Drug Allergy, Abuse, and Poisoning or Overdose



Drug Allergy, Abuse, and Poisoning or Overdose



Overview


Drug allergy, or allergic reaction to drugs, represents a type of adverse drug reaction. The effects are mediated by humoral (involving antibodies) or cell-mediated (eg, T-lymphocyte) immunologic mechanisms and can lead to consequences that are short- or long-term, restricted to a specific organ or involving the whole body, and trivial or life-threatening. The clinical manifestations of allergic reactions to drugs are varied and can include anaphylaxis (anaphylactic shock, ie, life-threatening changes in the vasculature [such as vasodilation and edema] and the bronchioles [such as bronchoconstriction] that are consistent with shock); bronchospasm; dermatitis; fever; granulocytopenia (abnormal reduction of the number of neutrophils, eosinophils, and basophils in the blood); hemolytic anemia (abnormal decrease in red blood cell number); hepatitis; lupus erythematosus–like syndrome; nephritis or pneumonitis (lung inflammation); thrombocytopenia (abnormal decrease in platelet number); and vasculitis (inflammation of blood or lymph vessels). Allergic reactions to drugs are typically characterized by the necessity for previous exposure to the drug or to a drug of similar chemical structure; lack of dose-related effect; similar manifestations independent of the drug (ie, not related to the therapeutic or toxic effects of the drug); and nonresponsiveness to receptor antagonists of the drug.


Drug abuse (addiction) is a multifaceted problem, typically involving a complex combination of psychosocial contributing factors. Hereditary predisposition is also suspected to play a role in some cases. Drug abuse is perhaps most succinctly defined as the continued inappropriate nonmedical use of a drug in the face of known negative medical or other consequences. To some extent, every drug that produces a detectable psychic effect is abused by someone, somewhere in the world. In addition, many, perhaps most, drug addicts abuse more than 1 drug. Hence, the list of abused drugs is extensive and includes some substances that are thought of primarily as mood or physique enhancers or as “recreational” drugs (eg, anabolic steroids, mushrooms, designer drugs, hallucinogens, inhalants, marijuana, nicotine). This chapter focuses on some of the major classes of therapeutic drugs that are abused.


Drug poisoning or overdose can be accidental (a result of medical errors or errors in the home) or intentional (suicide attempts). The substances involved include pharmaceuticals (most often analgesics and over-the-counter preparations), cleaning products, cosmetics, and plants or plant extracts. The symptoms and duration of the toxicity depend on the substance involved, the amount, and the site of exposure. The mechanisms can be specific (eg, receptor-mediated reactions) or nonspecific (eg, tissue necrosis). This chapter focuses on toxicity caused by selected pharmacologic agents.


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Figure 14-1 Allergic Reactions to Drugs
Only a few drugs have a molecular size (>10,000 d) sufficient to induce an allergic reaction by themselves. Induction of an immune response more often occurs when a small drug molecule, metabolite, or excipient (inert substance in a prescription) covalently binds to some large endogenous macromolecule (carrier), such as a protein, and becomes allergenic. The immune system becomes sensitized during the initial exposure, although the allergic response is not elicited at this time. Antigen-specific antibodies of the T- and B-cell type proliferate in lymphatic tissue, and some remain there (as memory cells) and are clinically silent until reexposure to the antigen (drug-carrier complex). The response to reexposure can be quick and severe, even to a small dose of the drug. Four types of drug allergy are generally distinguished: anaphylactic, cytotoxic, immune complex vasculitis, and cell mediated. Management generally involves treating the symptoms and supporting vital functions.

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Figure 14-2 Type I (Acute, Anaphylactic) Reactions
After initial exposure to drug antigen (drug-carrier complex), macrophages and interleukins convert B cells into IgE/receptor-expressing cells that circulate in blood (as basophil granulocytes) or reside in tissues (as mast cells). Reexposure to drug antigen results in binding to paired IgE receptors and release of various chemical mediators such as histamine, kinins, serotonin, prostaglandins, leukotrienes, platelet-activating factor, and eosinophilic chemotactic factor. Histamine and other bioactive substances released into the bloodstream cause blood vessels to dilate and tissues to swell. The effect may be life-threatening if airway obstruction, blood pressure decrease, or heart arrhythmias occur. Type I reactions can have a rapid onset (minutes) and are similar to those seen in hypersensitivity reactions to insect stings, extrinsic asthma, and seasonal rhinitis.

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Figure 14-3 Type II (Cytotoxic, Autoimmune) Reactions
If antigen (drug)-antibody (IgG) complexes adhere to a cell surface, the immune response can damage or kill the cell. This effect occurs because the binding of the complex activates complement, which is a family of proteins that circulate in the blood in an inactive form until activated by an appropriate stimulus. Activated complement is normally directed against microorganisms, but when directed against a cell, complement causes lysis and death of the cell, promotes phagocytosis, attracts neutrophil granulocytes (chemotaxis), and stimulates other inflammatory responses. An example is allergy to penicillin. Penicillin binds to red blood cells, antibodies bind to the penicillin, complement is activated, and the cell is damaged or dies, which leads to drug-induced autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia.

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Figure 14-4 Type III (Immune Complex, Serum Sickness, Arthus) Reactions
If drug antigen-antibody complexes adhere to cells of vascular tissue, the immune response can attack not only the antigen-antibody complex but also the healthy cells of the vessel to which the complex is attached. This result can cause damage or death of the vessel’s cells. Activated complement, inflammation, and vasculitis damage vessel walls and result in the symptoms of serum sickness, which include malaise, fever, rash, arthralgia (pain in a joint), lymphadenopathy, hepatitis, and characteristic rash and eruptions along the sides of the feet and hands.
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Jun 21, 2016 | Posted by in PHARMACY | Comments Off on Drug Allergy, Abuse, and Poisoning or Overdose

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