Routes Of Administration PDF

Principles of Psychopharmacology As we will see in this chapter, drugs have effects and sites of action. Drug effects are the changes we can observe in an animal’s physiological processes and behavior. For example, the effects of morphine, heroin, and other opiates include decreased sensitivity to p...

Principles of Psychopharmacology As we will see in this chapter, drugs have effects and sites of action. Drug effects are the changes we can observe in an animal’s physiological processes and behavior. For example, the effects of morphine, heroin, and other opiates include decreased sensitivity to pain, slowing of the digestive system, sedation, muscular relaxation, constriction of the pupils, and euphoria. The sites of action of drugs are the points at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells. For example, the sites of action of the opiates are specialized receptors situated in the membrane of some neurons. When molecules of opiates attach to and activate these receptors, the drugs alter the activity of these neurons and produce their effects. This chapter considers both the effects of drugs and their sites of action. Psychopharmacology is an important field of neuroscience. It has been responsible for the development of psychotherapeutic drugs, which are used to treat psychological and behavioral disorders. It has also provided tools that have enabled other investigators to study the functions of cells of the nervous system and the behaviors controlled by particular neural circuits. This chapter does not contain all this book has to say about the subject of psychopharmacology. Throughout the book you will learn about the use of drugs to investigate the nature of neural circuits involved in the control of perception, memory, and behavior. In addition, Chapters 16 and 17 discuss the use of drugs to study and treat mental disorders such as schizophrenia, depression, and the anxiety disorders, and Chapter 18 discusses the physiology of drug abuse. Principles of Psychopharmacology This chapter begins with a description of the basic principles of psychopharmacology: the routes of administration of drugs and their fate in the body. The second section discusses the sites of drug actions. The final section discusses specific neurotransmitters and neuromodulators and the physiological and behavioral effects of specific drugs that interact with them. Pharmacokinetics To be effective, a drug must reach its sites of action. To do so, molecules of the drug must enter the body and then enter the bloodstream so that they can be carried to the organ (or organs) on which they act. Once there, they must leave the bloodstream and come into contact with the molecules with which they interact. For almost all of the drugs we are interested in, this means that the molecules of the drug must enter the central nervous system (CNS). 101 Some behaviorally active drugs exert their effects on the peripheral nervous system, but these drugs are less important to us than the drugs that affect cells of the CNS. Molecules of drugs must cross several barriers to enter the body and find their way to their sites of action. Some molecules pass through these barriers easily and quickly; others do so very slowly. And once molecules of drugs enter the body, they begin to be metabolized—broken down by enzymes—or excreted in the urine (or both). In time, the molecules either disappear or are transformed into inactive fragments. The process by which drugs are absorbed, distributed within the body, metabolized, and excreted is referred to as pharmacokinetics (“movements of drugs”). ROUTES OF ADMINISTRATION First, let’s consider the routes by which drugs can be administered. For laboratory animals the most common route is injection. The drug is dissolved in a liquid (or, in some cases, suspended in a liquid in the form of fine particles) and injected through a hypodermic needle. The fastest route is intravenous (IV) injection—injection into a vein. The drug enters the bloodstream immediately and reaches the brain within a few seconds. The disadvantages of IV injections are the increased care and skill they require in comparison to most other forms of injection and the fact that the entire dose reaches the bloodstream at once. If an animal is especially sensitive to the drug, there may be little time to administer another drug to counteract its effects. An intraperitoneal (IP) injection is rapid but not as rapid as an IV injection. The drug is injected through the abdominal wall into the peritoneal cavity—the space that surrounds the stomach, intestines, liver, and other abdominal organs. IP injection is the most common route for administering drugs to small laboratory animals. An intramuscular (IM) injection is made directly into a large muscle, such as those found in the upper arm, thigh, or buttocks. The drug is absorbed into the bloodstream through the capillaries that supply the muscle. If very x drug effect The changes a drug produces in an animal’s physiological processes and behavior. x sites of action The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells. x pharmacokinetics The process by which drugs are absorbed, distributed within the body, metabolized, and excreted. x intravenous (IV) injection into a vein. Injection of a substance directly x intraperitoneal (IP) injection (in tra pair i toe nee ul) Injection of a substance into the peritoneal cavity—the space that surrounds the stomach, intestines, liver, and other abdominal organs. x intramuscular (IM) injection muscle. Injection of a substance into a 102 Chapter 4 Psychopharmacology slow absorption is desirable, the drug can be mixed with another drug (such as ephedrine) that constricts blood vessels and retards the flow of blood through the muscle. A drug can also be injected into the space beneath the skin by means of a subcutaneous (SC) injection. A subcutaneous injection is useful only if small amounts of drug need to be administered, because injecting large amounts would be painful. Some fat-soluble drugs can be dissolved in vegetable oil and administered subcutaneously. In this case, molecules of the drug will slowly leave the deposit of oil over a period of several days. If very slow and prolonged absorption of a drug is desirable, the drug can be formed into a dry pellet or placed in a sealed silicone rubber capsule and implanted beneath the skin. Oral administration is the most common form of administering medicinal drugs to humans. Because of the difficulty of getting laboratory animals to eat something that does not taste good to them, researchers seldom use this route. Some chemicals cannot be administered orally because they will be destroyed by stomach acid or digestive enzymes or because they are not absorbed from the digestive system into the bloodstream. For example, insulin, a peptide hormone, must be injected. Sublingual administration of certain drugs can be accomplished by placing them beneath the tongue. The drug is absorbed into the bloodstream by the capillaries that supply the mucous membrane that lines the mouth. (Obviously, this method works only with humans, who will cooperate and leave the capsule beneath their tongue.) Nitroglycerine, a drug that causes blood vessels to dilate, is taken sublingually by people who suffer the pains of angina pectoris, caused by obstructions in the coronary arteries. Drugs can also be administered at the opposite end of the digestive tract, in the form of suppositories. Intrarectal administration is rarely used to give drugs to experimental animals. For obvious reasons this process would be difficult with a small animal. In addition, when agitated, small animals such as rats tend to defecate, which would mean that the drug would not remain in place long enough to be absorbed. And I’m not sure I would want to try to administer a rectal suppository to a large animal. Rectal suppositories are most commonly used to administer drugs that might upset a person’s stomach. The lungs provide another route for drug administration: inhalation. Nicotine, freebase cocaine, and marijuana are usually smoked. In addition, drugs used to treat lung disorders are often inhaled in the form of a vapor or fine mist, and many general anesthetics are gasses that are administered through inhalation. The route from the lungs to the brain is very short, and drugs administered this way have very rapid effects. Some drugs can be absorbed directly through the skin, so they can be given by means of topical administration. Natural or artificial steroid hormones can be administered in this way, as can nicotine (as a treatment to make it easier for a person to stop smoking). The mucous membrane lining the nasal passages also provides a route for topical administration. Commonly abused drugs such as cocaine hydrochloride are often sniffed so that they come into contact with the nasal mucosa. This route delivers the drug to the brain very rapidly. (The technical, rarely used name for this route is insufflation. And note that sniffing is not the same as inhalation; when powdered cocaine is sniffed, it ends up in the mucous membrane of the nasal passages, not in the lungs.) Finally, drugs can be administered directly into the brain. As we saw in Chapter 2, the blood–brain barrier prevents certain chemicals from leaving capillaries and entering the brain. Some drugs cannot cross the blood–brain barrier. If these drugs are to reach the brain, they must be injected directly into the brain or into the cerebrospinal fluid in the brain’s ventricular system. To study the effects of a drug in a specific region of the brain (for example, in a particular nucleus of the hypothalamus), a researcher will inject a very small amount of the drug directly into the brain. This procedure, known as intracerebral administration, is described in more detail in Chapter 5. To achieve a widespread distribution of a drug in the brain, a researcher will get past the blood–brain barrier by injecting the drug into a cerebral ventricle. The drug is then absorbed into the brain tissue, where it can exert its effects. This route, intracerebroventricular (ICV) administration, is used very rarely in humans—primarily to deliver antibiotics directly to the brain to treat certain types of infections. Figure 4.1 shows the time course of blood levels of a commonly abused drug, cocaine, after intravenous injection, inhalation, oral administration, and sniffing. The amounts received were not identical, but the graph illustrates the relative rapidity with which the drug reaches the blood. (See Figure 4.1.) x subcutaneous (SC) injection space beneath the skin. Injection of a substance into the x oral administration Administration of a substance into the mouth so that it is swallowed. x sublingual administration (sub ling wul) Administration of a substance by placing it beneath the tongue. x intrarectal administration the rectum. Administration of a substance into x inhalation Administration of a vaporous substance into the lungs. x topical administration Administration of a substance directly onto the skin or mucous membrane. x intracerebral administration directly into the brain. Administration of a substance x intracerebroventricular (ICV) administration Administration of a substance into one of the cerebral ventricles. x dose-response curve A graph of the magnitude of an effect of a drug as a function of the amount of drug administered.