Extent of Absorption

• Incomplete absorption following oral drug administration is common.

  • For example, only 70% of a digoxin dose reaches systemic circulation. Factors:

    • Poor GI tract absorption

    • Digoxin (Lanoxin, Lanoxicaps):  metabolism by gastrointestinal flora

• Very hydrophilic drugs - not be well absorbed --cannot cross cell membrane lipid component

• Excessively lipid-soluble (hydrophobic) drugs may not be soluble enough to cross a water layer near the cell membrane.

Ion Trapping

• "Ion Trapping - Introduction"

  Attribution: Five Minute Phamacology https://www.youtube.com/watch?v=ZnoKKkwIHok Five Minute Pharmacology Youtube Channel https://www.youtube.com/channel/UCjrrt9QfvTysjjmIH7evLJA

• Kidney:

  • Nearly all drugs filtered at the glomerulus:

    • Most drugs in a lipid-soluble form will be reabsorbed by passive diffusion.

    • To increase excretion: change the urinary pH to favor the charged form of the drug since charged form cannot be readily reabsorbed since this form (charged) cannot readily pass through biological membranes.

      • Weak acids: excreted faster in alkaline pH (anion form favored)

      • Weak bases: excreted faster in acidic pH (cation form favored)

• Other sites:

  • Body fluids where pH differences from blood pH favor trapping or reabsorption:

    • Stomach contents

    • Small intestine

    • Breast milk

    • Aqueous humor (eye)

    • Vaginal secretions

    • Prostatic secretions

• Ion Trapping: Anesthesia Correlation:  Placental transfer of basic drugs

  Placental transfer of basic drugs from mother to fetus: local anesthetics. Fetal pH is lower than maternal pH. Lipid-soluble, nonionized local anesthetic crosses the placenta converted to poorly lipid-soluble ionized drug.  Anesthetic concentratin gradient is maintained for continual transfer of local anesthetic from maternal circulation to fetal circulation.  In fetal distress, acidosis contributes to local anesthetic accumulation.

   

Weak bases-- amines

•  N + 1 carbon (R) and 2 hydrogens: primary amine (reversible protonation)

•  N + 2 carbons (R) and 1 hydrogen: secondary amine (reversible protonation)

•  N + 3 carbons (R): tertiary amine (reversible protonation)

•  N + 4 carbons (R): quaternary amine (permanently charged)