What is the best anti-thyroid regimen in a pregnant woman who has clinically significant hyperthyroidism?
Answer(s): D
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?
Answer(s): A
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?
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?
Answer(s): E
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:
Answer(s): B
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.
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