Clinical Pharmacology Made Ridiculously Simple 5th Edition

Book Preface

Rational Therapeutics
There are thousands of drugs and hundreds of facts about each of them. Tt is unnecessary to memorize many of these facts if one learns to predict the behavior of each drug based on a few facts and an understanding of the principles of pharmacology.
This chapter presents the basic principles of phar­macology upon which drug therapy is based. As you read the chapter, try to apply the principles to a drug with which you are familiar, like aspirin. Refer to this chapter often as you learn the drugs presented in the rest of the book. Try to learn the “story” of each drug rather than isolated facts. The best way to develop a story about a drug is to associate, ask, and predict.
Associate each drug class with information that you already know about the drugs. Think of relatives or friends who have taken medicine from the class of drugs you are studying. Remember what you have read or heard about the drugs.

Ask yourself why some drugs are administered as shots and others as pills, why some drugs are taken four times daily and others only once, and why it is important for a health care provider to know the serum concentration of some drugs but not of others. As you read the following chapters, ask yourself “Why is this information important enough to be included in this book?”.
Predict the actions, clinical uses, side effects, and drug interactions of each drug based solely on its mechanism of action. If you can predict these charac­teristics, you will only have to memorize those facts that do not make intuitive sense.
Finally, envision the course of events that would occur as a drug enters the patient’s body. Continue this practice each time you prescribe, dispense or administer drugs to a patient. Your patients will benefit if your clinical decisions are determined rationally and based on a foundation of basic pharma­cology knowledge.

Drug Administration

Formulation
Clinically useful drugs are fonnulated by drug companies into preparations that can be administered orally, intravenously, or by another route. The formu­lation of a drug depends on the following factors:

• The barriers that the drug is capable of passing. Intravenous drugs are injected directly into the blood stream. In contrast, oral preparations must pass through the wall of the gastrointestinal tract and blood vessel walls before entering the bloodstream.
• The setting in which the drug will be used. An intravenous preparation might be appropriate for a drug which is administered during surgery, but would be inappropriate for home administration of aspirin.
• The urgency of the medical situation. The delay before onset of action varies betv.1een preparations of the same drug. Emergency situations o?en call for intravenous administration of agents which might normally be administered by another route.
• Stability of the drug. Drugs which are denatured by acid are not good candidates for oral preparations because they may be destroyed in the stomach
(stomach pH = 2).
• First Pass Effect. Blood from the gastrointestinal tract passes through the liver before entering any other organs. During this first pass through the liver, a fraction of the drug (in some cases nearly all) can be metabolized to an inactive or less active derivative. The inactivation of some drugs is so great that the agents are useless when administered orally.
ti Routes of Drug Administration
Routes of drug administration include:
• Oral (PO): Most compatible with drugs that are self­administered. Oral agents must be able Lo withstand the acidic environment of the stomach and must permeate the gut lining before entering the blood­stream. Absorption affected by gastric emptying and intestinal motility.
• SublinguaJ: Good absorption through capillary bed under tongue. Drugs are easily self-administered. Because the stomach is bypassed, acid-Jability and gut-permeability need not be considered.
• Rectal (PR) Useful for unconscious or vomiting patients or small children. Absorption is unreliable.
• Inhalation: Generally rapid absorption. Some agents, marketed in devices which deliver metered doses, are suitable for self-administration.

• Topical: Useful for local delivery of agents, particu­larly those which have toxic effects if administered systemically. Used for most dermatoJ.ogic, ophthal­mologic, nasal, vaginal, and otic preparations.
• Transdermal: A few drugs can be formulated such that a “patch” containing the drug is applied to the skin. The drug seeps out of the patch, through the skin and into the capillary bed. Very convenient for self-administration.
There are three drug administration techniques which have traditionally been labeled parenteral (“around the gastrointestinal tract”). Advantages include more rapid and predictable absorption and more accurate dose selection. Disadvantages include the need for strict asepsis, risk of infection, pain, and local irritation.

• lntravenous (JV): Rapid onset of action because agent is injected directly into the blood stream. Useful in emergencies and in patients that are unconscious. Insoluble drugs cannot be adminis­tered intravenously.
• lntramuscular (IM): Drug passes through capillary walls to enter the blood stream. Rate of absorption depends on formulation (oil-based preparations are absorbed slowly, aqueous preparations are absorbed rapidly). May be used for self-administration by trained patients.
• Subcutaneous (SubQ, SC): Drug is injected beneath the skin and permeates capillary walls to enter the blood stream. Absorption can be controlled by drug formuJation. Only nonirritating drugs can be used.
– Dosing Regimens
Three common dosing regimens are compared in Table 1.1. The half-life is the amount of time required for the plasma concentration of a drug to decrease by 50% after discontinuance of the drug. The distribution half-life (t112a) reflects the rapid decline in plasma drug concentration as a dose of drug is distributed through­out the body. The elimination half-life (tml3> is often much slower, reflecting the metabolism and excretion of the drug. Note that several half-lives pass before the serum concentration of a drug reaches steady state. Thus in order to obtain values which reflect the steady state, it is necessary to wait until the fourth or fifth half­life of a drug before the peak, trough or plasma level is measured.