Block 9 Pharm Antiadrenegic W Exp Prt 2

1. A new autonomic drug was tested on healthy volunteers. Subjects were treated with saline or with the drug and then their heart rate was measured under resting or exercise conditions. The results were the following:

The tested drug most likely belongs to which of the following drug classes?

Beta-blockers

Cholinergic agonists

Cholinergic antagonists

Ganglionic blockers

Alpha-1 blockers

Answer: A
The actions of a beta-blocker on the cardiovascular system are much more pronounced when
the sympathetic tone is high. Therefore, under resting conditions, the drug-induced decrease
of heart rate is minimal, while it is pronounced during exercise, when the sympathetic tone is
high.
B) A cholinergic agonist would cause a more pronounced decrease of the heart rate under
resting conditions, since the increased sympathetic tone during exercise would antagonize the
parasympathetic effect of the cholinergic agonist.
C, D, E) All these drugs tend to increase the heart rate under resting conditions.

Explanation

Answer: A
The actions of a beta-blocker on the cardiovascular system are much more pronounced when
the sympathetic tone is high. Therefore, under resting conditions, the drug-induced decrease
of heart rate is minimal, while it is pronounced during exercise, when the sympathetic tone is
high.
B) A cholinergic agonist would cause a more pronounced decrease of the heart rate under
resting conditions, since the increased sympathetic tone during exercise would antagonize the
parasympathetic effect of the cholinergic agonist.
C, D, E) All these drugs tend to increase the heart rate under resting conditions.

2. A 32-year-old man complained to his physician of fatigue, insomnia, loss of libido and depression. The man, diagnosed with chronic classic migraine three week previously, started a prophylactic treatment with a drug which reduced the frequency of the attacks. Which of the following drugs was he most likely taking?

Esmolol

Albuterol

Propranolol

Tamsulosin

Phenylephrine

Clonidine

Answer: C
The symptoms the patient was complaining were classic adverse effects of bet-blockers. These
drugs have been approved by FDA for migraine and are currently used to prevent migraine
attacks, even if their mechanism of action in this disorders remains elusive.
A) Esmolol is a beta-blocker with a very short half life ( about 10 minutes) used only by
parenteral injection or IV infusion.
B, D, E, F) These drug are not used for migraine.

Explanation

Answer: C
The symptoms the patient was complaining were classic adverse effects of bet-blockers. These
drugs have been approved by FDA for migraine and are currently used to prevent migraine
attacks, even if their mechanism of action in this disorders remains elusive.
A) Esmolol is a beta-blocker with a very short half life ( about 10 minutes) used only by
parenteral injection or IV infusion.
B, D, E, F) These drug are not used for migraine.

3. A 41-year-old man complained to his physician of painful erection and impaired ejaculation during sex. Two week ago he had been diagnosed with chronic bacterial prostatitis and had started an appropriate therapy. Which of the following drugs most likely caused the patient's symptoms?

Prazosin

Propranolol

Phenoxybenzamine

Metyrosine

Phenylephrine

Ephedrine

Answer: A
Chronic bacterial prostatitis is usually caused by sequestered urinary pathogens (Escherichia,
Klebsiella, Proteus) that antibiotics have not eradicated. When symptoms of urinary obstruction
are present alpha adrenergic blockers may be indicated. Painful erection and impaired
ejaculation are typical adverse effects of adrenergic blockers, since ejaculation is under control
of the sympathetic nervous system.
B, C, D, E, F) These drugs are not used in case of urinary obstruction and do not cause the
symptoms reported by the patient.

Explanation

Answer: A
Chronic bacterial prostatitis is usually caused by sequestered urinary pathogens (Escherichia,
Klebsiella, Proteus) that antibiotics have not eradicated. When symptoms of urinary obstruction
are present alpha adrenergic blockers may be indicated. Painful erection and impaired
ejaculation are typical adverse effects of adrenergic blockers, since ejaculation is under control
of the sympathetic nervous system.
B, C, D, E, F) These drugs are not used in case of urinary obstruction and do not cause the
symptoms reported by the patient.

4. A 44-year-old woman suffering from open-angle glaucoma had been receiving topical timolol for three months. The disease was well controlled and the treatment stopped the progression of optic nerve damage. Which of the following molecular actions most likely mediated the therapeutic effectiveness of the drug in this patient?

Opening of ligand gated K channels

Increased synthesis of diacylglycerol

Decreased synthesis of cGMP

Decreased synthesis of cAMP

Increased synthesis of tyrosine kinase

Opening of ligand gated Na channels

Answer: D
Activation of all beta receptors increases the synthesis of cAMP. By blocking these receptors
all beta-blockers decreased the synthesis of this second messengers.
A, B, C, E, F) (see explanation above)

Explanation

Answer: D
Activation of all beta receptors increases the synthesis of cAMP. By blocking these receptors
all beta-blockers decreased the synthesis of this second messengers.
A, B, C, E, F) (see explanation above)

5. A 65-year-old man complained to his physician of a fine, slow tremor of the hands brought out by performing skilled acts. The patient noticed that the tremor has been recently increased, getting worse especially when he felt tense and anxious. A preliminary diagnosis was made and an appropriate therapy was ordered. Which of the following drugs was most likely prescribed?

Prazosin

Clonidine

Albuterol

Physostigmine

Propranolol

Answer: E
The patient was most likely suffering from benign essential tremor, a disorder that is often
inherited (autosomal dominant in 50% of cases) and tends to increase with age. Propranolol
(and other non selective beta-blockers) are effective in treating the disorder. The mechanism
of this therapeutic effect is still uncertain but it seems related to the blockade of beta-2
receptor mediated increase in sequestration of cytosolic Ca++ and enhanced discharge of
muscle spindles.
A, B, C, D) All these listed drug are of no value for the treatment of essential tremor.

Explanation

Answer: E
The patient was most likely suffering from benign essential tremor, a disorder that is often
inherited (autosomal dominant in 50% of cases) and tends to increase with age. Propranolol
(and other non selective beta-blockers) are effective in treating the disorder. The mechanism
of this therapeutic effect is still uncertain but it seems related to the blockade of beta-2
receptor mediated increase in sequestration of cytosolic Ca++ and enhanced discharge of
muscle spindles.
A, B, C, D) All these listed drug are of no value for the treatment of essential tremor.

6. A 62-year-old woman, recently diagnosed with open angle glaucoma, started a topical therapy with timolol and apraclonidine. Which of the following was most likely the site of action of both drugs?

Ciliary muscle

Uveoscleral vessels

Conjunctival vessels

Ciliary epithelium

Retinal vessels

Schlemm’s canal

Answer: D
In the eye aqueous humor is manufactured by the cells of ciliary epithelium and is under the
control of both beta receptors (which increase the production) and alpha-2 receptors (which
decrease the production). Therefore the production of aqueous humor can be reduced either
by drugs that block beta receptors (like timolol) or by drugs that activate alpha-2 receptors (like
apraclonidine).The site of action of both drug is the ciliary epithelium.
A, B, D, E, F) (see explanation above)

Explanation

Answer: D
In the eye aqueous humor is manufactured by the cells of ciliary epithelium and is under the
control of both beta receptors (which increase the production) and alpha-2 receptors (which
decrease the production). Therefore the production of aqueous humor can be reduced either
by drugs that block beta receptors (like timolol) or by drugs that activate alpha-2 receptors (like
apraclonidine).The site of action of both drug is the ciliary epithelium.
A, B, D, E, F) (see explanation above)

7. A 32-year-old male was brought to the emergency department after the police found him shouting and acting crazily in the street. The man admitted to indulging in cocaine from a new dealer for the past four hours. He was agitated, anxious and exhibits psychotic behavior. Vital signs were: blood pressure 180/100 mm Hg, heart rate 160 bpm, respiratory rate 20/min. Which of the following pairs of drugs were most likely included in the treatment of this patient?

Prazosin and propranolol

Phenoxybenzamine and labetalol

Metyrosine and neostigmine

Bethanechol and phenylephrine

Clonidine and albuterol

Answer: A
The cardiovascular symptoms of the patient were most likely due to cocaine-induced
sympathetic activation. Cocaine inhibits the reuptake of norepinephrine into the adrenergic
terminals so increasing norepinephrine availability in the synaptic cleft. Both alpha and beta
blockers are therefore needed to counteract effectively norepinephrine induced activation of
alpha and beta receptors.
B) This drug combination could antagonize norepinephrine effects, but phenoxybenzamine is
an irreversible antagonist with a very long duration of action, and therefore not suitable for an
emergency treatment.
C, D, E) These drugs cannot antagonize norepinephrine effects.

Explanation

Answer: A
The cardiovascular symptoms of the patient were most likely due to cocaine-induced
sympathetic activation. Cocaine inhibits the reuptake of norepinephrine into the adrenergic
terminals so increasing norepinephrine availability in the synaptic cleft. Both alpha and beta
blockers are therefore needed to counteract effectively norepinephrine induced activation of
alpha and beta receptors.
B) This drug combination could antagonize norepinephrine effects, but phenoxybenzamine is
an irreversible antagonist with a very long duration of action, and therefore not suitable for an
emergency treatment.
C, D, E) These drugs cannot antagonize norepinephrine effects.

8. A 22-year-old previously healthy woman was brought to the emergency room because she had collapsed during jogging. She denied orthopnea, paroxysmal nocturnal dyspnea, chest pain or edema. Her younger brother was known to have had two episodes of syncope after exertion. The ECG indicated left ventricular hypertrophy and the echocardiogram showed an asymmetric septal hypertrophy. Which of the following drugs would be most appropriate for this patient?

Prazosin

Furosemide

Metoprolol

Dobutamine

Epinephrine

Answer: C
The history and the exam results indicate that the patient most likely is suffering from
hypertrophic obstructive cardiomyopathy a disorder usually inherited in an autosomal dominant
pattern. In this disease the asymmetric hypertrophy of the ventricular septum leads to left
ventricular outflow obstruction. Syncope usually occurs after exercise because the increased
contractile function worsens the obstruction and the vasodilation from increases circulating
epinephrine reduces diastolic ventricular filling. Other classic symptoms of the disease are
angina (a limited coronary blood flow reserve is present in hypertrophied states) and diastolic
heart failure (due to the reduced compliance of the hypertrophied left ventricle). Beta-blockers
(and calcium channel blockers that act on the heart, like verapamil and diltiazem) are drugs of
choice in this disease because they decrease cardiac contractility and increase diastolic
ventricular filling.
A, B, D, E) All the other listed drugs are contraindicated in hypertrophic obstructive
cardiomyopathy because either they decrease venous return (prazosin, diuretics) or increase
contractile function (dobutamine, epinephrine).

Explanation

Answer: C
The history and the exam results indicate that the patient most likely is suffering from
hypertrophic obstructive cardiomyopathy a disorder usually inherited in an autosomal dominant
pattern. In this disease the asymmetric hypertrophy of the ventricular septum leads to left
ventricular outflow obstruction. Syncope usually occurs after exercise because the increased
contractile function worsens the obstruction and the vasodilation from increases circulating
epinephrine reduces diastolic ventricular filling. Other classic symptoms of the disease are
angina (a limited coronary blood flow reserve is present in hypertrophied states) and diastolic
heart failure (due to the reduced compliance of the hypertrophied left ventricle). Beta-blockers
(and calcium channel blockers that act on the heart, like verapamil and diltiazem) are drugs of
choice in this disease because they decrease cardiac contractility and increase diastolic
ventricular filling.
A, B, D, E) All the other listed drugs are contraindicated in hypertrophic obstructive
cardiomyopathy because either they decrease venous return (prazosin, diuretics) or increase
contractile function (dobutamine, epinephrine).

9. A new drug was studied in laboratory animals. Epinephrine was given before and after the administration of the new drug, then some plasma values were recorded and reported in the table below:

Which of the following drugs does the new agent most closely resemble?

Albuterol

Timolol

Metoprolol

Atropine

Propranolol

Prazosin

The new drug completely antagonizes the epinephrine-induced increase in renin (which is mediated by beta-1 receptor activation) but does not antagonize the epinephrine-induced hyperglycemia (which is due to several actions including the beta-2 receptor mediated glycogenolysis).
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 those epinephrine-induced effects.

Explanation

The new drug completely antagonizes the epinephrine-induced increase in renin (which is mediated by beta-1 receptor activation) but does not antagonize the epinephrine-induced hyperglycemia (which is due to several actions including the beta-2 receptor mediated glycogenolysis).
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 those epinephrine-induced effects.

10. A 51-year-old woman presents with a one month history of palpitations, insomnia, nervousness, fatigue, diarrhea and heat intolerance. The physical examination reveals hyperreflexia, lid lag and mild tremor. Vital signs are: blood pressure 160/65, heart rate 95 bpm. Which of the following drugs was most likely included in the therapeutic management of this patient?

Pindolol

Propranolol

Labetalol

Prazosin

Phenoxybenzamine

Answer: B
The symptoms and signs of this patient clearly indicate that the woman is suffering from
hyperthyroidism. In addition to the specific therapy (antithyroid drugs, radioiodine), the
treatment of this disease almost always include the administration of beta-blockers that rapidly
decrease the nervousness, palpitations, heat intolerance, tremors and hypertension, likely
because many of these signs and symptoms are due to sympathetic overactivity. Propranolol is
the drug of choice.
A) Pindolol is a beta-blocker with intrinsic sympathomimetic activity (that is, it is a partial
agonist drug). Therefore it is not indicated in hyperthyroidism where the sympathetic nervous
system is already overactive.
C) Labetalol is contraindicated in hyperthyroidism since the alpha blocking activity can lower
the diastolic blood pressure which is already decreased in this disease.
D, E) Alpha-blocking drugs are contraindicated in hyperthyroidism (see explanation above)

Explanation

Answer: B
The symptoms and signs of this patient clearly indicate that the woman is suffering from
hyperthyroidism. In addition to the specific therapy (antithyroid drugs, radioiodine), the
treatment of this disease almost always include the administration of beta-blockers that rapidly
decrease the nervousness, palpitations, heat intolerance, tremors and hypertension, likely
because many of these signs and symptoms are due to sympathetic overactivity. Propranolol is
the drug of choice.
A) Pindolol is a beta-blocker with intrinsic sympathomimetic activity (that is, it is a partial
agonist drug). Therefore it is not indicated in hyperthyroidism where the sympathetic nervous
system is already overactive.
C) Labetalol is contraindicated in hyperthyroidism since the alpha blocking activity can lower
the diastolic blood pressure which is already decreased in this disease.
D, E) Alpha-blocking drugs are contraindicated in hyperthyroidism (see explanation above)

11. A 56-year-old man, recently diagnosed with exertional angina, started a therapy with propranolol. Which of the following cardiovascular parameters was most likely decreased in this patient?

End systolic volume

Ventricular ejection time

Cardiac ejection fraction

End diastolic volume

Venous tone

Answer: C
By blocking beta-1 and beta-2 receptors propranolol decreases cardiac contractility. The best
index of cardiac contractility is the ejection fraction, that is the fraction of the end diastolic
volume that is ejected during systole (remember that stroke volume is not the best index of
cardiac contractility since it also depends on preload).
A, D) Since contractility is decreased these volumes are actually increased, not decreased.
B) Beta-blockers actually increase ventricular ejection time.
E) Venous tone (which is mainly dependent on alpha-1 receptor activation) is minimally
affected by beta-blockers.

Explanation

Answer: C
By blocking beta-1 and beta-2 receptors propranolol decreases cardiac contractility. The best
index of cardiac contractility is the ejection fraction, that is the fraction of the end diastolic
volume that is ejected during systole (remember that stroke volume is not the best index of
cardiac contractility since it also depends on preload).
A, D) Since contractility is decreased these volumes are actually increased, not decreased.
B) Beta-blockers actually increase ventricular ejection time.
E) Venous tone (which is mainly dependent on alpha-1 receptor activation) is minimally
affected by beta-blockers.

12. A 36-year-old man who had been suffering from migraine for one year, was recently diagnosed with a moderate hypertension. The physician decided to start a treatment with propranolol, a drug that could also be useful in preventing migraine attacks. Which of the following pairs of adverse effects ware most likely to be expected during the first days of therapy?

Postural hypotension and fainting

Palpitations and flushing

Impairment of the far vision and photophobia

Insomnia and nightmares

Severe constipation and gastroesophageal reflux

Answer: D
The only drugs that are approved by FDA for both the treatment of migraine and of
hypertension are beta-blockers (mainly propranolol). Common adverse effects of propranolol
include insomnia and nightmares.
A) Beta-blockers do not cause postural hypotension since the preload and the baroreceptor
reflex are not affected by these drugs.
B) Beta-blockers decrease the heart rate and have antiarrhythmic properties, so palpitations
are quite unlikely. Beta-blockers block the beta-receptor mediated vasodilation so flushing is
quite unlikely.
C) Beta-blockers have no significant effect on eye accommodation do not cause mydriasis so
impairment of far vision and photophobia are quite unlikely.
E) Beta-blockers commonly cause diarrhea which is likely related to the blockade of beta-2
receptors in the gut and do not cause gastroesophageal reflux. Even if constipation can occur
with some beta-blockers, it is uncommon and never severe.

Explanation

Answer: D
The only drugs that are approved by FDA for both the treatment of migraine and of
hypertension are beta-blockers (mainly propranolol). Common adverse effects of propranolol
include insomnia and nightmares.
A) Beta-blockers do not cause postural hypotension since the preload and the baroreceptor
reflex are not affected by these drugs.
B) Beta-blockers decrease the heart rate and have antiarrhythmic properties, so palpitations
are quite unlikely. Beta-blockers block the beta-receptor mediated vasodilation so flushing is
quite unlikely.
C) Beta-blockers have no significant effect on eye accommodation do not cause mydriasis so
impairment of far vision and photophobia are quite unlikely.
E) Beta-blockers commonly cause diarrhea which is likely related to the blockade of beta-2
receptors in the gut and do not cause gastroesophageal reflux. Even if constipation can occur
with some beta-blockers, it is uncommon and never severe.

13. A 54-year-old woman, recently diagnosed with pheochromocytoma, was scheduled for surgery to remove the tumor. One week before surgery phenoxybenzamine was prescribed. Which of the following actions of norepinephrine was best antagonized by the given drug?

Dilation of skeletal muscle vessels

Increased heart rate

Bronchodilation

Decreased insulin secretion

Increased glycogenolysis

Answer: D
Phenoxybenzamine blocks irreversibly alpha-1 and alpha-2 receptors. Activation of alpha-2
receptors in pancreas decreases insulin secretion so leading to hyperglycemia. By blocking
alpha-2 receptors phenoxybenzamine counteracts this effect and so hyperglycemia is reduced.
A, B, C, E) All these action are due to activation of beta receptors and therefore are not
blocked by phenoxybenzamine

Explanation

Answer: D
Phenoxybenzamine blocks irreversibly alpha-1 and alpha-2 receptors. Activation of alpha-2
receptors in pancreas decreases insulin secretion so leading to hyperglycemia. By blocking
alpha-2 receptors phenoxybenzamine counteracts this effect and so hyperglycemia is reduced.
A, B, C, E) All these action are due to activation of beta receptors and therefore are not
blocked by phenoxybenzamine

14. A 57-year-old woman recently diagnosed with pheochromocytoma was under surgery to remove the tumor. With manipulation of the adrenal mass her blood pressure rose to 200/140 mm Hg. Which of the following pairs of drugs were most likely administered during the operation to reduce her blood pressure?

Phenoxybenzamine and propranolol

Prazosin and esmolol

Metyrosine and pindolol

Clonidine and propranolol

Clonidine and pindolol

Answer: B
Manipulation of pheochromocytoma during surgery can increase the release of performed
catecholamines so causing a profound increase of blood pressure. Short-acting alpha and beta
blockers are the best drugs to decrease the blood pressure and to avoid residual effects,
taking in account that, once the tumor is removed, catecholamine levels fall. Prazosin and
esmolol are short-acting drug (half-lives: prazosin . 3 hours, esmolol . 10 minutes) that can be
given by IV infusion.
A, C, D, E) All these drugs can decrease the blood pressure, but they are not suitable in this
setting since they have a long duration of action and are administered usually (propranolol) or
exclusively (all others) by oral route.

Explanation

Answer: B
Manipulation of pheochromocytoma during surgery can increase the release of performed
catecholamines so causing a profound increase of blood pressure. Short-acting alpha and beta
blockers are the best drugs to decrease the blood pressure and to avoid residual effects,
taking in account that, once the tumor is removed, catecholamine levels fall. Prazosin and
esmolol are short-acting drug (half-lives: prazosin . 3 hours, esmolol . 10 minutes) that can be
given by IV infusion.
A, C, D, E) All these drugs can decrease the blood pressure, but they are not suitable in this
setting since they have a long duration of action and are administered usually (propranolol) or
exclusively (all others) by oral route.

15. A 52-year-old woman suffering from severe bronchial asthma, presented for routine ophthalmic examination. She was found to have an intraocular pressure of 32 mm Hg in the right eye (normal: < 20 mm Hg) and a right visual field defect. An appropriate treatment was prescribed which most likely included the administration of which of the following drugs?

Carbachol

Epinephrine

Propranolol

Pilocarpine

Timolol

Answer: B
The patient most likely has open angle glaucoma, which is the most common cause of an
increased intraocular pressure. Epinephrine is used in this disease because it decreases
aqueous humor production by activating alpha-2 receptors in the ciliary epithelium, and it also
increases aqueous humor outflow through the uveoscleral route. Moreover in this patient:
A, C, D, E) All these drugs are effective in open angle glaucoma but are contraindicated in this
case because of severe asthma. In fact, even when given topically, beta-blocker and
cholinergic agonists can increase the risk of bronchospastic disorders from systemic
absorption via the nasolacrimal system.

Explanation

Answer: B
The patient most likely has open angle glaucoma, which is the most common cause of an
increased intraocular pressure. Epinephrine is used in this disease because it decreases
aqueous humor production by activating alpha-2 receptors in the ciliary epithelium, and it also
increases aqueous humor outflow through the uveoscleral route. Moreover in this patient:
A, C, D, E) All these drugs are effective in open angle glaucoma but are contraindicated in this
case because of severe asthma. In fact, even when given topically, beta-blocker and
cholinergic agonists can increase the risk of bronchospastic disorders from systemic
absorption via the nasolacrimal system.