A 37-year-old man comes to the emergency department due to fever, chills, and malaise.  He has no significant medical history but he uses illicit intravenous drugs on a regular basis.  The patient is febrile, tachycardic, and hypotensive.  Auscultation reveals a heart murmur.  A preliminary diagnosis of infective endocarditis is established.  Blood cultures grow methicillin-resistant Staphylococcus aureus, and the patient is prescribed an intravenous antibiotic administered every 12 hours.  Calculation of the maintenance dose will most likely require which of the following parameters?

In an experiment investigating vasoconstriction of the arterial wall, two samples of isolated porcine arterial vessels are studied.  Vascular tone is measured in the control vessel during infusion of increasing doses of norepinephrine.  The other vessel is pretreated with experimental drug A prior to infusion of norepinephrine.  A graph of the study results is depicted below.

Drug A is most similar to which of the following agents?

Physiologists conduct a series of experiments on hypophysectomized animals to investigate the effects of cortisol on vascular reactivity.  Their initial tests show that administration of cortisol alone does not elicit a vascular response.  Next, the researchers measure vascular reactivity to an infusion of norepinephrine both with and without pretreatment with cortisol.  The results of their experiments are shown in the graph below.

Which of the following pharmacologic principles best describes the effect of cortisol in this experiment?

A 4-year-old boy is brought to the hospital after several episodes of vomiting.  The boy’s mother reports that he was playing at a local park prior to the onset of illness.  While cleaning him after the first episode of emesis, she found several small brown mushrooms clenched in his hands and brought samples with her.  The boy is otherwise healthy and takes no medications.  He is intubated due to somnolence and admitted to the intensive care unit.  Analysis of the mushroom samples determines that the main poison stimulates muscarinic receptors.  Which of the following is the most direct effect of this poison?

A group of investigators is performing an experiment designed to assess genetic variability in drug biotransformation.  A fixed dose of isoniazid is given to a group of volunteers, and the plasma drug concentration is measured four hours following administration of the drug.  The following distribution of plasma drug concentration in these subjects is obtained.

Variation of which of the following processes provides the best explanation for the shaded area of the curve?

A 67-year-old man admitted for right lower lobe pneumonia subsequently develops hypotension and lactic acidosis.  He is started on a norepinephrine intravenous drip.  A few hours later, the antecubital vein being used for the infusion blanches and the tissues surrounding the IV site become cold, hard, and pale.  Local injection of the affected tissues with which of the following agents is most likely to be of greatest benefit?

Healthy adult volunteers are enrolled in a phase I clinical trial investigating the properties of a newly developed oral antimicrobial agent.  The drug is administered in different amounts to the volunteers over the course of several weeks to determine the best dosage that minimizes toxicity while maintaining trough levels above the minimum inhibitory concentration.  While reviewing the data, the researchers note that the drug’s half-life seems to vary amongst the study participants.  An increase in which of the following pharmacologic parameters is most likely responsible for the longer half-life seen in certain individuals?

A 64-year-old man is evaluated for persistent fever and weakness.  He has a history of aortic valve replacement for aortic stenosis.  Physical examination reveals a new cardiac murmur with scattered petechiae and splinter hemorrhages seen on his extremities.  Echocardiogram shows a vegetation involving one of the aortic valve leaflets, and blood cultures grow enterococci.  As part of the patient’s treatment, 240 mg of intravenous gentamicin is started.  The pharmacy calculates that, in this patient, gentamicin has a volume of distribution of 30 L, a half-life of 4 hours, and demonstrates first-order and one-compartment kinetics.  Which of the following is the most likely serum drug concentration just before the next dose 8 hours later?

A new aminoglycoside antibiotic is developed that is believed to be particularly effective against Pseudomonas.  The volume of distribution of the drug is measured in a group of volunteers and is determined to be 4.5 L.  This new drug is most likely to have which of the following properties?

A large, multinational drug corporation conducts a phase I clinical trial to evaluate the safety profile and pharmacokinetic properties of a new drug designed to treat refractory epilepsy.  Initial studies in animals showed that the drug undergoes extensive metabolism by the liver into glucuronidation byproducts that are primarily excreted by the kidneys.  The curve below demonstrates the glucuronidation rate of the drug over a wide range of doses.

Which of the following is the most accurate statement about this drug’s metabolism?

Three alpha-agonist drugs are tested as potential vasoconstrictors.  The degree of vasoconstriction is determined by measuring the cross-sectional area of an isolated vessel after application of the drug.  The following curves are obtained:

Which of the following is the best statement concerning the effects of these drugs?

A 35-year-old man comes to the physician because of a 2-week history of nasal congestion.  He has used a topical decongestant every few hours since his symptoms began.  He experienced relief for almost 1 week, but then his nasal congestion returned.  The patient has a history of allergic rhinitis and has had episodes of rhinorrhea in the past, but none of them lasted longer than a few days.  He denies fever, throat pain, headaches, cough, and lymph node enlargement.  Aside from his allergic rhinitis, the patient has no other medical problems.  Physical examination shows nasal mucosa that appears edematous and red with a few areas of punctate bleeding.  The remainder of the examination reveals no abnormalities.  Which of the following is the most appropriate next step in the management of this patient?

A group of investigators examined the effects of different muscarinic agonists and antagonists on the bladder musculature.  The curves presented below were constructed after application of different agents.  Curve A represents the effect of bethanechol, a pure cholinergic agonist.

Which of the curves most likely represents the effect of bethanechol after application of a reversible competitive antagonist?

A new antibiotic developed for the treatment of infections caused by resistant gram-positive cocci has a volume of distribution of 11L.  It is eliminated by first-order kinetics and has a half-life of 10 hours.  If given by a continuous infusion, approximately how much time would it require for the drug to achieve a 95% plasma steady state concentration?

A 55-year-old man comes to the office due to intermittent shortness of breath, cough, and chest tightness over the past 3 months.  The patient had asthma as a child that improved in adolescence, and he has not required inhalers or steroids since.  He feels that his current symptoms are similar to his prior asthma symptoms.  The patient was recently diagnosed with essential tremor, which has improved with medical therapy; he has no other chronic medical conditions.  He is a lifetime nonsmoker and does not use alcohol or illicit drugs.  Blood pressure is 125/75 mm Hg, pulse is 58/min, and respirations are 16/min.  Physical examination reveals bilateral scattered expiratory wheezes.  Heart sounds are normal and there is no extremity edema.  This patient’s symptom recurrence is most likely attributable to a medication that affects which of the following steps?

A pharmaceutical company has developed a novel medication for use in pregnancy.  In preclinical studies, labor is induced in experimental pregnant animals using oxytocin.  An intrauterine pressure catheter is used to monitor uterine contractions.  After measurable, regular uterine contractions are achieved, intravenous infusion of the new medication is started.  Observed changes in uterine activity are shown below.

In addition to its effects on uterine pressure, the new drug is found to lower serum potassium levels.  This novel medication most closely resembles which of the following agents?

A 60-year-old farmer is brought to the emergency department due to acute-onset confusion, muscle weakness, and difficulty breathing.  The patient has vomited twice and has had 3 loose bowel movements over the past 2 hours.  His medical history is insignificant and he currently takes no medications.  Blood pressure is 110/70 mm Hg, pulse is 58/min, and respirations are 26/min.  His pupils are constricted, symmetric, and reactive to light.  Examination reveals excessive sweating, lacrimation, and wheezing.  He is incontinent of urine.  Intravenous atropine is administered.  Which of the following findings is most likely to persist in this patient without additional therapy?

A 62-year-old woman is brought to the emergency department after a fall and is found to have a left femoral neck fracture.  The patient is admitted to the hospital, and a hip arthroplasty is planned.  Medical history is significant for long-standing type 2 diabetes mellitus, hypertension, hyperlipidemia, and migraines.  While hospitalized, the patient receives a combination of long- and short-acting insulin for diabetes management.  On the morning of surgery, fasting blood glucose level is 42 mg/dL.  The patient is awake and alert and says she feels hungry but has no other symptoms of hypoglycemia.  Concurrent use of which of the following medications best explains this finding?

Investigators assessing the bioavailability of a new drug administer it intravenously (IV) to a volunteer and measure plasma concentrations of the drug over time.  After the drug is completely cleared from the volunteer’s circulation, the investigators administer the same dose of the drug orally (PO) and again measure plasma concentrations of the drug over time.  The data obtained are plotted on the graph shown below.

Which of the following is the best determinant of oral bioavailability of this drug?

Succinate dehydrogenase (SDH) is an enzyme complex located within the inner mitochondrial membrane that catalyzes the oxidation of succinate to fumarate.  An experiment is conducted to determine if malate alters the rate of SDH activity.  Reaction velocity is measured with and without a fixed quantity of malate as succinate concentration is gradually increased.  Obtained results are shown below.

Which of the following is the most accurate statement about malate in this experiment?

A 55-year-old farmer is brought to the emergency department after his daughter found him confused and disoriented in the tool shed at home.  He has been otherwise healthy and does not take any medications.  On physical examination, blood pressure is 110/70 mm Hg and pulse is 50/min.  The patient’s pupils are symmetric, 2 mm, and reactive to light.  His eyes are tearing considerably.  There are scattered wheezes bilaterally on lung auscultation.  The patient’s skin is clammy and he is sweating profusely.  Impairment of which of the following steps at the neuromuscular junction is most likely responsible for his presentation?

A 32-year-old man is brought to the emergency department by police after an altercation at a local pub.  He is agitated and says that his chest hurts.  Blood pressure is 170/100 mm Hg and pulse is 130/min and regular.  On physical examination, the patient is combative and uncooperative.  There are no signs of physical injury.  His pupils are dilated and reactive to light.  Examination shows nasal perforation.  ECG reveals myocardial ischemia.  Inhibition of which of the following processes is most likely responsible for this patient’s presentation?

Which of the following medications is most likely to be drug A?

A 47-year-old man comes to the office for follow-up of his elevated blood pressure.  The patient’s medical history is significant for stable angina pectoris, for which he takes sublingual nitroglycerin as needed.  He has no orthopnea, paroxysmal nocturnal dyspnea, or lower extremity swelling.  His blood pressure is 154/107 mm Hg and pulse is 86/min.  Physical examination shows no abnormalities.  The patient is started on a low dose of atenolol.  Which of the following cellular changes will most likely occur as a direct effect of this medication?