Please I didn\'t get all my pharmacology question answered this is the full ques
ID: 144607 • Letter: P
Question
Please I didn't get all my pharmacology question answered this is the full question is a sheet by sheet. Thank you
Please is a pharmacology question I select biology for it to able to post it but is pharmacology question Thank you
Explanation / Answer
I) Ans. A. First order Kinetics
Explanation : Inspection of the serum concentrations (Cp) of chloramphenicol indicated that in successive 30-minute periods after i.v. administration the percent decrease is constant, whereas the absolute decrease becomes smaller. Your graph of the data with ln of Cp on the ordinate (y-axis) and time on the abscissa (x-axis) is linear. (If you had not made the logarithmic transformation of Cp and had graphed Cp vs. t, your data would be clearly curvilinear.) These observations are consistent with elimination by first-order kinetics. Note that, according to the definition of first-order kinetics, the rate of elimination of drug from plasma is proportional to the plasma concentration. This statement is describable as: Cp / t = kelCp. The integral of this differential equation is lnCp = lnC0 – kelt, where C0 is the plasma concentration at zero time. So data conforming to first-order elimination are described by an equation of this form. As in this case, with chloramphenicol, a plot of ln Cp vs. t is a straight line with an intercept on the ordinate of ln C0 and a slope of kel, the elimination rate constant. Note that the elimination t1/2 = 0.693/kel .
II) Ans. B. About 1 hour
Explanation : Since the elimination of chloramphenicol conforms to the laws of first-order kinetics, the data are described by the following equation:
ln Cp = ln C0 – kel
where kel, the slope of the plot of ln plasma concentration vs. time, is the fraction of the drug eliminated per unit time. The half-life is the time it takes to decrease the concentration (C) by half (1/2C).
Consequently, the half-life t1/2 = [ln (C/ 1/2C)]/kel = [ln 2]/kel = 0.693/kel. Thus:
t1/2 = 0.693/kel
Since kel = (ln C1 – ln C2)/(t1 – t2) = 0.64/hr, then t1/2 = 1.1 hr. By inspecting the data, you can see that Cp decreases to about half its value in 1 hour.
III) Ans. C. About 18 liters
Explanation : You have extrapolated the serum concentration to zero time after i.v. administration, 45 µg/ml (anti-ln of 3.8), and divided this number into the total dose, 825 mg, to determine Vd in liters, 18.3 l. Or you estimated the zero time level at about 48 µg/ml by realizing that the level is 24µg/ml at 1 hr after administration and because the half-life is about 1 hr, the zero time level would be two times higher.
IV) Ans. E. Greater than total body water
Explanation: 18.3 l represents 1.1 l/kg body weight or 110% of the total body weight of this subject, considerably higher than the average value of about 58% for total fluid volume. The drug may not distribute uniformly; sequestering at some site outside the plasma volume would reduce the value of the initial serum concentration and increase the apparent volume of distribution. Because the calculated Vd is so high, it is reasonable to conclude that choramphenicol readily crosses membranes and distributes into cells and fluid spaces such as the CSF.
V). Ans. C. The absorption of chloramphenicol is complete, since the area under the concentration vs. time curve after the p.o. route (83 mg hr/ml) is about equivalent to that after i.v. administration (70 mg hr/ml)*
Explanation: To quantitate the percent of the dose absorbed into the systemic circulation, the bioavailability (F), you can measure the area under the curve of serum concentration vs. time (AUC) for the p.o. route and compare this value to the area generated after i.v. administration. This approach is the standard procedure for assessing the bioavailability of formulations of a drug for oral use that may differ with respect to factors such as disintegration time, dissolution rate, stability, etc.
In this case, the AUCp.o. is 83 mg.hr/ml and the AUCi.v. is 70 mg.hr/ml, so the bioavailability appears to be 100%. Strictly speaking, 83/70 x 100% = 116% bioavailability. Theoretically, the bioavailability cannot exceed 100%. But this study was carried out in two dogs, each of which received the drug by only one route. AUC is determined by dose, bioavailability, and total clearance. Total clearance may have been slightly lower in the dog receiving the p.o. dose, in which case the estimate of bioavailability would be a little high. The preferred experimental design for studies of bioavailability entails administration of the same total dose of drug by both routes in each subject (cross-over design) with sufficient time between the doses to avoid possible drug accumulation or drug-induced changes in its own pharmacokinetics. This cross-over design minimizes differences in total clearance.
VI). Ans. A. Regardless of the route of administration, chloramphenicol is primarily eliminated from the body by a mechanism other than renal excretion
Explanation: Since only 7.4% and 9.3% are recovered in the urine after p.o. and i.v. administration respectively, most of the dose of chloramphenicol must be eliminated by another mechanism.
VII). Ans. b. 10 to 35 ml / min
Explanation: Based on 0-2 hr urinary recovery:
Based on 2-4 hr urinary recovery:
Note that your two estimates of ClR of chloramphenicol are very similar, as you would expect. Generally, the renal clearance is constant and not dependent on the dose of the drug or the time after drug administration. However, often experimental estimates of ClR may be quite variable. One cause of variability is incomplete collection of urine excreted during the study interval.
VIII) Ans. B. Chloramphenicol is incompletely filtered by the glomeruli and/or partially reabsorbed
Explanation: In the dog the renal clearance of chloramphenicol, about 20 ml/min, is less than half that for inulin, about 50 ml/min. Two explanations for a renal clearance less than the glomerular filtration rate are: 1) Not all the drug is filtered out of the blood because of binding to plasma proteins. Chloramphenicol is reported to be about 50% bound at therapeutic concentrations. 2) Some of the filtered drug is reabsorbed from the tubules. You have found that chloramphenicol appears to pass readily through cell membranes, so it is reasonable that some of the drug would be reabsorbed.
IX) Ans. B. Are unrelated to the pH of the urine
Explaination: Recovery of chloramphenicol in the urine (9% of the dose after i.v. administration) indicates that only a small amount of the drug is cleared from the blood by the kidney. The renal clearance indicates chloramphenicol may undergo partial tubular reabsorption. But the drug is a neutral compound that does not become ionized at physiologic pH. So the pH of the urine should not influence the degree of tubular reabsorption. Therefore the rate of renal excretion and renal clearance of chloramphenicol is NOT likely to be affected by renal pH.
X) Ans. D. Nonrenal mechanisms account for about 90% of the clearance of chloramphenicol
Explaination: This is true. The total clearance, based on your estimates of half-life or kel (see comment to Item IIb) and Vd (see comment to Item IIc), is 195 ml/min; renal clearance (see comment to Item VIIb) is 20 ml/min. The difference of 175 ml/min, which is 90% of the total, must reflect clearance by nonrenal mechanisms. Note: As would be expected, this estimate of nonrenal clearance (as a percent of total clearance) agrees with the percent of the dose which is not recovered in the urine, 100% – 9% = 91% (see comment to Item VIa), and which must be eliminated by biotransformation and/or nonrenal excretion.
XI) Ans. A. Chloramphenicol glucuronide is eliminated in part by renal tubular secretion, but a considerable portion of the dose is eliminated by another mechanism, possibly in the bile
Explaination: The ClR of the metabolite is greater than that of inulin in the dog, consistent with renal tubular secretion. This is not surprising since glucuronides are organic acids secreted by the carrier mechanisms in the proximal tubules. Glucuronide conjugates are also often secreted via the bile.
XII) Ans. E. A 1-hr reduction of the duration of bacteriostatic effect in the serum
Explanation: The duration of bacteriostatic effect is reduced by one elimination half-life, which for chloramphenicol is about 1 hour.
ClR = Excretion rate of drug = 55 mg / 120 min Cp at 1 hr 24.2 µg/ml = (0.019 mg•ml) •(1000 µg) µg•min mg = 19 ml/min