Pharmacology

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Pharmacology

WHY YOU NEED TO KNOW

HISTORY

Materia medica, in brief terms, is the collected knowledge and use of remedies to treat infection and disease. Most likely it began with the early recorded history of people; attempts to alleviate pain, treat physical maladies, overcome disease, and recover from its effects. Yet, in most cases, causes of the disease were unknown and effective outcome of treatment was uncertain.

Early concepts of disease were markedly influenced by superstitious, primitive, religious fantasies. Some early oral drug candidates persist today from readily available plants—grapes (alcohol) to sedate and poppies (opium) for pain, cinchona bark (quinine) for malaria, saffron (colchicine) for gout, castor beans (castor oil) as a laxative for gastrointestinal tract disturbances, ipecac to treat amoebic dysentery, and willow bark (salicylic acid) as an analgesic for pain remain. Experiences with these remedies formed the folklore basis for the primitive medical practice of witch doctors, and other practitioners. The need of records for medical histories, responses to therapies, preparation procedures, and constituents of medicaments became necessary for continuity, which led to the pharmaceutical and pharmacological sciences.

IMPACT

The history of pharmacology impacts us as an integrated science that continues to evolve with the development of its components:

Pharmacology is further challenged to answer questions concerning what drugs do to the body, what the body does to drugs, and what drugs do to each other. To illustrate the integrated nature of this science, some of the early scientific contributions to the development of pharmacology were made by:

• Paracelsus (1493–1541): An alchemist–chemist who introduced chemistry to medicine by proposing that disease results from an imbalance of the body’s chemicals that can be treated by chemicals.

• William Harvey (1578–1657): An anatomist–physician who demonstrated that blood circulates to reach all cells, which markedly influenced cause-and-effect interpretation and led to the development of the hypodermic needle. This proceeded to the intravenous route of drug administration, which ushered in a new approach to scientific studies of medical sciences in general and drug actions in particular.

• François Magendie (1783–1855): A physiologist who used experimental approaches to the study of pharmacological problems to demonstrate that effects of drugs were the result of drug actions within specific body organs.

• Friedrich W.A. Sertürner (1783–1841): An apothecary (pharmacist) who was the first to isolate an active constituent—the ammonium salt of morphine—from its botanical source (poppy). This led to the understanding that the therapeutic effects of drugs are due to their active constituents and the value of working with these unadulterated active constituents.

• Claude Bernard (1813–1878): A physiologist who demonstrated experimentally in animals specifically how and where drugs act in the body. He interpreted the results of curare’s action at the skeletal neuromuscular junction.

• James Blake (1815–1893): A physician who proposed that drug effects are determined, after reaching their sites of action, by their chemical structure and time at the site.

• Paul Ehrlich (1854–1915): A physician who proposed receptors as the cellular sites for drug action in studies with mercurial compounds to treat syphilis.

• William Morton (1819–1868): A dentist who was one of the first to anesthetize a patient with ether for surgical removal of a vascular tumor.

• Louis Pasteur (1822–1895): A microbiologist, who with Koch and others was a major contributor to the germ theory of disease. He demonstrated how to control microbial growth through what is now known as pasteurization (see Chapter 1, Scope of Microbiology; and Chapter 19, Physical and Chemical Methods of Control). He also used attenuated toxins to vaccinate.

FUTURE

The goal of medical practice is a rational or reasoned approach to the use of the tools available to the practitioner. Pharmacology is one of these tools. As an integrated science, its future is tied to the development of its parts. It is a dynamic science that continues to evolve at the rate at which scientific disciplines evolve or as new ones are added. One of the significant challenges for pharmacology is microorganisms that have developed resistance to antimicrobial drugs. In response to this challenge the Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and U.S. Department of Agriculture (USDA) have developed the National Antimicrobial Resistance Monitoring System (NARMS) to monitor and determine changes in antimicrobial drug resistance. The NARMS identifies antimicrobial drug resistance in humans and animals and provides timely information to physicians and veterinarians about antimicrobial drug resistance patterns. This increased monitoring is essential to keep abreast of changes. There is a need to exercise caution against the inadvertent development of new resistant strains after the introduction of new antibiotics.

Introduction

As already stated, pharmacology (from the Greek pharmakon [drug] and logia [the study of]) is an integrated medical science. With a few exceptions, such as antibiotics, drugs cannot and do not add any new physiological, biochemical, or other biological functions to living tissues. They alter the rates at which physiological responses can occur, such as adrenaline, which induces an increase in the heart rate.

HEALTHCARE APPLICATION
Examples of Drugs Used in the Various Organ Systems

Drug System/Condition Effect
Methylphenidate Central nervous Stimulant
Digitalis Cardiovascular Treats congestive heart failure
Colchicine Neuromuscular Analgesic
Quinidine Cardiovascular Antiarrhythmic
Procainamide Cardiovascular Antiarrhythmic
Phenytoin Central nervous Anticonvulsant
Verapamil Cardiovascular Antianginal
Nitroglycerin Cardiovascular Antianginal
Acetazolamide Renal Diuretic
Levothyroxine Endocrine Treats hypothyroidism
Barbiturate Central nervous Sedative
Benzodiazepine Central nervous Antianxiety
Prednisolone Respiratory Inhibits inflammatory responses
Sodium bicarbonate Gastrointestinal Increases stomach pH
Sildenafil Reproductive Treats erectile dysfunction
Sibutramine Obesity Inhibits reuptake of serotonin and norepinephrine that regulate food intake
Somatotropin Endocrine Antipituitary to block IGF action on liver cells.

IGF, Insulin-like growth factor.

Branches of Pharmacology

This chapter introduces some fundamentals of “physiological pharmacology” or “pharmacological physiology”—referring to the same anatomy, physiology, and biochemistry discussed in Chapter 2 (Chemistry of Life) and Chapter 3 (Cell Structure and Function). Although all drugs are potential poisons (substances that cause severe distress or death), when given in subtoxic doses they are medicinal tools. The goal of rational drug therapy is to aid and maintain the body and its biological systems in healthy working order. In therapy, drugs give living tissues added chemical support to prevent and to meet physical and pathological challenges to which biological systems are exposed. Pharmacology is organized into separate disciplines that describe actions of drugs:

• Pharmacodynamics addresses drug-induced responses of the physiological and biochemical systems of the body in health and disease.

• Pharmacokinetics addresses drug amounts at various sites in the body after their administration.

• Pharmacotherapeutics addresses issues associated with the choice and application of drugs to be used for disease prevention, treatment, or diagnosis.

• Toxicology is the study of the body’s response to poisons; their harmful effects, mechanisms of action, symptoms, treatment, and identification.

• Pharmacy, on the other hand, includes the preparation, compounding, dispensing of, and record keeping about therapeutic drugs, for which drug nomenclature is essential. In addition, pharmacy includes the following:

Drug Nomenclature

Because all drugs are potential poisons, understanding their nomenclature is essential. It is also practical because it specifically identifies the correct drug for the correct use. This starts with their manufacture in the pharmaceutical industry; continues to distribution at pharmacies where drugs are dispensed; and ends with medical personnel who administer them to patients. Moreover, drug nomenclature is needed for a precise chemical description that can help to avoid medical disasters.

In general, therapeutic chemicals are broadly divided into two groups, nonprescription and prescription drugs:

Individual drugs have three names: chemical, generic, and proprietary or trade (brand) name (Table 21.1):

TABLE 21.1

Examples of Drug Nomenclature

Trade or Brand (Proprietary) Name Generic (Nonproprietary) Name Chemical Name Therapeutic Class
Amoxil, Amoxicot, Trimox, DisperMox … Amoxicillin (2S,5R,6R)-6-[(R)-(–)-2-amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate Antibiotic
Advil, Motrin, Midol, Nuprin … Ibuprofen (±)-2-(p-Isobutylphenyl) propionic acid Antiinflammatory
Tylenol, Anacin-3 … Acetaminophen N-Acetyl-p-aminophenol Analgesic
Dilantin, Dilantin KAPSEALS Phenytoin Sodium 5,5-diphenyl-2,4 imidazolidinedione Anticonvulsants
Allegra Fexofenadine (±)-4-[1 hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α,α-dimethyl benzeneacetic acid hydrochloride Antihistamines

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Sources of Drug Information

Sources for drug information can be people or published information. People who generally have particular drug information include the following:

Published information can be found in the following:

Principles of Drug Action

Drugs alter physiological activity and for them to be effective they must reach their intended target site at the appropriate concentration (Table 21.2). This involves several processes collectively called pharmacokinetics. These principles include the following:

TABLE 21.2

Drug Losses at Sites of Action Through Administration

Route of Administration Drug Loss From:
Enteral route only Degradation in stomach
First-pass effect
Small intestine
Failure to be absorbed
Binding to food or other contents
Liver
Secretion in bile
Biotransformation
Tissue binding
Enteral and parenteral routes  
 General blood circulation Biotransformation
Binding to plasma proteins
 Distribution to body tissues Drug too dispersed, not sufficient at site of action
Tissue binding
Biotransformation
Metabolism
Excretion

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