23A02: Exam Report

Describe the factors affecting drug absorption throughout the gastrointestinal tract

39% of candidates passed this question.

This question required candidates to draw on knowledge across the syllabus. Many candidates did not appreciate the breadth required to adequately address this question unfortunately providing very detailed information on only aspects of the answer required to pass.

Excellent answers described the following: differences between different GI routes/ sites of absorption, mechanisms of absorption including Fick’s law of diffusion, drug formulations, drug factors (including concentration gradient, lipid solubility, ionisation, and molecular weight), site factors (including surface area, first pass metabolism, GI wall thickness, blood flow, and GI motility/ transit time). Marks were also given for consideration of drug interactions, enterohepatic recycling, and luminally active drugs.

Bii / 23A02: Describe the factors affecting drug absorption throughout the gastrointestinal tract

Gastrointestinal tract

1) Mouth

Sublingual and buccal drugs are absorbed directly via sublingual mucous membranes into the capillary venous system bypassing the portal circulation and first pass metabolism

2) Stomach and intestines

Oral drugs are absorbed through GI epithelium down their concentration gradient into the portal circulation, undergoing first pass metabolism

3) Rectum

PR drugs are absorbed directly via middle and inferior rectal veins bypassing the portal circulation and first pass metabolism

Factors affecting are governed by Fick’s Law of Diffusion

Diffusion = (Surface Area x Solubility x Concentration difference) / (Thickness x sqrt MW)

1) Drug factors

  1. Concentration gradient (Higher dose = faster absorption)
  2. Solubility (Depends on the nature of the drug – acid or base, pKa and the pH of the absorption membrane – low in stomach, high in SI. Acidic drugs are better absorbed in low pH environments, basic drugs are better absorbed in basic environments. More unionised = More lipid soluble = more readily absorbed.)
  3. MW (Low MW drugs more readily absorbed)
  4. Surface Area (For liquid drugs, increased volume of administered drug = increased 45efx area for absorption)
  5. Formulation (Liquids > suspensions > granules > tablets absorption. Slow release formulation protects the drug from breakdown in the stomach increases the amount of drug that reaches the duodenum and absorbed in the small intestine – Penicillin G, erythromycin)
  6. Drug interactions (Drug competition for absorption can decrease absorption)
  7. Binding (Tetracyclines reduced by Ca binding with milk)
  8. Enterohepatic re-circulation (NSAIDs such as indomethacin – increased concentration leading to increased risk of GI ulceration)

2) Patient factors

  1. Compliance with medication is required for absorption (Aim for less frequent dosing, webster packs, bigger tablets, combination tablets)
  2. Surface area (Small bowel has increased surface area so most absorption occurs here. However, can have decreased surface area in Eg gastritis, short gut syndrome, malabsorption syndromes)
  3. Thickness (Increased in inflammatory states and can decrease absorption)
  4. Concentration gradient (GI blood flow maintains a concentration gradient but it can be decreased in low flow states – shock, vasopressors, sympathetic stimulation – leading to decreased absorption, and increased in high flow states – ingestion with food has a positive effect)
  5. GI motility (Vomiting decreases time for absorption, gastroparesis/constipation leads to slower transit to small intestine and slower absorption – concurrent use of luminally active drugs such as opiates can exacerbate constipation, and aperients – can lead to diarrhoea)
  6. GI Metabolism (Bacteria in GI wall can metabolise – Nitrates, COCP = Decreased absorption)

3) Specific states

  1. Age (Extremes of age = variable CO and can lead to decreased rate of absorption)
  2. Pregnancy (Generally decreased absorption due to progesterone)
  3. Cardiac disease (Decreased CO = decreased blood flow and decreased concentration gradient for absorption)
  4. Metabolism (Decreased liver blood flow = decreased phase I metabolism = decreased metabolism of hepatic cleared drugs = decreased concentration gradient for absorption.
  5. Excretion (Decreased GFR = proportional decreased renal clearance = decreased concentration gradient for absorption)


Ho Medical – General Pharmacology

Author: Daniel Chan