QUESTION: 5

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 moo d 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?

Diltiazem therapy
Iodine therapy
Methimazole therapy
Propranolol therapy
Referral to a surgeon

Answer(s): 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.

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QUESTION: 6

What is the best anti-thyroid regimen in a pregnant woman who has clinically significant hyperthyroidism?

Stop treatment and resume post-partum
Propylthiouracil
Methimazole
Propylthiouracil first trimester followed by methimazole for the remainder of pregnancy
Methimazole first trimester followed by propylthiouracil for the remainder of pregnancy

Answer(s): 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.

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QUESTION: 7

Which of the following is true regarding extent of absorption of drugs?

After oral ingestion of drugs, the absorption of drug may be incomplete
Drugs which are too lipophilic cannot cross the lipid cell membrane
Drugs which are too hydrophilic 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 enhances the absorption of drug
Grape juice activates P-glycoprotein leading to substantial inhibition of absorption of drugs

Answer(s): 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.

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QUESTION: 8

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?

Clopidogrel
Ticlopidine
Eptifibatide
Aspirin
Warfarin

Answer(s): 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.

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