NABP NABP-NAPLEX - Questions & Answers

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.

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.

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 question 50, have various side effects including cardiac conduction abnormalities and drug-drug 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.

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.

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.

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.

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, 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.

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.

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.