Section 2. Drugs

Chapter 12. Drug Dynamics

Topics: Introduction | Site Selectivity | Drug Action

Site Selectivity

After being swallowed, injected, inhaled, or absorbed through the skin, most drugs enter the bloodstream and circulate throughout the body. Some drugs are administered directly to the area where they are wanted--for example, to the eyes in eyedrops. The drugs then interact with cells or tissues where they produce their intended effects (target sites). Some drugs are relatively nonselective; they affect many different tissues or organs. For example, atropine, a drug given to relax muscles in the digestive tract, may also relax muscles in the eyes and in the respiratory tract. Other drugs are relatively selective. For example, nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen (see Section 6, Chapter 78), target any area where inflammation is present. Still other drugs are highly selective; they affect mainly a single organ or system. For example, digoxin, a drug given to manage heart failure, affects mainly the heart, increasing its pumping efficiency. Sleep aids target certain nerve cells of the brain.

How do drugs know where to exert their effects? The answer involves how they interact with cells or substances such as enzymes.

Receptors on Cells

On their surface, most cells have many different types of receptors. A receptor is a molecule with a specific three-dimensional structure, which allows only substances that fit precisely to attach to it--as a key fits in its lock. Receptors enable natural (originating in the body) substances outside the cell, such as neurotransmitters and hormones, to influence the activity of the cell. Drugs tend to mimic these natural substances and thus use receptors in the same way. For example, morphine and related pain-relieving drugs use the same receptors in the brain used by endorphins, which are substances produced by the body to help control pain. Some drugs attach to only one type of receptor; others, like a master key, can attach to several types of receptors throughout the body. A drug's selectivity can often be explained by how selectively it attaches to receptors.

See the figure A Perfect Fit.

Drugs that target receptors are classified as agonists or antagonists. Agonist drugs activate, or stimulate, their receptors, triggering a response that increases or decreases the cell's activity. Antagonist drugs block the access or attachment of the body's natural agonists, usually neurotransmitters, to their receptors and thereby prevent or reduce cell responses to natural agonists.

Agonist and antagonist drugs can be used together in patients with asthma. For example, albuterol can be used with ipratropium. Albuterol, an agonist, attaches to specific (adrenergic) receptors on cells in the respiratory tract, causing relaxation of smooth muscle cells and thus widening of the airways (bronchodilation). Ipratropium, an antagonist, attaches to other (cholinergic) receptors, blocking the attachment of acetylcholine, a neurotransmitter that causes contraction of smooth muscle cells and thus narrowing of the airways (bronchoconstriction). Both drugs widen the airways (and make breathing easier) but in different ways.

Beta-blockers, such as propranolol, are a widely used group of antagonists. These drugs are used to treat high blood pressure, angina (chest pain due to an inadequate blood supply to the heart muscle), and certain abnormal heart rhythms. They block or reduce stimulation of the heart by the agonist hormones epinephrine (adrenaline) and norepinephrine (noradrenaline), which are released during stress. Antagonists such as beta-blockers are most effective when the local concentration of the agonist is high. Similar to the way a roadblock stops more vehicles during the 5:00 pm rush hour than at 3:00 am, beta-blockers, given in doses that have little effect on normal heart function, may have a greater effect during sudden surges of hormones released during stress and thereby protect the heart from excess stimulation.

See the table Targets in the Body: Cell Receptors.

Enzymes

Instead of receptors, some drugs target enzymes, which regulate the rate of chemical reactions. Drugs that target enzymes are classified as inhibitors or activators (inducers). For example, the cholesterol-lowering drug lovastatin inhibits an enzyme called HMG-CoA reductase, which is critical in the body's production of cholesterol. A side effect of the antibiotic rifampin is the activation of the enzymes involved in metabolizing oral contraceptives. When women who are taking an oral contraceptive also take rifampin, the contraceptive is metabolized and removed from the body more quickly than usual and may therefore be ineffective.