Which of the following represents the major route of metabolism for acetaminophen?
A
Explanation:
Acetaminophen is metabolized by choices A through D. The major route is glucuronidation catalyzed
by UDP- glucuronyl transferase in the liver. Sulfation is the next most common route and is the target
mechanism for NAC therapy. Oxidation by cytochrome P-450 results in the formation of N-acetyl-p-
benzoquinone imine, which is responsible for the hepatic necrosis caused by acetaminophen
overdose. Direct renal excretion represents approximately 5% of the metabolism of acetaminophen.
Plasma metabolism of acetaminophen does not generally occur.
A 15-year-old presents with 6 days of nasal congestion with thin, clear rhinorrhe
a. She notes mild facial pain but has had no fevers. She feels her symptoms are improving.
What is the most likely cause of her symptoms?
B
Explanation:
This patient shows symptoms of acute sinusitis. The most common etiology of which is viruses.
Indications that an infection is viral as opposed to bacterial included a shorter infection tie (less than
10 days) and no purulent discharge (hers is watery). She does not show any evidence of a
complication developing and even notes that her symptoms are improving. If her symptoms were
attributed to a bacterium, then the most common cause of acute sinusitis is Streptococcus
pneumoniae followed by Haemophilus influenza, then Moraxella catarrhalis. Anaerobic species such
as Bacteroides fragilis and Staphylococcus aureus are more commonly found in patients with chronic
sinusitis (sinusitis lasting longer than 12 weeks). This is important to realize before indiscriminately
providing antibiotics for these patients.
A 72-year-old woman suffers from a major depressive episode. She has a history of coronary artery
disease, atrial fibrillation on anticoagulation therapy, sick sinus syndrome, glaucoma, and chronic
obstructive pulmonary disease.
Which of the following medications is most appropriate for the treatment of her depression?
E
Explanation:
In older adults, selection of antidepressant medication should be done with various considerations in
mind, most notably side effects and risk of drug-drug interactions. The tricyclic antidepressants
(TCAs), as discussed on
interactions that make them undesirable for the treatment of depression in older adults. A selective
serotonin reuptake inhibitor is more favorable than a TCA in this patient. Fluvoxamine has a high risk
for drug-drug interactions, whereas escitalopram does not. Fluvoxamine also has high protein
binding, and can therefore interact with anticoagulant medications, such a warfarin. Therefore, of
the medications listed, escitalopram is the most appropriate in this patient. In older adults,
psychotropic medications should be started at a low dose and titrated up slowly to the lowest
effective dose.
E
A 20-year-old student came to the emergency department with primary complaints of palpitations,
low-grade fever, and anxiety for 2 months. She reports that she is irritable and suffers severe mood
swings that is interfering with her sleep and relationships (she admits to crying spells and frequent
fights with friends and family). She has also lost 12 pounds in the past 2 months with no apparent
alteration in her diet or physical activity (though she is happy with her weight loss). She denies any
past medical problems, though her friends have always been worried that she eats too little.
Her temperature is 38.0 C (100.4 F), blood pressure is 148/62 mm Hg, pulse is 122/min and regular,
and respiratory rate is 28/min. Examination reveals a bruit heard over the anterior neck, fine tremor
of the hands, and warm, moist skin. Her eyes and eyelids do not move together during finger
following test (with steady head). Laboratory work is sent, including a thyroid panel, but will not be
available until tomorrow morning.
Which of the following is the most appropriate initial management at this time?
D
Explanation:
This patient had hyperthyroidism, though the exact cause of her condition is not currently clear. The
immediate treatment should focus on controlling the patient’s symptoms for which a non-specific
beta-blocker is
seemingly an ideal choice. Propranolol therapy can be initiated without any adverse effects while the
patient undergoes further workup of her condition. As the treatment for hyperthyroidism varies
depending upon the cause of the condition, more definitive therapy should be avoided. Diltiazem
(choice A) helps control heart rate
but does not have the same antiadrenegenic properties as beta-blockers/ The initial treatment for
symptomatic hyperthyroidism is propranolol. Iodine (choice B) can be used in high doses to inhibit
thyroid production of T3 and T4. Until it’s clear that this patient does not have an exogenous source
of thyroid hormone (and until it is clear she is not pregnant), this agent should not be considered.
Propylthiouracil (PTU) and Methimazole (choice C) inhibit the organification of iodine to tyrosine
residues. If this patient has Graves diseases, this would be an appropriate treatment. Until a
diagnosis is made, however, initial therapy should consist of a beta- blocker. Surgical treatment
(choice E) of hyperthyroidism is often a reasonable treatment for patients who cannot tolerate
medical therapy of radioactive iodine ablation.
What is the best anti-thyroid regimen in a pregnant woman who has clinically significant
hyperthyroidism?
D
Explanation:
Propylthiouracil (PTU) is recommended for treatment of hyperthyroidism in women who are in their
first trimester of pregnancy by the American Thyroid Association (ATA). Methimazole has been
associated with congenital malformations including aplasia cutis in rare cases and thus it is not
recommended in the first trimester. The ATA recommends switching to methimazole once in the
second trimester as there is a risk of liver injury associated with the use of PTU.
Which of the following is true regarding extent of absorption of drugs?
A
Explanation:
It is not necessary that all the drugs get completely absorbed after oral administration. Most of them
are incompletely absorbed. The extent of absorption varies from 5 to less than 100 % with oral
ingestion of drugs.
Drugs which are too hydrophilic like atenolol are incompletely absorbed because the drug cannot
cross the
lipid membrane due to high hydrophilic nature of the drug. Similarly, drugs which are too lipophilic
like acyclovir are not soluble enough to cross the water layer adjacent to the cell. P-glycoprotein is an
efflux transporter which is present in the enterocytes and it inhibits absorption of drug. It is also
known as export transporter or reverse transporter. It has many drugs as its substrate. Grape juice in
fact inhibits P-glycoprotein in the intestine thereby decreasing the efflux of drug from the cells by P-
glycoprotein. Thus ingestion of grape juice may lead to significantly increased absorption of the drug.
Your patient is a 58-year-old male who presents with onset of severe substernal chest pain and
shortness of breath. An ECG reveals an acute STEMI, and he is on his way to the cardiac
catheterization suite for percutaneous coronary intervention.
Which of the following drugs used in acute coronary syndromes treated with PCI must undergo
oxidation by hepatic P450 enzymes to an active form?
A
Explanation:
Clopidogrel and ticlopidine are ADP receptor pathway inhibitors. The irreversible inhibition of the
ADP- dependent pathway of platelet activation is thought to be the result of covalent modification
and inactivation of the platelet P2Y ADP receptor. This receptor is coupled to the inhibition of
adenylyl cyclase. Both drugs are prodrugs and undergo conversion to active metabolites in the liver.
However, clopidogrel must undergo oxidation by hepatic P450 enzymes to its active form. This is
significant because many drugs are metabolized the hepatic P450 enzymes, including statins, and
clopidogrel may interact with these medications. Clopidogrel is a second-generation thienopyridine
and ticlopidine is a first-generation thienopyridine. Both drugs are indicated in combination with
aspirin to prevent stent thrombosis. Eptifibatide is a GPIIb-IIIa receptor antagonist that is used to
treat unstable angina and non-ST segment elevation myocardial infarction. Eptifibatide is also used to
reduce ischemic events in patients who are undergoing percutaneous coronary intervention. The
drug is a synthetic peptide that directly antagonizes the GPIIb-IIIa receptor on the platelet. Aspirin is
an antiplatelet drug that works by inhibition of synthesis of prostaglandins. Prostaglandin G2 is the
result of a synthesis pathway that is activated by platelets and endothelial cells, and results in
localized
vasoconstriction and induction of platelet aggregation, as well as causing release of platelet granules.
Warfarin is an anticoagulant that acts on vitamin K-dependent reactions in the coagulation pathway.
Vitamin K is necessary for hepatic synthesis of coagulation factors II, VII, IX and X, protein C and
protein S. Vitamin K- dependent carboxylation is necessary for induction of enzymatic activity of
these coagulation factors. Take- home message: Clopidogrel, a second-generation thienopyridine
ADP receptor pathway inhibitor, is indicated in combination with aspirin to prevent stent thrombosis
in patients who undergo percutaneous coronary intervention after myocardial infarction. Clopidogrel
is a prodrug that must undergo oxidation by hepatic P450 enzymes, and therefore may affect the
activity of statins and other drugs dependent on the hepatic P450 enzymes.
A patient with multibacillary leprosy is on dapsone, clofazimine, and rifampin. Which of the following
is true regarding the mechanism of action of the medications listed?
E
Explanation:
A, B – false – dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-
aminobenzoate for the active site of dihydropteroate synthetase. Dapsone is both bacteriostatic and
weakly bactericidal against M. leprae. Neither of the listed mechanisms are the cause of these
effects. C – False – A substance with both anti-leprosy and anti-inflammatory activity, clofazimine is
weakly bactericidal against M. leprae by binding to the guanine bases of bacterial DNA, not DNA
polymerase directly. D – False – See below. E – True – Rifampin is bactericidal by inhibiting RNA
synthesis by blocking DNA-dependent RNA polymerase.
You prescribe doxepin to a 37-year-old woman to treat neurotic excoriations on her arms. The
patient is concerned about the side effects of this drug. Which of the following is not a side effect of
doxepin:
B
Explanation:
A,C,D,E – False – Doxepin is a tricyclic antidepressant with H1 and H2 antihistamine activity. Side
effects include sedation and anticholinergic effects (dry mouth, urinary retention, and constipation).
Although extensively metabolized by the liver and excreted by the kidney, liver toxicity is very rare.
Nephrotoxicity, on the other hand, is a well-known serious adverse effect of long term doxepin use.
Which of the following illnesses is an example of a type III hypersensitivity reaction?
A
Explanation:
A type III hypersensitivity reaction is mediated by immune complex deposition. In lupus, auto-
antibodies are formed and these complexes are deposited in other tissues, especially in the kidneys,
skin, and joints. Graves disease and myasthenia gravis are examples of type II but in some
classification systems they are called type V reactions. The auto-antibodies created in Graves attack
TSH receptors in the thyroid, whereas in
Myasthenia the target is the acetylcholine receptor. Hashimoto’s thyroiditis is usually considered an
example of a combination of type II and IV reactions, as T cells are directed at thyroid antigens and
antibodies are also produced. Allergic rhinitis is a classic example of a type I, IgE mediated reaction.
Which of the following is a side effect of valproic acid?
B
Explanation:
Pancreatitis is one of the most serious adverse effects that can be caused by valproic acid. Gingival
hyperplasia is a side effect of Phenytoin. Kidney stones and weight loss can be a side effect of
zonisamide or topiramate.
A 55-year-old female is receiving chemotherapy for metastatic carcinom
a. She threatens to stop her treatment because of severe nausea and vomiting. The oncologist plans
to use prochlorperazine to reduce the nausea and vomiting associated with chemotherapeutic
agents. What is the mechanism of action of prochlorperazine?
B
Explanation:
B: A variety of drugs have been found to be of some value in the prevention and treatment of
vomiting, especially cancer chemotherapy-induced vomiting. With the exception of thioridazine,
most of the neuroleptic drugs have antiemetic effects that are mediated by blocking D2
dopaminergic receptors of the chemoreceptor trigger zone of the medulla. Phenothiazines, such as
prochlorperazine, were the first drugs shown to be effective antiemetic agents and act by blocking
dopamine receptors. They are effective against low to moderately emetogenic chemotherapeutic
agents (for example, fluorouracil and doxorubicin). Although increasing the dose improves
antiemetic activity, side effects, including hypotension and restlessness, are dose limiting. Other
adverse reactions include extrapyramidal symptom and sedation. A: Serotonin 5-HT3 antagonist is
incorrect. The specific antagonists of the 5-HT3 receptor, ondansetron and granisetron, selectively
block 5-HT3 receptors in the periphery and in the brain (chemoreceptor trigger zone). C:
Cannabinoids related is incorrect. Cannabinoids are marijuana derivatives including dronabinol and
nabilone and are effective against moderately emetogenic chemotherapy. However, they are seldom
first-line antiemetics because of serious side effects. D: Blockage of prostaglandins is incorrect.
Dexamethasone and methylprednisolone used alone are effective against mildly to moderately
emetogenic chemotherapy. Their antiemetic mechanism is not known, but it may involve blockade of
prostaglandins. E: H2 receptor antagonist is incorrect. Antagonists of histamine H2 receptor block the
action of histamine at all H2 receptors; their chief clinical use is as inhibitors of gastric acid secretion.
A 27-year-old female with ovarian cancer is undergoing chemotherapy. She develops subsequent
renal failure.
Which of the following drugs is most likely responsible for this?
C
Explanation:
Cisplatin. All chemotherapeutics have similar generalized side effects related to their effects on
rapidly growing cells. These include hair loss, nausea, and fatigue. However, many
chemotherapeutics have unique toxicities as well which are often tested. Cisplatin (C) is notable for
its nephrotoxicity and ototoxicity. Cyclophosphamide
(A) is known to cause hemorrhagic cystitis. This is a distinct process from nephrotoxicity. The most
noteworthy side effect of bleomycin (B) is pulmonary toxicity that can lead to pulmonary fibrosis.
Vinblastine (D) is known for bone marrow suppression. Vincristine (E) causes neuropathy.
Your patient is a 43-year-old male who is experiencing post-operative voiding difficulty after an
elective inguinal hernia repair. His post void residual volume was 280 cc.
Which of the following medications is the most appropriate choice of therapy for this patient?
A
Explanation:
The patient is experiencing a common complication of low abdominal surgery. Post-operative urinary
retention occurs in almost 25% of patients after low abdominal surgical procedures. A normal post-
void residual volume is less than 50 cc or urine. The effects of anesthesia and analgesia both
contribute to bladder distension, decreased micturition reflex, reduction of contractility of the
detrusor muscle of the bladder, and incomplete voiding. The detrusor muscle of the bladder is
stimulated to contract by muscarinic cholinergic agonists. Bethanechol is a muscarinic agonist and is
frequently used in this setting to improve bladder emptying. Finasteride is a drug that is a 5 alpha
reductase inhibitor indicated for use in patients with bladder outlet obstruction as a result of
prostatic hypertrophy. The inhibition of 5 alpha reductase decreases local conversion of testosterone
to dihydrotestosterone in the prostate gland, which results in gradual shrinkage over a period of six
to twelve months. Phenylephrine is an alpha-adrenergic agonist that is selective for alpha-1
receptors. Activation of the alpha 1 receptors in the bladder results in contraction of the trigone
muscle and sphincter.
This promotes urinary retention. Oxybutynin is an antimuscarinic agent that is useful for treatment
of urge incontinence, and would have a detrimental effect on this patient’s bladder disorder.
Imipramine is a medication with anticholinergic properties that would also cause worsening of the
patient’s condition. Take home message: Post-operative urinary retention with concomitant
incomplete voiding is a complication that results from a decreased micturition reflex, increased
vesical sphincter tone, or decreased contractility of the detrusor muscle of the bladder. It can be
successfully treated with a muscarinic agonist, such as bethanechol, or with an alpha-1 adrenergic
antagonist.