Routes of Administration

• Oral Administration

  • Most convenient, most economical

•  Disadvantages:

  • Emesis (drug irritation of the gastrointestinal mucosa)

  • Digestive enzymes/gastric acidity destroys the drug

  • Unreliable or inconsistent absorption due to food or other drug effects

  • Metabolism of the drug by gastrointestinal flora

• Factors determining rate of drug effect onset

  • Primary factor:

    • Rate & absorption extent by GI tract

  • Absorption Site:

    • Mainly small intestine because of large surface area

  • Drug ionization state:

    • Nonionized (lipid-soluble) forms favor absorption

      • Weak acids may be highly ionized in the alkaline intestinal pH (not favoring absorption) but this effect is counterbalanced by the large surface-area effect

      • Drugs which are weak acids are readily absorbed in the stomach

• First-Pass Effect

  • Drugs absorbed from the GI tract passes through the  portal venous system then through the liver and finally into the systemic circulation when drugs interact with receptors in target tissues.

  • Extensive hepatic metabolism/extraction result in minimal drug delivery to the systemic circulation for certain agents.

  • Drugs with large first pass effect exhibit significant differences in pharmacological effects comparing oral vs. IV administration

    • Examples:

      • Propranolol

      • Lidocaine

• Transdermal Administration

  • Advantages:

    • Sustained, therapeutic plasma levels (reduced peaks/valleys associated with intermittent drug administrations)

    • Avoids continuous infusion technique difficulties

    • Low side effect incidence (smaller doses)

    • Generally good patient compliance

  • Factors contributing to reliable transdermal drug absorption:

    • Molecular weight < 1000

    • pH range 5-9 in aqueous medium

    • No histamine-releasing action

    • Daily drug requirement <10 mg

  • Example of drugs available for transdermal delivery:

    • Scopolamine:-tolerance may eventually occur; resulting in loss of therapeutic action

    • Fentanyl (Sublimaze)

    • Clonidine (Catapres)

    • Nitroglycerin-tolerance may eventually occur; resulting in loss of therapeutic action.

• Rectal Administration

  • Proximal rectum administration: Absorption into superior hemorrhoidal veins then enters the portal venous system  then to the liver (possible first pass hepatic effect) and finally into the systemic circulation

  • Low rectal administration of drug may allow the drug to enter the systemic circulation without passing through the liver

  •  Generally unpredictable pharmacological responses for the above reasons

  • Rectal mucosal irritation possible

• Parenteral Administration

• Ensures active drug absorption

• Subcutaneously intramuscular injection: more rapid/predictable than oral administration route

• Only route of administration acceptable for:

  • Uncooperative patients

  • Unconscious patients

• Factors the determine rate of systemic absorption:

  • Absorbing capillary membrane surface area

  • Drug solubility in interstitial fluid

  • Aqueous channels (vascular endothelium) promote high diffusion rates of drugs, independent of their lipid solubility

• Advantages of IV administration

  • Rapid/precise blood drug levels obtained (e.g., no first-pass effect)

  • Irritant drugs: more comfortably administered (blood vessels relatively insensitive); drug rapidly diluted (particularly if administered into large forearm vein)

   

  References

  Stoelting, R.K., "Pharmacokinetics and Pharmacodynamics of Injected and Inhaled Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 1-17.