1.
Which of the following autonomic receptors is most prevalent in vascular endothelium?
Correct Answer
H. M3
Explanation
Cells of vascular endothelium have non innervated M3 receptors. Activation of these receptors
triggers the release of nitric oxide which diffuses to adjacent smooth muscle cells and causes
them to relax.
2.
Which of the following autonomic receptors is most prevalent in cell body of neurons of otic ganglion?
Correct Answer
A. Nn
Explanation
The otic ganglion is a parasympathetic ganglion. The receptors located on the cell body of
neurons of all autonomic ganglia are primarily Nn receptors.
3.
Which of the following effects of epinephrine is mainly mediated by the activation of alpha-2 receptors?
Correct Answer
E. Decreased production of aqueous humor
Explanation
Activation of alpha-2 receptors decreases the production, whereas activation of beta receptors
(mainly beta-2) increases the production.
A, B, C, D, F, G) These effect of epinephrine are not mediated by the activation of alpha-2
receptors
4.
Which of the following statements best explains why an IV injection of norepinephrine usually causes very little effects on cardiac output in normal subjects?
Correct Answer
C. The reflex bradycardia balances the direct increased stroke volume
Explanation
An IV injection of norepinephrine would cause an increase in stroke volume and heart rate, both
due to the activation of beta-1 receptors. The consequent increase in both systolic and diastolic
pressure elicits a reflex effect which overcomes the direct chronotropic activity so leading to a
net decrease in heart rate. Since CO = SV x HR, even if the stroke volume is increased, cardiac
output is not substantially affected.
A) The norepinephrine-induced vasoconstriction tends to decrease the end diastolic volume,
but this has little consequence on the stroke volume which is still increased, due to the increase
in cardiac contractility.
B) (see explanation A)
D) The end systolic volume has nothing to do with cardiac contractility.
E) Actually an increased total peripheral resistance would cause an increased firing of
baroreceptors (they are stretch receptors).
5.
A 53-year-old man was brought to the emergency room because of a crushing substernal pain of one hour duration. Vital signs on admission were: BP 88/50, pulse 115 bpm, cardiac output 2.3 L/min. A diagnosis of cardiogenic shock was made and a therapy was started which included an IV infusion of a drug. Which of the following molecular actions most likely mediated the therapeutic effectiveness of the drug in this patient?
Correct Answer
C. Increased synthesis of cAMP
Explanation
The therapy of cardiogenic shock requires a rapid acting inotropic drug to increase myocardial
contractility and cardiac output. Dobutamine and dopamine are the two drugs most frequently
used. In both cases the therapeutic efficacy is mediated mainly by the direct (dobutamine) or
indirect (dopamine) activation of beta-1 receptors which in turn increases the synthesis of
cAMP.
6.
A 52-year-old man was admitted to the coronary care unit with a diagnosis of myocardial infarction. Two hours later he developed a ventricular fibrillation and was defibrillated immediately but without success. A cardiopulmonary resuscitation (CPR) was started, two additional shocks were given at a higher energy, but the patient remained unresponsive. At this time a bolus of epinephrine was given IV, while continuing the CPR. The beneficial effect of the drug in this setting seems mainly related to which of the following actions?
Correct Answer
A. AlpHa-1 receptor mediated vasoconstriction
Explanation
The most appropriate management of cardiac arrest induced by ventricular fibrillation is a 200-
joule defibrillation. Additional shocks at higher energy should be given in case of initial failure. If
ventricular fibrillation persists, the American Heart Association indicates that epinephrine should
be administered. Most likely epinephrine increases brain and heart flow during cardiopulmonary
resuscitation by two main mechanisms:
1) It prevents arterial collapse at the thoracic inlet. Collapse results from high extravascular
intrathoracic pressure coupled with low intravascular pressure and loss of arteriolar tone. By
constricting arterial vessels and by increasing venous return, epinephrine increases the aortic
diastolic pressure during closed chest compression.
2) Preferentially reduces blood flow to the renal and splanchnic beds, so facilitating the
distribution of the limited cardiac output to the cerebral and coronary circulation during the
external cardiac massage. In fact cerebral blood vessels are relatively insensitive to the
vasoconstricting effect of alpha-agonists and perfusion pressure of the brain is increased.
It seems therefore that the main beneficial effects of epinephrine in cardiac arrest are related to
its alpha-1 receptor activation.
It is worth to note that, unlike what happens in the normal person, epinephrine increases TPR in
persons with cardiac arrest. In fact in this condition there is a complete loss of arteriolar tone
and therefore the beta-2 mediated vasodilation cannot occur, whereas the alpha-1 mediated
vasoconstriction can be still operative.
Additional beneficial effects that are instead related mainly to beta-1 receptor activation are:
3) To change a fine ventricular fibrillation into a coarse one which is more susceptible to
electrical defibrillation.
4) To stimulate spontaneous ventricular contraction in case of asystole.
Since the benefits of epinephrine are mainly due to alpha-1 mediated vasoconstriction,
norepinephrine could also be used. In fact a large prehospital trial failed to identify any
difference in survival following treatment with norepinephrine or standard doses of epinephrine.
Other vasoconstricting agents have also been evaluated. Vasopressin has recently been tested,
with promising results.
The fact that epinephrine is still the agent of choice in cardiac arrest is likely related to the long
experience achieved with this drug, as well as to the additional benefits listed above. For
example epinephrine activates bot beta-1 and beta-2 receptors and therefore it is likely more
effective than norepinephrine in stimulating spontaneous contraction of the heart during
asystole.
B) The beta-2 receptor mediated vasodilation would be counterproductive, but does not occur in
cardiac arrest (see explanation above).
C) This action of the drug could add an additional benefit (see explanation above), but it is
mainly related to beta-1 receptor activation (the increase in cardiac contractility due to beta-2
receptor activation is minor). In any case the main mechanism is MOST LIKELY the alpha-1
receptor mediated vasoconstriction.
D, E) The beneficial effects of epinephrine induced increase in renin secretion and of
epinephrine induced bronchodilation are, at the most, only marginal.
7.
A 54-year-old patient suffering from postural hypotension was admitted to the hospital for evaluation. A tyramine infusion was not able to rise the blood pressure, while a very small dose of norepinephrine caused a transient and big elevation of blood pressure. These results would suggest a degeneration of which of the following structures?
Correct Answer
E. Postganglionic sympathetic neurons
Explanation
Tyramine is a normal byproduct of tyrosine metabolism in the body and is also found in high
concentration in fermented food. It is normally inactive if ingested because of a very large firstpass
effect (metabolism by hepatic MAO). If administered parenterally it has an indirect
sympathomimetic action due to the release of stored catecholamines. This is the basis of the
tyramine test, sometimes used clinically for the diagnosis of some ANS diseases.
In the present case the patient is most likely affected by pure autonomic failure, a rare
degenerative disorder of the ANS presenting in middle to late life. In this disease there is a
degeneration of postganglionic sympathetic neurons which can explain the postural
hypotension. An IV injection of tyramine normally causes an elevation of blood pressure due to
the release of stored catecholamines. In the present case however the elevation did not occur
because catecholamines had been lost from the nerve endings. On the contrary an IV injection
of norepinephrine caused a big elevation, since norepinephrine directly activates adrenergic
receptors. Moreover these receptors were up-regulated, due to a decrease availability of the
neurotransmitter (denervation supersensitivity).
B) A lesion of the preganglionic sympathetic nerve would have caused orthostatic hypotension,
but tyramine would have caused hypertension, since the postganglionic adrenergic neurons
were intact.
C, D) In case of a lesion of either pre or postganglionic parasympathetic nerves tyramine would
have been effective.
E) Lesions of the sympathetic pathways in the medulla oblongata would have caused symptoms
similar to those due to lesions of the preganglionic sympathetic nerves. In this case too tyramine
would have been effective.
8.
The following diagram represents a noradrenergic terminal.
Which of the following sites in the diagram represents the site of
action of metyrosine?
Correct Answer
B. B
Explanation
Metyrosine inhibits the enzyme tyrosine hydroxylase, which catalyzes the hydroxylation of
tyrosine to DOPA. This is the rate-limiting step in norepinephrine biosynthesis and the inhibition
of the enzyme can cause up to a 70% decrease of norepinephrine content in adrenergic
terminals, so leading to antiadrenergic effects.
9.
Which of the following actions most likely contribute to the tachycardia that may occur after the administration of prazosin?
Correct Answer
A. Decreased firing rates of carotid baroreceptors
Explanation
Prazosin is a alpha-1 selective adrenergic blocker. The blockade of alpha-1 receptors causes
peripheral vasodilation which in turn decreases the blood pressure. A reduction in blood
pressure decreases the firing rate of carotid baroreceptors, which are stretch receptors. Since
the baroreceptor discharge excites the vagal outflow to the heart, a decrease firing rate will have
the opposite effect, that is it will increase the sympathetic outflow.
B) Cardiac contractility has nothing to do with cardiac rate.
C) Prazosin has no actions on presynaptic alpha-2 receptors.
D) By causing peripheral vasodilation prazosin actually decreases venous return to the heart.
E) Prazosin has no action on muscarinic receptors of the heart.
10.
Which of the following effects can be elicited by both nonselective and selective beta blockers?
Correct Answer
C. Increased duration of the diastole
Explanation
Selective beta blockers blocks mainly beta-1 receptors. Therefore the effect common to both
selective and nonselective agents must be mediated by beta-1 receptor blockade. The
decreased heart rate is due to blockade of beta-1 receptors and leads to an increased duration
of diastole.
A, D, E) These effects are mainly due to blockade of beta-2 receptors.
B) This effect is mediated by alpha-1 receptor activation or M3 receptor blockade.
F) This effect is mediated by M3 receptor blockade.
11.
An IV injection of drug X was given to a laboratory animal before and after the administration of atropine and the heart rate was recorded. The results are depicted below:
Which of the following drugs was most likely drug X?
Correct Answer
B. NorepinepHrine
Explanation
The drug causes a decrease in heart rate that is reversed by a pretreatment with atropine. This
suggest that the bradycardia is caused by a reflex vagal discharge. Norepinephrine is the only
listed drug that causes a vagal reflex bradycardia but can also causes direct tachycardia.
12.
An IV injection of epinephrine was given to a laboratory animal before and after the administration of a new drug X. The change in heart rate and bronchiolar resistance were recorded. The results are depicted in the following figure:
Which of the following drugs does the new agent most closely resemble?
Correct Answer
C. Metoprolol
Explanation
The new drug completely antagonizes the epinephrine-induced increase in heart rate (which is
mediated by beta-1 receptor activation) but does not antagonize the epinephrine-induced
bronchodilation (which is mediated by beta-2 receptor activation). Therefore the drug must be a
selective beta blocker like metoprolol.
B, E) These drugs are nonselective beta blockers and so they would antagonize both effects of
epinephrine.
A, D, F) These drugs cannot antagonize (in fact they might enhance) the epinephrine-induced
increase in heart rate.
13.
A 55-year-old alcoholic man with liver cirrhosis was admitted to the
intensive care unit with a two week history of intermittent melena.
Esophagoscopy revealed three chains of large varices in the lower
esophagus with signs of recent bleeding. An appropriate treatment
was performed which included a drug aimed at reducing portal
pressure. Which of the following drugs was most likely
administered ?
Correct Answer
B. Propranolol
Explanation
The creation of arteriovenous anastomoses, which occurs in cirrhosis, allows the perfusion
pressure of the hepatic artery being partly transmitted into the portal vein. Therefore
arteriovenous anastomoses are a main cause of portal hypertension in cirrhosis. Since the
esophageal veins are tributaries of the portal vein, the portal hypertension cause the
esophageal veins to dilate and become varicose. By blocking beta-2 receptors (particularly
abundant in liver vascular bed) liver arterial vessels are constricted and the pressure
transmitted into the portal vein decreases.
A, F) Activation of beta-2 receptors by albuterol would worsen the varices by increasing the
portal pressure.
C, D, E) These drugs can reduce the systemic blood pressure but they have unpredictable
effects on the perfusion pressure of liver arterial vessels.
14.
A new autonomic drug that does not enter the brain was given IV to
healthy volunteers. The cardiovascular effects are tabulated below
The effects of the new drug are most similar to those of which of
the following agents?
Correct Answer
D. NorepinepHrine
Explanation
The investigational drug causes a parallel increase in both systolic and diastolic pressure and a
concomitant decrease in heart rate. This pattern suggests that the decrease in heart rate is due
to a reflex vagal discharge. Drugs that cause this effect must be vasoconstricting agents (like
norepinephrine and phenylephrine) devoid of vasodilating activity. In this case however stroke
volume is substantially increased (stroke volume = cardiac output/heart rate; from 78.6 mL to
100 mL). Phenylephrine would increase the stroke volume only slightly (if venous constriction
causes an increase in venous return) or not at all, since it has no beta-adrenergic activity.
Moreover the ejection fraction is increased, which confirms that the drug does increase cardiac
contractility. (the ejection fraction is the ratio of the stroke volume to the end diastolic volume.
Remember that the only way to increase the ejection fraction is to increase cardiac contractility).
A, B, C) Epinephrine, dobutamine and isoproterenol would increases, not decrease, the cardiac
output of the heart.
E) (see explanation above)
15.
A new synthetic drug X is to be studied for its cardiovascular
effects. The drug is given IV to three animals while the heart rate
and blood pressure are recorded. The first animals has received no
pretreatment, the second has received an effective dose of
prazosin before drug X, and the third has received an effective dose
of propranolol before drug X. The NET CHANGES (+ or -) in heart
rate and mean blood pressure induced by drug X (not by the
pretreatment) are shown in the following table.
Which of the following agents does drug X most closely resemble?
Correct Answer
B. EpinepHrine
Explanation
The drug causes no variation in the mean blood pressure and an increase in heart rate. This
suggests that the increased in heart rate is a direct effect, since reflex variation in heart rate can
occur only when there is a variation in mean blood pressure. Moreover in this case:
A) Norepinephrine would have caused an increase in mean blood pressure, so causing reflex
bradycardia. This reflex effect usually overcomes the direct effect of the drug on the heart rate,
so the final effect would have been a decrease, not an increase, in heart rate.
C) Phenylephrine would have caused an increase in mean blood pressure, so causing reflex
bradycardia.
D, E) Isoproterenol and albuterol would have caused a decrease in mean blood pressure, due to
the beta-2 receptor mediated vasodilation.
The fact that the drug under study is similar to epinephrine can also be predicted from the
results of the pretreatments. Epinephrine causes negligible changes in mean blood pressure
due to the opposite effects of alpha-1 and beta-2 receptor activation. Prazosin blocks alpha-1
receptors so unmasking the beta-2 mediated vasodilation. Propranolol blocks beta-1 and beta-2
receptors so counteracting the effect on heart rate and unmasking the alpha-1 mediated
vasoconstriction.
16.
A 25-year-old man complained to his physician of insomnia and
night-mares. He also felt pain with ambulation at both calves. The
man, recently diagnosed with benign essential tremor, started two
week ago a drug treatment that was able to improve the tremor. A
drug with which of the following mechanisms of action was the
patient most likely taking?
Correct Answer
E. Blockade of beta receptors in striated muscle
Explanation
16) Answer: E
Beta-blockers are effectively used in case of benign essential tremor. The mechanism of this
therapeutic effect is still not clear but it seems related to the involvement of beta-2 receptors in
the pathogenesis of tremor. In fact beta-2 receptor activation accelerates the sequestration of
cytosolic Ca++ in striated muscle and enhances the discharge of muscle spindles. The
symptoms reported by the patient are typical adverse effects of beta blockers. These drug can
cause insomnia and nightmares in about 10% of cases, and can cause calf pain by blocking
beta-2 receptor mediated vasodilation in skeletal muscle vessels.
A) This would be the mechanism of action of local anesthetics. These drugs are not used for
essential tremor and do not cause the adverse effects reported by the patient.
B) Drugs with this mechanism of action (clonidine, tizanidine) are used to treat spasticity, but
not essential tremor.
C) This would be the mechanism of action of neuromuscular blocking drugs. These drugs are
not used for essential tremor and do not cause the adverse effects reported by the patient
D) This would be the mechanism of action of baclofen a drug used to treat spasticity, but not
essential tremor.
17.
A 57-year-old man suffering from open-angle glaucoma has been
receiving a topical drug that decreases the production of aqueous
humor. Which of the labeled structures of the eye, in the diagram
below, is the most likely site of action of that drug?
Correct Answer
D. D
Explanation
Glaucoma is characterized by an increased intraocular pressure, which in turn is due to an
excessive amount of aqueous humor in the anterior chamber of the eye. Therefore the
pharmacological therapy of this disease is aimed to decrease this amount, either by lowering
aqueous humor production or by increasing aqueous humor outflow.
All drugs that decreases the production of aqueous humor act on the ciliary epithelium, which is
the tissue that actually produces the humor (site D in the figure).
Activation of alpha-2 receptors in that tissue decrease the production, whereas activation of
beta-2 receptors increases the production. Therefore in order to decrease the production, a
drug must either activate alpha-2 receptors (like apraclonidine) or block beta-2 receptors (like
timolol).
A) The site A is the ciliary muscle. Drugs that contract this muscle promote the outflow of the
aqueous humor but have no effect on the production.
B) The site B is the iris. Drugs acting on iris muscles have no effect on aqueous humor
production.
C) The site C represents the trabecular meshwork and the Schlemm’s canal. These structures
can influence the outflow, not the production, of aqueous humor.
E) The lens is not involved in the regulation of aqueous humor production.
18.
The following picture represents different parts of the heart. For
the myocytes present in the part indicated by the arrow, which of
the following would be the prevalent autonomic postreceptor
mechanism?
Correct Answer
C. Opening of ligand-gated K+ channels
Explanation
The main nerve innervating the sinoatrial node is the vagus nerve and the main autonomic
receptors located on the myocytes of the SA node are M2 receptors. Activation of these
receptors triggers the opening of ligand-gated K+ channels, which in turn causes an outward K+
current. In the resting cells, outward K+ current always cause hyperpolarization of cell
membrane.
A) This postreceptor mechanism is mediated by the activation of nicotinic receptors
B) This postreceptor mechanism is mediated by the activation of M1, M3 or alpha-1 receptors.
D) This postreceptor mechanism is mediated by the activation of M1, M3 or alpha-1 receptors.
E) This postreceptor mechanism is mediated mainly by the activation of beta receptors.
19.
A 67-year-old patient presented for routine ophthalmic
examination. Tonometry measured an intraocular pressure of 28
mm Hg in both eyes (normal 10-20). The patient has been suffering
from complete AV block for two years. The ophthalmologist
prescribed a treatment with drugs to be given locally by eye drops.
Which of the following drugs was most likely included in the
treatment?
Correct Answer
D. Pilocarpine
Explanation
The patient is most likely suffering from open angle glaucoma. Pilocarpine historically was the
initial treatment of choice, but today is used only as an alternative therapy when other drugs are
contraindicated, as in the present case (see below)
A) Beta-blockers are first-line therapy for glaucoma but are contraindicated in this case because
of the AV block. In fact systemic effects can occur even after a topical administration, especially
in the elderly secondary to inadvertent overdose due to poor administration technique. In
patients with complete AV block the heart rate is maintained by a rhythm which is driven by a
ventricular pacemaker and is about 50 bpm. By blocking beta receptors in the ventricle a beta
blocker can reduce this barely sufficient heart rate, so causing heart failure. Pilocarpine is not
dangerous since in a patient with a complete AV block the AV conduction is, by definition,
already completely blocked and the parasympathetic control of the ventricle is negligible, due to
lack of innervation.
B, C, E) These drugs are not used for the therapy of glaucoma.
20.
A 82-year-old man resident of a nursing facility complained of
frequent urinary urges which often resulted in urine leakage. A
drug from which of the following classes would be appropriate to
manage the patient’s incontinence?
Correct Answer
A. Antimuscarinics
Explanation
The incontinence of the patient is most likely an urge incontinence, due to an overreactive
bladder. This is the most common form of incontinence affecting the elderly. Since the major
physiological stimulus for muscle contraction is the acetylcholine induced activation of M3
receptors on bladder smooth muscle, antimuscarinics can depress involuntary bladder
contraction from any etiology. Tolterodine, a selective antagonist on M3 receptors, is the drug
most frequently used for urge incontinence.
B, C, D, E) (see explanation above)