Pharmacokinetics

Question 1

describe oral route

Answer 1

• ingested drugs suffer first pass effect
  
  • a fraction of the drug is metabolizd in the gut wall and the liver before reaching systemic circulation

Question 2

describe the effect of pH on weak acids

Answer 2

• HA –> A^- + H⁺
• The uncharged form HA will permeate through membranes and the charged form A- will not

Question 3

describe the effect of pH on weak bases

Answer 3

• BH⁺ –> B + H⁺
• the uncharged form B will permeate through the cell membrane whereas the charged form BH+ will not

Question 4

describe ion trapping

Answer 4

• if a drug is in a liposoluble form during its passage down the renal tubule, a significant fraction will be reabsorbed by passive diffusion
• if the goal is to accelerate excretion of the drug, it is important to prevent its reabsorption from the tubule
  
  • weak acids are excreted faster in alkaline urine
  • weak bases are excreted fast in acidic urine

Question 5

describe the P-glycoprotein

Answer 5

• it is a transporter protein responsible for transporting several drugs across cell membranes
• P-glycoprotein reduces drug absorption

Question 6

define bioavailability

Answer 6

• fraction of administered dose of a drug that reaches the systemic circulation
• bioavailability is determined comparing the AUC after a particular route of administratino with the AUC after IV injection

Question 7

describe the distribution of drug (where it goes first)

Answer 7

• initially, liver, kidney, brain and other well-pefused organs receive most of the drug
• delivery to muscle, most viscera, skin and fat is slower

Question 8

describe phase I reactions

Answer 8

• phase I reactions include oxidations, reductions, decarboxylation, deaminations and hydrolytic reactions
  
  • converts the parent drug to a more polar metabolite
  • generally results in inactive metabolites
• most phase I reactions are catalyzed by the cytochrome P450 system

Question 9

describe phase II reactions

Answer 9

• phase II reactions consist of conjugation reactions
  
  • conjugation reactions form a covalent bond between the drug molecule and glucuronate, acetate, glutathione, amino acids or sulfate

Question 10

describe renal excretion and the 3 processes

Answer 10

1. glomerular filtration
   
   • lipid solubility and pH don’t influence the passage of drugs into the glomerular filtrate
2. active tubular secretion
   
   • in the proximal tubule, drug molecules are pumped into the lumen of the tubule
3. passive diffusion across tubular epithelium
   
   • lipsoluble drugs can be passively reabsorbed