Medical Pharmacology Chapter 2: General Principles: Pharmacokinetics
Most convenient, most economical
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
Rate and absorption extent by GI tract
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
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
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
Nitroglycerin-tolerance may eventually occur; resulting in loss of therapeutic action.
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
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:
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.
Stoelting, R.K., "Pharmacokinetics and Pharmacodynamics of Injected and Inhaled Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 1-17.
Dolin, S. J. "Drugs and pharmacology" in Total Intravenous Anesthesia, pp. 13-35 (Nicholas L. Padfield, ed), Butterworth Heinemann, Oxford, 2000