Sedative-Hypnotics.

Ethanol is the most widely abused central nervous system depressant, as discussed before. Barbiturates are circulated illegally and are known as downers. They

Figure 9-8Effects of cocaine on neurotransmitters. Cocaine inhibits the reuptake of the neurotransmitters dopamine and norepinephrine in the central and peripheral nervous systems.

TABLE 9-7-- Mechanisms of Adverse Drug Reactions

Mechanism Example Adverse Effect

Toxicity due to overdose Acetaminophen Liver necrosis and failure

Predictable reaction based on pharmacologic mechanism Nonselective, nonsteroidal anti-inflammatory drugs Peptic ulcer

Altered drug metabolism related to:

••Thiopurine S-methyltransferase deficiency Azathioprine Bone marrow failure

••Cytochrome P-450 CYP2C9 variants Oral anticoagulants Bleeding

••Cytochrome P-450 CYP2D6 variants Some antipsychotic drugs Excessive sedation; parkinsonism

••N-acetyltransferase, slow acetylator phenotype Hydralazine Lupus

Idiopathic Chloramphenicol Aplastic anemia

and numbness. PCP characteristically induces nystagmus. High doses can induce coma lasting a few hours up to 10 days. Lysergic acid diethylamide (LSD) is a potent synthetic drug

usually taken orally. It is absorbed rapidly and produces psychic effects, visual illusions, and altered perception for up to 12 hours. In high doses, LSD can cause death.

THERAPEUTIC DRUGS

An adverse drug reaction is defined as a toxic or undesired response to a drug used at therapeutic doses to prevent, diagnose, or treat disease. It is estimated that approximately 2 million

hospitalized patients suffered from serious adverse drug reactions in 1994, resulting in 106,000 deaths. These estimates are conservative because they do not include errors in drug dosage

or administration or patient noncompliance.[24] In Table 9-7 , adverse drug reactions are classified on the basis of their underlying mechanisms. Predictable reactions are based on the

known toxicity or mechanism of action of a drug; these reactions are usually related to dose. Individual variations or polymorphisms in drug-metabolizing enzymes contribute to variable

responses to drug therapy and an increased incidence of side effects. At least 5% of commonly prescribed drugs are metabolized by the cytochrome P-450 CYP1A2 pathway;

approximately 12% of Caucasians carry variant alleles that reduce drug metabolism by this pathway. [25] Pharmacogenomics is a new field that uses genotyping to predict and prevent

adverse drug reactions; for example, children with leukemia are screened for thiopurine methyltransferase variants to determine the optimal dose of azathiopurine,[26] and genotyping for

the cytochrome P-450 CYP2D6 enzyme will help individualize doses of antipsychotic drugs to reduce side effects.[27] In contrast to these predictable types of adverse drug reactions,

idiopathic or idiosyncratic reactions are rare and unpredictable, although the consequences may be severe or even fatal.

Herbal medicines are widely used in the United States and throughout the world; although many of these preparations have been shown to be effective in short-term trials, there is lack of

quality control in this industry and few long-term studies of effectiveness and safety. As summarized in Table 9-8 , the most commonly used herbal medicines in the United States can

produce adverse effects, including allergic or hypersensitivity reactions, and potentially serious interactions with prescription drugs.[28]

Date: 2016-04-22; view: 608