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4

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, atropineSome Trade Names
ATROPEN
, 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 (NSAIDs), such as aspirinSome Trade Names
BAYER
and ibuprofenSome Trade Names
ADVIL MOTRIN
(see Pain: Nonopioid Analgesics), target any area where inflammation is present. Still other drugs are highly selective. They affect mainly a single organ or system. For example, digoxinSome Trade Names
LANOXIN
, 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. That influence may be to stimulate or inhibit a process inside the cell. Drugs tend to mimic these natural substances and thus use receptors in the same way. For example, morphineSome Trade Names
MS CONTIN ORAMORPH
and related pain-relieving drugs act on or affect 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. Other drugs, 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.

A Perfect Fit A receptor on the cell's surface has a three-dimensional structure that allows a specific substance, such as a drug, hormone, or neurotransmitter, to bind to it because the substance has a three-dimensional structure that perfectly fits the receptor, as a key fits a lock.

Agonists and Antagonists: 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, albuterolSome Trade Names
PROVENTIL-HFA VENTOLIN HFA
can be used with ipratropiumSome Trade Names
ATROVENT
. AlbuterolSome Trade Names
PROVENTIL-HFA VENTOLIN HFA
, 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). IpratropiumSome Trade Names
ATROVENT
, 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 propranololSome Trade Names
INDERAL
, are a widely used group of antagonists. These drugs are used to treat high blood pressure, angina (chest pain caused by an inadequate blood supply to the heart muscle), and certain abnormal heart rhythms and to prevent migraines. 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 concentration of the agonist is high in a specific part of the body. 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.

Targets in The Body: Cell Receptors Certain natural substances in the body, such as neurotransmitters and hormones, target specific receptors on the surface of cells. When these substances bind with the receptor on a cell, they stimulate that receptor to perform its function, which is to produce or to inhibit a specific action in the cell. Drugs can also target and bind with these receptors. Some drugs act as agonists, stimulating the receptor in the same way that the body's natural substances do. Others act as antagonists, blocking the action of the natural substance on the receptor. Each type of receptor has many subtypes, and drugs may act on one or several subtypes of receptors. Type of Receptor Body's Natural Agonist Resulting Action Drugs That Target the Receptor Adrenergic Alpha1 Epinephrine and norepinephrine “Fight-or-flight” reactions: Constriction of the blood vessels in the skin, digestive tract, and urinary tract Breakdown of glucose in the liver (releasing energy) Decrease in activity of the stomach and intestines Contraction of smooth muscle in the genital and urinary organs Agonist: Methoxamine and phenylephrineSome Trade Names PROMETH VC PLAIN Antagonist: DoxazosinSome Trade Names CARDURA , prazosinSome Trade Names MINIPRESS , tamsulosinSome Trade Names FLOMAX , and terazosinSome Trade Names HYTRIN Alpha2 Epinephrine and norepinephrine A decrease in insulin secretion, in the clumping of platelets, in the constriction of blood vessels in the skin and intestines, and in the release of norepinephrine from nerves Agonist: ClonidineSome Trade Names CATAPRES Antagonist: YohimbineSome Trade Names YOCON Beta1 Epinephrine and norepinephrine An increase in heart rate, in the force of heart contraction, and in secretion of renin (a hormone involved in controlling blood pressure) Agonist: Dobutamine and isoproterenolSome Trade Names ISUPREL Antagonist: Beta-blockers (used to treat hypertension and heart disease), such as atenololSome Trade Names TENORMIN and metoprololSome Trade Names LOPRESSOR TOPROL-XL Beta2 Epinephrine and norepinephrine Dilation of smooth muscle in the blood vessels, airways, digestive tract, and urinary tract Breakdown of glycogen in skeletal muscles (releasing glucose for energy) Agonist: AlbuterolSome Trade Names PROVENTIL-HFA VENTOLIN HFA , isoetharine, and terbutaline Antagonist: PropranololSome Trade Names INDERAL Cholinergic Muscarinic Acetylcholine A decrease in heart rate and the force of the heart's contraction Constriction of airways Dilation of blood vessels throughout the body Increase in activity of the stomach, intestines, bladder, and salivary, lacrimal, and sweat glands Agonist: BethanecholSome Trade Names URECHOLINE and carbacholSome Trade Names MIOSTAT Antagonist: AtropineSome Trade Names ATROPEN , ipratropiumSome Trade Names ATROVENT , and scopolamineSome Trade Names TRANSDERM SCOP Nicotinic Acetylcholine Contraction of skeletal muscles Agonist: None commonly used Antagonist: Atracurium, pancuronium, and tubocurarine Histaminergic H1 Histamine Production of an allergic response Contraction of muscles in the airways and digestive tract Dilation of small blood vessels Drowsiness (sedation) Agonist: None commonly used Antagonist: CetirizineSome Trade Names ZYRTEC , chlorpheniramineSome Trade Names CHLOR-TRIMETON , clemastineSome Trade Names TAVIST-1 , diphenhydramineSome Trade Names BENADRYL , fexofenadineSome Trade Names ALLEGRA , and loratadineSome Trade Names CLARITIN H2 Histamine Stimulation of stomach secretions Agonist: None commonly used Antagonist: CimetidineSome Trade Names TAGAMET , famotidineSome Trade Names PEPCID , nizatidineSome Trade Names AXID , and ranitidineSome Trade Names ZANTAC Serotoninergic Serotonin Constriction of blood vessels within the brain Stimulation of activity (motility) in the digestive tract Contraction of blood vessels Effects on sleep, memory, sensory perception, temperature regulation, mood, appetite, and hormone secretion Partial agonist: BuspironeSome Trade Names BUSPAR Agonist*: Sumitriptan and zomitriptan Antagonist: Methysergide and ondansetronSome Trade Names ZOFRAN Dopaminergic Dopamine Involvement in movement, mood, thinking, learning, and reward-seeking Also increases blood flow to the kidneys, which allows for increased urine excretion Agonist: PramipexoleSome Trade Names MIRAPEX and ropiniroleSome Trade Names REQUIP Antagonist: OlanzapineSome Trade Names ZYPREXA and risperidoneSome Trade Names RISPERDAL *Antidepressants called serotonin reuptake inhibitors (SSRIs) act by enhancing the effects of serotonin but are not agonists (they do not act on the serotonin receptor).

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 lovastatinSome Trade Names
MEVACOR
inhibits an enzyme called HMG-CoA reductase, which is critical in the body's production of cholesterol. A side effect of the antibiotic rifampinSome Trade Names
RIFADIN RIMACTANE
is the activation of the enzymes involved in metabolizing oral contraceptives. When women who are taking an oral contraceptive also take rifampinSome Trade Names
RIFADIN RIMACTANE
, the contraceptive is metabolized (that is, broken down into inactive components) and removed from the body more quickly than usual and may therefore be ineffective.

Last full review/revision November 2007 by Angela Cafiero Moroney, PharmD