Right. An irreversible competitive antagonist acts by decreasing the number of receptors available for binding an agonist. Therefore, even a high agonist concentration cannot overcome a irreversible blockade, and the maximal effect of an agonist is smaller in the presence than in the absence of an irreversible antagonist. There is, however, one other true statement in this item. Go back to Item III and try to find it.

Right. A high dose of epinephrine would markedly increase both the blood pressure and the heart rate of an anesthetized cat. Go to Item XVI.

Right. Pretreatment with propranolol would block the stimulation of beta receptors by epinephrine. Therefore, only increased blood pressure, mediated by stimulation of alpha adrenergic receptors, and reflex bradycardia, would be observed after administration of epinephrine in a patient treated chronically with propranolol. There is, however, another drug or drug combination which would induce similar changes. Go back to Item XVI and try to find it.

Wrong. Isoproterenol and norepinephrine are both full agonists at cardiac receptors, so they should have similar maximal effects.

Wrong. You either skipped or forgot the answer to Item XII. Go back and answer Item XII before you try to answer Item XVII again.

Right. The dose of drug A which is required to produce effect Y is lower than an equipotent dose of drug C. Since potency varies inversely with the magnitude of the dose required to produce a given effect, drug A is more potent than drug C. There is, however, one other true statement in this item. Go back to Item I and try to find it.

Wrong. Acetylcholine administration would produce a decrease of the blood pressure but the heart rate would not decrease. Actually the heart rate after acetylcholine is usually slightly elevated because decrease of the blood pressure induces sympathetic activation through baroreceptors. Go back to Item XI.

Right. Atropine would increase the tachycardia induced by epinephrine because it prevents the reflex inhibition of the heart rate evoked by the increased blood pressure. There is, however, another drug which would also modify the epinephrine effect. Go back to Item XVI and think about it again.

Wrong. Pretreatment with phenoxybenzamine blocks the alpha adrenergic receptors. Therefore, phenylephrine cannot have a greater effect in a preparation pretreated with phenoxybenzamine than when it is given alone. Go back to Item IX.

Wrong. Physostigmine potentiates the effects of acetylcholine, which means that the same dose of acetylcholine will produce a greater effect in the presence of physostigmine. Curve D indicates smaller effects of the same doses than Curve C. Go back to Item IV.

Wrong. Pretreatment with d-tubocurarine blocks the effect of acetylcholine. Therefore, acetylcholine cannot have a greater effect in a preparation pretreated with d-tubocurarine, than when it is given alone. Go back to Item X.

Right. Occlusion of carotid arteries would decrease the blood pressure at the carotid sinus, and would produce an increased sympathetic outflow which would increase both heart rate and peripheral blood pressure. Go on to Item XIII.

Right. Cocaine potentiates norepinephrine by inhibiting the reuptake of norepinephrine into the sympathetic nerve endings. Since this uptake is the major mechanism for terminating norepinephrine effect, inhibition of the uptake shifts the dose-effect curve of norepinephrine to the left. Go to Item VII.

Wrong. Succinylcholine is a depolarizing blocking agent at the neuromuscular junction. You have to keep in mind that the effect of succinylcholine cannot be abolished by increasing the dose of acetylcholine. Go back to Item VIII.

Wrong. Propranolol would abolish the effect of carotid occlusion on the heart rate but not the effect of carotid occlusion or distal vagal verve stimulation on the blood pressure. Go back to Item XIII.

Wrong. Carotid occlusion produces an increase in the blood pressure and this increase would be antagonized by the alpha blocking agent phenoxybenzamine. Go back to Item XVIII.

Right. Phentolamine does not affect the increase of heart rate of an isolated heart because this effect is mediated through beta receptors and phentolamine is an alpha receptor blocking agent. Go to Item VIII.

Wrong. Prazosin is a pharmacological antagonist of norepinephrine, not of acetylcholine. Go back to Item II.

Right. Histamine would decrease blood pressure and induce secondary reflex tachycardia. There is, however, another treatment which would produce similar effects. Go back to Item XIX and try to find it.

Right. An average dose of epinephrine would increase both the heart rate, through simulation of beta adrenergic receptors, and the blood pressure, through stimulation of alpha adrenergic receptors. There is, however, one more drug or drug combination which would produce this effect. Go back to Item XIV and try to find it.

Right. A non-competitive antagonist reduces the maximal effect, but does not change the ED50. There is, however, one other true statement in this item. Go back to Item III and try to find it.

Wrong. There is one drug listed which would markedly increase both the blood pressure and the heart rate. Go back to Item XV and try to find it.

Wrong. You forgot one other agent which would also modify and/or abolish the heart rate changes observed following the administration of a high dose of epinephrine. Read a comment corresponding to this agent before proceeding to Item XVII.

Wrong. Physiological antagonism is caused by agonist and antagonist acting at two independent sites and inducing independent, but opposite effects. Phentolamine and norepinephrine act at the same site (alpha-receptor). Go back to Item II.

Wrong. There is a curve which represents the effect of phenylephrine in a preparation pretreated with phenoxybenzamine. Go back to Item IX and try to find it.

Wrong. You forgot one other treatment which would also increase the blood pressure and decrease the heart rate. Read a comment corresponding to this agent before proceeding to Item XVII.

Right. Isoproterenol is more potent than norepinephrine at cardiac B1 receptors. Go to Item VI.

Wrong. Physostigmine modifies acetylcholine effects. Before you go back to Item IV, review the pharmacologic effects and mechanism of action of physostigmine.

Right. D-tubocurarine is a reversible competitive antagonist of acetylcholine at the neuromuscular junction. The blocking effect of d-tubocurarine can be overcome by anticholinesterase drugs, which increase the concentration of acetylcholine at the neuromuscular junction.

Wrong. There is one condition which would produce changes of the blood pressure and heart rate similar to those which occurred 3 minutes after the beginning of the experiment. Go back to Item XI and try to find it.

Wrong. The effect of norepinephrine in a preparation pretreated with phentolamine is represented by a different curve. Go back to Item VII.

Wrong. There is a curve representing the effect of acetylcholine in a preparation pretreated with physostigmine. Go back to Item IV and think about it again.

Wrong. There is only one drug or procedure which would simultaneously increase both blood pressure and heart rate. Go back to Item XII and try to find it.

Wrong. There is a curve which represents the curve for acetylcholine in a preparation pretreated with succinylcholine. Go back to Item VIII and think about it again.

Wrong. Cocaine modifies norepinephrine effects. Before you go back to Item VI, review the pharmacological effects and mechanism of action of cocaine.

Wrong. Tyramine would increase blood pressure mainly through release of norepinephrine from the nerve endings. However, there would be a decrease of the heart rate mediated through stimulation of carotid baroreceptors. Go back to Item XV.

Wrong. You do not understand the concept of potency and intrinsic activity. Review these terms in the Glossary of Terms and Symbols Used in Pharmacology (Course Manual, Chapter 3), and then go back to Item I.

Right. Acetylcholine would decrease blood pressure and induce secondary reflex tachycardia. There is, however, another treatment which would produce similar effects. Go back to Item XIX and try to find it.

Wrong. Review the cardiovascular effects of catecholamines and histamine before going back to Item XIV.

Right. Hexamethonium would prevent both the effects of distal vagal nerve stimulation and carotid occlusion by blocking transmission at the parasympathetic and sympathetic ganglia. Go to Item XIV.

Wrong. Chlorpheniramine modifies the effect of histamine on blood vessels. Before you go back to Item V, review the pharmacology of chlorpheniramine and other antihistamines.

Wrong. There is a curve which represents the curve for norepinephrine in the presence of phentolamine. Go back to Item VII and think about it again.

Wrong. Histamine would produce slight tachycardia, but it would markedly decrease the blood pressure by dilation of small blood vessels. Go back to Item XIV.

Very good. I hope you chose a and c as the right answers. Go to Item XVIII.

Right. A low dose of epinephrine decreases blood pressure and this decrease would be enhanced by blockade of alpha adrenergic receptors. Go to Item XIX.

Right. Ipratropium is a pharmacological antagonist of acetylcholine because it acts at the same site (receptor) as acetylcholine. Go to Item III.

Right. Methoxamine selectively stimulates the alpha adrenergic receptors and, therefore, would produce an increase of blood pressure and reflex bradycardia. There is, however, another drug or drug combination which would induce similar changes. Go back to Item XVI and try to find it.

Wrong. A reversible competitive antagonist acts by competing with the agonist for receptor binding. Therefore it is possible to overcome a competitive blockade by increasing the concentration of agonist. The presence of a competitive antagonist usually shifts the dose-effect curve to the right, but it does not change the maximal effect. Go back to Item III.

Wrong. Pretreatment with d-tubocurarine blocks the effects of acetylcholine. Therefore, acetylcholine cannot have greater effect in a preparation pretreated with d-tubocurarine than when it is given alone. Go back to Item X.

Wrong. There is a curve for norepinephrine in the presence of cocaine. Go back to Item VI and think about it again.

Wrong. There is only one true statement listed. Go back to Item XVIII and try to find it.

Wrong. There is only one drug which would diminish the blood pressure changes resulting from both distal vagal nerve stimulation and carotid occlusion. Go back to Item XIII and try to find it.

Right. The intrinsic activity depends on the amount of biological effect produced per unit of drug-receptor complex formed. An agent producing greater maximum effect (in our case drug B) has the greater intrinsic activity. There is, however, one other true statement in this item. Go back to Item I and try to find it.

Right. Phenoxybenzamine binds irreversibly to alpha adrenergic receptors. and therefore produces a non-competitive block of these receptors. The effect of phenylephrine, which stimulates vascular alpha receptors, is inhibited in a preparation pretreated with phenoxybenzamine. Go on to Item X.

Very good. I hope you consider histamine and acetylcholine to be the right answer. You are now at the end of the program and I hope that you learned something in answering it.

Wrong. Pretreatment with succinylcholine blocks the effect of acetylcholine at the neuromuscular junction. Therefore, acetylcholine cannot have greater effect in a preparation pretreated with succinylcholine than when it is given alone. Go back to Item VIII.

Very good. Propranolol would decrease, and atropine and hexamethonium would increase, the heart rate changes observed following the administration of a high dose of epinephrine. Go to Item XVII.

Wrong. There is only one drug or procedure which would simultaneously increase both blood pressure and heart rate. Go back to Item XII and try to find it.

Right. Stimulation of the distal vagus would decrease both the blood pressure, due to vasodilation, and the heart rate, due to direct parasympathetic inhibition of the sinus node. Go on to Item XII

Right. Physostigmine potentiates the effects of acetylcholine by inhibiting acetylcholinesterase, an enzyme which hydrolyzes acetylcholine. Potentiation of an agonist effect shifts the dose-effect curve to the left. Go to Item V.

Wrong. Chemical antagonism is caused by a combination of agonist with antagonist, resulting in inactivation of the agonist. Phenoxybenzamine antagonizes norepinephrine by decreasing the number of alpha-receptors available for norepinephrine. Go back to Item II.

Wrong. Phentolamine would abolish the effect of carotid occlusion, but not the effect of distal vagal nerve stimulation. Go back to Item XIII.

Very good. All of the listed treatments would simultaneously increase the blood pressure and decrease the heart rate. Go on to Item XVII.

Wrong. There is one treatment listed which does not simultaneously decrease the blood pressure and increase the heart rate. Go back to Item XVII and try to find it.

Wrong. The effect of norepinephrine in a preparation pretreated with phentolamine is represented by a different curve. Go back to Item VII.

Wrong. Histamine administration would decrease the blood pressure not the heart rate. The heart rate after histamine is usually slightly elevated because decrease of the blood pressure induces sympathetic activation through baroreceptors. Go back to Item XI.

Wrong. Cocaine itself does not produce vasoconstriction and, therefore, it cannot increase the maximal effect of norepinephrine. Go back to Item VI.

Right. Phentolamine pretreatment would block the alpha adrenergic receptors, but since phentolamine is a competitive inhibitor, a large dose of norepinephrine would still slightly increase the blood pressure. At the same time, phentolamine would not affect the increase of heart rate produced by stimulation of beta adrenergic receptors. However, there is one more drug which would also produce this effect. Go back to Item XIV and try to find it.

Wrong. The maximal effect produced by drug B is larger than the maximal effect of drug A, which indicates that drug B might have higher intrinsic activity. However, the dose of drug B which is required to produce effect Y is higher than an equipotent dose of drug A. Since potency varies inversely with the magnitude of the dose required to produce a given effect, drug A is more potent than drug B. Go back to Item I and try again.

Wrong. A low dose of epinephrine would increase heart rate, but at the same time it would decrease blood pressure because it would produce vasodilation through stimulation of adrenergic beta receptors. Go back to Item XII.

Wrong. Isoproterenol and norepinephrine have different potencies at cardiac adrenergic receptors. Go back to Item V.

Wrong. Phenoxybenzamine is not a reversible competitive antagonist of phenylephrine. Therefore, in a preparation treated with phenoxybenzamine, even high doses of phenylephrine will not produce a substantial increase of the blood pressure. Go back to Item IX.

Wrong. Succinylcholine modifies the effect of acetylcholine on skeletal muscle. Before you go back to Item VIII, review the pharmacological effects and mechanisms of action of succinylcholine and other neuromuscular blocking agents.

Wrong. There is only one drug listed which would markedly increase both the blood pressure and the heart rate. Go back to Item XV and try to find it.

Right. Propranolol would diminish or abolish the increased heart rate produced by epinephrine because it blocks cardiac beta adrenergic receptors. There is, however, another drug which would also modify the epinephrine effect. Go back to Item XVI and think about it again.

Wrong. There is only one true statement listed. Go back to Item XVIII and try to find it.

Right. Isoproterenol stimulates chiefly beta adrenergic receptors and would, therefore, produce tachycardia and decrease the blood pressure, due to peripheral vasodilation. There is, however, another treatment which would produce similar changes. Go back to Item XVII and try to find it.

Wrong. D-tubocurarine is a reversible competitive antagonist of acetylcholine. By increasing the dose of acetylcholine, it is possible to obtain the same maximal effect in the presence of d-tubocurarine as with acetylcholine alone. Go back to Item X.

Wrong. There is one treatment listed which does not simultaneously decrease the blood pressure and increase the heart rate. Go back to Item XIX and try to find it.

Right. Statements b and d are both correct. A decrease in the Emax with no shift in the EC50 is seen either in the presence of a non-competitive antagonist or after treatment with an irreversible competitive antagonist.

Right. Hexamethonium would increase the tachycardia induced by epinephrine, because it prevents the reflex cholinergic inhibition of the heart rate evoked by the increased blood pressure. There is, however, another drug which would also modify the effect of epinephrine. Go back to Item XVI and think about it again.

Very good. I hope you considered statement a and c to be true. If you did, you have a good understanding of the concepts of potency and intrinsic activity. If you thought that statement b is true, you should review the comment to Item Ib. Now you can go to Item II.

Wrong. Isoproterenol decreased blood pressure by stimulating beta receptors; this effect would be unaffected or enhanced by phenoxybenzamine pretreatment. Go back to Item XVIII.

Right. Phentolamine blocks alpha adrenergic receptors; therefore epinephrine, in a preparation pretreated with phentolamine, stimulates only beta receptors and produces tachycardia and vasodilation. There is, however, another treatment which would produce similar changes. Go back to Item XVII and try to find it.

Wrong. Phenylephrine would increase blood pressure by producing vasoconstriction, but this increase of blood pressure would induce bradycardia through stimulation of carotid baroreceptors. Go back to Item XII.

Wrong. You either skipped or forgot Item XI. Go back to Item XI before trying to answer Item XIX again.

Wrong. Physiological antagonism is caused by agonist and antagonist acting at two independent sites and inducing independent, but opposite, effects. Atropine acts at the same site as acetylcholine. Go back to Item II.

Right. Tranylcypromine inhibits monamine oxidase, the enzyme which metabolizes many biogenic amines. Some kinds of heavy cheese have a high content of substances, mainly tyramine, which can produce an increase in blood pressure. Normally, after ingestion of such cheese, these substances are broken down rapidly by monamine oxidase. In a patient treated with tranylcypromine, metabolism of these amines is inhibited, and, therefore, they can produce a dangerous rise of blood pressure accompanied by a reflex bradycardia. There is, however, another drug or drug combination which would induce similar changes. Go back to Item XVI and try to find it.

Wrong. Physostigmine does not have an effect by itself and, therefore, it cannot increase the maximal effect of acetylcholine. Go back to Item IV.

Wrong. D-tubocurarine modifies the pharmacological effect of acetylcholine on skeletal muscles. Before you go back to Item X, review the pharmacological effects and mechanisms of action of d-tubocurarine and other neuromuscular blocking agents.

Wrong. Intravenous administration of guanethidine would increase blood pressure by releasing norepinephrine from the nerve endings. There would be, however, a decrease of the heart rate mediated through stimulation of carotid baroreceptors. Go back to Item XV.

Wrong. Cocaine potentiates the effects of norepinephrine. That means that the same dose of norepinephrine will produce a greater effect in the presence of cocaine. Curve D indicates a smaller effect of the same dose than Curve C. Go back to Item VI.

Right. Succinylcholine is a depolarizing neuromuscular blocking agent which prevents the effect of acetylcholine by initially depolarizing the membrane (phase I) and then desensitizing the receptors (phase II). Therefore, its blockade cannot be abolished by increasing the dose of acetylcholine.

Wrong. Isoproterenol is not less potent than norepinephrine at cardiac receptors. Go back to Item V.

Wrong. Pretreatment with phenoxybenzamine modifies the effect of phenylephrine on blood vessels. Before you go back to Item IX, review the pharmacological effects and mechanisms of action of phenoxybenzamine and other sympathetic blocking agents.

Wrong. The effect of norepinephrine in a preparation pretreated with phentolamine is represented by a different curve. Go back to Item VII.

Very good. I hope you consider a and b as the right answers. Go to Item XV.

Wrong. An irreversible competitive antagonist acts by decreasing the number of receptors available for binding an agonist. Therefore even high agonist concentration cannot overcome an irreversible blockade, and the maximal effect of an agonist is smaller in the presence than in the absence of an irreversible antagonist. Go back to Item III.

Wrong. Atropine would abolish the effect of vagal nerve stimulation but it would not decrease the response to carotid occlusion. Go back to Item XIII.

Wrong. All of the drugs listed, as well as vagus nerve stimulation, would induce a decrease in blood pressure. However, only one of these conditions would produce a decrease of the heart rate also. Go back to Item XI and try to find it.