Pharmaco*kinetics is the process of drug movement to achieve drug action. The four processes are absorption, distribution, metabolism (or biotransformation), and excretion (or elimination). The nurse applies knowledge of pharmaco*kinetics when assessing the patient for possible adverse drug effects. The nurse communicates assessment findings to members of the health care team in a timely manner to promote safe and effective drug therapy for the patient.
Absorption
Absorption is the movement of drug particles from the GI tract to body fluids by passive absorption, active absorption, or pinocytosis. Most oral drugs are absorbed into the surface area of the small intestine through the action of the extensive mucosal villi. Absorption is reduced if the villi are decreased in number because of disease, drug effect, or the removal of small intestine. Protein-based drugs such as insulin and growth hormones are destroyed in the small intestine by digestive enzymes. Passive absorption occurs mostly by diffusion (movement from higher concentration to lower concentration). With the process of diffusion, the drug does not require energy to move across the membrane. Active absorption requires a carrier such as an enzyme or protein to move the drug against a concentration gradient. Energy is required for active absorption. Pinocytosis is a process by which cells carry a drug across their membrane by engulfing the drug particles (Figure 1-2).
The GI membrane is composed mostly of lipid (fat) and protein, so drugs that are lipid soluble pass rapidly through the GI membrane. Water-soluble drugs need a carrier, either enzyme or protein, to pass through the membrane. Large particles pass through the cell membrane if they are nonionized (have no positive or negative charge). Weak acid drugs such as aspirin are less ionized in the stomach, and they pass through the stomach lining easily and rapidly. An infant’s gastric secretions have a higher pH (alkaline) than those of adults; therefore, infants can absorb more penicillin. Certain drugs such as calcium carbonate and many of the antifungals need an acidic environment to achieve greater drug absorption; thus food can stimulate the production of gastric acid. Hydrochloric acid destroys some drugs such as penicillin G; therefore a large oral dosage of penicillin is needed to offset the partial dose loss. Drugs administered by many routes do not pass through the GI tract or liver. These include parenteral drugs, eyedrops, eardrops, nasal sprays, respiratory inhalants, transdermal drugs, and sublingual drugs. Remember, drugs that are lipid soluble and nonionized are absorbed faster than water-soluble and ionized drugs.
Blood flow, pain, stress, hunger, fasting, food, and pH affect drug absorption. Poor circulation to the stomach as a result of shock, vasoconstrictor drugs, or disease hampers absorption. Pain, stress, and foods that are solid, hot, or high in fat can slow gastric emptying time, so the drug remains in the stomach longer. Exercise can decrease blood flow by causing more blood to flow to the peripheral muscle, thereby decreasing blood circulation to the GI tract.
Drugs given IM are absorbed faster in muscles that have more blood vessels (e.g., deltoids) than in those that have fewer blood vessels (e.g., gluteals). Subcutaneous tissue has fewer blood vessels, so absorption is slower in such tissue.
Some drugs do not go directly into the systemic circulation following oral absorption but pass from the intestinal lumen to the liver via the portal vein. In the liver, some drugs may be metabolized to an inactive form that may then be excreted, thus reducing the amount of active drug. Some drugs do not undergo metabolism at all in the liver, and others may be metabolized to drug metabolite, which may be equally or more active than the original drug. The process in which the drug passes to the liver first is called the first-pass effect, or hepatic first pass.
Most drugs given orally are affected by first-pass metabolism. Lidocaine and some nitroglycerins are not given orally because they have extensive first-pass metabolism and therefore most of the dose would be destroyed.
Bioavailability is a subcategory of absorption. It is the percentage of the administered drug dose that reaches the systemic circulation. For the oral route of drug administration, bioavailability occurs after absorption and first-pass metabolism. The percentage of bioavailability for the oral route is always less than 100%, but for the IV route it is 100%. Oral drugs that have a high first-pass hepatic metabolism may have a bioavailability of only 20% to 40% on entering systemic circulation. To obtain the desired drug effect, the oral dose could be higher than the drug dose for IV use.
Factors that alter bioavailability include (1) the drug form (e.g., tablet, capsule, sustained-release, liquid, transdermal patch, rectal suppository, inhalation), (2) route of administration (e.g., oral, rectal, topical, parenteral), (3) GI mucosa and motility, (4) food and other drugs, and (5) changes in liver metabolism caused by liver dysfunction or inadequate hepatic blood flow. A decrease in liver function or a decrease in hepatic blood flow can increase the bioavailability of a drug, but only if the drug is metabolized by the liver. Less drug is destroyed by hepatic metabolism in the presence of liver disorder.
With some oral drugs, rapid absorption increases the bioavailability of the drug and can cause an increase in drug concentration. Drug toxicity may result. Slow absorption can limit the bioavailability of the drug, thus causing a decrease in drug serum concentration.
