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Charold Baer, Bradley R. Williams, Clinical Pharmacology and Nursing, Springhouse Pub Co; 1991, pp. 3-16
With the growing use of drugs that improve life and health has come an increasing incidence of adverse drug reactions. This increase has occurred because every drug has the potential to affect a patient adversely. Most drugs produce a spectrum of effects that range from the desired and routinely anticipated response to the unexplained and potentially life-threatening response. In all drug therapy, the physician and patient must weigh the drug’s beneficial effects against its possible adverse effects. A drug’s desired effect is the expected therapeutic response. An adverse drug reaction, also called a side effect or adverse effect, is a harmful, undesirable response, which may result from any clinically useful drug. Adverse drug reactions can range from mild ones that disappear when the drug is discontinued to debilitating diseases that become chronic. Some adverse reactions are related to the drug dose and may be preventable with careful prescription and administration or may be inseparable from the drug’s primary therapeutic effects. Others are related to patient sensitivity and may not be predictable. In this era of sophisticated, complex pharmacotherapy, physicians must be able to identify and respond to adverse drug reactions. Determining if an effect is desired or adverse may depend on the disorder being treated. For the common cold, for instance, diphenhydramine reduces nasal stuffiness and rhinorrhea. Unfortunately, the drug causes drowsiness, which may interfere with the patient’s safe driving of a vehicle. In this case, the reduced nasal stuffiness represents the desired effect, and drowsiness represents the adverse reaction. In contrast, when diphenhydramine is used to treat insomnia, its ability to induce drowsiness is the desired effect. The adverse reaction in using diphenhydramine for insomnia is dry mucous membranes. Although physicians, nurses, and pharmacists cannot always predict who will experience an adverse drug reaction, they can identify factors that increase the patient’s risk and may prevent or minimize the patient’s adverse response. FACTORS THAT LEAD TO ADVERSE DRUG REACTIONS A patient’s therapeutic responses to a drug result from the interplay among patient characteristics, drug characteristics, and exogenous (external) factors. Patient, drug, and exogenous factors can alter that interplay to produce adverse drug reactions. PREDISPOSING PATIENT FACTORS Patient factors include extremes of age, extremes of body weight, genetic variations, the patient’s temperament and attitudes, circadian rhythms, changes associated with disease, and changes associated with pregnancy. Extremes of age The absorption, distribution, metabolism, and excretion of drugs are different in infants and elderly patients than in young adults. Infants lack certain drug-metabolizing enzymes and have decreased renal blood flow. These physiological factors increase drug and metabolic blood levels. The breast-feeding infant also may develop adverse reactions to drugs that pass into the mother’s breast milk. Elderly patients have decreased blood flow to all organs, especially the liver and kidneys. These conditions result in increased drug concentration levels as well as changes in drug distribution and greater risk of toxicity. Extremes of body weight Recommended dosages typically are based on the average-sized adult. Therefore, the extremely thin or obese patient requires an individualized dosage calculation to prevent overdosing
and excretion of certain drugs. Circadian rhythms Normal physiologic rhythms can influence drug action and lead to adverse drug reactions. and fetal age determine the potential for adverse reactions in the fetus. the pregnant patient is not necessarily at higher risk for adverse drug reactions. Changes associated with disease Pathophysiologic changes associated with various diseases may cause adverse drug reactions. Especially at risk is the patient with a history of eczema. and endocrine agents. additives. a pregnant patient may have a decreased blood concentration level of a drug. . dosage. and other regulatory processes to drug effectiveness and adverse drug reactions. additives. adverse drug reactions can occur when a patient uses a drug after its expiration date or uses one that has been stored in an unfavourable environment. bioavailability may vary because of differences in manufacturing. including bioavailability. The patient also may feel community and cultural pressures when interpreting drug effects and reporting undesirable reactions. administration. and drug degradation Among different brands of the same drug. urinary excretion. hay fever. and duration of action among different products may lead to adverse drug reactions. PREDISPOSING DRUG FACTORS Several drug factors influence adverse reactions. metabolism. necessitating dosage adjustment. stabilizing agents. and excretion can alter drug actions and effects. anticoagulants.or lower-than-expected drug concentration levels in tissues and at receptor sites. resulting in higher. health care professionals are concerned with the potential adverse effects of drugs on the fetus. These patient characteristics can affect the incidence of self-diagnosed adverse reactions and the frequency and thoroughness of reporting patterns. its concentration level. An inherited predisposition to allergies increases the patient’s risk of an allergic response to a drug. digitalis. the manufacturers may reformulate the product. Bioavailability. Diseases of organs responsible for drug absorption. hormone secretion. especially its metabolism. Patient expectations of a drug’s reaction also can affect response. Although uncommon. When an additive produces widespread problems. angiodema. thereby leading to abnormal drug concentration levels. The physician and pharmacist must exercise caution when substituting different forms of such drugs as anticonvulsants. Attitudes can shape a patient’s patterns of drug taking and can lead to erratic and unsafe self-medication. or hives. and other additives can produce adverse drug reactions in certain patients. For example. such as an anticonvulsant. Abnormal thinness or obesity may alter drug distribution. metabolism. cirrhosis of the liver may alter a drug’s pharmacokinetic properties. Temperament and attitudes Psychological factors and personal values and beliefs can predispose a patient to adverse drug reactions. buffering preparations.or underdosing. and the number of drugs administered. Although many drugs cross the placenta. Genetic variations Genetic variations that alter enzyme activity or cause enzyme deficiency affect drug metabolism or drug action. Changes in drug distribution and excretion rates probably produce the decrease in blood concentration levels during a patient’s pregnancy. peak concentration levels. Differences in onset of action. and hypochondriacal behaviour may report adverse drug reactions more frequently than one without these psychological factors. Dyes. However. the type of drug. removing the offending or substituting a less toxic compound. Changes associated with pregnancy Although numerous physiologic changes occur during pregnancy. a patient who exhibits emotional. Research suggests that normal human biological rhythms can alter the absorption. For instance. asthma. excitable. Researchers are studying the contribution of sleep rhythms.
Drug dosage factors A patient receiving higher dosages for prolonged periods may have an increased probability for an adverse reaction. Administration via unrecommended routes may cause adverse drug reactions. For example. Pesticides. For example. Excessive therapeutic effect Such effects occur most commonly from miscalculations and overdose of a drug that requires precise. Environmental factors A patient’s environment may influence the relationship between physiologic function and drug effects and contribute to adverse reactions. carbamazepine absorption is increased. administering some intravenous drugs too rapidly can alter distribution and produce a toxic response. a diabetic patient being treated with insulin may experience hypoglycemia from even a slight miscalculation of the insulin dose. such as charcoal-broiled meats. and red wine can precipitate a hypertensive crisis when ingested while a patient is taking monoamine oxidase inhibitors. Dose-related adverse reactions Most adverse drug reactions result from the known pharmacologic effects of a drug and typically are dose-related. Therefore. The presence of food in the patient’s stomach can alter drug absorption. beer. Administration routes and techniques Parenteral drug treatment. PREDISPOSING EXOGENOUS FACTORS Dietary and environmental factors also influence a patient’s predisposition to adverse drug reactions. . For example. tyramine in some cheeses. Certain foods. Number of drugs administered The risk of adverse drug reactions increases in direct relationship to the number of drugs administered to the patient. Dietary factors also can influence the pharmacokinetics of a drug. which makes it more quickly available at receptor sites. Administering an excessive amount intramuscularly may cause tissue necrosis. can stimulate the activity of liver enzymes. especially administered intravenously. Foods can bind drugs and delay gastric emptying times. and those containing caffeine. Tetracycline absorption is decreased by food. and alcohol may alter the pharmacokinetics of certain drugs and increase the patient’s risk of adverse drug reactions. instilling an otic solution into the eye may cause pain and irritation because the otic solution is not formulated to the pH of the eye. improper administration can cause adverse drug reactions. increasing the drug metabolism rate.V. Toxicity (a condition caused by excess drug in the body) and hypersensitivity occur more commonly in these circumstances. they can be predicted in most cases. causes more frequent adverse reactions because a parenterally administered drug does not have to be absorbed through the gastrointestinal (GI) tract before distribution into the blood. Dietary factors Substances in foods may interfere with the activity of certain drugs. tobacco. individualized dosage calculation. Drugs are manufactured for administration via designated routes. Green leafy vegetables may interfere with oral coagulants because of their high vitamin K content. For example.) Even when the appropriate route is used. Complex interactions between drugs also may minimize some therapeutic effects and enhance others. (I. Suspensions intended for intramuscular or subcutaneous injections may be lethal if administered intravenously. CLASSIFICATION OF ADVERSE DRUG REACTIONS Adverse drug reactions can be classified as dose-related or patient sensitivity-related. vegetables from the Brassica family (cabbage and broccoli).
to a contact dermatitis secondary to topical application of neomycin cream. to induce sleep because the secondary action of an antihistamine is drowsiness from central nervous system depression. such as aspirin. which leads to alopecia (hair loss). Extreme patient sensitivity may be manifested as a drug allergy or as an idiosyncratic response. Previous exposure to the drug or to one with similar chemical characteristics sensitizes the patient’s immune system. but also additional and inseparable secondary pharmacologic actions that can be adverse. some drugs. A patient’s idiosyncratic response sometimes has a genetic cause. For example. corticosteroids. a patient’s immune system identifies a drug. Obtaining complete medical and drug histories from the patient helps reduce the risk of iatrogenic effects. commonly cause GI irritation and bleeding. Drug allergy Occasionally. The adverse reaction may vary in intensity from an immediate. For example. Toxic effects may cause only transient changes in affected organs or more serious. a patient may experience nervousness and excitability after ingesting phenobarbital. These adverse reactions arise from unique tissue response rather than from an extension or alteration of the expected pharmacologic action. known as iatrogenic effects. Idiosyncratic response Patient sensitivity-related adverse reactions that do not result from known pharmacologic properties of a drug or from patient allergy but are peculiar to the patient are called idiosyncratic responses. typically used for allergies. a drug metabolite. A physician may prescribe a drug for its secondary pharmacologic effects. life-threatening anaphylactic reaction to penicillin. and subsequent exposure mobilizes the system and cause an allergic reaction (hypersensitivity). Toxic effects may seriously damage tissues and organs and precipitate drug-induced diseases. but also produces broader systemic damage by initiating cellular release of vasoactive and inflammatory substances. Hypersusceptibility to pharmacologic actions A patient may be extremely susceptible to the primary or secondary pharmacologic actions of a drug. or when drug concentration levels exceed the threshold needed for therapeutic effect. chronic health problems. For example. a hypersusceptible patient can experience an excessive therapeutic response or augmented secondary effects. Sensitivity-related adverse reactions A less common type of adverse reaction is unrelated to dosage and results from a patient’s unusual and extreme sensitivity to a drug or its components. the physician may prescribe an antihistamine. as when chemotherapeutic agents accumulate in and damage hair follicle cells. Dose-related toxic effects may result from the local accumulation of a drug. or a drug contaminant as a dangerous foreign substance that must be neutralized or destroyed. A drug allergy can be categorized according to the underlying immunologic mechanism it provokes. may mimic pathologic disorders. Such conditions result from treatment with various drugs and can lead to serious. Systemic drug effects also can produce toxicity. Iatrogenic drug effects Some adverse drug effects induced by the prescribed drug. Overdose toxicity Most drugs produce toxicity if given in large enough doses.Secondary reactions A drug typically produces not only a major therapeutic effect. Al allergic reaction not only directly injures cells and tissues. irreversible changes. and indomethacin. For example. normally a tranquilizing agent. . Even when given a usual therapeutic dose. morphine for pain control may lead to two undesirable secondary effects: constipation and respiratory depression.
morbilliform or maculopapular eruptions. syncope. uremia. coma. hypocalcemia. loss of taste. heartburn. stinging. bloody urine. nephrosis. increased intraocular pressure. drooling. cataracts. angioneurotic edema. renal dysfunction. blurred vision. weight loss anuria. hiccups. speech disturbances. hyperuricemia. ectopic CV heartbeats. eye pain. muscle pain. edema. hypercholesterolemia. fatigue. sodium loss acute attacks of gout. malaise. sensitivity to cold. delusion. psychosis. dyspepsia. DERM eczema. anxiety. scotoma. nephrotoxicity. gastroenteritis. tingling of hands. normochromic anemia. hyperventilation. joint swelling and pain. dyspnea. contact dermatitis (with topical application). visual disturbances abdominal cramps. peripheral neuropathy. warmth at injection site METABOLIC electrolyte imbalance. weakness altered blood pressure. mild anemia. crystalluria. rhinorrhea. mania. nightmares. giddiness. transient deafness. hematoma. heaviness of extremities. dilated pupils. photosensitivity. mottling of the skin. pseudomembranous colitis. hemoptysis. fever. paranoia. ichthyosis. dyskinesia. painful urination. proteinuria. increased susceptibility to infection IMMUNE induration. stupor. unusual bleeding altered liver enzyme levels. hearing loss. flulike symptoms. glossitis. oliguria. renal failure. restlessness. polyphagia. increased salivation. hepatotoxicity. diplopia. dry eye. diaphoresis. tremor. tenderness. euphoria. angina. optic atrophy. eosinophilia. increase in varicosities.Prescriber information. orthostatic hypotension. LOCAL vein irritation. urine retention agranulocytosis. impaired sense of taste. ototoxicity. irritability. livedo reticularis. tinnitus. excessive sweating. alopecia. tissue sloughing. phlebitis at injection site. itching. thrombocytopenic purpura. tachycardia acne. sore skin. melasma. headache. sterile abscess. sudden decrease in amount of urine. thrush. reduced creatinine clearance. inflammation. lacrimation. chills. memory loss. tea-colored urine. light-headedness. folic acid deficiency. seizure. nausea. peripheral vasodilation. hirsutism. muscle twitching. amblyopia. purpuric lesions. ataxia. gum hemorrhage. dysphagia. excitement. somnolence. moniliasis. epistaxis. hyperactivity. drying and irritation of nose. pharyngitis. arrhythmia. insomnia. 1994 abnormal movements. asthenia. anemia. mental changes. cholestasis. urticaria abnormal vision. HEMA leukopenia. delirium. pain. mild leg cramps. retinal pigmentation. arthralgia. constipation. confusion. bradycardia. nocturia. lethargy. transient burning. hepatic necrosis. hoarseness. slurred speech. erratic blood pressure. epigastric pain. sweating. glaucoma. pyuria. petechiae. hangover effect. EENT decreased visual acuity. mydriasis. miosis. asthmatic episodes. chest pain. conjunctivitis. nervousness. rash. unusual bruising. gynecomastia. GU ketonuria. drowsiness. nasal congestion. thrombophlebitis. fluid imbalance. dysuria. hypotension. vomiting. wheezing CNS . paresthesia. azotemia. hematuria. pallor. retinopathy. normocytic anemia. metallic taste. loss of appetite. difficulty GI swallowing. bloating. nystagmus. tic.EXAMPLES OF ADVERSE DRUG REACTIONS Drug finder . photophobia. dryness. OTHER bacterial or fungal superinfection. erythema. hemolytic anemia. shortness of breath. severe HEPATIC liver damage immunosuppresion. taste disturbance. dry mouth. vertigo. swollen parotid gland. hostility. methemoglobinemia. neuralgia. neutropenia. unexplained sore throat. cycloplegia. pruritus. hemosiderosis. itchy nose. diarrhea. agitation. diuresis. bitter after-taste. stomatitis. facial flushing. dizziness. hallucinations. Springhouse Corporation. clamminess. enuresis. urinary incontinence. hypoglycemia.