Anesthesia Pharmacology: General Principles: Pharmacokinetics

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  • 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 and 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

            • Ldocaine

  • 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: is often more rapid and predictable compared to the oral administration route

    • May be the 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 promote high diffusion rates of drugs, independent of their lipid solubility

    • Advantages of IV administration

      • Rapid/precise blood drug levels obtained since the drug does not first pass through the liver where the drug may be metabolized before reaching the systemic circulation. 

        • If the drug is metabolized by the liver first, such as after oral administration, this occurrence is described as the "first-pass effect."

      • Irritant drug are more comfortably administered by IV since blood vessels are relatively insensitive.

      • Drug rapidly diluted in the blood volume, particularly if the drug is administered into large forearm vein.

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

  2. Dolin, S. J. "Drugs and pharmacology" in Total Intravenous Anesthesia, pp. 13-35 (Nicholas L. Padfield, ed), Butterworth Heinemann, Oxford, 2000