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Assignment 3 by Rebecca Aw

Assignment 3 by Rebecca Aw . Qn (a) The GI absorption of drug ___ when given in solution is the most sensitive to changes in the intestinal pH (5-8). Answer: Drug B Only the unionised species is being absorbed in the GI tract. Drug C:

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Assignment 3 by Rebecca Aw

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  1. Assignment 3by Rebecca Aw

  2. Qn (a) The GI absorption of drug ___ when given in solution is the most sensitive to changes in the intestinal pH (5-8) Answer: Drug B Only the unionised species is being absorbed in the GI tract Drug C: • Being neutral, it doesn’t possess basic and acidic groups. Hence, any changes in the pH will not give rise to any changes in the ionisation of the Drug C Drug D: • The positive charge on the quaternary ammonium ion is permanent regardless of the pH of the solution (i.e. always in ionised state) • Hence GI absorption of Drug D both will not change when intestinal pH changes

  3. Qn (a) The GI absorption of drug __ when given in solution is the most sensitive to pH changes in the intestinal pH (5-8) Since Drug A is an acid, using Hendersen-Hasselbalch equation At pH 5  % unionised At pH 8  % unionised

  4. (a) The GI absorption of drug __ when given in solution is the most sensitive to pH changes in the intestinal pH (5-8) Difference in % unionised = 99.96% - 71.5% = 28.46% Assuming pH changes from pH 5 to 8; Fold change in % of unionised species Assuming pH changes from pH8 to 5; Fold change in % of unionised species

  5. Qn (a) The GI absorption of drug __ when given in solution is the most sensitive to pH changes in the intestinal pH (5-8) Since Drug B is basic; At pH 5 = 10(5-9.8) = 1.58 x 10−5 % unionised At pH 8 = 10(5-9.8) = 1.58 x 10−2 % unionised

  6. (a) The GI absorption of drug __ when given in solution is the most sensitive to pH changes in the intestinal pH (5-8) Difference in % of unionised species = 1.559% - 1.579 x 10-3% = 1.557% Assuming pH changes from 5 to 8; Fold change in % of unionised species Assuming pH changes from 8 to 5; Fold change in % of unionised species Conclusion: Comparing between Drug A and B, Drug B has a greater fold change in % of unionised species as the intestinal pH changes from 5 to 8 or vice versa. Hence, Drug B’s absorption in the GIT is most sensitive to the intestinal pH changes.

  7. Qn(b) The greatest diffusion limitation is crossing the intestinal epithelium is likely to be seen with drug(s) ____. Answer: Drugs C, D Reasoning: What limits diffusion across the intestinal epithelium? -High ionization of compound -Low lipophilicity -Large atomic/molecular radius -Strong acidity or basicity For Drug C; Drug C is polar, less lipophilic  Less permeable, difficult to diffuse intestinal epithelium For Drug D; Drug D is a quaternary ammonium ion  Ionised and hence is less permeable to diffuse through the epithelium

  8. Qn C Delayed gastric emptying slows the absorption of drug(s) ___ when given orally in solution.( Assume drug stability in GIT) Answer: Drugs A, B, C,D Assuming drug stability in GIT, factors that affect drug absorption are surface area of the intestinal wall, permeability of drug and blood flow Hence, absorption for all compounds-acids, bases or neutral compounds-is faster from the small intestine than from the stomach Gastric emptying time delays transit from stomach to intestine stays longer in stomach Since absorption is greater in the small intestine, delayed gastric emptying slows down drug absorption, even when given in oral solution

  9. d)Muscle blood flow is likely to be a major determinant in the absorption of drug(s) ___, when injected i.m. as an aqueous solution, pH=7.4. Answer : Drugs A, B, C and D Absorption of drug in solution from muscle and subcutaneous tissue is normally perfusion rate-limited For highly permeable drugs, blood flow is a rate-limiting step for drug absorption Present in the muscles are capillaries which contain large pores, also known as fenestrations These fenestrations allow molecules of less than 5kDa or 5000MW to pass through Since Drugs A, B, C and D all have molecular weights way below 5000MW, absorption of drugs are no longer limited by their permeability, but rather by the rate of perfusion to the site of administration

  10. Qn (e) The GI absorption of drug(s) __, when taken orally as a tablet, is unlikely to be rate-limited by dissolution. Answers: Drugs B ,C, D Dissolution rate depends on how well the drug can solubilize In order for dissolution rate to limit GI absorption, drug must be poorly soluble For Drug B; Majority present in ionised form at the pH of 6.6-7.5 (pH of the intestinal epithelium)  soluble in water  dissolution rate is not limiting absorption Even if Drug B is not in its ionised form, its solubility is already high in its unionised form For Drug C; It is a polar drug and hence is soluble in water  dissolution rate is fast, will not limit GI absorption For Drug D; Quaternary ammonium cation  highly ionised  highly soluble and hence dissolution rate is fast, will not limit rate of GI absorption

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