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BASIC OF PHARMACOLOGY




The goal of drug therapy is to prevent, cure, or control various disease states. To achieve this goal, adequate drug doses must be delivered to the target tissues so that therapeutic yet nontoxic levels are obtained. Pharmacokinetics examines the movement of a drug over time through the body. Pharmacological as well as toxicological actions of drugs are primarily related to the plasma concentrations of drugs. Thus, the clinician must recognize that the speed of onset of drug action, the intensity of the drug's effect, and the duration of drug action are controlled by four fundamental pathways of drug movement and modification in the body 





First, drug absorption from the site of administration (Absorption) permits entry of the therapeutic agent (either directly or indirectly) into plasma. 

Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids (Distribution). 

Third, the drug may be metabolized by the liver, kidney, or other tissues (Metabolism). Finally, the drug and its metabolites are removed from the body in urine, bile, or feces (Elimination). This chapter describes how knowledge of these four processes (Absorption, Distribution, Metabolism, and Elimination) influences the clinician's decision of the route of administration for a specific drug, the amount and frequency of each dose, and the dosing intervals.







Most drugs exert their effects, both beneficial and harmful, by interacting with receptors—that is, specialized target macromolecules—present on the cell surface or intracellularly. Receptors bind drugs and initiate events leading to alterations in biochemical and/or biophysical activity of a cell, and consequently, the function of an organ



Drugs may interact with receptors in many different ways. Drugs may bind to enzymes (for example, inhibition of dihydrofolate reductase by trimethoprim), nucleic acids (for example, blockade of transcription by dactinomycin), or membrane receptors (for example, alteration of membrane permeability by pilocarpine). 
In each case, the formation of the drug–receptor complex leads to a biologic response. Most receptors are named to indicate the type of drug/chemical that interacts best with it; for example, the receptor for histamine is called a histamine receptor. Cells may have tens of thousands of receptors for certain ligands (drugs). Cells may also have different types of receptors, each of which is specific for a particular ligand. On the heart, for example, there are β receptors for norepinephrine, and muscarinic receptors for acetylcholine. These receptors dynamically interact to control vital functions of the heart. The magnitude of the response is proportional to the number of drug–receptor complexes.

This concept is closely related to the formation of complexes between enzyme and substrate,1 or antigen and antibody; these interactions have many common features, perhaps the most noteworthy being specificity of the receptor for a given ligand. However, the receptor not only has the ability to recognize a ligand, but can also couple or transduce this binding into a response by causing a conformational change or a biochemical effect. 

Although much of this chapter will be centered on the interaction of drugs with specific receptors, it is important to be aware that not all drugs exert their effects by interacting with a receptor; for example, antacids chemically neutralize excess gastric acid, reducing the symptoms of “heartburn.” This chapter introduces the study of pharmacodynamics—the influence of drug concentrations on the magnitude of the response. It deals with the interaction of drugs with receptors, the molecular consequences of these interactions, and their effects in the patient. A fundamental principle of pharmacodynamics is that drugs only modify underlying biochemical and physiological processes; they do not create effects de novo.

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