s). The description most closely fi ts the characteristics of what class of drugs?

A	α-Adrenergic agonist
B	Atropine-like/antimuscarinic drug
C	β-Adrenergic agonist
D	β-Adrenergic blocker
E	Muscarinic receptor agonist (parasympathomimetic)

Question 15 Explanation: 

Ritodrine may no longer be used for suppressing premature uterine contractions (a tocolytic effect), but the description of this drug’s actions, I think, helps you work through your understanding of basic autonomic function and drugs. Ritodrine is a relatively selective β2-adrenergic agonist that relaxes uterine smooth muscle. Note the word “relatively;” the preferential β2 effects (vs β1) are not absolute, and they are dose-dependent. Yes, ritodrine, the uterine-relaxing drug is classified mechanistically the same as, for example, albuterol, salmeterol, or terbutaline, and several other drugs typically used as adrenergic bronchodilators for asthma. Will, or can, ritodrine cause bronchodilation? Absolutely, even at the relatively low doses used for uterine-relaxing effects! And when blood levels become sufficiently high (and perhaps even still in the therapeutic range for uterine effects) the preferential activation of β2 receptors is lost, and the drug behaves just like isoproterenol, the prototype β1/β2 agonist, to cause not only bronchodilation but also cardiac stimulation, enhanced renin secretion, hyperglycemia, and more. This dose-dependent loss of β2-adrenergic agonist “selectivity” is a property of all the drugs classified, quite imprecisely, as selective β2 agonists or (even less precisely) as selective adrenergic bronchodilators.

Question 16

A patient with a history of asthma experiences s ignificant bronchoconstriction and urticaria, and drug-induced histamine release i s a main contributor to these Which drug i s most l ikely to have caused these problems—not because i t has any bronchoconstrictor or histamine agonist effects in i ts own right, but because i t quite effectively releases histamine from mast cells?

A	Atropine
B	Morphine
C	Neostigmine
D	Pancuronium
E	Propranolol

Question 16 Explanation: 

Morphine is one of several drugs that can cause a “direct” degranulating effect on mast cells, causing the release of not only histamine but also of many other mast cell-derived mediators. The histamine-releasing effect is not clinically significant for patients who do not have asthma, but for many who do the bronchoconstriction can be intense and problematic. You’ll probably see the manifestations of this, even if the response is “mild.” They typically appear in the form of cutaneous flushing (largely histaminemediated), particularly in the neck and face regions. Atropine (a) causes bronchodilation by blocking muscarinic receptors on airway smooth muscle cells. Pancuronium (d) does not cause significant histamine release, nor do its related nondepolarizing skeletal neuromuscular blockers (eg, vecuronium). (D-tubocurarine, which used to be the prototype of this class of neuromuscular blockers, did cause appreciable histamine release, but it is no longer used.) Neostigmine (c) can cause significant bronchoconstriction in asthmatics, but that occurs because the drug inhibits metabolic inactivation (by AChE) of acetylcholine —another bronchoconstrictor agonist to which the airways of asthmatics are exquisitely sensitive. Propranolol (e) can provoke severe and sometimes fatal airway smooth muscle contraction in asthmatics, but that is due to blockade of epinephrine’s agonist (bronchodilator) actions on β2 receptors. It does not involve histamine release from mast cells.

Question 17

During surgery the anesthesiologist administers trimethaphan, classified as an autonomic ganglionic blocker to an anesthetized What would you expect in response to this drug?

A	Bradycardia mediated by activation of the baroreceptor reflex
B	Increased GI tract motility, possible spontaneous defecation
C	Increased salivary secretions
D	Miosis
E	Vasodilation

Question 17 Explanation: 

Answering this question requires your knowledge of two things: how trimethaphan is classified (what it does); and which branch of the autonomic nervous system, parasympathetic or sympathetic, exerts “predominant resting tone” over various structures and their functions. Trimethaphan is an autonomic ganglionic blocking drug, preventing activation of N N receptors found on all postganglionic nerves (and on the adrenal/suprarenal medulla). Upon giving this drug we essentially denervate distal structures by a pharmacologic means. (If you have not specifically learned or read about trimethaphan, perhaps you know about other and very old ganglionic blocking drugs such as hexamethonium. It’s OK to consider these ganglionic blockers equivalent for the purpose of answering this question.) Now, we observe how things change. For all the structures and functions listed (and several others that weren’t), with the exception of controlling vascular smooth muscle and peripheral resistance (vasomotor tone), it is the parasympathetic nervous system that exerts the predominant resting tone. In contrast, control of vascular smooth muscle tone (and, therefore, of peripheral resistance and blood pressure) is primarily regulated by the sympathetic nervous system. Block all ganglionic transmission and vasodilation will occur as predominant SNS influences on the vessels are removed. As far as the other structures go—all of which, I said, have predominant PNS tone at rest—you would observe a rise of heart rate (not bradycardia, a); decreases of bladder and gut tone (eg, reduced tone of the bladder detrusor and longitudinal muscles of the gut), not increases (b); contraction of sphincters in the GI and urinary tracts; mydriasis; and reduced salivary secretions (xerostomia), not increases (c). Eccrine sweat gland secretions, which are mainly under sympathetic-cholinergic influences, would decrease too. In terms of pupil size, ganglionic blockade would lead to mydriasis, not miosis (d). Finally, realize that in the presence of an autonomic ganglionic blocking drug no autonomic reflexes (eg, baroreceptor reflexes; pupillary constriction in response to bright light) can occur. Although the afferent pathways that are important in eliciting those reflexes are unimpaired, responses such as changes in heart rate or pupil size depend on intact efferent pathways, and ganglionic blockade interrupts those pathways and the reflex responses that otherwise might occur.

Once you are finished, click the button below. Any items you have not completed will be marked incorrect. Get Results

There are 17 questions to complete.

←

List

→

Return

Shaded items are complete.

1	2	3	4	5
6	7	8	9	10
11	12	13	14	15
16	17	End

Return

You have completed

questions

question

Your score is

Correct

Wrong

Partial-Credit

You have not finished your quiz. If you leave this page, your progress will be lost.

Correct Answer

You Selected

Not Attempted

Final Score on Quiz

Attempted Questions Correct

Attempted Questions Wrong

Questions Not Attempted

Total Questions on Quiz

Question Details

Results

Date

Score

Hint

Time allowed

minutes

seconds

Time used

Answer Choice(s) Selected

Question Text

All done

Need more practice!

Keep trying!

Not bad!

Good work!

Perfect!

Part 1 | Part 2 | Part 3 | Part 4 

II. Preview all questions below

1.A patient presents with an anaphylactic reaction following a wasp What i s the drug of choice for treating the multiple cardiovascular and pulmonary problems that, i f not promptly corrected, could lead to the patient’s death?

1. Atropine
2. Diphenhydramine
3. Epinephrine
4. Isoproterenol
5. Norepinephrine

2. Cardiac output improves when dobutamine i s given, by IV infusion, to a 60-year-old man with acute, symptomatic heart By what adrenergic receptor-mediated actions, and through which ultimate effects of i t, do therapeutic doses of dobutamine mainly raise cardiac output?

1. α-adrenergic agonist
2. α-adrenergic antagonist
3. β₁-adrenergic agonist
4. β₁-adrenergic antagonist.
5. Mixed α and β agonist
6. Mixed α and β antagonist

3. We are using novel in vi tro methods to investigate the fate and post-synaptic actions of norepinephrine, released upon an action potential generated in an adrenergic An action potential i s generated and the postsynaptic effector briefly responds. Almost instantaneously the response i s over. What process mainly accounted for the brevity of the response, and termination of the released NE’s actions?

1. Metabolism by enzyme(s) located near the postsynaptic receptor(s) and/or in the synaptic cleft
2. Reuptake into the nerve ending
3. Metabolism by catechol-O-methyltransferase (COMT)
4. Degradation by mitochondrial monoamine oxidase (MAO)
5. Conversion to a “false neurotransmitter” in the nerve ending

4. We are contemplating administration of a nonselective β-adrenergic blocker to a In which of the following conditions i s thisconsidered generally acceptable, appropriate, and safe?

1. Angina, vasospastic (“variant”; Prinzmetal)
2. Asthma
3. Bradycardia
4. Diabetes mellitus, insulin-dependent and poorly controlled
5. Heart block (second degree or greater)
6. Hyperthyroidism, symptomatic and acute
7. Severe congestive heart failure

5. A patient presents in the Emergency Department in great distress and with the following s igns and symptoms:

Which drug most l ikely caused these s igns and symptoms?

1. AChE inhibitor
2. α-adrenergic blocker
3. Antimuscarinic
4. β-adrenergic blocker
5. Parasympathomimetic (muscarinic agonist)
6. Peripherally acting (neuronal) catecholamine depletor

7. Acebutolol and pindolol are classified as β-adrenergic blockers with intrinsic sympathomimetic activity (ISA). In a practical sense, what does ISA mean apropos the actions of these two drugs?

1. Are partial agonists (mixed agonist/antagonists)
2. Cause norepinephrine and epinephrine release
3. Induce catecholamine synthesis
4. Potentiate the actions of norepinephrine on α-adrenergic receptors
5. Useful when cardiac positive inotropic and chronotropic effects are wanted

8. A 10-year-old boy i s diagnosed with Attention Deficit/Attention Deficit-Hyperactivity disorder (ADD/ADHD). Which drug i s most l ikely to prove effective for relieving the boy’s main symptoms?

1. Dobutamine
2. Methylphenidate
3. Pancuronium
4. Prazosin
5. Scopolamine
6. Terbutaline

Questions 8 to 14

The table below shows the perioperative medication administration record (MAR) for an otherwise healthy 50-year-old woman. (To make things interesting—and write some additional questions—I’ll deviate from her actual MAR and ask a few questions about relevant but hypothetical scenarios.) She i s a nonsmoker, consumes no more than four glasses of wine per week, and has no personal or familial ri sk factors for heart disease or diabetes. She i s taking no other medications. This patient had two scheduled (nonemergent) laparoscopic abdominal surgeries done back-to-back in the OR. The fi rst was to remove  an adnexal (ovary and/or fallopian tube) mass that had been present for a  couple of years  and grew s lowly and i rregularly over a couple of years, and to get a pathology report to see whether i t i s cancerous. Her pathology affected one ovary. Once the ovary was removed a different surgeon performed a second procedure, through the same belly incisions, to alleviate some inconvenient urinary bladder problems.

Her MAR i s very typical  of what you  would find for many otherwise healthy patients undergoing the  same or s imilar surgeries. The  fi rst drug l i sted, midazolam, was given in the preop area right before she was transported to the OR (and I will address i ts use in the CNS questions; the abbreviation IVP next to midazolam means “IV push,” that i s , a bolus injection). All the rest were given in the OR by a CRNA (certified registered nurse anesthetist).

Use the table’s data, or what you should be able to infer from i t, to answer the next seven questions.

8. Ephedrine was the fi rst drug administered after anesthesia premedication and induction with several parenteral What best describes ephedrine’s mechanism of action?

1. Directly, selectively, strongly stimulates α-adrenergic receptors in the peripheral vasculature
2. Enhances norepinephrine release by blocking presynaptic α-receptors
3. Increases norepinephrine synthesis
4. Inhibits norepinephrine’s intraneuronal metabolic inactivation
5. Releases intraneuronal norepinephrine into the synapse, also weakly but directly activates all adrenergic receptors

9. Ephedrine and drugs that act in s imilar ways or cause s imilar effects have a variety of therapeutic Given the background information provided for this patient, and the timing of ephedrine administration on the medication administration record, what i s the most l ikely reason why the ephedrine was given?

1. Cause bronchodilation so mechanical support of ventilation would be easier
2. Counteract CNS depression caused by the induction agents
3. Inhibit s inoatrial and atrioventricular nodal automaticity to terminate or prevent anesthesia-related cardiac arrhythmias
4. Lower heart rate that was raised excessively by the anesthetic drugs
5. Raise blood pressure that was lowered excessively by the induction agents

10. Assume, hypothetically, that the surgery had to be done The patient had been taking another drug—still in her ci rculation at usually effective concentrations—that weakened but did not completely eliminate all of ephedrine’s peripheral autonomic effects. Which drug(s) would be most l ikely to do that?

1. Atenolol (or metoprolol)
2. Cocaine or a tri cyclic antidepressant (eg, imipramine)
3. Trimethaphan (or hexamethonium)
4. Pargyline (or a s imilar nonselective MAO inhibitor)
5. Propranolol

11. Shortly after the surgical wounds were closed and dressed, and right before the patient was transferred to the postanesthesia care unit (PACU), she received What was the reason for which i t was given?

1. Raise and support blood pressure during recovery
2. Raise or otherwise control bradycardia upon recovery from anesthesia
3. Restore normal neurotransmission in the brain, s ince i t had been suppressed by the induction and anesthetic agents
4. Reverse skeletal neuromuscular blockade/paralysis
5. Suppress urinary bladder function to reduce the ri sk of postoperative bladder incontinence

12. The patient got her dose of glycopyrrolate mere seconds before the neostigmine was This i s done routinely in thousands of surgeries in which the drugs used are identical or at least very s imilar to those used here. To which pharmacologic class does glycopyrrolate most l ikely belong?

1. α-Adrenergic agonist
2. Antimuscarinic (atropine-like)
3. Cholinesterase inhibitor
4. Muscarinic receptor agonist
5. Nicotinic receptor (skeletal muscle; NM) agonist

13. The patient in the case presented here was not facing any emergent or imminently l i fe-threatening problems, so skeletal muscle paralysis and intubation were relatively straightforward procedures, not at all Now assume, hypothetically, that emergency intubation was required, and succinylcholine (SuCh) was used because of i ts very rapid onset of action. Assume further that a s low infusion of SuCh was used to maintain paralysis throughout the procedure; blood levels of the drug were kept well in the therapeutic range; no curare-like (nondepolarizing) blocker was used; and the patient had no genetic or other factors that would affect the drug’s pharmacokinetics or action. When the surgery i s done, what drug would be given to reverse succinylcholine’s effects?

1. Atropine
2. Bethanechol
3. Neostigmine
4. Physostigmine
5. Nothing

14. Now assume this patient received bethanechol several hours after her abdominal surgery, after effects of all the drugs used intraoperatively, except for morphine and ketorolac (analgesics) had worn Her heart rate fell s l ightly and she experienced some wheezing. Which word or phrase most l ikely accounts for or describes these cardiac and pulmonary responses?

1. Expected s ide effects
2. Idiosyncrasy
3. Parasympathetic ganglionic activation
4. Reflex (baroreceptor) suppression of cardiac rate
5. Undiagnosed asthma

15. Until recently the drug ri todrine has been used to suppress uterine contractions in some women who are in premature Side effects of the drug include ri ses of heart rate and increases in the force of contraction of the heart. High-output heart failure (caused by excessively increased cardiac output) and pulmonary edema have occurred, and in some cases the outcome has been fatal. Ritodrine also causes bronchodilation. It has no vasoconstrictor effects, nor any effects on the s i ze of the pupil(s) of the eye(s). The description most closely fi ts the characteristics of what class of drugs?

1. α-Adrenergic agonist
2. Atropine-like/antimuscarinic drug
3. β-Adrenergic agonist
4. β-Adrenergic blocker
5. Muscarinic receptor agonist (parasympathomimetic)

16. A patient with a history of asthma experiences s ignificant bronchoconstriction and urticaria, and drug-induced histamine release i s a main contributor to these Which drug i s most l ikely to have caused these problems—not because i t has any bronchoconstrictor or histamine agonist effects in i ts own right, but because i t quite effectively releases histamine from mast cells?

1. Atropine
2. Morphine
3. Neostigmine
4. Pancuronium
5. Propranolol

17. During surgery the anesthesiologist administers trimethaphan, classified as an autonomic ganglionic blocker to an anesthetized What would you expect in response to this drug?

1. Bradycardia mediated by activation of the baroreceptor reflex
2. Increased GI tract motility, possible spontaneous defecation
3. Increased salivary secretions
4. Miosis
5. Vasodilation