1
Q
- A 27-year-old compulsive drug user injected a drug he thought was methamphetamine, but he has not developed any signs of methamphetamine action. He has been admitted to the emergency department and antimuscarinic drug overdose is suspected. Probable signs of atropine overdose include which one of the following?
A. Gastrointestinal smooth muscle cramping
B. Increased heart rate
C. Increased gastric secretion
D. Pupillary constriction
E. Urinary frequency
A
B. Increased heart rate
Atropine is an antimuscarinic drug that blocks the action of acetylcholine at muscarinic receptors. One of the effects of this blockade is an increase in heart rate, or tachycardia. While bradycardia (a slowed heart rate) can sometimes be observed after small doses of atropine, tachycardia is the more characteristic sign of an overdose. Neither gastrointestinal cramping, increased gastric secretion, pupillary constriction, nor urinary frequency are typical signs of atropine or methamphetamine overdose.
Atropine overdose leads to the inhibition of parasympathetic nervous system effects, resulting in symptoms that are often summarized by the phrase “hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter.”
2
Q
- Which of 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
A
D. Hyperthermia
Hyperthermia in Infants: Atropine and other belladonna alkaloids can cause a range of symptoms. In infants, the inability to sweat due to the antimuscarinic effects can lead to a dangerous increase in body temperature, or hyperthermia. This is especially concerning because infants have a limited ability to regulate their body temperature. Enhanced Rationale: The use of atropine-containing eye drops in children has been linked to cases of severe hyperthermia, emphasizing the need for caution when using these medications in pediatric populations.
3
Q
- 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. Sweating caused by exercise
A
E. Sweating caused by exercise
Sweating caused by exercise: Atropine’s primary mechanism of action is the blockade of muscarinic receptors. While nicotine can induce a range of effects, including those that mimic the sympathetic and parasympathetic nervous systems, the effects related to blood pressure and heart rate are not typically blocked by atropine. However, sweating, which is mediated by acetylcholine released from sympathetic nerve fibers at sweat glands, can be blocked by atropine. Enhanced Rationale: This highlights the unique role of acetylcholine in mediating sweat production, even though it’s released from sympathetic fibers.
4
Q
Questions 4-5. 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
A
E. Nicotine
Drug X: The response pattern of Drug X suggests that it acts as a ganglion stimulant. The increased blood pressure response in the atropine-pretreated animal indicates that the drug’s effect might have been partially offset by a compensatory vagal discharge in the control animal. Enhanced Rationale: Nicotine, a known ganglion stimulant, produces similar effects, emphasizing the importance of understanding the interactions between drugs and the autonomic nervous system.
5
Q
Questions 4-5. 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 in heart rate induced by drug Y in these experiments are shown in the following graph.
Drug Y is probably a drug similar to
A. Acetylcholine
B. Edrohonium
C. Hexamethonium
D. Nicotine
E. Pralidoxime
A
A. Acetylcholine
Drug Y: The effects of Drug Y suggest that it acts as a direct-acting muscarinic stimulant. The reversal of its effect by a ganglion blocker indicates involvement of the baroreceptor reflex. Enhanced Rationale: Acetylcholine, when given in doses that significantly lower blood pressure, can produce a similar response pattern. This underscores the intricate balance of the autonomic nervous system and how drugs can tip this balance in various directions.
6
Q
- 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. Cycloplegia
B. Dry skin in a warm environment
C. Miosis
D. Postural hypotension
E. Tachycardia
A
D. Postural hypotension
Postural hypotension: Both ganglion blockers and muscarinic blockers can produce a range of symptoms. However, postural hypotension, a drop in blood pressure upon standing, is indicative of sympathetic blockade. Enhanced Rationale: This symptom highlights the role of the sympathetic nervous system in maintaining blood pressure, especially during postural changes.
7
Q
- Which of the following is an accepted therapeutic indication for the use of antimuscarinic drugs?
A. Atrial fibrillation
B. Botulinum poisoning
C. Chronic obstructive pulmonary disease (COPD)
D. Glaucoma
E. Postoperative urinary retention
A
C. Chronic obstructive pulmonary disease (COPD)
COPD: Antimuscarinic drugs can be beneficial in conditions like COPD where bronchospasm, or tightening of the airways, is a concern. Enhanced Rationale: By blocking the effects of acetylcholine on the airways, antimuscarinic drugs can help relax and open the airways, improving breathing in conditions like COPD.
8
Q
- 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 IP; (inositol trisphosphate) in intestinal smooth muscle
D. Increased potassium efflux from smooth muscle
E. Increased sodium influx into the skeletal muscle end plate
A
B. Decreased DAG (diacylglycerol) in salivary gland tissue
DAG in salivary gland tissue: Muscarinic receptors play a role in various cellular pathways. Blocking these receptors can impact these pathways and the cellular responses they mediate. Enhanced Rationale: Understanding the cellular effects of drugs provides insights into their broader physiological effects.
9
Q
- Which one of the following drugs causes vasodilation that can be blocked by atropine?
A. Benztropine
B. Bethanechol
C. Botulinum toxin
D. Cyclopentolate
E. Edrophonium
F. Neostigmine
G. Pralidoxime
A
B. Bethanechol
Bethanechol: This drug can cause vasodilation by directly activating muscarinic receptors on blood vessel endothelium. Enhanced Rationale: This effect underscores the diverse roles of muscarinic receptors in the body, from the heart to the blood vessels to the glands.
10
Q
- 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
A
G. Pralidoxime
Pralidoxime: This drug has a high affinity for the phosphorus atom in certain insecticides, making it valuable in treating toxicities from these chemicals. Enhanced Rationale: The ability of pralidoxime to bind to and neutralize these insecticides can be life-saving in cases of poisoning.
11
Q
Questions 1 and 2. While playing in the garden, a 7-year-old boy is stung by 3 bees. Because he has a previous history of bee sting allergy, he is brought to the emergency department by his mother who is very concerned about a possible anaphylactic reaction.
- Which of the following are probable signs of an anaphylactic reaction to bee stings?
(A) Bronchodilation, tachycardia, hypertension, vomiting, diarrhea
(B) Bronchospasm, tachycardia, hypotension, laryngeal edema
(C) Diarrhea, bradycardia, vomiting
(D) Laryngeal edema, bradycardia, hypotension, diarrhea
(E) Miosis, tachycardia, vomiting, diarrhea
A
(B) Bronchospasm, tachycardia, hypotension, laryngeal edema
12
Q
Questions 1 and 2. While playing in the garden, a 7-year-old boy is stung by 3 bees. Because he has a previous history of bee sting allergy, he is brought to the emergency department by his mother who is very concerned about a possible anaphylactic reaction.
- If this child has signs of anaphylaxis, what is the treatment of choice?
(A) Diphenhydramine (an antihistamine)
(B) Ephedrine
(C) Epinephrine
(D) Isoproterenol
(E) Methylprednisolone (a corticosteroid)
A
(C) Epinephrine
13
Q
Questions 1 and 2. While playing in the garden, a 7-year-old boy is stung by 3 bees. Because he has a previous history of bee sting allergy, he is brought to the emergency department by his mother who is very concerned about a possible anaphylactic reaction.
- A 65-year-old woman with impaired renal function and a necrotic ulcer in the sole of her right foot is admitted to the ward from the emergency department. She has long-standing type 2 diabetes mellitus and you wish to examine her retinas for possible vascular 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
A
(C) Phenylephrine
14
Q
- A 60-year-old woman was told she had hypertension and should be taking antihypertensive medication. She decides to take an herbal medication from an online “holistic pharmacy.” One week after starting the medication, she is found unconscious in her apartment. In the emergency department, her blood pressure is 50/0 mm Hg and heart rate is 40 bpm. Respirations are 20/min; pupils are slightly constricted. Bowel sounds are present. Which of the following would be the most effective cardiovascular stimulant?
(A) Amphetamine
(B) Clonidine
(C) Isoproterenol
(D) Norepinephrine
(E) Tyramine
A
(D) Norepinephrine
15
Q
- A group of volunteers are involved in a phase 1 clinical trial of a new autonomic drug. When administered by intravenous bolus, the blood pressure increases. When given orally for 1 week, the blood pressure decreases. Which of the following standard agents does the new drug most resemble?
(A) Atropine
(B) Clonidine
(C) Phentolamine (an a blocker)
(D) Phenylephrine
(E) Propranolol (a ß blocker)
A
(B) Clonidine
16
Q
- Your 30-year-old patient has moderately severe new onset asthma, and you prescribe a highly selective 2 agonist inhaler to be used when needed. In considering the possible drug effects in this patient, you would note that 2 stimulants frequently cause
(A) Direct stimulation of renin release
(B) Hypoglycemia
(C) Itching due to increased GMP (cyclic guanine mono-phosphate) in mast cells
(D) Skeletal muscle tremor
(E) Vasodilation in the skin
A
(D) Skeletal muscle tremor
17
Q
- Mr Green, a 54-year-old banker, 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
A
(E) Phenylephrine
18
Q
Questions 8 and 9. Several new drugs with autonomic actions were studied in preclinical tests in animals. Autonomic drugs X and Y were given in moderate doses as intravenous boluses. The systolic and diastolic blood pressures changed as shown in the diagram below.
- Which of the following drugs most resembles drug X?
(A) Bethanechol
(B) Epinephrine
(C) Isoproterenol
(D) Methacholine
(E) Phenylephrine
A
(C) 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 3-agonist effects. The fact that it also markedly increased pulse pressure suggests that it strongly increased stroke volume, a ß-agonist effect. The drug with these ß effects is isoproterenol (Figure 9-1). The answer is C.
19
Q
Questions 8 and 9. Several new drugs with autonomic actions were studied in preclinical tests in animals. Autonomic drugs X and Y were given in moderate doses as intravenous boluses. The systolic and diastolic blood pressures changed as shown in the diagram below.
- Which of the following most resembles drug Y?
(A) Bethanechol
(B) Epinephrine
(C) Isoproterenol
(D) Methacholine
(E) Phenylephrine
A
(E) Phenylephrine
20
Q
- 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
A
(B) Epinephrine
21
Q
- A patient presents at the emergency department with threatened anaphylaxis. Respiratory obstruction appears likely if she is not treated immediately. Her past medical history includes hypertension, for which she is receiving an adrenoceptor blocker. The emergency physician plans to use epinephrine to treat her anaphylactic reaction. Which of the following effects of epinephrine would be blocked by prazosin but not by metoprolol?
(A) Cardiac stimulation
(B) Increase of cAMP (cyclic adenosine monophosphate) in fat cells
(C) Mydriasis
(D) Relaxation of bronchial smooth muscle
(E) Relaxation of the uterus
A
(C) Mydriasis
Mydriasis caused by contraction of the pupillary dilator radial smooth muscle is mediated by a receptors. All the other effects listed are mediated by ß receptors.
22
Q
- 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 a-blocking agents)
(B) Acute heart failure exacerbation (from ß blockers)
(C) Impaired blood sugar response (with a blockers)
(D) Increased intraocular pressure (with ß blockers)
(E) Sleep disturbances (from a-blocking drugs)
A
(B) Acute heart failure exacerbation (from ß blockers)
Although chronic heart failure is often treated with certain B blockers, acute heart failure can be precipitated or made worse by any ß blocker. Choices A, C, and E reverse the correct pairing of receptor subtype (a versus B) with effect. Choice D reverses the direction of change of intraocular pressure.
23
Q
- 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
(A) Bradycardia induced by phenylephrine
Phenylephrine, an a agonist, increases blood pressure and causes bradycardia through the baroreceptor reflex. Blockade of this drug’s d-mediated vasoconstrictor effect prevents the bradycardia.
24
Q
- Your 75-year-old patient with multiple comorbidities is to receive aß-blocking drug. For which of the following conditions are ß-blocking drugs NOT indicated?
(A) Acute arrhythmias during surgery
(B) Atherosclerotic angina pectoris (angina of effort)
(C) Chronic heart failure
(D) Hypertension
(E) Hypoglycemia in diabetes
A
(D) Hypertension
The ß blockers have several important cardiovascular indica-tions, including acute arrhythmias, angina, chronic (but not acute) heart failure, and hypertension. In addition they are useful in glaucoma, hyperthyroidism, tremor, and possibly, COPD. However, they mask the signs of hypoglycemia and are potentially hazardous in diabetic patients.
25
9. A 56-year-old man has hypertension and an enlarged pros-tate, 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 a blocker is appropriate therapy in a man with both hypertension and benign prostatic hyperplasia because both conditions involve contraction of smooth muscle containing a receptors. Prazosin is the only a blocker in the list of choices.
26
1. A 32-year-old woman with hypertension wishes to become pregnant. Her physician informs her that she will have to switch to another antihypertensive drug. Which of the following drugs is absolutely contraindicated in pregnancy?
(A) Atenolol
(B) Losartan
(C) Methyldopa
(D) Nifedipine
(E) Propranolol
(B) Losartan
Methyldopa is recommended in pregnancy due to its safety record.
ACE inhibitors and ARBs are contraindicated as they can be teratogenic.
Calcium channel blockers are not contraindicated.
27
2. A patient is admitted to the emergency department with severe tachycardia after a drug overdose. His family reports that he has been depressed about his hypertension. Which one of the following drugs increases the heart rate in a dose-dependent manner?
(A) Captopril
(B) Hydrochlorothiazide
(C) Losartan
(D) Minoxidil
(E) Verapamil
(D) Minoxidil
ACE inhibitors, ARBs, and diuretics do not significantly increase heart rate.
Verapamil and diltiazem inhibit the sinoatrial node and decrease heart rate.
Other direct vasodilators increase heart rate.
28
3. Which one of the following is characteristic of nifedipine treatment in patients with essential hypertension?
(A) Competitively blocks angiotensin II at its receptor
(B) Decreases calcium efflux from skeletal muscle
(C) Decreases renin concentration in the blood
(D) Decreases calcium influx into smooth muscle
(E) Increases calcium excretion in the urine
(D) Decreases calcium influx into smooth muscle
Nifedipine is a calcium channel blocker that lowers blood pressure by reducing calcium influx.
It has no effect on angiotensin-converting enzyme.
Calcium efflux from skeletal muscle cells is not involved.
Plasma renin levels may increase due to reduced blood pressure.
Calcium channel blockers have negligible effects on urine calcium.
29
4. A 73-year-old man with a history of a recent change in his treatment for moderately severe hypertension is brought to the emergency department because of a fall at home. Which of the following drug groups is most likely to cause postural hypotension and thus an increased risk of falls?
(A) ACE inhibitors
(B) Alpha,-selective receptor blockers
(C) Arteriolar dilators
(D) Beta1-selective receptor blockers
(E) Calcium channel blockers
(B) Alpha1-selective receptor blockers
Drug-induced postural (orthostatic) hypotension is due to venous pooling or excessive diuresis.
Alpha-1 blockers like prazosin can exacerbate orthostatic hypotension.
30
5. A significant number of patients started on ACE inhibitor therapy for hypertension are intolerant and must be switched to a different class of drug. What is the most common manifestation of this intolerance?
(A) Angioedema
(B) Glaucoma
(C) Headache
(D) Incessant cough
(E) Ventricular arrhythmias
(D) Incessant cough
Chronic cough is an adverse effect of ACE inhibitors like captopril.
It may be associated with increased bradykinin levels.
ACE inhibitors are commonly used in hypertensive diabetic patients.
ACE inhibitors are not associated with glaucoma.
Angioedema is less common than cough.
31
6. Which one of the following is a significant unwanted effect of the drug named?
(A) Constipation with verapamil
(B) Heart failure with hydralazine
(C) Hemolytic anemia with atenolol
(D) Hypokalemia with aliskiren
(E) Lupus-like syndrome with hydrochlorothiazide
(A) Constipation with verapamil
Hydralazine is sometimes used in heart failure.
Beta blockers are not associated with hematologic abnormalities.
Thiazide diuretics often cause mild hyperglycemia, hyperuricemia, and hyperlipidemia.
Hydralazine is associated with a lupus-like syndrome.
Aliskiren and other renin-angiotensin-aldosterone system inhibitors may cause hyperkalemia, not hypokalemia.
Verapamil often causes constipation.
32
7. Comparison of prazosin with atenolol shows that
(A) Both decrease heart rate
(B) Both increase cardiac output
(C) Both increase renin secretion
(D) Both increase sympathetic outflow from the CNS
(E) Both produce orthostatic hypotension
(D) Both increase sympathetic outflow from the CNS
Atenolol may decrease heart rate.
Prazosin may increase cardiac output and renin output.
Beta blockers do not cause orthostatic hypotension.
Both drugs may increase central sympathetic outflow as a compensatory response.
33
8. A patient with hypertension and angina is referred for treat-ment. Metoprolol and verapamil are among the drugs con-sidered. Both metoprolol and verapamil are associated with which one of the following?
(A) Diarrhea
(B) Hypoglycemia
(C) Increased PR interval
(D) Tachycardia
(E) Thyrotoxicosis
(C) Increased PR interval
Neither beta blockers nor calcium channel blockers cause diarrhea.
Hypoglycemia is not a common effect of antihypertensive drugs.
Thyroid disorders are not associated with either drug group.
Calcium blockers and beta blockers can depress cardiac processes.
Dihydropyridines do not often cause cardiac depression.
34
9. A 45-year-old man is brought to the emergency department with mental obtundation. He is found to have a blood pressure of 220/160 mm Hg and retinal hemorrhages. Which one of the following is used in severe hypertensive emergencies, is short-acting, acts on a G-protein-coupled receptor, and must be given by intravenous infusion?
(A) Aliskiren
(B) Captopril
(C) Fenoldopam
(D) Hydralazine
(E) Losartan
(F) Metoprolol
(G) Nitroprusside
(H) Prazosin
(I) Propranolol
(C) Fenoldopam
Fenoldopam, nitroprusside, and propranolol are the drugs in the list that have been used in hypertensive emergencies.
Fenoldopam and nitroprusside are used by infusion only, but nitroprusside releases nitric oxide, which acts on intracellular guanylyl cyclase. The answer is C.
35
10. Which of the following is very short-acting and acts by releasing nitric oxide?
(A) Atenolol
(B) Captopril
(C) Diltiazem
(D) Fenoldopam
(E) Hydrochlorothiazide
(F) Losartan
(G) Minoxidil
(H) Nitroprusside
(I) Prazosin
(H) Nitroprusside
Hydralazine and nitroprusside act via a nitric oxide mechanism.
Hydralazine has a longer duration of action, while nitroprusside acts briefly and requires intravenous infusion.
36
Questions 1-4. A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin.
1. Which of the following is a common direct or reflex effect of nitroglycerin?
(A) Decreased heart rate
(B) Decreased venous capacitance
(C) Increased afterload
(D) Increased cardiac force
(E) Increased diastolic myocardial fiber tension
(D) Increased cardiac force
Nitroglycerin increases heart rate and venous capacitance and decreases afterload and diastolic fiber tension. It increases cardiac contractile force because the decrease in blood pressure evokes a compensatory increase in sympathetic discharge.
The answer is D.
37
Questions 1-4. A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin.
2. In advising the patient about the adverse effects she may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. Which of the following effects might occur due to the mechanism listed?
(A) Constipation due to reduced colonic activity
(B) Dizziness due to reduced cardiac force of contraction
(C) Diuresis due to sympathetic discharge
(D) Headache due to meningeal vasodilation
(E) Hypertension due to reflex tachycardia
(D) Headache due to meningeal vasodilation
The nitrates relax many types of smooth muscle, but the effect on motility in the colon is insignificant. Nitroglycerin causes hypotension as a result of arterial and venous dilation. Dilation of arteries in the meninges has no effect on central nervous system function but does cause headache. The answer is D.
38
Questions 1-4. A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin.
3. One year later, the patient returns complaining that her nitroglycerin works well when she takes it for an acute attack but that she is now having more frequent attacks and would like something to prevent them. Useful drugs for the prophylaxis of angina of effort include
(A) Amyl nitrite
(B) Esmolol
(C) Sublingual isosorbide dinitrate
(D) Sublingual nitroglycerin
(E) Verapamil
(E) Verapamil
The calcium channel blockers and the ß blockers are generally effective in reducing the number of attacks of angina of effort, and most have durations of 4-8 h. Oral and transdermal nitrates have similar or longer durations. Amyl nitrite and the sublingual nitrates have short durations of action (a few minutes to 30 min). Esmolol (an intravenous ß blocker) must be given intravenously and also has a very short duration of action. Thus, nitrites, sublingual nitrates, and esmolol are of no value in prophylaxis. The answer is E
39
Questions 1-4. A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin.
4. If a beta blocker were to be used for prophylaxis in this patient, what is the most probable mechanism of action in angina?
(A) Block of exercise-induced tachycardia
(B) Decreased end-diastolic ventricular volume
(C) Increased double product
(D) Increased cardiac force
(E) Decreased ventricular ejection time
(A) Block of exercise-induced tachycardia
Propranolol blocks tachycardia but has none of the other effects listed. Only revascularization increases double prod-uct; drugs that decrease cardiac work increase exercise time by decreasing double product.
40
5. A new 60-year old patient presents to the medical clinic with hypertension and angina. He is 1.8 meters tall with a wait measurement of 1.1 m. Weight is 97 kg, blood pressure is 150/95 mm Hg, and pulse is 85. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is
(A) Bradycardia
(B) Impaired sexual function
(C) Lupus erythematosus syndrome
(D) Orthostatic hypotension
(E) Weight gain
(D) Orthostatic hypotension
Both drugs cause venodilation and reduce venous return sufficiently to cause some degree of postural hypotension. Bra-dycardia, lupus, and urinary retention occur with neither of them, but prazosin has been used to relieve urinary retention in men with prostatic hyperplasia. While this patient has a high body mass index of 29.9, weight gain is not a risk with either drug.
41
6. A 25-year-old man is admitted to the emergency department with a brownish cyanotic appearance, marked shortness of breath, and hypotension. He has needle marks in both arms. Which of the following is most likely to cause methemoglobinemia?
(A) Amyl nitrite
(B) Isosorbide dinitrate
(C) Isosorbide mononitrate
(D) Nitroglycerin
(E) Sodium cyanide
(A) Amyl nitrite
Read carefully! Nitrites, not nitrates, cause methemoglobin-emia in adults. Methemoglobinemia is deliberately induced in one of the treatments of cyanide poisoning. Amyl nitrite and isobutyl nitrite, obtained as street drugs, have been heavily used as sex-enhancers. The answer is A.
42
7. Another patient is admitted to the emergency department after a drug overdose. He is noted to have hypotension and severe bradycardia. He has been receiving therapy for hypertension and angina. Which of the following drugs in high doses causes bradycardia?
(A) Amlodipine
(B) Isosorbide dinitrate
(C) Nitroglycerin
(D) Prazosin
(E) Verapamil
(E) Verapamil
Isosorbide dinitrate (like all the nitrates) and prazosin can cause reflex tachycardia. Amlodipine, a dihydropyridine calcium channel blocker, causes much more vasodilation than cardiac depression and may also cause reflex tachycardia. Verapamil typically slows heart rate and high doses may cause severe bra-dycardia.
43
8. Asine eld he devices anilip demier highene
the following is relatively contraindicated because of her migraines?
(A) Amlodipine
(B) Diltiazem
(C) Metoprolol
(D) Nitroglycerin
(E) Verapamil
(D) Nitroglycerin
Acute migraine headache is associated with vasodilation of meningeal arteries. Of the drugs listed, only nitroglycerin is commonly associated with headache. In fact, calcium channel blockers and ß blockers have been used with some success as prophylaxis for migraine. The
44
9. When nitrates are used in combination with other drugs for the treatment of angina, which one of the following combinations results in additive effects on the variable specified?
(A) Beta blockers and nitrates on end diastolic cardiac size
(B) Beta blockers and nitrates on heart rate
(C) Beta blockers and nitrates on venous tone
(D) Calcium channel blockers and beta blockers on cardiac force
(E) Calcium channel blockers and nitrates on heart rate
(D) Calcium channel blockers and beta blockers on cardiac force
The effects of B blockers and nitrates on heart size, force, venous tone, and heart rate are opposite. The effects of ß blockers and calcium channel blockers on heart size, force, and rate are similar. The answer is D.
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10. Certain drugs can cause severe hypotension when combined with nitrates. Which of the following interacts with nitroglycerin by inhibiting the metabolism of cGMP?
(A) Atenolol
(B) Hydralazine
(C) Isosorbide mononitrate
(D) Nifedipine
(E) Ranolazine
(F) Sildenafil
(G) Terbutaline
(F) Sildenafil
Sildenafil inhibits phosphodiesterase 5, an enzyme that inactivates GMP. The nitrates (via nitric oxide) increase the synthesis of GMP. This combination is synergistic. The answer is F.
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Questions 1-2. A 73-year-old man with an inadequate response to other drugs is to receive digoxin for chronic heart failure. He is in normal sinus rhythm with a heart rate of 88 bpm and blood pressure of 135/85 mm Hg.
1. Which of the following is the best-documented mechanism of beneficial action of cardiac glycosides?
(A) A decrease in calcium uptake by the sarcoplasmic reticulum
(B) An increase in a late transmembrane sodium current
(C) A modification of the actin molecule
(D) An increase in systolic cytoplasmic calcium levels
(E) A block of cardiac B adrenoceptors
(D) An increase in systolic cytoplasmic calcium levels
Digitalis does not decrease calcium uptake by the sarcoplas-mic reticulum or increase sodium current; it does not modify actin. Cardiac adrenoceptors are not affected. The most accurate description of digitalis's mechanism in this list is that it increases systolic cytoplasmic calcium by inhibiting Na'/K* transport by the ATPase sodium pump and indirectly altering Na*/Ca* exchange. The answer is
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Questions 1-2. A 73-year-old man with an inadequate response to other drugs is to receive digoxin for chronic heart failure. He is in normal sinus rhythm with a heart rate of 88 bpm and blood pressure of 135/85 mm Hg.
After your patient has been receiving digoxin for 3 weeks, he presents to the emergency department with an arrhythmia.
Which one of the following is most likely to contribute to the arrhythmogenic effect of digoxin?
(A) Increased parasympathetic discharge
(B) Increased intracellular calcium
(C) Decreased sympathetic discharge
(D) Decreased intracellular ATP
(E) Increased extracellular potassium
(B) Increased intracellular calcium
The effects of digitalis include increased vagal action on the heart (not arrhythmogenic) and increased intracellular calcium, including calcium overload, the most important cause of toxicity. Decreased sympathetic discharge and increased extracellular potassium and magnesium reduce digitalis arrhythmogenesis. The answer is B.
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A patient who has been taking digoxin for several years for atrial fibrillation and chronic heart failure is about to receive atropine for another condition. A common effect of digoxin (at therapeutic blood levels) that can be almost entirely blocked by atropine is
(A) Decreased appetite
(B) Headaches
(C) Increased atrial contractility
(D) Increased PR interval on ECG
(E) Tachycardia
(D) Increased PR interval on ECG
The parasympathomimetic effects of digitalis can be blocked by muscarinic blockers such as atropine. The only parasympathomimetic effect in the list provided is increased PR interval, a manifestation of slowed AV conduction. The answer is D.
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A 65-year-old African-American man has long-standing hypertension and moderate heart failure with reduced ejection fraction. His treatment has included furosemide plus digoxin but he continues to have symptoms of shortness of breath and easy fatigue. Which of the following combinations has been shown to be useful in this type of patient?
(A) Digoxin + spironolactone
(B) Furosemide + nesiritide
(C) Hydralazine + isosorbide dinitrate
(D) Isosorbide dinitrate + propranolol
(E) Spironolactone + potassium supplements
(C) Hydralazine + isosorbide dinitrate
Chronic congestive failure with hypertension often benefits from a vasodilator that reduces blood pressure and venous pressure. Hydralazine effectively reduces arterial pressure (see Chapter 11) and isosorbide dinitrate is an effective venodila-tor (see Chapter 12). This combination has been shown to reduce hospitalizations in African Americans with heart fail-ure. The answer is C.
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A 72-year-old woman has long-standing heart failure. Which one of the following drugs has been shown to reduce mortality in chronic heart failure?
(A) Atenolol
(B) Digoxin
(C) Furosemide
(D) Nitroprusside
(E) Spironolactone
(E) Spironolactone
Of the drugs listed, only spironolactone has been shown to reduce mortality in this highly lethal disease. Digoxin, furose-mide, and nitroprusside are used in the management of symp-toms. The answer is E.
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Which of the following drugs increases the plasma levels of endogenous BNP and is combined with another agent that blocks angiotensin receptors?
(A) Furosemide
(B) Losartan
(C) Nesiritide
(D) Sacubitril
(E) Spironolactone
(D) Sacubitril
Furosemide has no significant effect on peptide metabolism and does not block AT, receptors. Losartan blocks AT, receptors but has no effect on peptide metabolism. Nesiritide is a synthetic BNP and does not block AT, receptors. Spirono-lactone blocks the aldosterone receptor in the kidney. Only sacubitril/valsartan has the combined effect listed in the stem of this question. The answer is D.
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7. Which one of the following drugs is associated with clinically useful or physiologically important positive inotropic effects?
(A) Captopril
(B) Dobutamine
(C) Enalapril
(D) Losartan
(E) Nesiritide
(B) Dobutamine
Although they are extremely useful in heart failure, ACE inhibitors (eg, captopril, enalapril), and angiotensin receptor blockers (ARBs, eg, losartan) have no positive inotropic effect on the heart. Nesiritide is a vasodilator with diuretic effects and renal toxicity. Dobutamine is a B,-selective adrenoceptor agonist. The answer is B.
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8. A 68-year-old man with a history of chronic heart failure goes on vacation and abandons his low-salt diet. Three days later, he develops severe shortness of breath and is admitted to the local hospital emergency department with significant pulmonary edema. The first-line drug of choice in most cases of acute decompensation in patients with chronic heart failure is
(A) Atenolol
(B) Captopril
(C) Carvedilol
(D) Digoxin
(E) Diltiazem
(F) Dobutamine
(G) Enalapril
(H) Furosemide
(I) Nesiritide
(J) Spironolactone
(H) Furosemide
In both acute and chronic failure and systolic (HFrEF) and diastolic heart failure (HFpEF), the initial treatment of choice is usually furosemide. The answer is H.
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9. Which of the following has been shown to prolong life in patients with chronic congestive failure in spite of having a negative inotropic effect on cardiac contractility?
(A) Carvedilol
(B) Digoxin
(C) Dobutamine
(D) Enalapril
(E) Furosemide
(A) Carvedilol
Several B blockers, including carvedilol, have been shown to prolong life in heart failure patients even though these drugs may have a negative inotropic action on the heart. Their benefits presumably result from some other ß-mediated effect, and at least one other ß blocker has failed to show a mortality benefit. The answer is A.
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10. A 5-year-old child was vomiting and was brought to the emergency department with sinus arrest and a ventricular rate of 35 bpm. An empty bottle of his uncle's digoxin was found where he was playing. Which of the following is the drug of choice in treating a severe overdose of digoxin?
(A) Digoxin antibodies
(B) Lidocaine infusion
(C) Magnesium infusion
(D) Phenytoin by mouth
(E) Potassium by mouth
(A) Digoxin antibodies
The drug of choice in severe, massive overdose with any cardiac glycoside is digoxin antibody, Digibind. The other drugs listed are used in moderate overdosage associated with increased automaticity. The answer is A.
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(A) Acetazolamide
1. Although acetazolamide is rarely used in heart failure, carbonic anhydrase inhibitors are quite valuable in patients with edema and metabolic alkalosis. The high bicarbonate levels in these patients make them particularly susceptible to the action of carbonic anhydrase inhibitors. This patient has both high pH and bicarbonate. Digoxin is useful in chronic systolic failure but is not first-line therapy and may cause vomiting, with depletion of stomach acid and reduced serum chloride; increasing the digoxin dose might cause arrhythmias. Tolvap-tan might be useful if the patient were hyponatremic. Hydro-chlorothiazide and eplerenone are not adequate for first-line therapy of edema in acute heart failure. The answer is A.
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(A) Chlorthalidone
2. The thiazides are useful in the prevention of calcium stones because these drugs reduce tubular calcium concentration, probably by increasing passive proximal tubular and distal convoluted tubule reabsorption of calcium. In contrast, the loop agents (choice C) facilitate calcium excretion. Diazoxide is a thiazide-like vasodilator drug but has no diuretic action; in fact, it may cause sodium retention. It is used in hypertension and insulinoma (see Chapter 11). The answer is A.
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(D) Metabolic alkalosis
3. Loop diuretics increase urinary calcium excretion and decrease blood pressure (in hypertension) and pulmonary vascular pressure (in congestive heart failure). They have no recognized teratogenic action. They cause metabolic alkalosis (Table 15-1). Loop diuretics also cause ototoxicity. The answer is D.
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(E) Drug: Mannitol, Urine Na: (-), Urine K: (++), Metabolic change: (Alkalosis)
4. Acetazolamide causes metabolic acidosis. Furosemide causes a marked increase in sodium and a moderate increase in potassium excretion. Thiazides cause alkalosis and a greater increase in sodium than potassium excretion. Mannitol causes a small increase in both sodium and potassium excretion and no change in body pH. Spironolactone causes the changes indicated. The answer is D.
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(E) Mannitol
5. An osmotic agent is needed to remove water from the cells of the edematous brain and reduce intracranial pressure rapidly.
The answer is E.
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(B) Furosemideplus salineinfusion
6. Diuretic therapy of hypercalcemia requires a reduction in calcium reabsorption in the thick ascending limb, an effect of loop diuretics. However, a loop diuretic alone would reduce blood volume around the remaining calcium so that serum calcium would not decrease appropriately. Therefore, a saline infusion should accompany the loop diuretic. The answer is B.
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(C) Furosemide
7. Orthostatic hypotension is associated with reduced blood vol-ume, which may occur with excessive diuresis. The observation that the patient also has hearing impairment suggests the use of an ototoxic drug, eg, loop agent like furosemide. The answer is C.
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(B) Dapagliflozin
8. Diabetes is associated with increased susceptibility to infec-tion. The fact that the patient has a normal blood glucose indicates that her medications are reducing blood glucose and, combined with a urinary tract infection, further suggests that urine glucose is elevated. Increased glucose excretion in the urine is an effect of the SGLT2 inhibitors. The answer is B, dapagliflozin.
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(I) Tolvaptan
9. Retention of water with hyponatremia and inability to form dilute urine in the fully hydrated condition is characteristic of
SIADH. Antagonists of ADH are needed to treat this condi-tion. The answer is I, tolvaptan.
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(A) Acetazolamide
10. Carbonic anhydrase inhibitors are useful for the prevention of altitude sickness. The answer is A.
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1. PJ is a 5-year-old boy. At his checkup, the pediatrician notices cutaneous xanthomas and orders a lipid panel. Repeated measures confirm that the patient's serum cholesterol levels are high (936 mg/dL). Further testing confirms a diagnosis of homozygous familial hypercholesterolemia. Which of the following interventions will be least effective in this patient?
(A) Atorvastatin
(B) Ezetimibe
(C) Lomitapide
(D) Mipomersen
(E) Niacin
(A) Atorvastatin
Homozygous Familial Hypercholesterolemia:
Caused by mutations that result in dysfunctional LDL receptors that can't uptake LDL from the bloodstream.
Lomitapide and mipomersen are specifically indicated for patients with this condition.
Reductase inhibitors like atorvastatin need functional LDL receptors to work, so they're ineffective for these patients.
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A 46-year-old woman with a history of hyperlipidemia was treated with a drug. The chart below shows the results of the patient's fasting lipid panel before treatment and 6 months after initiating drug therapy. Normal values are also shown.
Which of the following drugs is most likely to be the one that this patient received?
(A) Colestipol
(B) Ezetimibe
(C) Gemfibrozil
(D) Lovastatin
(E) Niacin
(E) Niacin
Hypertriglyceridemia, Elevated VLDL, and Low HDL:
Patient presents with significant hypertriglyceridemia, high VLDL cholesterol, and low HDL cholesterol.
Six months after drug treatment, there are dramatic improvements in these values.
Niacin is the drug most likely responsible for these changes.
Gemfibrozil doesn't cause such large HDL increases or LDL decreases.
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3. Based on her lipid values which of the following drugs would be contraindicated as monotherapy in this patient?
(A) Atorvastatin
(B) Cholestyramine
(C) Ezetimibe
(D) Gemfibrozil
(E) Niacin
(B) Cholestyramine
Familial Combined Hyperlipidemia:
In some patients, resins can increase VLDL and triglyceride concentrations even while lowering LDL cholesterol.
Given the patient's high TG levels, increasing TG and VLDL isn't advised.
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4. If this patient is pregnant, which of the following drugs should be avoided because of a risk of harming the fetus?
(A) Cholestyramine
(B) Ezetimibe
(C) Fenofibrate
(D) Niacin
(E) Pravastatin
(E) Pravastatin
HMG-CoA Reductase Inhibitors and Pregnancy:
These inhibitors are contraindicated in pregnancy due to teratogenic risks.
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5. The patient is started on niacin and a second a drug to specifically target her most elevated lipid values. Which of the following is a major mechanism of this drug's action?
(A) Increased excretion of bile acid salts
(B) Increased expression of high-affinity LDL receptors
(C) Increased secretion of VLDL by the liver
(D) Increased triglyceride hydrolysis by lipoprotein lipase
(E) Reduced uptake of dietary cholesterol
(D) Increased triglyceride hydrolysis by lipoprotein lipase
Elevated Triglycerides Treatment:
Based on the patient's high triglycerides, gemfibrozil (a fibrate) is started.
Fibrates increase activity of lipoprotein lipase associated with capillary endothelial cells.
They decrease VLDL secretion by stimulating hepatic fatty acid oxidation.
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6. The patient developed severe and sudden pain in the upper right abdomen, nausea and vomiting and she confirmed clay colored stools. A diagnosis of biliary obstruction secondary to gallstones was made. Which of the following most likely caused this?
(A) Atorvastatin
(B) Cholestyramine
(C) Ezetimibe
(D) Gemfibrozil
(E) Niacin
(D) Gemfibrozil
Fibrate Toxicity:
A major toxicity of fibrates is the increased risk of gallstone formation due to enhanced biliary excretion of cholesterol.
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Questions 7-10. A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week.
7. Consumption of alcohol is associated with which of the following changes in serum lipid concentrations?
(A) Decreased chylomicions
(B) Decreased HDL cholesterol
(C) Decreased VLDL cholesterol
(D) Increased LDL cholesterol
(E) Increased triglyceride
(E) Increased triglyceride
Effects of Chronic Ethanol Ingestion:
Increases serum concentrations of VLDL and triglycerides, risking pancreatitis.
Can also beneficially increase serum HDL concentrations.
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Questions 7-10. A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week.
8. If the patient has a history of gout, which of the following drugs is most likely to exacerbate this condition?
(A) Colestipol
(B) Ezetimibe
(C) Gemfibrozil
(D) Niacin
(E) Simvastatin
(D) Niacin
Niacin's Adverse Effects:
Exacerbates hyperuricemia and glucose intolerance.
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Questions 7-10. A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week.
9. After being counseled about lifestyle and dietary changes, the patient was started on atorvastatin. During his treatment with atorvastatin, it is important to routinely monitor serum concentrations of which of the following?
(A) Blood urea nitrogen
(B) Alanine and aspartate aminotransferase
(C) Platelets
(D) Red blood cells
(E) Uric acid
(B) Alanine and aspartate aminotransferase
Adverse Effects of HMG-CoA Reductase Inhibitors:
Two primary adverse effects are hepatotoxicity and myopathy.
Liver function tests are recommended before and during therapy.
Alanine and aspartate aminotransferase are markers of hepatocellular toxicity.
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Questions 7-10. A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week.
10. Six months after beginning atorvastatin, the patient's total and LDL cholesterol concentrations remained above normal, and he continued to have anginal attacks despite good adherence to his antianginal medications. His physician decided to add ezetimibe. Which of the following is the most accurate description of ezetimibe's mechanism of an action?
(A) Decreased lipid synthesis in adipose tissue
(B) Decreased secretion of VLDL by the liver
(C) Decreased gastrointestinal absorption of cholesterol
(D) Increased endocytosis of HDL by the liver
(E) Increased lipid hydrolysis by lipoprotein lipase
(C) Decreased gastrointestinal absorption of cholesterol
Effect of Ezetimibe:
Its main effect is inhibiting cholesterol absorption in the intestine.
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Pharma 1
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