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General Principles of Pharmacology- Part 1
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1.You want to estimate, following drug administration, some measure that reliably reflects the total amount of drug reaching target ti ssue(s) over The drug i s being given orally. What would you assess to get the desired information?
- Area under the blood concentration-time curve (AUC)
- Peak (maximum) blood concentration
- Product of the apparent volume of distribution (Vd) and the fi rst-order rate constant
- Time-to-peak blood concentration
2. The FDA assigns the letters A, B, C, D, and X to drugs i t approves for human To what does this classification refer or apply?
- Amount of dosage reduction needed as plasma creatinine clearances fall
- Amount of dosage reduction needed in the presence of l iver dysfunction
- Fetal ri sk when given to pregnant women
- Relative margins of safety (or therapeutic index)
- The number of unlabeled uses for a drug
3. You orally administer a weak acid drug (A) with a pKa of 4. Gut pH i s 1.4 and blood pH i s 7.4. Assume the drug crosses membranes by s imple passive diffusion (eg, no transporters are involved). Which observation would be true?
- Only the ionized form of the drug, A, will be absorbed from the gut
- The concentration ratio of total drug (A + HA–) would be 10,000:1 (gut:plasma)
- The drug will be hydrolyzed by reaction with HCl, and so cannot be absorbed
- The drug will not be absorbed unless we raise gastric pH to equal pKa, as might be done with an antacid
- The drug would be absorbed, and at equilibrium the plasma concentration of the nonionized moiety (HA) would be 104 times higher than the plasma concentration of A–.
4. Experiments show that 95% of an oral 80-mg dose of verapamil i s absorbed in a 70-kg test However, because of extensive biotransformation during i ts fi rst pass through the hepatic portal ci rculation, the bioavailability was only 0.25 (25%). Assuming a l iver blood flow of 1500 mL/min, what i s the hepatic clearance of verapamil in this s i tuation?
- 60 mL/min
- 375 mL/min
- 740 mL/min
- 1110 mL/min
- 1425 mL/min
5. Such substances as inositol tri sphosphate (IP3), diacetyl glycerol (DAG), cyclic AMP (cAMP), cAMP-dependent protein kinases, and changes in such functions as membrane ion conductance (eg, of gK+ and gCa 2+) are important with respect to the effects of l igands on cell responses. Which best summarizes where they are found or what they do?
- Are present in nerve cells, but not the various types of muscles or glands
- Are the receptors for various agonists and antagonist drugs
- Interact with neurotransmitters or hormones (endogenous l igands), but not to chemicals that are not found naturally in the body
- Mediate excitatory, but not inhibitory, responses in various target structures
- Transduce a chemical “s ignal” from a l igand into the final cell response(s)
6. Azithromycin, an antibiotic, has an apparent volume of distribution (Vd) of approximately 30 L/kg. What i s the main interpretation of this information?
- Effective only when given intravenously
- El iminated mainly by renal excretion, without prior metabolism
- Extensively distributed to s i tes outside the vascular and interstitial spaces
- Not extensively bound to plasma proteins
- Unable to cross the blood-brain or placental “barriers”
7. A cardiovascular pharmacologist i s assessing the inotropic (contractile) responses of cardiac muscle to a variety of She uses a small animal i solated papillary muscle preparation to gain her data. The experimental setup i s shown here:
The papillary muscle has been excised from the animal’s heart and put into a “physiologic” solution that will keep the muscle alive and fully functional for several hours. The muscle i s electrically stimulated at a constant rate so that there are no usual rate-dependent effects on contractile force development, and all neural influences on papillary muscle function or drug responses are absent.
A reference standard positive inotropic drug i s administered, in varying concentrations, to determine the maximum increase of contractile force (the inotropic response; maximum i s set at 100% as caused by the standard drug). Thereafter, three other drugs—X, Y, and Z—are tested and their ability to increase contractile force development (compared with the standard or reference drug) i s measured. The dose-response curves to X, Y, and Z are shown here:
Which statement describes the findings of this experimental study involving drugs X, Y, and Z?
- Drug X i s the most efficacious because i ts ED50 i s lowest
- Drug Y i s the least potent drug among the three drugs shown
- Drug Z i s the most potent cardiac inotrope
- Drug Y i s more potent than drug Z, and more efficacious than drug X
- Drug X i s more potent than drug Y, and more efficacious thandrug Z
8. A patient needs a drug that has an apparent volume of distribution of 20 L. The plan i s to administer a loading dose to reach a target plasma level of 5 mcg/mL. This plasma concentration i s the target steady-state concentration (CSS), and i t will be maintained by subsequent oral maintenance What IV loading dose would be needed to yield that 5 mcg/mL target?
- 1 mg
- 5 mg
- 10 mg
- 20 mg
- 100 mg
9. We are repeatedly administering a drug Every dose i s 50 mg; the interval between doses i s 8 h, which i s identical to the drug’s plasma (overall elimination) half-life. The bioavailability i s 0.5. For as long as the drug i s administered no interacting drugs are added or stopped, and there are no applicable factors affecting such things as absorption or elimination that might change the drug’s pharmacokinetics.
Which formula gives the best estimate of how long i t will take for the drug to reach steady-state plasma concentrations (CSS)?
Cl = clearance (mL/min)
D = dose (mg)
F = bioavailability
ke = elimination rate constant
t1/2 = half-life (h)
Vd = volume of distribution
- (0.693 × Vd)/Cl
- 4.5 × t1/2
- (t1/2) ×(ke)
- D/(F ×t1/2)
10. A classmate i s doing summer research, in your school’s cl inical pharmacology division, between her fi rst and second years of medical school. Her topic involves new investigations into the roles of P-glycoprotein. Which statement accurately summarizes the biologic role of P-glycoproteins, particularly as i t affects drugs and their actions?
- Conjugates a variety of drugs, or their metabolites, to facilitate their ultimate renal elimination from the body
- Maintains structural integrity of cell membranes and the surface receptors found on them
- Phosphorylates certain substances, such as in the conversion of adenosine monophosphate (AMP) into the diphosphate and triphosphate forms (ADP, ATP)
- Transports certain drugs and xenobiotics across cell membranes
- Works, in conjunction with various G-proteins, to transduce (convert) interactions between drugs and their receptors into biologic responses
11. You are conducting pharmacokinetic studies on a new drug that we hope will be approved for cl inical We insert a venous catheter to sample blood at various times after drug administration, and also take a sample for the immediate pre-drug blood concentrations of the drug (which should be zero). After assaying the blood samples for the drug we make a graph that plots plasma drug concentrations over time, continuing until tests reveal undetectable blood levels. What can you calculate or estimate based on the ratio of the area under the curve (AUC) obtained by oral administration versus the AUC for intravenous administration of the same drug?
- El iminationrate constant e. Extraction ratio
- Volume of distribution
12. Identical doses of a drug are given orally and We sample blood at various times, measure blood concentrations of the drug, and plot the data (shown below).
Further analysis of only these data will allow you to determine which of the following?
- El imination route(s)
- Extent of plasma protein binding
- Oral bioavailability
- Therapeutic effectiveness
13. During your career you may have patients in age ranges from very young to very old, and adjustments in drug dosages or intervals between repeated doses may be required based on Assume you consider only the effects of one drug; no interacting drugs or comorbidities are involved. What statement best describes the general relationship between chronologic age and the overall elimination plasma half-lives of drugs?
- Depends on chemical class of drug (eg, benzodiazepine, catecholamine, and dihydropyridine)
- Depends on renal function (eg, creatinine clearance), not age per se
- Linear: half-life lengthens in direct proportion to age
- No generally applicable relationship because elimination half-life depends on the drug, not i ts class
- Peaks at around age 18 to 20 years, with half-lives being much longer at younger or older ages
14. The elimination of a drug and i ts numerous metabolites i s described as being heavily dependent on Phase II metabolic Which of the following i s a Phase II reaction?
- Ester hydrolysis
- Nitro reduction
- Sulfoxide formation
15. The hospital pharmacy sends up a solution of a drug that i s to be infused intravenously at a constant, specified It has been diluted to the proper concentration in a suitable IV administration fluid. Assuming that no patient- or drug-related variables change during the administration period, which one of the following will be the main determinant of how long i t will take for blood concentrations of this drug to reach steady state (plateau; no change of mean blood levels over time)?
- Bioavailability of the drug
- Concentration of the drug in the solution that will be infused
- Half-life of the drug
- Presence or absence of cardiovascular or renal disease
- Plasma creatinine concentration (or creatinine clearance)
- Total dose per 24 hours
- Volume of drug administered per minute
16. Yee et (Effect of grapefruit juice on blood cyclosporine concentration. Lancet 1995;345:955–956) examined several pharmacokinetic variables related to oral cyclosporine administration with water, grapefruit juice, and orange juice:
The numbers l i sted are arithmetic means ± one standard deviation of the mean. Cmax i s the peak blood concentration, and Tmax i s the time after administration at which peak plasma concentrations of the drug are reached. The p values are based on analysis of variance (ANOVA) corrected for repeated measures.
These data, and what you should have learned from your basic pharmacology studies, are most consistent with an hypothesis that grapefruit juice does which of the following?
- Acidifies the urine, favoring cyclosporine’s tubular reabsorption via a pH-dependent effect
- Activates an intestinal wall transporter for cyclosporine
- Alters the route(s) of elimination for cyclosporine
- Inhibits metabolism of cyclosporine
- Reduces binding of cyclosporine to plasma proteins, thereby raising free (active) drug levels in the ci rculation
17. A 60-year-old man with rheumatoid arthritis will be started on a nonsteroidal anti-inflammatory drug (NSAID) to suppress the joint Published pharmacokinetic data for this drug include:
Bioavailability (F): 1.0 (100%) Plasma half-life (t1/2) = 0.5 hour
Apparent volume of distribution (Vd): 45 L
For this drug i t i s important to maintain an average steady-state concentration of 2.0 mcg/mL in order to ensure adequate and continued anti- inflammatory activity.
The drug will be given (taken) every 4 hours.
What dose will be needed to obtain this 2 mcg/mL average steady-state drug concentration?
- 5 mg
- 100 mg
- 325 mg
- 500 mg
- 625 mg
18. We take a blood sample from a patient (baseline measurement) and then administer drug A We take additional blood samples periodically thereafter and measure drug concentration in each sample. We repeat the experiment, this time giving the same drug orally. Then we plot the logarithm of drug concentration versus time with data from both administration routes to find comparable elimination “curves” indicative of fi rst-order elimination. What do the s lopes of the resulting concentration versus time curves indicate about the pharmacokinetics of drug A?
- Area under the curve (AUC)
- El imination rate constant
- Extraction ratio
- Volume of distribution