Autonomic Nervous System I, II & III

Stimulation of the sympathetic N.S. causes: a. Contraction of the ciliary muscle for near vision. b. Mostly generalized actions affecting many systems. c. Bronchoconstriction. d. Decreased glycogenolysis & lipolysis. e. Increased gastric HCl & pepsin secretion.

*The answer is B.* Stimulation of the sympathetic N.S. causes mostly generalized actions affecting many systems.

A patient on a diagnostic test for myasthenia gravis would be expected to have improved neuromuscular function after being treated with: A. Donepezil. B. Edrophonium. C. Atropine. D. Echothiophate. E. Neostigmine.

*The answer is B.* Edrophonium is a short-acting inhibitor of acetylcholinesterase (AChE) that is used to diagnose myasthenia gravis. It is a quaternary compound and does not enter the central nervous system. Donepezil, isoflurophate, and neostigmine are also AChEs but with longer actions. Donepezil is used in the treatment of Alzheimer disease. Echothiophate has some activity in treating open-angle glaucoma. Neostigmine is used in the treatment of myasthenia gravis but is not used in its diagnosis. Atropine is a cholinergic antagonist and, thus, would have the opposite effects.

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

*The answer is B.* 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).

Most of the parasympathetic outflow is provided by: a. The pelvic nerves b. The vagus nerve c. The collateral ganglia d. The glossopharyngeal nerve

*The answer is B.* Most of the parasympathetic outflow is provided by the vagus nerve.

Which of the following is an expected effect of a therapeutic dose of an antimuscarinic drug? (A) Decreased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased DAG (diacylglycerol) in salivary gland tissue (C) Increased IP3 (inositol trisphosphate) in intestinal smooth muscle (D) Increased potassium efflux from smooth muscle (E) Increased sodium influx into the skeletal muscle end plate

*The answer is B.* Muscarinic M1 and M3 receptors mediate increases in IP3 and DAG in target tissues (intestine, salivary glands). M2 receptors (heart) mediate a decrease in cAMP and an increase in potassium permeability. Antimuscarinic agents block these effects.

An "effective dose" of a drug is given and the following responses occur: • Stimulates heart rate and left ventricular stroke volume • Dilates some blood vessels but constricts none • Dilates bronchi (relaxes airway smooth muscles) • Raises blood glucose levels • Neither dilates nor constricts the pupil of the eye What drug is capable of causing all these responses? A. Atropine B. Epinephrine C. Isoproterenol D. Norepinephrine E. Phenylephrine

*The answer is C.* Isoproterenol is a non-selective β-adrenergic blocker, which results in these effects.

A 3-year-old child has swallowed the contents of 2 bottles of a nasal decongestant whose primary ingredient is a potent, selective α-adrenoceptor agonist drug. Which of the following is a sign of α-receptor activation that may occur in this patient? (A) Bronchodilation (B) Cardiac acceleration (tachycardia) (C) Pupillary dilation (mydriasis) (D) Renin release from the kidneys (E) Vasodilation of the splanchnic vessels

*The answer is C.* Mydriasis can be caused by contraction of the radial fibers of the iris; these smooth muscle cells have α receptors. All the other responses are mediated by β adrenoceptors.

Which one of the following is the neurotransmitter agent normally released in the sinoatrial node of the heart in response to a blood pressure increase? (A) Acetylcholine (B) Dopamine (C) Epinephrine (D) Glutamate (E) Norepinephrine

*The answer is A.* Acetylcholine is the transmitter at parasympathetic nerve endings innervating the sinus node (nerve endings of the vagus nerve). When blood pressure increases, the parasympathetic system is activated and heart rate slows.

The synthesis of norepinephrine is prevented by : a. Alpha-methyltyrosine. b. Ephedrine. c. Pilocarpine. d. Reserprine. e. Hexamethonium. f. None of the above.

*The answer is A.* Alpha-methyltyrosine is an indirect adrenergic antagonist. It is a competitive inhibitor of tyrosine hydroxylase and inhibits the synthesis of NE.

Injection of atropine is liable to cause: a. Constipation. b. Diarrhoea. c. Bronchial constriction. d. Bradycardia. e. No effect on either reading or micturition.

*The answer is A.* Atropine blocks muscarinic receptors, which would decrease parasympathetic tone.

Nicotinic receptor sites do not include which one of the following sites? (A) Bronchial smooth muscle (B) Adrenal medullary cells (C) Parasympathetic ganglia (D) Skeletal muscle end plates (E) Sympathetic ganglia

*The answer is A.* Both types of ganglia and the skeletal muscle neuromuscular junction have nicotinic cholinoceptors, as does the adrenal medulla (a modified form of sympathetic postganglionic neuron tissue). Bronchial smooth muscle contains muscarinic cholinoceptors and noncholinergic receptors.

A drug that acts at prejunctional α2-adrenoceptors and is used to treat hypertension is (A) Clonidine (B) Methoxamine (C) Metaproterenol (D) Dobutamine (E) Dopamine

*The answer is A.* Clonidine acts at prejunctional α2-adrenoceptors and is used to treat hypertension. Methoxamine is a non-selective α-adrenoceptor agonist. Metaproterenol is a selective b2-adrenoceptor agonist. Dobutamine is a relatively selective β1-adrenoceptor agonist. Dopamine activates both pre-junctional and postjunctional dopamine receptors and also b1-adrenoceptor.

Patient presents with salivation, lacrimation, urination and defecation as side effects of a medication. Which one of the following receptors mediates the actions of this drug? A. Nicotinic receptors. B. α Receptors. C. Muscarinic receptors. D. β Receptors.

*The answer is C.* The muscarinic receptors of the parasympathetic nervous system maintain essential body functions such as digestion and waste elimination. The nicotinic receptors are a receptor for acetylcholine. It plays a major role in skeletal muscles, ganglia and synthesis of catecholamines in the adrenal medulla. α and β receptor are receptors for norepinephrine and epinephrine and activation

A 32-year-old woman with change in vision presents to the ambulatory care clinic complaining of dry eye and visual field changes. She is seen by the on-call ophthalmologist who wants to evaluate the eye with a funduscopic examination. The following figure shows two medications that could be given to facili-tate the examination. Which of the following statements is true? (A) Atropine is represented by letter B (B) Carbachol is represented by letter A (C) Mydriasis would challenge visualization during the examination (D) The untreated eye is appropriate for examination

*The answer A.* Atropine is a muscarinic blocker and will cause mydriasis. This dilation of the pupil facilitates ophthalmologic examination. (B) Pilocarpine is represented by letter A. This agent will cause contraction of the pupil. (C) Mydriasis would facilitate ophthalmologic examination. (D) The untreated eye has a narrow pupil which would not allow for complete examination of the fundus.

A 7-year-old boy is brought in by his parents for complaints of hyperactivity at school. He is also inattentive and impulsive at home. After a detailed interview, the physician decides to give the boy amphetamine-containing medication for presumed attention hyperactivity disorder. Amphetamine (A) Inhibits epinephrine reuptake (B) Indirectly acts on norepinephrine receptors (C) Blocks effects of norepinephrine (D) Directly acts on cholinoreceptors (E) Inhibits serotonin reuptake

*The answer B.* Amphetamine and similar compounds are stimulants used for treatment of attention-deficit/hyperactivity disorder (ADHD) in which they are thought to act centrally to increase attention span. Currently there is no medication on the U.S. market that inhibits reuptake of epinephrine. Blocking of the effects of norepinephrine will not alleviate symptoms of ADHD. Direct-acting cholinoceptor agonists are not used in treatment of ADHD. Serotonin reuptake inhibitors are used for depression and some other conditions.

Nearly every structure that is influenced by the sympathetic nervous activity has postganglionic sympathetic (adrenergic) nerves innervating it. Which one of the following structures is most definitely affected by sympathetic nervous system influences, and responds to epinephrine, but lacks innervation by postganglionic adrenergic fibers and so is not affected by norepinephrine released from adrenergic nerves? a Airway (eg, bronchiolar) smooth muscl e b. Arteriolar smooth muscle c. Iris dilator muscles of the eyes d. Sinoatrial cells (pacemaker) of the heart e. Ventricular myocytes

*The answer is A. 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 receptor 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.

What is the mechanism of action of cocaine? (A) Propagation of action of norepinephrine by inhibiting its active transport from the synapse (B) Oxidative deamination of norepinephrine in nerve terminals and the effector cells (C) Inhibition of metabolism of norepinephrine in nerve terminals (D) Potentiation of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of norepinephrine (E) Promotion of release of norepinephrine from adrenergic nerve endings

*The answer is A.* Cocaine is a potent inhibitor of norepinephrine uptake, a process that normally terminates norepinephrine's action. Oxidative deamination of norepinephrine in nerve terminals and the effector cells describes the action of monoamine oxidase, which is targeted by certain antidepressant medications. Inhibition of metabolism of norepinephrine in nerve terminals describes catechol-O-methyltransferase, which is found in nerve and other effector cells. Potentiation of tyrosine dehydroxylase would, in fact, cause excessive amounts of norepinephrine to accumulate; however, this enzyme is not affected by cocaine. Norepinephrine release can be blocked, not promoted, by agents such as bretylium and guanethidine.

Dantrolene is the drug of choice to treat malignant hyperthermia caused by succinylcholine because dantrolene (A) Blocks Ca2+ release from sarcoplasmic reticulum (B) Induces contraction of skeletal muscle (C) Increases the rate of succinylcholine metabolism (D) Inhibits succinylcholine binding to nicotinic receptors (E) Acts centrally to reduce fever

*The answer is A.* In patients with malignant hyperthermia, a rare hereditary disorder, an impaired sarcoplasmic reticulum is unable to sequester calcium. The sudden release of calcium results in extensive muscle contraction that can be reduced with dantrolene.

In the parasympathetic system: a. Axons of the postganglionic neurons are shorter than those of preganglionic neurons b. Preganglionic neurons are more numerous than the postganglionic neurons c. Choline acetylase is the transmitter between the preganglionic and postganglionic neurons d. Axons of preganglionic neurons from the spinal sacral segments pass through the ventral roots of the spinal sacral nerves

*The answer is A.* In the parasympathetic system, axons of the postganglionic neurons are shorter than those of preganglionic neurons.

Commonalities of the sympathetic, parasympathetic, and somatic nervous systems involve which of the following neuroeffector transmitters? (A) Acetylcholine (B) Dopamine (C) Epinephrine (D) Norepinephrine (E) Serotonin

*The answer is A.* In the somatic and autonomic nervous system, the common neuroeffector transmitter is acetylcholine. However, in sympathetic stimulation of the adrenal medulla, epinephrine is released into the blood. In the sympathetic nervous system, norepinephrine is released by the postganglionic neurons. (B) Dopamine is a not a preganglionic neurotransmitter for the autonomic or somatic nervous systems. (C) Epinephrine is released as a postganglionic neurotransmitter in sympathetic stimulation of the adrenal medulla. (D) Norepinephrine is released as the postganglionic neurotransmitter of the sympathetic nervous system. (E) Serotonin is a not a preganglionic neurotransmitter for the autonomic or somatic nervous systems.

Inhibitors of choline esterase enzymes: a. Enhance the effects of parasympathetic stimulation b. Inhibit the effect of parasympathetic stimulation c. Inhibit acetylcholine release by cholinergic nerve terminals d. Block the action of acetylcholine in autonomic ganglia

*The answer is A.* Inhibitors of choline esterase enzymes enhance the effects of parasympathetic stimulation.

Festoterodine is a relatively new drug that was heavily marketed to prescribers and directly to consumers. It is 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 simultaneously prevents relaxation of the sphincter. Side effects include constipation, dry mouth, blurred vision, photophobia, urinary retention, and slight 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 is most like festoterodine? a. Atropine b. ß-adrenergic blockers (eg, propranolol) c. Isoproterenol d. Neostigmine e. Phentolamine

*The answer is A.* The description of this drug is, in reality, also an excellent description of many of the properties of atropine, the prototype muscarinic receptor locking drug , and of nearly a dozen other antimuscarinics marketed for "overactive bladder." In terms of bladder function, paras ympa thetic 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.

For this question, use the accompanying diagram. Assume that the diagram can represent either the sympathetic or the parasympathetic system. If the effector cell in the diagram is a thermoregulatory sweat gland, which of the following transmitters is released from structure 5? (A) Acetylcholine (B) Dopamine (C) Epinephrine (D) Norepinephrine

*The answer is A.* The nerves innervating the thermoregulatory (eccrine) sweat glands are sympathetic cholinergic nerves.

A 15-year-old boy attempts suicide and is brought to the emergency department by the local rescue squad. He was found in the garage with an opened spray bottle of insecticide nearby. He has lost conscious-ness. His heart rate is 45 beats/minute, and his blood pressure is 80/40 mm Hg. He is sweating and salivating profusely. What is the most appropriate treatment for this patient? (A) Atropine (B) Edrophonium (C) Norepinephrine (D) Physostigmine (E) Trimethaphan

*The answer is A.* The patient is exhibiting signs of cholinergic stimulation. Insecticide poisoning is a likely diagnosis. Thus, either intravenous or intramuscular doses of atropine are indicated to antagonize the muscarinic symptoms.

Assume that the diagram below represents a sympathetic postganglionic nerve ending. Which of the following inhibits the carrier denoted "z" in the diagram? (A) Cocaine (B) Dopamine (C) Hemicholinium (D) Reserpine (E) Vesamicol

*The answer is A.* The reuptake carrier in sympathetic postganglionic nerve endings can be blocked by cocaine or tricyclic antidepressants. Hemicholiniums and vesamicol block transporters in cholinergic nerves

The sympathetic supply is not responsible for: a. Constriction of the pupil. b. Erection of hair. c. Secretion of eccrine sweat glands. d. Dilatation of skeletal muscle blood vessels. e. Spleen contraction

*The answer is A.* The sympathetic supply is not responsible for the constriction of the pupil; is is responsible for pupil dilation.

A floor nurse pages you about a patient who is having chest pain. You order an electrocardiogram and rush to see the patient. He describes the pain as tight pressure and is demonstrably sweating and gasping for air. The ECG comes back with acute ST-segment elevations in inferior leads, and you diagnose a myocardial infarction. You start giving the patient oxygen and give him sublingual nitroglycerin and morphine for pain. You also give him another medication, which you have read may prolong his survival in this dire situation. What class of medication is it? (A) β-Blocker (B) α-Agonist (C) Muscarinic agonist (D) Neuromuscular blocker (E) Dopamine agonist

*The answer is A.* β-Blockers such as atenolol are now part of the management of acute myocardial infarction, along with oxygen, nitroglycerin, and morphine. They reduce sympathetic activity and heart contractility, thereby reducing the oxygen demand. α-Agonists such as phenylephrine are used in management of hypotension due to shock. Muscarinic agonists such as pilocarpine can be used in the management of glaucoma. Neuromuscular blockers such as atracuronium are used in anesthesia. Dopamine agonists are used in management of Parkinson disease.

Sympathetic activity is not enhanced by administration of: a. A drug that inhibit monoamine oxidase enzyme b. A drug that inhibit nicotinic receptor c. A drug that inhibit norepinephrine reuptake by nerve terminals d. A drug that enhanced norepinephrine storage in presynaptics

*The answer is B.* A drug that inhibits nicotinic receptors would block the receptor on sympathethic postganglionic neurons.

All the following about acetylcholine is correct except: a. It causes slowing of the heart rate. b. It is released by the parasympathetic nerve endings in the sweat glands . c. It is the neurotransmitter in the suprarenal medullae. d. It is not affected by the enzyme COMT. e. Its synthesis requires the enzyme choline acetylase.

*The answer is B.* Acetylcholine is released by sympathethic nerve endings int he sweat glands.

Administration of a muscarinic receptor antagonist leads to: a. Increased sweat secretion b. Decreased sweat secretion c. Increased gastric motility d. Bronchoconstriction

*The answer is B.* Administration of a muscarinic receptor antagonist leads to decreases sweat secretion.

All preganglionic autonomic neurons secrete: a. Epinephrine. b. Acetylcholine. c. Nicotine. d. Dopamine.

*The answer is B.* All preganglionic autonomic neurons secrete acetylcholine.

Ms Brown has been treated for myasthenia gravis for several years. She reports to the emergency department complaining of recent onset of weakness of her hands, diplopia, and difficulty swallowing. She may be suffering from a change in response to her myasthenia therapy, that is, a cholinergic or a myasthenic crisis. Which of the following is the best drug for distinguishing between myasthenic crisis (insufficient therapy) and cholinergic crisis (excessive therapy)? (A) Atropine (B) Edrophonium (C) Physostigmine (D) Pralidoxime (E) Pyridostigmine

*The answer is B.* Any of the cholinesterase inhibitors (choices B, C, or E) would effectively correct myasthenic crisis. However, because cholinergic crisis (if that is what is causing the symptoms) would be worsened by a cholinomimetic, we choose the shortest-acting cholinesterase inhibitor, edrophonium.

Several children at a summer camp were hospitalized with symptoms thought to be due to ingestion of food containing botulinum toxin. Which one of the following signs or symptoms is consistent with the diagnosis of botulinum poisoning? (A) Bronchospasm (B) Cycloplegia (C) Diarrhea (D) Skeletal muscle spasms (E) Hyperventilation

*The answer is B.* Botulinum toxin impairs all types of cholinergic transmission, including transmission at ganglionic synapses and somatic motor nerve endings. Botulinum toxin prevents discharge of vesicular transmitter content from cholinergic nerve endings. All of the signs listed except cycloplegia indicate increased muscle contraction; cycloplegia (paralysis of accommodation) results in blurred near vision.

A substance abuser self-administers cocaine and experiences cardiovascular function, in addition to the CNS-stimulating effects for which the drug was used. What statement describes the mechanism by which the cocaine caused its 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 sympathomimetic (adrenomimetic) responses d. Inhibits MAO, leading to increased intraneuronal NE levels e. Prevents NE exocytosis

*The answer is B.* 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 ) re-enters 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 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.

A 67-year-old man with early onset of Alzheimer's disease is being seen by his primary care physician. Consideration is being made to begin preemptive therapy with an anticholinesterase inhibitor. The patient and family are made aware of such side effects as nausea, vomiting, diarrhea, and muscle cramps. The mechanism of action of these effects likely involves which of the following? A) Adrenergic transmission (B) Cholinergic transmission (C) Purine metabolism impairment (D) Transaminase enzyme elevation (E) Uremia

*The answer is B.* Common adverse effects of anticholinesterase inhibitors to treat Alzheimer's disease include nausea, diarrhea, vomiting, anorexia, tremors, bradycardia, and muscle cramps, all of which are predicted by the actions of the drugs to enhance cholinergic neurotransmission. (A) Anticholinesterase inhibitors do not affect adrenergic transmission. (C) Purine metabolism is not impaired by anticholinesterase inhibitors. (D) Transaminase enzyme elevation is unlikely in patients taking anti-cholinesterase inhibitors. (E) There is no evidence to suggest uremia in this case.

Which of the following may be produced by parasympathetic stimulation: a. Acceleration of the heart. b. Contraction of the urinary bladder wall. c. Vasodilation of skeletal muscle blood vessels. d. Dilatation of the pupil. e. Relaxation of the GIT wall

*The answer is B.* Contraction of the urinary bladder wall may occur via parasympathetic stimulation.

Actions and clinical uses of muscarinic cholinoceptor agonists include which one of the following? (A) Bronchodilation (asthma) (B) Improved aqueous humor drainage (glaucoma) (C) Decreased gastrointestinal motility (diarrhea) (D) Decreased neuromuscular transmission and relaxation of skeletal muscle (during surgical anesthesia) (E) Increased sweating (fever)

*The answer is B.* Muscarinic agonists cause accommodation and cyclospasm, the opposite of paralysis of accommodation (cycloplegia). In open-angle glaucoma, this results in increased outflow of aqueous and decreased intraocular pressure. These agents may cause bronchospasm but have no effect on neuromuscular transmission. They may cause diarrhea and are not used in its treatment. Muscarinic agonists may also cause sweating, but drug-induced sweating is of no value in the treatment of fever.

A child overdoses on a drug that affects both the autonomic and somatic nervous systems. As blood levels of the drug rise he experiences hypertension and tachycardia, accompanied by skeletal muscle tremor. Further elevations of blood levels of the drug cause all the expected signs and symptoms of autonomic ga nglionic blockade, plus weakness and eventual paralysis of skeletal muscle. Which drug did the child most likely ingest? a. Bethanechol b. Nicotine c. Pilocarpine d. Propranolol (or another β-adrenergic blocker) e. Scopolamine

*The answer is B.* Nicotine initially stimulates and then blocks nicotinic-skeletal muscular (NM) and nicotonic-neural (NN; in autonomic ganglia and on adrenal medullary cells) cholinergic receptors. Initial ganglionic stimulation leads to vasoconstriction and hypertension, both of which are manifestation of sympathetic activation. Bradycardia may or may not occur; parasympathetic ganglionic activation is likely to increase the predominant parasympathetic (bradycardic) tone on heart rate, but sympathetic activation may cause the opposite effect. Initial stimulation of skeletal muscle NM receptors would account for the tremor. As nicotine's blood levels rise we get autonomic ganglionic blockade, leading to hypotension and bradycardia. Subsequent blockade at the skeletal neuromuscular junction leads to muscle weakness and respiratory depression caused by interference with the function of the diaphragm and intercostals.

Not shown in the diagram is an enzyme that has the ability to metabolically inactivate NE that has diffused away from the synapse. It is also present in the liver (as is MAO) and in the intestinal walls. Among other things, the rapidity with which this enzyme catabolizes its substrate 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 thisdrug is used therapeutically, but not for its autonomic effects. What is the name of this enzyme? a. Aromatic l-amino acid decarboxylase b. Catechol O-methyltransferase (COMT) c. Dopamine ß-hydroxylase d. Phenylethanolamine N-methyltransferase e. Tyrosine hydroxylase

*The answer is B.* 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).

Prolonged apnea may occur following administration of succinylcholine to a patient with a hereditary deficiency of which of the following enzymes? (A) Glucose-6-phosphate dehydrogenase (B) Plasma cholinesterase (C) Monoamine oxidase (D) Cytochrome P4503A (E) Acetylcholinesterase

*The answer is B.* Plasma cholinesterase is responsible for the rapid inactivation of succinylcholine.

The para-sympathetic nervous system has a discrete response. The ganglia are close to the target organs. The para-sympathetic nervous system has long preganglionic fibers and short postganglionic fibers. (A) The sym-pathetic nervous system has a diffuse response. (B) The sympathetic nervous system has extensive preganglionic fiber branching. (C) The sympathetic nervous system has ganglia that are close to the spinal cord. (E) The sympathetic nervous system has a wide distribution.

*The answer is B.* Potency is defined as the amount of drug it takes to have a certain effect. Efficacy is defined as the greatest effect a drug can possibly have. Imagine two drugs, A and B. We will say Drug A has a maximal effect at a concentration of 1 mg/mL. Giving more Drug A past this level produces no increase in response. Now, let us say Drug B produces the same maximal effect but at a concentration of 0.01 mg/mL. Giving more Drug B past this level will have no in-crease in response. Although both drugs have the same maximal effect, Drug B exerts that effect at a much lower concentration than Drug A. We can say then that Drug A and Drug B have the same efficacy, but Drug B is more potent than Drug A. In the presence of competitive inhibition, more native ligand or substrate is needed to achieve any given effect. Therefore, potency is decreased with competitive inhibition.

We are using novel in vitro methods to investigate the fate and post-synaptic actions of norepinephrine, released upon an action potential generated in an adrenergic nerve. An action potential is generated and the post-synaptic effector briefly responds. Almost instantaneously the response is 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-methyltransferse (COMT) D. Degradation by mitochondrial monoamine oxidase (MAO) E. Conversion to a "false neurotransmitter" in the nerve ending

*The answer is B.* Reuptake into the nerve ending mainly accounts for the brevity of the response, and termination of the released NE's actions.

Which of the following visceral tissues receives sympathetic postganglionic neurons only? a. Adrenal medulla b. Sweat glands c. Anal sphincters d. The iris

*The answer is B.* Sweat glands only receive sympathetic postganglionic neurons.

A 2-year-old child has been admitted to the emergency department. Antimuscarinic drug overdose is suspected Probable signs of atropine overdose include which one of the following? (A) Gastrointestinal smooth muscle cramping (B) Increased heart rate (C) Increased gastric secretion (D) Pupillary constriction (E) Urinary frequency

*The answer is B.* Tachycardia is a characteristic atropine overdose effect. Bradycardia is sometimes observed after small doses.

Which statement correctly describes what is rather unique about nerve g, the postganglionic fibers that innervate eccrine sweat glands, compared with virtually all other postganglionic sympathetic nerves? a. Cocaine blocks release of its 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 its neurotransmitter

*The answer is B.* 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 arrestor 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 innerva te most sweat glandsand arrector pili muscles, of course.

A medical student is involved in a summer research project evaluating the potencies of the α-adrenergic agonists at different receptor sites. Which of the following α-adrenergic agonists would be expected to have the strongest potency at the α-receptor? (A) Acetylcholine (B) Epinephrine (C) Isoproterenol (D) Metanephrine (E) Norepinephrine

*The answer is B.* The α-adrenoceptors show a weak response to the synthetic agonist isoproter-enol, but they are responsive to the naturally occurring catecholamines: epinephrine and norepinephrine. For receptors, the rank order of potency is epinephrine < norepinephrine < isoproterenol. (A) Acetylcholine is a cholinomimetic agent. (C) Isoproterenol is the least potent receptor agonist. (D) Metanephrine is a break-down product of catecholamines. (E) Norepinephrine has intermediate potency at the α-receptor sites.

The direct cardiac effects of dobutamine would be blocked by which one of the following agents? (A) Prazosin (B) Metoprolol (C) Clonidine (D) Isoproterenol

*The answer is B.* The β1-adrenoceptor antagonist metoprolol blocks the β1-adrenoceptor activity of dobutamine.

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 is free in the nerve terminal C. Metabolizes dopamine to norepinephrine D. Provides metabolic energy for non-exocytotic release of norepinephrine in response to amphetamines and other catecholamine-releasing drugs E. Synthesizes ATP that is required to transport free intraneuronal norepinephrine into the storage granules/vesicles

*The answer is B.* While mitochondria in virtually all cells in which they are found are important 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 shown in the diagram are responsible for intraneuronal movement of NE-containing storage vesicles to, an 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 non-exocytotic NE release (d), and plays no role in ATP synthesis (e).

What intracellular effect does albuterol, a β2-agonist, produce? (A) Allows passage of sodium through a ligand-gated ion channel (B) Activates Gs-protein, resulting in stimulation of adenylyl cyclase (C) Activates Gq-protein, resulting in increase of phosphatidylinositol and calcium mobilization (D) Activates Gi-protein, resulting in inhibition of adenylyl cyclase (E) Binds to μ-receptors in the specific areas of the brain

*The answer is B.* β2-agonists, like albuterol, activate Gs-protein, which results in stimulation of adenylyl cyclase, with subsequent increase in intracellular cAMP. Passage of sodium via ligand-gated ion channel is manifested by nicotinic acetylcholine receptors. Activation of Gq-protein resulting in increase of phosphatidylinositol and calcium mobilization refers to the mechanism of action of muscarinic receptors type M1 and M3, as well as α1-adrenoceptors. Activation of Gq-protein resulting in an increase of phosphatidylinositol and calcium mobilization refers to the mechanism of action of M2-cholinoceptors and α2 adrenoceptors. Finally, binding to μ-receptors in the specific areas of the brain describes the action of opioid agents.

A drugs which blocks beta adrenoceptors is likely to cause: a. Relaxation of sphincters in the alimentary tract. b. Dilatation of the bronchi. c. A decrease in the force of myocardial contraction in someone with heart failure. d. A decreased dilatation by the blood vessels of skeletal muscles in response to circulating adrenaline.

*The answer is C.* A drugs which blocks beta adrenoceptors (more specifically, beta 1) is likely to cause a decrease in the force of myocardial contraction in someone with heart failure.

A morbidly obese person visits the local bariatric (weight loss) clinic seeking a pill that will help shed weight. The physician prescribes dextroamphetamine. In addition to causing its expected centrally mediated anorexigenic (appetite-suppressant) and cortical-stimulating effects it 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 activa ting a2 receptors

*The answer is C.* Amphetamines (dextroamphetamine, methamphetamine, amphetamine, and several related drugs) can be classified as indirect-acting sympathomimetics (adrenomimetic). 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.

Multidisciplinary assessments of nerve d, a typical postganglionic sympathetic nerve, indicate that it is quite different from all the other nerves shown in the peripheral nervous system schematic. 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 it is activated c. It is adrenergic d. The primary neurotransmitter synthesized by nerve d is epinephrine e. When nerve d is physiologically activated by an action potential, actions of its released neurotransmitter are terminated mainly by hydrolysis in the synaptic cleft

*The answer is C.* 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 and release 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 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.

A 65-year-old woman with long-standing diabetes mellitus is admitted to the ward from the emergency department, and you wish to examine her retinas for possible changes. Which of the following drugs is a good choice when pupillary dilation—but not cycloplegia—is desired? (A) Isoproterenol (B) Norepinephrine (C) Phenylephrine (D) Pilocarpine (E) Tropicamide

*The answer is C.* Antimuscarinics (tropicamide) are mydriatic and cycloplegic; α-sympathomimetic agonists are only mydriatic. Isoproterenol has negligible effects on the eye. Norepinephrine penetrates the conjunctiva poorly and would produce intense vasoconstriction. Pilocarpine causes miosis.

A drug which blocks the beta adrenergic receptors causes: a. Dilatation of the bronchial muscle. b. Relaxation of the sphincters in the alimentary canal. c. Inhibition of cardiac properties. d. Dilatation of the visceral blood vessels. e. Reduction of the blood glucose due to stimulation of insulin release.

*The answer is C.* Beta 1 adrenergic antagonists decrease heart rate and contractility.

A drug that blocks the beta adrenergic receptors in likely to cause: a. Relaxation of the sphincters of the GIT. b. An increase in the cardiac properties. c. Increased glycogenolysis & lipolysis in response to epinephrine. d. Bronchoconstriction. e. Excessive V.D. in skeletal muscles in response to epinephrine

*The answer is C.* Beta 2 adrenergic antagonists inhibit bronchodilation.

Botulinum toxin causes paralysis by (A) Inhibiting choline acetyltransferase (B) Blocking transport of choline into neurons (C) Blocking release of acetylcholine from storage vesicles (D) Inhibiting acetylcholinesterase (E) Blocking the synapse at ganglia

*The answer is C.* Botulinum toxin blocks calcium-dependent exocytosis of acetylcholine from storage vesicles, producing paralysis. Common sources of botulinum toxin include canned home goods and, in cases of infant botulism, honey. The condition is life threatening, and urgent care is necessary. Choline acetyltransferase is an enzyme catalyzing synthesis of acetylcholine from an acetate and choline. Sodium-dependent transport of choline can be blocked by hemicholinium. Enzyme acetylcholinesterase is responsible for catalyzing hydrolysis of acetylcholine. Acetylcholine synapses at the ganglia of many neurons and tissues, and this step is not blocked by botulinum toxin.

A novel medication to treat gastric motility disorders will act at the terminal step in the synthesis/breakdown of acetylcholine. Which of the following is the terminal step in the synthesis and release of acetylcholine? (A) Degradation (B) Release of neurotransmitter (C) Recycling of choline (D) Synthesis (E) Uptake into storage vesicles

*The answer is C.* Choline may be recaptured by a sodium-coupled, high-affinity uptake system that transports the molecule back into the neuron. There, it is acetylated into ACh that is stored until released by a subsequent action potential.

Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic insufficiency). You are considering different therapies for his disease. Pyridostigmine and neostigmine may cause which one of the following? (A) Bronchodilation (B) Cycloplegia (C) Diarrhea (D) Irreversible inhibition of acetylcholinesterase (E) Reduced gastric acid secretion

*The answer is C.* Cholinesterase inhibition is typically associated with increased (never decreased) bowel activity. (Fortunately, many patients become tolerant to this effect.)

Cardiac output improves when dobutamine is given, by IV infusion, to a 60-year-old man with acute, symptomatic heart failure. By what adrenergic receptor-mediated actions, and through which ultimate effects of it, do therapeutic doses of dobutamine mainly rise 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

*The answer is C.* Dobutamine is mainly 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.

Emergency treatment of acute heart failure is best managed with which of the following drugs? (A) Metaproterenol (B) Phenylephrine (C) Dobutamine (D) Norepinephrine (E) Isoproterenol

*The answer is C.* Dobutamine, a relatively selective β1-adrenoceptor agonist, increases cardiac output and lowers peripheral resistance. Metaproterenol has a relatively more selective action on the respiratory system than the cardiovascular system. Phenylephrine and norepinephrine increase peripheral resistance. Isoproterenol increases heart rate.

Four new synthetic drugs (designated W, X, Y, and Z) are to be studied for their cardiovascular effects. They are given to 4 anesthetized animals while the heart rate is recorded. The first animal has received no pretreatment (control); the second has received an effective dose of hexamethonium; the third has received an effective dose of atropine; and the fourth has received an effective dose of phenoxybenzamine. The net changes induced by the new drugs (not by the blocking drugs) are described in the following questions. Drug Y had the effects shown in the table below. Drug Y is probably a drug similar to (A) Acetylcholine (B) Edrophonium (C) Isoproterenol (D) Norepinephrine (E) Prazosin

*The answer is C.* Drug Y causes tachycardia that is not significantly influenced by any of the blockers; therefore, drug Y must have a direct β-agonist effect on the heart.

Which of the following statements is correct about the normal functioning of the nicotinic receptors in a 19-year-old man college student athlete from the college baseball team? (A) Nicotine at high doses stimulates the receptor (B) Nicotinic receptors are located in the adrenal cortex (C) Nicotinic receptors are located in the autonomic ganglia (D) Nicotinic receptors located at the neuromuscular junction are known as NN receptors

*The answer is C.* Nicotine at low concentration stimulates the receptor and at high concentration blocks the receptor. Nicotinic receptors are located in the CNS, adrenal medulla, autonomic ganglia, and the neuromuscular junction (NMJ). Those at the NMJ are sometimes designated NM and the others, NN. The nicotinic receptors of autonomic ganglia differ from those of the NMJ. For example, ganglionic receptors are selectively blocked by hexamethonium, whereas NMJ receptors are specifically blocked by tubocura-rine.

For this question, use the accompanying diagram. Assume that the diagram can represent either the sympathetic or the parasympathetic system. Norepinephrine acts at which of the following sites in the diagram? (A) Sites 1 and 2 (B) Sites 3 and 4 (C) Sites 5 and 6

*The answer is C.* Norepinephrine acts at presynaptic α2 regulatory receptors (site 5) and postsynaptic α1 adrenoceptors (site 6). It may be metabolized by enzymes outside the synapse or transported back into the nerve terminal.

A soldier's unit has come under attack with a nerve agent. The symptoms exhibited are skeletal muscle paralysis, profuse bronchial secretions, miosis, bradycardia, and convulsions. The alarm indicates exposure to an organophosphate. What is the correct treatment? A. Do nothing until you can confirm the nature of the nerve agent. B. Administer atropine, and attempt to confirm the nature of the nerve agent. C. Administer atropine and 2-PAM (pralidoxime). D. Administer pralidoxime.

*The answer is C.* Organophosphates exert their effect by irreversibly binding to acetylcholinesterase (AChE) and, thus, can cause a cholinergic crisis. Administration of atropine will block the muscarinic sites, but it will not reactivate the enzyme, which will remain blocked for a long period of time. Therefore, it is essential to also administer pralidoxime as soon as possible to reactivate the enzyme before aging occurs. Administering pralidoxime alone will not protect the patient against the effects of acetylcholine resulting from AChE inhibition.

Parasympathetic preganglionic neurons: a. Are much shorter than the postganglionic neurons b. Are more numerous than the postganglionic neurons c. Secrete the same transmitter as the postganglionic neurons d. Originate from all the sacral segments of the spinal cord

*The answer is C.* Parasympathetic preganglionic neurons secrete the same transmitter as the postganglionic neurons - acetylcholine.

Phenylephrine is used to treat patients with nasal mucosa stuffiness because it causes vasoconstriction by (A) Blocking nicotinic cholinoceptors (B) Blocking β-adrenoceptors (C) Stimulating α-adrenoceptors (D) Stimulating muscarinic cholinoceptors

*The answer is C.* Phenylephrine activates α-adrenoceptors, producing vasoconstriction.

Full activation of the sympathetic nervous system, as in the fight-or-flight reaction, may occur during maximal exercise. Which of the following effects is likely to occur? (A) Bronchoconstriction (B) Increased intestinal motility (C) Decreased renal blood flow (D) Miosis (E) Decreased heart rate (bradycardia)

*The answer is C.* Sympathetic discharge causes constriction of the renal resistance vessels and a fall in renal blood flow. This is the typical response in severe exercise or hypotension. The other effects are parasympathomimetic actions.

Sympathetic stimulation of the iris causes: a. Astigmatism. b. Pupillary constriction. c. Pupillary dilation. d. Vitreous secretion

*The answer is C.* Sympathetic stimulation of the iris causes pupillary dilation.

A researcher who is interested in creating an anticholinergic agent that would be useful in patients with irritative bladder symptoms would be interested in targeting which of the following receptors? (A) M1 (B) M2 (C) M3 (D) M4 (E) M5

*The answer is C.* The M3 receptor is felt to be bladder specific. However, this receptor is also found on exocrine glands such as salivary glands and smooth muscle. Specifically, although all five subtypes have been found on neurons, M1 receptors are also found on gastric parietal cells and M2 receptors on cardiac cells and smooth muscle. (A) M1 receptors are found on gastric parietal cells. (B) M2 receptors are found on cardiac cells and smooth muscle. (D) M4 receptors are found on neurons. (E) M5 receptors are found on neurons.

We administer a drug that is a selective antagonist at the presynaptic α-receptors (α₂) in the peripheral nervous systems. It has no effect on α₁ receptors, β receptors, or any other ligand receptors that are important in peripheral nervous system function. What is the main response that is likely 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

*The answer is C.* 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 a 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.

We administer a pharmacologic dose of epinephrine and observe (among other responses) a direct increase of cardiac rate, contra ctility, andelectrical impulse conduction rates. Which adrenergic receptor was responsible for these direct cardiac effects ? a. α1 b. α2 c. β1 d. β2 e. β3a

*The answer is C.* 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 epinephrine-induced increased dirign rate of the SA node, increased conduction velocity through the AV node and His-Purkinje system, and increased contractility and condution velocity of atrial and ventricular muscle.

Nerve g, the postganglionic nerve innervating eccrine sweat glands and arrector pili muscles, is 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 е. β₁ adrenergic f. β₂ adrenergic

*The answer is C.* 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.

Which one of the following is characteristic of parasympathetic stimulation? A. Decrease in intestinal motility. B. Inhibition of bronchial secretion. C. Contraction of sphincter muscle in the iris of the eye (miosis). D. Contraction of sphincter of urinary bladder. E. Increase in heart rate.

*The answer is C.* The parasympathetic nervous system is essential in maintenance activities, such as digestion and waste removal. Therefore, increased intestinal motility to facilitate peristalsis, relaxation of urinary bladder sphincters to cause urination, and increased bronchial secretions result. Increase in heart rate is a function of the sympathetic nervous system.

Which one of the following statements concerning the parasympathetic nervous system is correct? A. The parasympathetic system uses norepinephrine as a neurotransmitter. B. The parasympathetic system often discharges as a single, functional system. C. The parasympathetic division is involved in accommodation of near vision, movement of food, and urination. D. The postganglionic fibers of the parasympathetic division are long compared to those of the sympathetic nervous system. E. The parasympathetic system controls the secretion of the adrenal medulla.

*The answer is C.* The parasympathetic system maintains essential bodily functions, such as vision, movement of food, and urination. It uses acetylcholine, not norepinephrine, as a neurotransmitter, and it discharges as discrete fibers that are activated separately. The postganglionic fibers of the parasympathetic system are short compared to those of the sympathetic division. The adrenal medulla is under control of the sympathetic system.

A group of teenage boys comes to the emergency department after ingesting a plant they heard would make them high. One member of the group still had some plant parts in his pocket, which you use to identify deadly nightshade that contains compounds metabolized to atropine. Which of the following is an effect of atropine? (A) Bronchospasm (B) Lacrimation (C) Mydriasis (D) Salivation (E) Urination

*The answer is C.* The sympathetic and para-sympathetic nervous systems often work simultaneously on the same organ. The net effect on an organ is deter-mined by which branch of the autonomic nervous system is most active at any given time. The sympathetic nervous system's effector neurotransmitter is generally norepinephrine, whereas the parasympathetic nervous system's is acetylcholine. Atropine is a cholinergic antagonist. Exposure to atropine would result in a clinical picture in which the parasympathetic nervous system (PNS) appeared to be missing, leaving control to the sympathetic nervous system (SNS). The PNS would normally push equilibrium toward bronchospasm, lacrimation, meiosis, salivation, and urination. Leaving the SNS in control then would lead to bronchodilation; mydriasis; and decreased lacrimation, salivation, and urination.

The following about sympathetic nervous system is true except: a. All its preganglionic fibres are cholinergic. b. It is involved in stress & emergency conditions. c. It has a vasodilation effect on skeletal muscle blood vessels during rest. d. Its stimulation increases the cardiac properties. e. Its stimulation causes urine retention.

*The answer is C.* The sympathetic nervous system does not have a a vasodilation effect on skeletal muscle blood vessels during rest.

A patient presents in the Emergency Department in great distress and with the following signs and symptoms: Which drug most likely caused these signs and symptoms? A. AChE inhibitor B. α-adrenergic blocker B. Antimuscarinic D. β-adrenergic blocker E. Parasympathomimetic (muscarinic agonist) F. Peripherally acting (neuronal) catecholamine depletor

*The answer is C.* 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: "Dry as a bone, blind as a bat, red as a beet, mad as a hatter" • Mydriasis, cycloplegia • Dry mouth • Tachycardia • Hot and flush skin, increased body temperature • Agitation and delirium

A 47-year-old man is given atropine to decrease dental secretions during a root canal procedure. This agent is most likely to have an effect on which of the following target organs/glands? (A) Adrenal medulla (B) Kidney (C) Pilomotor muscles (D) Salivary glands (E) Sweat glands

*The answer is D.* Although most tissues receive dual innervation, some effector organs, such as the adrenal medulla, kidney, pilomotor mus-cles, and sweat glands, receive innervation only from the sympathetic system. The salivary glands receive cholinergic innervation and would be affected by administration of atropine. (A) The adrenal medulla receives only sympathetic innervation. (B) The kid-ney only receives sympathetic innervation. (C) The pilomotor muscles only receive sympathetic innervation. (E) The sweat glands only receive sympathetic innervation.

An injection of atropine causes all the following effects except: a. An increase in the heart rate. b. Pupillo-dilatation. c. Difficult micturition. d. Constriction of the bronchi. e. Diminished intestinal motility.

*The answer is D.* Atropine is an antimuscarinic drug, which blocks muscarinic receptors. Therefore, an injection of atropine will decrease parasympathetic tone and increase sympathetic tone.

Which one of the following agents, when applied topically to the eye, would cause both mydriasis and cycloplegia? (A) Phenylephrine (B) Carbachol (C) Prazosin (D) Atropine

*The answer is D.* Atropine produces both mydriasis and cycloplegia (the inability to accommodate for near vision). Phenylephrine causes mydriasis without cycloplegia. Carbachol causes pupillary constriction. Prazosin is an α-adrenoceptor antagonist.

Blockade of alpha adrenoreceptor is likely to cause a. A reduction in sweat production. b. Constriction of the bronchi. c. A reduction in gastrointestinal motility. d. A reduction in the arterial blood pressure due to arterial V.D. e. Slowing of the heart.

*The answer is D.* Blockade of alpha adrenoreceptor is likely to cause a reduction in the arterial blood pressure due to arterial V.D.

A 30-year-old man has been treated with several autonomic drugs for 4 weeks. He is now admitted to the emergency department showing signs of drug toxicity. Which of the following signs would distinguish between an overdose of a ganglion blocker versus a muscarinic blocker? (A) Blurred vision (B) Dry mouth, constipation (C) Mydriasis (D) Postural hypotension (E) Tachycardia

*The answer is D.* Both ganglion blockers and muscarinic blockers can cause mydriasis, increase resting heart rate, blur vision, and cause dry mouth and constipation, because these are determined largely by parasympathetic tone. Postural hypotension, on the other hand, is a sign of sympathetic blockade, which would occur with ganglion blockers but not muscarinic blockers.

Neurotransmitters released by the parasympathetic preganglionic and postganglionic nerve fibres are: a. Acetylcholine and norepinephrine b. Acetylcholine and epinephrine c. Norepinephrine and acetylcholine d. Acetylcholine and acetylcholine

*The answer is D.* Both the preganglionic and postganglionic nerve fibers release acetylcholine.

Which of the following is the primary second-messenger process in the contraction of the ciliary muscle when focusing on near objects? (A) cAMP (cyclic adenosine monophosphate) (B) DAG (diacylglycerol) (C) Depolarizing influx of sodium ions via a channel (D) IP3 (inositol 1,4,5-trisphosphate) (E) NO (nitric oxide)

*The answer is D.* Cholinomimetics cause smooth muscle contraction mainly through the release of intracellular calcium. This release is triggered by an increase in IP3 acting on receptors in the endoplasmic reticulum.

Which of the following drugs is used to diagnose myasthenia gravis? (A) Atropine (B) Neostigmine (C) Bethanechol (D) Edrophonium (E) Pralidoxime

*The answer is D.* Edrophonium, which will increase muscle strength in untreated myasthenic patients, is the preferred acetylcholinesterase inhibitor (Tensilon test) because it has a short duration of action.

You give an "effective dose" of atropine to a person who was poisoned with AChe inhibitor. What structure will continued to be overactivated by the excess Ach after atropine is given? A. Aitway smooth muscle B. S-A node of the heart C. Salivary and lacrimal glands D. Skeletal muscle E. Vascular smooth muscle

*The answer is D.* In "cholinesterase poisoning," we are dealing with overstimulation (from accumulated ACh) of both peripheral muscarinic and nicotinic receptors. Recall that atropine is a specific muscarinic receptor blocker, and the muscarinic receptors are the ones found on such structures as smooth muscle, cardiac nodal tissue, and exocrine glands. In contrast, the cholinergic receptor on skeletal muscle is nicotinic, so skeletal muscle isn't affected by atropine. If one receives a lethal dose of a cholinesterase inhibitor, he or she may be a little more comfortable (less defecation, urination, respiratory tract mucus hypersection and bronchoconstriction, after the atropine is given, but they are still likely to die from skeletal muscle (NM nicotinic) overstimulation and then paralysis. Paralysis of the diaphragm and intercostal muscles are the most lethal consequences.

Four new synthetic drugs (designated W, X, Y, and Z) are to be studied for their cardiovascular effects. They are given to 4 anesthetized animals while the heart rate is recorded. The first animal has received no pretreatment (control); the second has received an effective dose of hexamethonium; the third has received an effective dose of atropine; and the fourth has received an effective dose of phenoxybenzamine. The net changes induced by the new drugs (not by the blocking drugs) are described in the following questions. Drug W increased heart rate in the control animal, the atropine-pretreated animal, and the phenoxybenzamine-pretreated animal. However, drug W had no effect on heart rate in the hexamethonium-pretreated animal. Drug W is probably a drug similar to (A) Acetylcholine (B) Edrophonium (C) Isoproterenol (D) Nicotine (E) Norepinephrine

*The answer is D.* In developing a strategy for this type of question, consider first the actions of the known blocking drugs. Hexamethonium blocks reflexes as well as the direct action of nicotine. Atropine would block direct muscarinic effects of an unknown drug (if it had any) or reflex slowing of the heart mediated by the vagus. Phenoxybenzamine blocks only α-receptor-mediated processes. If the response produced in the non-pretreated animal is blocked or reversed by hexamethonium, it is probably a direct nicotinic effect or a reflex response to hypotension. In that case, consider all the receptors involved in mediating the reflex. Drug W causes tachycardia that is prevented by ganglion blockade. The only drug in the list of choices that causes hypotension and tachycardia that is not blocked by atropine is isoproterenol, and the tachycardia caused by isoproterenol is not blocked by ganglionic blockade. Thus, drug W must be nicotine.

Administration of a drug which inhibits norepinephrine synthesis is expected to: a. Cause bronchodilatation b. Inhibit intestinal motility c. Decrease insulin secretion by pancreas d. Decrease the heart rate

*The answer is D.* Inhibiting norepinephrine synthesis will prevent the activity of the beta 1 receptor, which works to increase heart rate and contractility.

Pheochromocytoma is thought to result from an imbalance in the synthesis and release of norepinephrine from the adrenergic neuron. The following is a diagram of this process. In which of the following steps is norepinephrine binding to receptors? (A) Letter A (B) Letter B (C) Letter C (D) Letter D (E) Letter E

*The answer is D.* Letter D represents the binding to the receptor. The postsynaptic receptor is activated by the binding of neurotransmitter. (A) Letter A represents the synthesis of norepinephrine. (B) Letter B represents the uptake of norepinephrine into storage vesicles. (C) Letter C represents the release of neurotransmitter via exocytosis. (E) Letter E represents the removal of norepinephrine through reuptake into the neuron.

A 32-year-old man presents to his primary care physician because of a 2-week history of nasal stuffiness, cough, and sinus pain. He is prescribed with phenylephrine. He must be aware of which of the following potential adverse effects? (A) Constipation (B) Diarrhea (C) Epistaxis (D) Hypertension (E) Tinnitus

*The answer is D.* Phenylephrine is a vasoconstrictor that raises both systolic and diastolic blood pressures. It has no effect on the heart itself but rather induces reflex bradycardia when given parenterally. It is often used topically on the nasal mucous membranes and in ophthalmic solutions for mydriasis. Phenylephrine acts as a nasal decongestant (applied every 4 h) and produces vasoconstriction. The drug is used to raise blood pressure and to terminate episodes of supraventricular tachycardia (rapid heart action arising both from the AV junction and from atria). Large doses can cause hypertensive headache and cardiac irregularities. (A) This agent does not cause constipation. (B) This agent does not cause diarrhea. (C) Epistaxis is unlikely following administration of phenylephrine. (E) Tinnitus is unlikely following administration of phenylephrine.

Many studies have shown that a large fraction of norepinephrine (NE) in the normal resting adrenergic neuron is stored in membrane-bound vesicles or granules. We administer a drug that, over time, depletes this supply of neurotransmitter and decreases the intensity of responses to sympathetic nerve activation. In vitro studies reveal that the drug acts by inhibiting uptake of intraneuronal NE into the vesicles; it has no direct effect on catecholamine synthesis, release, or interactions with its receptors. Which drug fits this description best? a. Pargyline b. Prazosin c. Propranolol d. Reserpine e. Tyramine

*The answer is D.* 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, 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 β₂, 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.

Reuptake (into the nerve) is 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 b c. Nerve c d. Nerve d e. Nerve e f. Nerve f g. Nerve g h. Nerve h

*The answer is D.* 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 andmore prolonged adrenergic effects of NE because NE lingers longer and a ccumulates in the synapse, exposed to its postsynaptic targets. All theother nerves shown in the diagram are cholinergic; the actions of the ACh they release are terminated promptly by hydrolysis (via acetylcholinesterase).

There are major differences in the anatomical arrangement of neurons, which lead to variations of the functions in each division of the nervous system. Which of the following features describes the parasympathetic nervous system? (A) Diffuse response (B) Extensive preganglionic fiber branching (C) Ganglia close to the spinal cord (D) Short postganglionic fibers (E) Wide distribution

*The answer is D.* The para-sympathetic nervous system has a discrete response. The ganglia are close to the target organs. The parasympathetic nervous system has long preganglionic fibers and short postganglionic fibers. (A) The sympathetic nervous system has a diffuse response. (B) The sympathetic nervous system has extensive preganglionic fiber branching. (C) The sympathetic nervous system has ganglia that are close to the spinal cord. (E) The sympathetic nervous system has a wide distribution.

The parasympathetic nervous system affects all of these organs EXCEPT: a. Heart. b. Pupillary smooth muscles. c. Salivary glands. d. Adrenal glands.

*The answer is D.* The parasympathetic nervous system affects all of these organs EXCEPT the adrenal glands.

Which of the following is characteristic of the sympathetic nervous system? A Discrete response to activation. B. Actions mediated by muscarinic and nicotinic receptors. C. Effects only mediated by norepinephrine. D. Responses predominate during physical activity or when experiencing fright. E. Subjected to voluntary control.

*The answer is D.* The sympathetic nervous system is activated by "fight or flight" stimuli. To achieve rapid activation of this system, the sympathetic nervous system often discharges as a unit. The receptors that mediate sympathetic nervous system effects on neuroeffector organs are α and β receptors. Because the sympathetic nervous system is a division of the autonomic nervous system, it is not subject to voluntary control and functions below conscious thought.

Your new 10-year-old patient has asthma, and you decide to treat her with a β2 agonist. In considering the possible drug effects in this patient, you would note that β2 stimulants frequently cause (A) Direct stimulation of renin release (B) Hypoglycemia (C) Increased cGMP (cyclic guanine monophosphate) in mast cells (D) Skeletal muscle tremor (E) Vasodilation in the skin

*The answer is D.* Tremor is a common β2 effect. Blood vessels in the skin have almost exclusively α (vasoconstrictor) receptors. Stimulation of renin release is a β1 effect. Beta2 agonists cause hyperglycemia.

A physiological action of epinephrine produced by contact with the beta adrenergic receptors is a. V.C. in skeletal muscles. b. Dilatation of the pupil. c. Intestinal contraction. d. Contraction of the erector pilli muscles. e. Increased strength of myocardial contraction.

*The answer is E.* A physiological action of epinephrine produced by contact with the beta adrenergic receptors is increased strength of myocardial contraction.

Acetylcholine is secreted at all the following sites except: a. Postgang. Sympathetic nerve terminals at skeletal muscles . b. Postgang. Parasymp. Nerve terminal . c. Pregang. Symp. & parasymp nerve terminals. d. Myoneural junctions. e. Postgang. Symp. Noradrenergic nerve terminals.

*The answer is E.* Acetylcholine is secreted at all the following sites except postganglionic sympathethicm oradrenergic nerve terminals.

Which one of the following can be blocked by atropine? (A) Decreased blood pressure caused by hexamethonium (B) Increased blood pressure caused by nicotine (C) Increased skeletal muscle strength caused by neostigmine (D) Tachycardia caused by exercise (E) Tachycardia caused by infusion of acetylcholine

*The answer is E.* Atropine blocks muscarinic receptors and inhibits parasympathomimetic effects. Nicotine can induce both parasympathomimetic and sympathomimetic effects by virtue of its ganglion-stimulating action. Hypertension and exerciseinduced tachycardia reflect sympathetic discharge and therefore would not be blocked by atropine.

Poisoning with an insecticide containing an acetylcholinesterase inhibitor is best managed by administration of which one of the following agents? (A) Physostigmine (B) Bethanechol (C) Propranolol (D) Pilocarpine (E) Atropine

*The answer is E.* Atropine blocks the effects of increased acetylcholine resulting from cholinesterase inhibition. Physostigmine indirectly activates cholinoceptors; bethanechol and pilocarpine directly activate cholinoceptors. Propanolol is a β adrenoceptor antagonist.

Two new synthetic drugs (X and Y) are to be studied for their cardiovascular effects. The drugs are given to three anesthetized animals while the blood pressure is recorded. The first animal has received no pretreatment (control), the second has received an effective dose of a long-acting ganglion blocker, and the third has received an effective dose of a long-acting muscarinic antagonist. Drug X caused a 50 mm Hg rise in mean blood pressure in the control animal, no blood pressure change in the ganglion-blocked animal, and a 75 mm mean blood pressure rise in the atropine-pretreated animal. Drug X is probably a drug similar to (A) Acetylcholine (B) Atropine (C) Epinephrine (D) Hexamethonium (E) Nicotine

*The answer is E.* Drug X causes an increase in blood pressure that is blocked by a ganglion blocker but not by a muscarinic blocker. The pressor response is actually increased by pretreatment with atropine, a muscarinic blocker, suggesting that compensatory vagal discharge might have blunted the full response. This description fits a ganglion stimulant like nicotine but not epinephrine, since epinephrine's pressor effects are produced at α receptors, not in the ganglia.

We administer a therapeutic dose of a drug that selectively and competitively blocks the postsynaptic α-adrenergic (α₁) receptors. 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 is the most likely drug? a. Clonidine b. Phentolamine c. Phenoxybenzamine d. Phenylephrine e. Prazosin

*The answer is E.* Prazosin selectively and competitively blocks adrenergic receptors and, unlike many other a-blockers (phentolamine, phenoxybenzamine), has virtually no presynaptic (a) 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 actions last far longer than those of phentolamine, and they arise from noncompetitive/reversible α-blockade (Rather than merely occupying the receptors, as is the case with most antagonists, phenoxybenzamine alkylates the receptors, permanently impairing the 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.

A crop duster pilot has been accidentally exposed to a high concentration of a highly toxic agricultural organophosphate insecticide. If untreated, the cause of death from such exposure would probably be (A) Cardiac arrhythmia (B) Gastrointestinal bleeding (C) Heart failure (D) Hypotension (E) Respiratory failure

*The answer is E.* Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important cause of acute deaths in cholinesterase inhibitor toxicity.

The alpha adrenergic receptors mediate all the following effects except: a. Vasoconstriction. b. Pupil dilatation. c. Spleen contraction. d. Relaxation of the intestinal wall. e. Increased cardiac activity.

*The answer is E.* The alpha adrenergic receptors mediate all the following effects except increased cardiac activity. This is mediated by beta adrenergic receptors.

The parasympathetic effects can be stimulated by: a. Atropine which exerts similar effects as muscarine. b. Ephedrine which stimulates the synthesis of acetylcholine. c. Large doses of nicotine which have a effects similar to acetylcholine. d. Alpha methyldopa (aldomet) which increases the release of acetylcholine. e. Physostigmine which inhibits the acetylcholinesterase enzyme.

*The answer is E.* The parasympathetic effects can be stimulated by physostigmine which inhibits the acetylcholinesterase enzyme.

A man who has been surfing the Web in search of an aphrodisiac or some other agent to enhance sexual prowess and performance discovers yohimbine. He consumes the drug in excess and develops symptoms of toxicity that require your intervention. You consult your preferred drug reference and learn that yohimbine is a selective α2-adrenergic antagonist that acts mainly in the brain's medullary cardiovascular controlcenter. What would you expect as a response to this drug? a. Bradycardia b. Bronchoconstriction c. Excessive secretions by exocrine glands (salivary, lacrimal, etc) d. Reduced cardiac output from reduced left ventricular contractility e. Rise of blood pressure

*The answer is E.* The α2-adrenergic receptor, when stimulated by a suitable agonist, turns off further NE release. So when we block those receptors with yohimbine, we enhance the apparent overall activity of the sympathetic nervous system on its effectors by interfering with norepinephrine's ability to turn-off its own release. Of the responses listed, only hypertension (owing to the vasoconstriction effects of NE on postsynaptic α-adrenegeric receptors) occurs as a result of yohimbine (or of NE excess). The other main effects you should anticipate would be cardiac stimulation, and usually of less clinical consequence, mydriasis.

An anesthetized dog is prepared for recording blood pressure and heart rate in a study of a new blocking drug. Results show that the new drug prevents the tachycardia evoked by isoproterenol? Which of the following standard agents does the new drug most resemble? (A) Atropine (B) Hexamethonium (C) Phentolamine (an α blocker) (D) Physostigmine (E) Propranolol (a β blocker)

*The answer is E.* When considering questions that may involve reflex homeostatic responses, it helps to recall the pathway and receptors involved in the baroceptor reflex. In the case of isoproterenol-induced tachycardia, a reflex is evoked by the β2-mediated decrease in blood pressure. This reflex will be processed by the vasomotor center and result in increased sympathetic autonomic nervous system outflow to the sinus node to increase heart rate. This reflex would be blocked by a ganglion blocker such as hexamethonium. However, isoproterenol also causes tachycardia directly by activating the β receptors in the sinus node, an effect not blocked by ganglion blockers. Only a β blocker (propranolol) will prevent both the reflex tachycardia and the direct tachycardia induced by isoproterenol.

Nerve d, the more typical postganglionic sympathetic nerve, is activated by a normally generated action potential followed by neurotransmitter release into the synapse. On which receptor type does the neurotransmitter 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 tissue (effector) type

*The answer is G.*T he 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 a1 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.

Two new synthetic drugs (X and Y) are to be studied for their cardiovascular effects. The drugs are given to three anesthetized animals while the blood pressure is recorded. The first animal has received no pretreatment (control), the second has received an effective dose of a long-acting ganglion blocker, and the third has received an effective dose of a long-acting muscarinic antagonist. The net changes induced by drug Y in these experiments are shown in the following graph. Drug Y is probably a drug similar to (A) Acetylcholine (B) Edrophonium (C) Hexamethonium (D) Nicotine (E) Pralidoxime

*The answer is Z.* Drug Y causes a decrease in blood pressure that is blocked by a muscarinic blocker but not by a ganglion blocker. Therefore, the depressor effect must be evoked at a site distal to the ganglia. In fact, the drop in blood pressure is actually greater in the presence of ganglion blockade, suggesting that compensatory sympathetic discharge might have blunted the full depressor action of drug Y in the control animal. The description fits a direct-acting muscarinic stimulant such as acetylcholine (given in high dosage). Indirect-acting cholinomimetics (cholinesterase inhibitors) would not produce this pattern because the vascular muscarinic receptors involved in the depressor response are not innervated and are unresponsive to indirectly acting agents.