Page 34 - Basic _ Clinical Pharmacology ( PDFDrive )

2 Drug Receptors &
C H A P T E R

Pharmacodynamics

*
Mark von Zastrow, MD, PhD

C ASE STUD Y

A 51-year-old man presents to the emergency department medical history is remarkable only for mild hypertension that
due to acute difficulty breathing. The patient is afebrile and is being treated with propranolol. The physician instructs the
normotensive but anxious, tachycardic, and markedly tachy- patient to discontinue use of propranolol, and changes the
pneic. Auscultation of the chest reveals diffuse wheezes. The patient’s antihypertensive medication to verapamil. Why is
physician provisionally makes the diagnosis of bronchial the physician correct to discontinue propranolol? Why is
asthma and administers epinephrine by intramuscular injec- verapamil a better choice for managing hypertension in this
tion, improving the patient’s breathing over several minutes. patient? What alternative treatment change might the physi-
A normal chest X-ray is subsequently obtained, and the cian consider?

Therapeutic and toxic effects of drugs result from their interac- 1. Receptors largely determine the quantitative relations
tions with molecules in the patient. Most drugs act by associating between dose or concentration of drug and pharmacologic
with specific macromolecules in ways that alter the macromol- effects. The receptor’s affinity for binding a drug determines the
ecules’ biochemical or biophysical activities. This idea, more than concentration of drug required to form a significant number of
a century old, is embodied in the term receptor: the component drug-receptor complexes, and the total number of receptors
of a cell or organism that interacts with a drug and initiates the may limit the maximal effect a drug may produce.
chain of events leading to the drug’s observed effects. 2. Receptors are responsible for selectivity of drug action.
Receptors have become the central focus of investigation of The molecular size, shape, and electrical charge of a drug
drug effects and their mechanisms of action (pharmacodynamics). determine whether—and with what affinity—it will bind to
The receptor concept, extended to endocrinology, immunology, a particular receptor among the vast array of chemically dif-
and molecular biology, has proved essential for explaining many ferent binding sites available in a cell, tissue, or patient.
aspects of biologic regulation. Many drug receptors have been iso- Accordingly, changes in the chemical structure of a drug can
lated and characterized in detail, thus opening the way to precise dramatically increase or decrease a new drug’s affinities for
understanding of the molecular basis of drug action. different classes of receptors, with resulting alterations in
The receptor concept has important practical consequences for therapeutic and toxic effects.
the development of drugs and for arriving at therapeutic decisions 3. Receptors mediate the actions of pharmacologic agonists
in clinical practice. These consequences form the basis for under- and antagonists. Some drugs and many natural ligands, such
standing the actions and clinical uses of drugs described in almost as hormones and neurotransmitters, regulate the function of
every chapter of this book. They may be briefly summarized as receptor macromolecules as agonists; this means that they acti-
follows: vate the receptor to signal as a direct result of binding to it.
Some agonists activate a single kind of receptor to produce all
* The author thanks Henry R. Bourne, MD, for major contributions to their biologic functions, whereas others selectively promote
this chapter. one receptor function more than another.
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