P-Chapter 1 Pharmacokinetics Flashcards
(10 cards)
An 18-year-old female patient is brought to the emergency department due to drug overdose. Which of the following routes of administration is the most desirable for administering the antidote for the drug overdose? A. Intramuscular.
B. Subcutaneous.
C. Transdermal.
D. Oral.
E. Intravenous.
E. The intravenous route of administration is the most desirable because it results in achievement of therapeutic plasma levels of the antidote rapidly.
Chlorothiazide is a weakly acidic drug with a pKa of 6.5. If administered orally, at which of the following sites of absorption will the drug be able to readily pass through the membrane?
A. Mouth (pH approximately 7.0).
B. Stomach (pH of 2.5).
C. Duodenum (pH approximately 6.1).
D. Jejunum (pH approximately 8.0).
E. Ileum (pH approximately 7.0).
B. Because chlorothiazide is a weakly acidic drug (pKa = 6.5), it will be predominantly in nonionized form in the stomach (pH of 2.5). For weak acids, the nonionized form will permeate through cell membrane readily.
Which of the following types of drugs will have maximum oral bioavailability?
A. Drugs with high first-pass metabolism.
B. Highly hydrophilic drugs.
C. Largely hydrophobic, yet soluble in aqueous solutions.
D. Chemically unstable drugs.
E. Drugs that are P-glycoprotein substrates
C. Highly hydrophilic drugs have poor oral bioavailability, because they are poorly absorbed due to their inability to cross the lipid-rich cell membranes. Highly lipophilic (hydrophobic) drugs also have poor oral bioavailability, because they are poorly absorbed due their insolubility in aqueous stomach fluids and therefore cannot gain access to the surface of cells. Therefore, drugs that are largely hydrophobic, yet have aqueous solubility have greater oral bioavailability because they are readily absorbed.
Which of the following is true about the blood–brain barrier? A. Endothelial cells of the blood–brain barrier have slit junctions.
B. Ionized or polar drugs can cross the blood–brain barrier easily.
C. Drugs cannot cross the blood–brain barrier through specific transporters.
D. Lipid-soluble drugs readily cross the blood–brain barrier.
E. The capillary structure of the blood–brain barrier is similar to that of the liver and spleen.
D. Lipid-soluble drugs readily cross the blood–brain barrier because they can dissolve easily in the membrane of endothelial cells. Ionized or polar drugs generally fail to cross the blood–brain barrier because they are unable to pass through the endothelial cells, which do not have slit junctions.
A 40-year-old male patient (70 kg) was recently diagnosed with infection involving methicillin-resistant S. aureus. He received 2000 mg of vancomycin as an IV loading dose. The peak plasma concentration of vancomycin was reported to be 28.5 mg/L. The apparent volume of distribution is:
A. 1 L/kg.
B. 10 L/kg.
C. 7 L/kg.
D. 70 L/kg.
E. 14 L/kg.
A. Vd = dose/C = 2000 mg/28.5 mg/L = 70.1 L. Because the patient is 70 kg, the apparent volume of distribution in L/kg will be approximately 1 L/kg (70.1 L/70 kg).
A 65-year-old female patient (60 kg) with a history of ischemic stroke was prescribed clopidogrel for stroke prevention. She was hospitalized again after 6 months due to recurrent ischemic stroke. Which of the following is a likely reason she did not respond to clopidogrel therapy? She is a:
A. Poor CYP2D6 metabolizer.
B. Fast CYP1A2 metabolizer.
C. Poor CYP2E1 metabolizer.
D. Fast CYP3A4 metabolizer.
E. Poor CYP2C19 metabolizer.
E. Clopidogrel is a prodrug, and it is activated by CYP2C19, which is a cytochrome P450 (CYP450) enzyme. Thus, patients who are poor CYP2C19 metabolizers have a higher incidence of cardiovascular events (for example, stroke or myocardial infarction) when taking clopidogrel.
Which of the following phase II metabolic reactions makes phase I metabolites readily excretable in urine?
A. Oxidation.
B. Reduction.
C. Glucuronidation.
D. Hydrolysis.
E. Alcohol dehydrogenation
C. Many phase I metabolites are too lipophilic to be retained in the kidney tubules. A subsequent phase II conjugation reaction with an endogenous substrate, such as glucuronic acid, results in more watersoluble conjugates that excrete readily in urine.
Alkalization of urine by giving bicarbonate is used to treat patients presenting with phenobarbital (weak acid) overdose. Which of the following best describes the rationale for alkalization of urine in this setting?
A. To reduce tubular reabsorption of phenobarbital. B. To decrease ionization of phenobarbital.
C. To increase glomerular filtration of phenobarbital.
D. To decrease proximal tubular secretion.
E. To increase tubular reabsorption of phenobarbital
A. As a general rule, weak acid drugs such as phenobarbital can be eliminated faster by alkalization of the urine. Bicarbonate alkalizes urine and keeps phenobarbital ionized, thus decreasing its reabsorption
A drug with a half-life of 10 hours is administered by continuous intravenous infusion. Which of the following best approximates the time for the drug to reach steady state? A. 10 hours.
B. 20 hours.
C. 33 hours.
D. 40 hours.
E. 60 hours.
D. A drug will reach steady state in about four to five half-lives. Thus, for this drug with a half-life of 10 hours, the approximate time to reach steady state will be 40 hours.
A 55-year-old male patient (70 kg) is going to be treated with an experimental drug, Drug X, for an irregular heart rhythm. If the Vd is 1 L/kg and the desired steadystate plasma concentration is 2.5 mg/L, which of the following is the most appropriate intravenous loading dose for Drug X?
A. 175 mg.
B. 70 mg.
C. 28 mg.
D. 10 mg.
E. 1 mg.
A. For IV infusion, Loading dose = (Vd) × (desired steady-state plasma concentration). The Vd in this case corrected to the patient’s weight is 70 L. Thus, Loading dose = 70 L × 2.5 mg/L = 175 mg.
