McKenna's Pharmacology, 2e

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P A R T 1  Introduction to nursing pharmacology

In the same way, people in a cold environment may have constricted blood vessels (vasoconstriction) in the extremities, which would prevent blood flow to those areas. The circulating blood would be unable to deliver drugs to those areas and the person would receive little therapeutic effect from drugs intended to react with those tissues. Many drugs are bound to proteins and are not lipid soluble. These drugs cannot be distributed to the central nervous system (CNS) because of the effective blood– brain barrier (see later discussion), which is highly selective in allowing lipid soluble substances to pass into the CNS. Pharmacology: Distribution Protein binding Most drugs are bound to some extent to proteins in the blood to be carried into circulation. The protein–drug complex is relatively large and cannot enter into capil­ laries and then into tissues to react. The drug must be freed from the protein’s binding site at the tissues. Many drugs are extensively bound to proteins and it should be noted that only the unbound fraction of the drug can reach the site of action in responsive tissues. Some drugs compete with each other for protein binding sites, altering effectiveness or causing toxicity when the two drugs are given together. The toxicity is attributed to sudden increase in the fraction of the previously pro­ tein-bound drug that is now free. Pharmacology: Drug binding Blood–brain barrier The blood–brain barrier is a protective system of cellular membranes that keep many things (e.g. foreign invaders, poisons) away from the CNS. The fundamental structural difference of the membranes forming the blood-brain barrier is the use of so called tight-junctions between cells, leaving no gaps between the cells. Drugs that are highly lipid soluble are more likely to pass through the blood–brain barrier and reach the CNS. Drugs that are not lipid soluble are not able to pass the blood–brain barrier. This is clinically significant in treating a brain infection with antibiotics. Almost all antibiotics are not lipid soluble and cannot cross the blood–brain barrier. Effective antibiotic treatment can occur only when the infection is severe enough to damage the blood–brain barrier and allow antibiotics to cross. Although many drugs can cause adverse CNS effects, these are often the result of indirect drug effects and not the actual reaction of the drug with CNS tissue. For example, alterations in glucose levels and electro­ lyte changes can interfere with nerve functioning and produce CNS effects such as dizziness, confusion or changes in thinking ability.

(the blood vessels that flow through the liver on their way back to the heart). Aspirin and alcohol are two drugs that are known to be absorbed from the lower end of the stomach. The portal veins deliver these absorbed molecules into the liver, which immediately transforms most of the chemicals delivered to it by a series of liver enzymes. These enzymes break the drug into metabo­ lites, some of which are active and cause effects in the body and some of which are deactivated and can be readily excreted. As a result, a large percentage of the oral dose is destroyed at this point and never reaches the tissues. This phenomenon is known as the first-pass effect . The portion of the drug that gets through the first-pass effect is delivered to the circulatory system for transport throughout the body. Injected drugs and drugs absorbed from sites other than the GI tract undergo a similar biotransformation when they pass through the liver. Because some of the active drug already has had a chance to reach the respon­ sive tissues before reaching the liver, the injected drug is often more effective at a lower dose than the oral equiva­ lent. Thus, the recommended dose for oral drugs can be considerably higher than the recommended dose for par­ enteral drugs, taking the first-pass effect into account. Bioavailability and bioequivalence Bioavailability refers to the proportion of drug that passes through to systemic circulation after oral admin­ istration, taking into account both absorption and metabolic degradation. It relates to the total proportion of drug that reaches the systemic circulation. The use of the concept of bioavailability is limited as it relates only to the total proportion of the drug that reaches the systemic circulation and neglects the rate of absorption. Regulatory authorities make decisions about the “generic equivalence” of patented products. The concept of bio­ availability may be used to provide evidence that a new product behaves sufficiently similar to the existing one to be substituted for without causing clinical problems ( bioequivalence ). Distribution Distribution involves the movement of a drug to the body’s tissues (Figure 2.2). As with absorption, factors that can affect distribution include the drug’s lipid solu­ bility and ionisation, and the perfusion of the responsive tissue. For example, tissue perfusion is a factor in caring for a person with diabetes who has a lower-leg infec­ tion and needs antibiotics to destroy the bacteria in the area. In this case, systemic drugs may not be effective because part of the disease process involves changes in the vasculature and decreased blood flow to some areas, particularly the lower limbs. If there is not adequate blood flow to the area, little antibiotic can be delivered to the tissues and little antibiotic effect will be seen.