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1.

A 3-ycar--old child has been admitted to the emergency department having swallowed the
contents of 2 bottles of a nasal decongestant. The active ingredient of the medication is
phenylephrine, a potent, selective a-adre.noceptor agorust drug. Which of the following is a sign
of a-receptor activation that may occw- in this child?
(A) Bronchodilation
(B) Cardiac a~eration (tachycardia)
(C) Pupillary dilation (mydriasis)
(D) Rcnin release from the kidneys
(E) Vasodilation of blood vessels
Mydriasis can be caused by contraction of the radial fibers of the iris; these smooth muscle cells
have a receptors. All the other listed responses are mediated by~ adrenoceptors (Table 6-3).

2. Mr Green is a 60-year-old man with atherosclerosis and poorly controlled hypertension of


170/110 mm Hg. He has been taking several antihypertensive drugs, including minoxidil.
Minoxidil is a powerful arteriolar vasodilator that does not act on autonomic receptors. Which of
the following effects will be observed if no other drugs are used?
(A) Tachycardia and increased cardiac contractility
(B) Tachycardia and decreased cardiac output
(C) Decreased mean arterial pressure and decreased cardiac contractility
(D) Decreased mean arterial pressure and increased salt and water excretion by the kidney
(E) Bradycardia and decreased cardiac contractility
Because of the compensatory responses, a drug that directly decreases blood pressure through a
decrease in peripheral vascular resistance will cause a reflex increase in sympathetic outflow, an
increase in renin rdease, and a decrease in parasympathetic outflow. As a result, heart rate and
cardiac force will increase. In addition, salt and water retention will occur.

3. Full activation of the parasympathetic nerves is likely to produce which of the following
effects?
(A) Bronchodilation
(B) Decreased intestinal motility
(C) Increased thermoregulatory sweating
(D) Increased pupillary constrictor tone (miosis)
(E) Increased heart rate (tachycardia)
Parasympathetic nerve discharge causes bronchial and intestinal smooth muscle contraction and
bradycardia. Thcrmoregulatory (cccrine) sweat glands are innervated by sympathetic cholinergic
fibers, not parasympathetic. The pupillary constrictor muscle is under parasympathetic
cholinergic control.

Quations 4-S. For these questions, use the accompanying diagram. Assume that the diagram can
represent either the sympathetic or the parasympathetic system.

4. Assuming the structure is part of the sympathetic system, norepinephrine acts at which of the
following sites in the diagram?
(A) Sites 2 and 4
(B) Site 4 only
(C) Sites 5 and 6
(D) Site 7 only

5. If the effector cell in the diagram is a pupillary dilator smooth muscle cell, which of the
following receptor types is denoted by structure 6?
(A) Alpha1 adrenoceptor
(B) Beta1 adrenoceptor
(C) Beta2 adrenoceptor
(D) M3 cholinoceptor
(E) Ng cholinoceptor
The nerves innervating the pupillary dilator muscle arc postganglionic sympathetic adrenergic
nerves. The pupillary constrictor muscle contains M3 cholinoceptors. The answer is A.

1. A 30-year-old woman undergoes abdominal surgery. In spite of minimal tissue damage,


complete ileus (absence of bowel motility) follows, and she complains of severe bloating. She
also finds it difficult to urinate. Mild cholinomimetic stimulation with bethanechol or
neostigmine is often effective in relieving these complications of surgery. Neostigmine and
bethanechol in moderate doses have significantly dijformt effects on which one of the following?
(A) Gastric secretory cdls
(B) Vascular endothelium
(C) Salivary glands
(D) Sweat glands
(E) Ureteral tone
Because neostigmine acts on the enzyme cholinesterase, which is present at all cholinergic
synapses, this drug increases acetylcholine effects at nicotinic junctions as well as muscarinic
ones. Bethanechol, on the other hand, is a direct-acting agent that activates muscarinic receptors
regardless of whether the receptors are innervated or not. The muscarinic receptors on most
vascular endothelial cells are not innervated and respond only to direct-acting drugs. The answer
is B.

2. JR, a 35-year-old farm worker, is admitted to the emergency department suffering from
insecticide poisoning. Parathion has which one of the following characteristics?
(A) It is inactivated by conversion to paraoxon
(B) It is less toxic to humans than malathion
(C) It is more persistent in the environment than DDT
(D) It is poorly absorbed through skin and lungs
(E) If treated early, its toxicity may be partly reversed by pralidoxime
The "-thion" organophosphates (those containing the P = S bond) are activated, not inactivated,
by conversion to "-oxon" (P = 0) derivatives. They are less stable than halogenated hydrocarbon
insecticides of the DDT type; therefore, they are less persistent in the environment. Parathion is
more toxic than malathion. It is very lipid soluble and rapidly absorbed through the lungs and
skin. Pralidoxime has very high affinity for the phosphorus atom and is a chemical antagonist of
organophosphates. The answer is E.

3. Ms Brown, a 28-year-old accountant, has been treated for myasthenia gravis for several years.
She reports to the emergency department complaining of recent onset of weakness of her hands,
diplopia, and difficulty swallowing. She may be suffering from a change in response to her
myasthenia therapy, that is, a cholinergic or a myasthenic crisis. Which of the following is the
best drug for distinguishing between myasthenic crisis (insufficient therapy) and cholinergic
crisis (excessive therapy)?
(A) Atropine
(B) Edrophonium
(C) Physostigmine
(D) Pralidoxime
(E) Pyridostigmine
Any of the cholinesterase inhibitors (choices B, C, or E) would effectively correct myasthenic
crisis. However, because cholinergic crisis (if that is what is causing the symptoms) would be
worsened by a cholinomimetic, we choose the shortest-acting cholinesterase inhibitor,
edrophonium. The answer is B.

4. A crop duster pilot has been accidentally exposed to a high concentration of a highly toxic
agricultural organophosphate insecticide. If untreated, the cause of death from such exposure
would probably be
(A) Cardiac arrhythmia
(B) Gastrointestinal bleeding
(C) Heart failure
(D) Hypotension
(E) Respiratory failure
Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important
cause of acute deaths in cholinesterase inhibitor toxicity. The answer is E.

5. Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic
insufficiency). You are considering different therapies for his disease. Pyridostigmine and
neostigmine may cause which one of the following in this patient?
(A) Bronchodilation
(B) Cycloplegia
(C) Diarrhea
(D) Irreversible inhibition of acetylcholinesterase
(E) Reduced gastric acid secretion
Cholinesterase inhibition is typically associated with increased (never decreased) bowel activity.
(Fortunately, many patients become tolerant to this effect.) The answer is C.

. A 27-year-old compulsive drug user injected a drug he thought was methamphetamine, hut 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

2. Which of the following is the most dangerous effect of bdladonna alkaloids in infants and
toddlers?
(A) Dehydration
(B) Hallucinations
(C) Hypertension
(D) Hyperthermia
(E) lntraventricular heart block
3. 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

Questions 4-5. Two new synthetic drugs (X and Y) are to be studied for their cardiovascular
effects. The drugs are given to three anesthefu. ed 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.
4. Drug X caused a 50 mm Hg rise in mean blood pressure in the control animal, no blood
pressure change in the ganglionblocked animal, and a 75 mm mean blood pressure rise in the
atropine-pretreated animal. Drug Xis probably a drug similar to
(A) Acetylcholine
(B) Atropine
(C) Epinephrine
(D) Hexamethonium
(E) Nicotine

5. The net changes in hean 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) Edrophonium
(C) Hexamethonium
(D) Nicotine
(E) Pralidoxime
Q_uestiom land 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.

I. Which of the following arc probable signs of an anaphylactic reaction to bee stings?
(A) Bronchodilation, tachycardia, hypertension, vomiting, diarrhea
(B) Bronchospasm, tachycardia, hypotcnsion, laryngeal edema
(C) Diarrhea, bradycardia, vomiting
(D) Laryngeal edema, bradycardia, hypotension, diarrhea
(E) Miosis, tachycardia, vomiting, diarrhea

2. If this child has signs of anaphylaxis, what is the treatment of choice?


(A) Diphenhydraminc (an antihistamine)
(B) Ephedrine
(C) Epinephrine
(D) Isoproterenol
(E) Methylprednisolonc (a corticosteroid)

3. 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 cycloplegiais desired?
(A)
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
Methyldopa is often rt:commmd.ed in pregnant patients because it has a ~od safety record.
Calcium channel blockers (choice D) and p blockers (choices A and E) are not contraindicated.
In contrast, ACE inhibitors andARBs (choice B) have been shown to be teratogenic, causing
severe renal abnormalities in the fetus.

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
ACE inhibitors (choice A), ARBs (choice C), and diuretics (choice B) do not significantly
increase heart rate. Although dihydropyridine calcium channel blockers do not usually reduce
rate markedly (and may increase it), verapamil (choice E) and diltiazem do inhibit the sinoatrial
node and predictably decrease rate. Other direct vasodilators (choice D) regularly inmase heart
rate, and minoxidil, a very efficacious vasodilator, may cause severe tachycardia that must be
controlled with ~ blockers.

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
Nifedipine is a prototype L-type calcium channel blocker and lowers blood pressure by reducing
calcium influx into vascular smooth muscle. It has no effect on angiotensin~converting enzyme.
Calcium efflux from skeletal muscle cells does not involve the L-type ca2+ channel. The plasma
renin level may inert:ase as a result of the compensatory response to reduced blood pressure.
Calcium channel blockers have negligible effects on urine calcium. The answer is D.

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) Alpha1-selective receptor blockers
(C) Arteriolar dilators
(D) Beta1-selective receptor blockers
(E) Calcium channel blockers
Drug-induced postural (orthostatic) hypotension is usually due to venous pooling or excessive
diuresis and inadequate blood volume. Venous pooling is normally prevented by a-receptor
activation in vascular smooth muscle; thus, orthostatic hypotension may be caused or
exacerbated by <X1 blockers, cg, prazosin.

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
Chronic, intolerable cough is an important adverse effect of captopril and other ACE inhibitors.
It may be associated with increased bradykinin levels because ARBs are not as frequently
associated with cough. The ACE inhibitors are very commonly used in hypertensive diabetic
patients because of their proven benefits in reducing diabetic renal damage. The ACE inhibitors
are not associated with glaucoma; angioedema is not as common as cough; and headache and
arrhythmias are rare.

27.1 Which is correct regarding the pharmacokinetics of the bisphosphonates?

A. Bisphosphonates are well absorbed after oral administration.


B. Food or other medications greatly impair absorption of bisphosphonates.

C. Bisphosphonates are mainly metabolized via the cytochrome P450 system.

D. Elimination half-life of bisphosphonates ranges from 4 to 6 hours.

27.2 Which agent is administered once yearly to treat osteoporosis?

A. Abaloparatide

B. Denosumab

C. Risedronate

D. Zoledronic acid

27.3 Which osteoporosis medication works by preferentially stimulating activity of osteoblasts?

A. Denosumab

B. Ibandronate

C. Raloxifene

D. Teriparatide

Correct answer = D. Teriparatide is a parathyroid hormone analog that has anabolic effects on
bone through stimulation of osteoblast activity. The other medications work primarily by
inhibiting osteoclast activity (inhibition of bone resorption).

27.4 Which best describes the mechanism of action of denosumab in the treatment of osteoporosis?

A. Parathyroid hormone analog

B. RANKL inhibitor

C. Selective estrogen receptor modulator

D. Vitamin D analog

27.5 A 52-year-old woman has a history of rheumatoid arthritis, diabetes, hypertension, and heartburn.
Her daily medications include methotrexate, prednisone, metformin, hydrochlorothiazide, and lisinopril,
and calcium carbonate as needed for heartburn symptoms. She is worried about the risk of osteoporosis
as she approaches menopause. Which of her medications is most likely to contribute to the risk of
developing osteoporosis?

A. Calcium carbonate

B. Hydrochlorothiazide

C. Lisinopril

D. Prednisone

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