McKenna's Pharmacology, 2e

21

C H A P T E R 2  Drugs and the body

under the skin, where it is slowly absorbed into circu­ lation. Timing of absorption varies with subcutaneous injection, depending on the fat content of the injection site and the state of local circulation. Table 2.1 outlines the various factors that affect drug absorption for differ­ ent routes of administration. Absorption processes Drugs can be absorbed into cells through various pro­ cesses, which include passive diffusion, active transport and filtration. Passive diffusion is the major process by which drugs are absorbed into the body. Passive diffu­ sion occurs across a concentration gradient. When there is a greater concentration of drug on one side of a cell membrane, the drug will move through the membrane to the area of lower concentration. This process does not require any cellular energy. It occurs more quickly if the drug molecule is small, is soluble in water and in lipids (cell membranes are made of lipids and proteins—see

Chapter 7) and has no electrical charge that could repel it from the cell membrane. Unlike passive diffusion, active transport is a process that uses energy to actively move a molecule across a cell membrane. The molecule may be large, or it may be moving against a concentration gradient. This process is not very important in the absorption of most drugs, but it is often a very important process in drug excretion in the kidney. Filtration involves movement through pores in the cell membrane, either down a concentration gradient or as a result of the pull of plasma proteins (when pushed by hydrostatic, blood or osmotic pressure). Filtration is another process the body commonly uses in drug excretion. Factors affecting gastrointestinal absorption Numerous factors can affect or alter the absorption of oral drugs. Some are physiological barriers and some are due to the formulation of the drug. The main factors are: • Gastrointestinal motility • Splanchnic blood flow • Particle size and formulation • Physicochemical factors Many disease conditions can slow down drug absorp­ tion. For example diabetic neuropathy and migraine are conditions that affect gastric stasis. There are also drug treatments that can affect gastric motility. Drugs that block the muscarinic receptors reduce gastric motility and some drugs such as metoclopromide increase gastric motility. A drug taken after a meal is often more slowly absorbed because its movement to the small intestines is delayed in the presence of food. However, not all drugs taken after a meal can result in slow absorption of the drug. Propanol when taken with meals reaches higher plasma concentration because the drug increases splanch­ nic blood flow. In clinical situations where a person is hypovolaemic, splanchnic blood flow is slow and results in a slowing of absorption of oral drugs. Formulation and particle size have major effects in the absorption of oral drugs. Capsules may be designed to remain intact for some hours after the person takes the drug in order to delay absorption. In some cases, tablets may have a resist­ ant coating to give the same effect. Slow-release capsules and sustained release capsules are formulated to produce rapid but sustained absorption of the drug. Physicochem­ ical factors such as changes in gastric pH due to ageing and presence of other drugs can all affect drug absorp­ tion. Tetracycline, an antibiotic, binds strongly to Ca 2 +. Absorption of this drug is prevented if administered with calcium rich foods (especially milk). First-pass effect Drugs that are taken orally are usually absorbed from the small intestine directly into the portal venous system

■■ TABLE 2.1 Factors that affect absorption of drugs Route Factors affecting absorption

IV (intravenous)

None: direct entry into the venous system Perfusion or blood flow to the muscle cold causes vasoconstriction and decreases absorption; heat causes vasodilation and increases absorption Perfusion or blood flow to the tissue Fat content of the tissue Temperature of the tissue: cold causes vasoconstriction and decreases absorption; heat causes vasodilation and increases absorption Acidity of stomach Length of time in stomach Blood flow to gastrointestinal tract Presence of interacting foods or drugs Perfusion or blood flow to the rectum Lesions in the rectum Length of time retained for absorption Perfusion or blood flow to the area Integrity of the mucous membranes Presence of food or smoking Length of time retained in area Perfusion or blood flow to the area Integrity of skin Perfusion or blood flow to the area Integrity of lung lining Ability to administer drug properly Fat content of the muscle Temperature of the muscle:

IM (intramuscular)

Subcutaneous

PO (oral)

PR (rectal)

Mucous

membranes (sublingual, buccal)

Topical (skin)

Inhalation