Katzung & Trevor's Pharmacology Examination & Board Review - 10E - Part II (Autonomic Drugs)

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

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

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

(A) Acetylcholine 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.

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. The results of the test of drug Z are shown in the graph. Drug Z is probably a drug similar to: (A) Acetylcholine (B) Edrophonium (C) Isoproterenol (D) Norepinephrine (E) Pralidoxime

(A) Acetylcholine Drug Z causes tachycardia that is converted to bradycardia by hexamethonium and blocked completely by atropine. This indicates that the tachycardia is a reflex evoked by vasodilation. Drug Z causes bradycardia when the ganglia are blocked, indi- cating that it also has a direct muscarinic action on the heart. This is confirmed by the ability of atropine to block both the tachycardia and the bradycardia.

For these questions, 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

(A) Acetylcholine The nerves innervating the thermoregulatory (eccrine) sweat glands are sympathetic cholinergic nerves.

7. Accepted therapeutic indications for the use of antimuscarinic drugs include all of the following except (A) Atrial fibrillation (B) Motion sickness (C) Parkinson's disease (D) Postoperative bladder spasm (E) To antidote parathion poisoning

(A) Atrial fibrillation Atrial fibrillation and other arrhythmias are not responsive to antimuscarinic agents.

When given to a patient, phentolamine blocks which one of the following? (A) Bradycardia induced by phenylephrine (B) Bronchodilation induced by epinephrine (C) Increased cardiac contractile force induced by norepinephrine (D) Miosis induced by acetylcholine (E) Vasodilation induced by isoproterenol

(A) Bradycardia induced by phenylephrine Phenylephrine, an α agonist, induces bradycardia through the baroreceptor reflex. Blockade of this drug's α-mediated vaso- constrictor effect prevents the bradycardia.

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

(A) Bronchial smooth muscle 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.

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

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

Ms Green is a 60-year-old woman with poorly controlled hypertension of 170/110 mm Hg. She is to receive minoxidil. The active metabolite of minoxidil is a powerful arteriolar vasodilator that does not act on autonomic receptors. Which of the following effects will be observed if no other drugs are used? (A) Tachycardia and increased cardiac contractility (B) Tachycardia and decreased cardiac output (C) Decreased mean arterial pressure and decreased cardiac contractility (D) Decreased mean arterial pressure and increased salt and water excretion by the kidney (E) No change in mean arterial pressure and decreased cardiac contractility

(A) Tachycardia and increased cardiac contractility Because of the compensatory responses, a drug that directly decreases blood pressure through a decrease in peripheral vascular resistance will cause a reflex increase in sympathetic outflow, an increase in renin release, and a decrease in para- sympathetic outflow. As a result, heart rate and cardiac force will increase. In addition, salt and water retention will occur.

Clinical studies have shown that adrenoceptor blockers have many useful effects in patients. However, a number of drug toxicities have been documented. Adverse effects that limit the use of adrenoceptor blockers include which one of the following? (A) Bronchoconstriction from α-blocking agents (B) Acute heart failure exacerbation from β blockers (C) Impaired blood sugar response with α blockers (D) Increased intraocular pressure with β blockers (E) Sleep disturbances from α-blocking drugs

(B) Acute heart failure exacerbation from β blockers Although chronic heart failure is often treated with β blockers, acute heart failure can be precipitated by these drugs. Choices A, C, and E reverse the correct pairing of receptor subtype (α versus β) with effect. Choice D reverses the direction of change of intraocular pressure.

9. Which one of the following drugs causes vasodilation that can be blocked by atropine? (A) Benztropine (B) Bethanechol (C) Botulinum (D) Cyclopentolate (E) Edrophonium (F) Neostigmine (G) Pralidoxime

(B) Bethanechol Bethanechol (Chapter 7) causes vasodilation by activating muscarinic receptors on the endothelium of blood vessels. This effect can be blocked by atropine.

A 7-year-old boy with a previous history of bee sting allergy is brought to the emergency department after being stung by 3 bees. Which of the following are probable signs of the anaphylactic reaction to bee stings? (A) Bronchodilation, tachycardia, hypertension, vomiting, diarrhea (B) Bronchospasm, tachycardia, hypotension (C) Bronchodilation, bradycardia, vomiting, diarrhea (D) Bronchospasm, bradycardia, hypotension, diarrhea (E) Bronchodilation, tachycardia, vomiting, diarrhea

(B) Bronchospasm, tachycardia, hypotension Anaphylaxis is caused by the release of several mediators. Leukotrienes and certain proteins are the most important of these. They cause bronchospasm and laryngeal edema and marked vasodilation with severe hypotension. Tachycardia is a common reflex response to the hypotension. Gastrointestinal disturbance is not as common nor as dangerous.

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

(B) Cycloplegia 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.

8. 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

(B) Decreased DAG (diacylglycerol) in salivary gland tissue 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 potas- sium permeability. Antimuscarinic agents block these effects.

3. Ms Brown has been treated for myasthenia gravis for several years. She reports to the emergency department complain- ing 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

(B) Edrophonium 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.

7. 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)

(B) Improved aqueous humor drainage (glaucoma) Muscarinic agonists cause accommodation and cyclospasm, the opposite of paralysis of accommodation (cycloplegia). In open-angle glaucoma, this results in increased outflowof 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.

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

(B) Increased heart rate Tachycardia is a characteristic atropine overdose effect. Bradycardia is sometimes observed after small doses.

A 30-year-old woman undergoes abdominal surgery. In spite of minimal tissue damage, complete ileus (absence of bowel motility) follows, and she complains of severe bloating. She also finds it difficult to urinate. Mild cholinomimetic stimu- lation with bethanechol or neostigmine is often effective in relieving these complications of surgery. Neostigmine and bethanechol in moderate doses have significantly different effects on which one of the following? (A) Gastric secretion (B) Neuromuscular end plate (C) Salivary glands (D) Sweat glands (E) Ureteral tone

(B) Neuromuscular end plate Because neostigmine acts on the enzyme cholinesterase, which is present at all cholinergic synapses, this drug increases acetylcholine effects at nicotinic junctions as well as muscarinic ones. Bethanechol, on the other hand, is a direct-acting agent that is selective for muscarinic receptors and has no effect on nicotinic junctions such as the skeletal muscle end plate.

3. 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)

(C) Decreased renal blood flow Sympathetic discharge causes constriction of the renal resis- tance vessels and a fall in renal blood flow. This is the typical response in severe exercise or hypotension. The other effects are parasympathomimetic actions.

5. Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic insufficiency). You are consid- ering 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

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

A 7-year-old boy with a previous history of bee sting allergy is brought to the emergency department after being stung by 3 bees. If this child has signs of anaphylaxis, what is the treatment of choice? (A) Diphenhydramine (an antihistamine) (B) Ephedrine (C) Epinephrine (D) Methylprednisolone (a corticosteroid) (E) Phenylephrine

(C) Epinephrine The treatment of anaphylaxis requires a powerful physiologic antagonist with the ability to cause bronchodilation (β2 effect), and vasoconstriction (α effect). Epinephrine is the most effective agent with these properties. Antihistamines and corticosteroids are sometimes used as supplementary agents, but the use of epinephrine is mandatory.

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

(C) Isoproterenol 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.

A new drug was administered to an anesthetized animal with the results shown here. A large dose of epinephrine (epi) was administered before and after the new agent for comparison. Which of the following agents does the new drug most closely resemble? (A) Atenolol (B) Atropine (C) Labetalol (D) Phenoxybenzamine (E) Propranolol

(C) Labetalol The new drug blocks both the α-mediated effects (increased diastolic and mean arterial blood pressure) and β-mediated action (increased cardiac force). In addition, it does not cause epinephrine reversal. Therefore, the drug must have both α- and β-blocking effects.

A patient is to receive epinephrine. She has previously received an adrenoceptor-blocking agent. Which of the following effects of epinephrine would be blocked by phentolamine but not by metoprolol? (A) Cardiac stimulation (B) Increase of cAMP (cyclic adenosine monophosphate) in fat (C) Mydriasis (D) Relaxation of bronchial smooth muscle (E) Relaxation of the uterus

(C) Mydriasis Mydriasis caused by contraction of the pupillary dilator radial smooth muscle is mediated by α receptors. All the other effects listed are mediated by β receptors.

9. A 3-year-old child is admitted after taking a drug from her parents' medicine cabinet. The signs suggest that the drug is an indirect-acting cholinomimetic with little or no CNS effect and a duration of action of about 2-4 h. Which of the following is the most likely cause of these effects? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Physostigmine (E) Pilocarpine

(C) Neostigmine Neostigmine is the prototypical indirect-acting cholinomi- metic; it is a quaternary (charged) substance with poor lipid solubility; its duration of action is about 2-4 h. Physostigmine is similar but has good lipid solubility and significant CNS effects.

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

(C) Phenylephrine 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 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

(C) Pupillary dilation (mydriasis) 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 (Table 6-4).

For these questions, 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

(C) Sites 5 and 6 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.

Which of the following is the most dangerous effect of belladonna alkaloids in infants and toddlers? (A) Dehydration (B) Hallucinations (C) Hypertension (D) Hyperthermia (E) Intraventricular heart block

(D) Hyperthermia Choices B, D, and E are all possible effects of the atropine group. In infants, however, the most dangerous effect is hyperthermia. Deaths with body temperatures in excess of 42°C have occurred after the use of atropine-containing eye drops in children.

10. Which of the following is the primary second-messenger pro- cess 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)

(D) IP3 (inositol 1,4,5-trisphosphate) 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.

6. Parasympathetic nerve stimulation and a slow infusion of bethanechol will each: (A) Cause ganglion cell depolarization (B) Cause skeletal muscle end plate depolarization (C) Cause vasodilation (D) Increase bladder tone (E) Increase heart rate

(D) Increase bladder tone Choice (E) is not correct because the vagus slows the heart. Parasympathetic nerve stimulation does not cause vasodila- tion (most vessels do not receive parasympathetic innerva- tion), so choice (C) is incorrect. Ganglion cells and the end plate contain nicotinic receptors, which are not affected by bethanechol, a direct-acting muscarinic agonist.

Several new drugs with autonomic actions are being studied in phase 1 clinical trials. Autonomic drugs X and Y were given in moderate doses as intravenous boluses to normal volunteers. The systolic and diastolic blood pressures changed as shown in the diagram below. Which of the following drugs most resembles drug X? (A) Atropine (B) Bethanechol (C) Epinephrine (D) Isoproterenol (E) Norepinephrine

(D) Isoproterenol The drug X dose caused a decrease in diastolic blood pressure and little change in systolic pressure. Thus, there was a large increase in pulse pressure. The decrease in diastolic pressure suggests that the drug decreased vascular resistance, that is, it must have significant muscarinic or β-agonist effects. The fact that it also markedly increased pulse pressure suggests that it strongly increased stroke volume, a β-agonist effect. The drug with these beta effects is isoproterenol (Figure 9-1).

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

(D) Nicotine 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 nonpretreated animal is blocked or reversed by hexamethonium, it is prob- ably a direct nicotinic effect or a reflex response to hypo- tension. 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.

A 30-year-old man is admitted to the emergency depart- ment after taking a suicidal overdose of reserpine. His blood pressure is 50/0 mm Hg and heart rate is 40 bpm. Which of the following would be the most effective cardiovascular stimulant? (A) Amphetamine (B) Clonidine (C) Cocaine (D) Norepinephrine (E) Tyramine

(D) Norepinephrine A large overdose of reserpine causes marked depletion of stored catecholamine transmitter. The indirect-acting agents (amphetamines, cocaine, and tyramine) act through catecholamines in (or released from) the nerve terminal and would therefore be ineffective in this patient. Clonidine acts primarily on presynaptic nerve endings although it can activate α2 receptors located elsewhere. Norepinephrine has the necessary combination of direct action and a spectrum that includes α1, α2, and β1 effects.

A new drug was given by subcutaneous injection to 25 normal subjects in a phase 1 clinical trial. The cardiovascular effects are summarized in the table below. Which of the following drugs does the new experimental agent most resemble? (A) Atropine (B) Epinephrine (C) Isoproterenol (D) Phenylephrine (E) Physostigmine

(D) Phenylephrine The investigational agent caused a marked increase in diastolic pressure but a small increase in pulse pressure (from 40 to 48 mm Hg). These changes suggest a strong alpha effect on vessels but an increase in venous return and stroke volume or a small β-agonist action in the heart. The heart rate decreased markedly, reflecting a baroreceptor reflex compensatory response. Note that the stroke volume increased slightly (cardiac output divided by heart rate—from 75.8 to 86.6 mL). This is to be expected even in the absence of beta effects if bradycardia causes increased diastolic filling time. The drug behaves most like a pure α agonist.

6. 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

(D) Postural hypotension 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 (Chapter 6).

A 56-year-old man has hypertension and an enlarged prostate, which biopsy shows to be benign prostatic hyperplasia. He complains of urinary retention. Which of the following drugs would be the most appropriate initial therapy? (A) Albuterol (B) Atenolol (C) Metoprolol (D) Prazosin (E) Timolol

(D) Prazosin An α blocker is appropriate therapy in a man with both hypertension and benign prostatic hyperplasia because both conditions involve contraction of smooth muscle containing α receptors.

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

(D) Skeletal muscle tremor 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.

Parathion has which one of the following characteristics? (A) It is inactivated by conversion to paraoxon (B) It is less toxic to humans than malathion (C) It is more persistent in the environment than DDT (D) It is poorly absorbed through skin and lungs (E) If treated early, its toxicity may be partly reversed by pralidoxime

(E) If treated early, its toxicity may be partly reversed by pralidoxime The "-thion" organophosphates (those containing the PÓS bond) are activated, not inactivated, by conversion to "-oxon" (PÓO) derivatives. They are less stable than halogenated hydrocarbon insecticides of the DDT type; therefore, they are less persistent in the environment. Parathion is more toxic than malathion. It is very lipid-soluble and rapidly absorbed through the lungs and skin. Pralidoxime has very high affinity for the phosphorus atom and is a chemical antagonist of organophosphates.

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

(E) Nicotine 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.

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 X had the effects shown in the table below. Drug X is probably a drug similar to: (A) Acetylcholine (B) Albuterol (C) Edrophonium (D) Isoproterenol (E) Norepinephrine

(E) Norepinephrine Drug X causes slowing of the heart rate, but this is con- verted into tachycardia by hexamethonium and atropine, demonstrating that the bradycardia is caused by reflex vagal discharge. Phenoxybenzamine also reverses the bradycardia to tachycardia, suggesting that α receptors are needed to induce the reflex bradycardia and that X also has direct β-agonist actions. The choices that evoke a vagal reflex bradycardia (vasoconstrictors) but can also cause direct tachycardia (beta agonists) are limited.

Several new drugs with autonomic actions are being studied in phase 1 clinical trials. Autonomic drugs X and Y were given in moderate doses as intravenous boluses to normal volunteers. The systolic and diastolic blood pressures changed as shown in the diagram below. Which of the following most resembles drug Y? (A) Atropine (B) Bethanechol (C) Epinephrine (D) Isoproterenol (E) Norepinephrine

(E) Norepinephrine Drug Y caused a marked increase in diastolic pressure, sug- gesting strong α vasoconstrictor effects. It also caused a small increase in pulse pressure, suggesting some β-agonist action. An increase in stroke volume may also result from increased venous return (an α-agonist effect) and stroke volume. The drug that best matches this description is norepinephrine.

Mr Green, a 54-year-old man, had a cardiac transplant 6 months ago. His current blood pressure is 120/70 mm Hg and heart rate is 100 bpm. Which of the following drugs would have the least effect on Mr Green's heart rate? (A) Albuterol (B) Epinephrine (C) Isoproterenol (D) Norepinephrine (E) Phenylephrine

(E) Phenylephrine Heart transplantation involves the cutting of autonomic nerves to the heart. As a result, autonomic nerve endings degenerate, and cardiac transmitter stores are absent for 2 years or longer after surgery. Therefore, indirect-acting sympathomimetics are ineffective in changing heart rate. All the drugs listed are direct-acting, and all but phenylephrine have significant effects on β receptors. Phenylephrine usually causes reflex bradycardia, which requires intact vagal innerva- tion. (Note that denervation may result in upregulation of both β1 and β2 receptors so that direct-acting β agonists have a greater than normal effect.)

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)

(E) Propranolol (a β blocker) 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.

Assume that the diagram below represents a sympathetic postganglionic nerve ending. Which of the following blocks the carrier represented by "y" in the diagram? (A) Amphetamine (B) Botulinum toxin (C) Cocaine (D) Hemicholinium (E) Reserpine

(E) Reserpine The vesicular carrier in the diagram transports dopamine and norepinephrine into the vesicles for storage. It can be blocked by reserpine.

4. 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 expo- sure would probably be (A) Cardiac arrhythmia (B) Gastrointestinal bleeding (C) Heart failure (D) Hypotension (E) Respiratory failure

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

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

(E) Tachycardia caused by infusion of acetylcholine Atropine blocks muscarinic receptors and inhibits parasym- pathomimetic effects. Nicotine can induce both parasym- pathomimetic and sympathomimetic effects by virtue of its ganglion-stimulating action. Hypertension and exercise- induced tachycardia reflect sympathetic discharge and there- fore would not be blocked by atropine.

Your 75-year-old patient with angina and glaucoma is to receive a β-blocking drug. Which of the following statements is most correct regarding β-blocking drugs? (A) Esmolol's pharmacokinetics are compatible with chronic topical use (B) Metoprolol blocks β2 receptors selectively (C) Nadolol lacks β2-blocking action (D) Pindolol is a β antagonist with high membrane-stabilizing (local anesthetic) activity (E) Timolol lacks the local anesthetic effects of propranolol

(E) Timolol lacks the local anesthetic effects of propranolol Esmolol is a short-acting β blocker for parenteral use only. Nadolol is a nonselective β blocker, and metoprolol is a β1-selective blocker. Timolol is useful in glaucoma because it does not anesthetize the cornea.

8. Which of the following is a direct-acting cholinomimetic that is lipid-soluble and is used to facilitate smoking cessation? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Physostigmine (E) Varenicline

(E) Varenicline Varenicline is a lipid-soluble partial agonist at nicotinic recep- tors and is used to reduce craving for tobacco in smokers.

10. Which one of the following drugs has a very high affinity for the phosphorus atom in parathion and is often used to treat life-threatening insecticide toxicity? (A) Atropine (B) Benztropine (C) Bethanechol (D) Botulinum (E) Cyclopentolate (F) Neostigmine (G) Pralidoxime

(G) Pralidoxime Pralidoxime has a very high affinity for the phosphorus atom in organophosphate insecticides.