Adverse reactions of drugs are surprisingly common, being found in 2% to 5% of patients hospitalized on medical services; of these reactions, 2% to 12% are fatal.

Untoward effects of drugs result from overdose, an exaggerated physiologic response, a genetic predisposition, hypersensitivity mechanisms, interactions with other drugs, and other, unknown factors.

An overdose implies an excessive pharmacologic effect of the drug.

The intake of excessive amount of a drug can be a deliberate suicide attempt or can be accidental, as often happens in children or in those who are addicted to illicit drugs

The lethal physiological effect may be different from the desired effect at lower doses - for example, depression of the respiratory centers in barbiturate poisioning.

A minor physiological effect may be dangerous in a susceptible person, as with lethal cardiac arrhythmias in some cocaine users.

A dose considered safe for the general population may be excessive in someone who has a genetically slow metabolizing apparatus.

Others may show an exaggerated reactivity (Eg. neurologic or cardiovascular) to the pharmacologic action of specific drugs.

It is often not appreciated that drug reactions can produce a bewildering variety of disorders in virtually all organs.

Gastrointestinal Tract:

Gastritis is a common reaction, particularly with aspirin and other nonsteroidal anti-inflammatory agents.

This damage may progress to hemorrhagic gastritis severe enough to cause anemia and even exsanguinations.

Peptic ulceration is also seen with these agents, as well as with corticosteroids.

Jejunal ulceration may be particularly troublesome with enteric coated potassium supplements.

Pancreatitis, another complication of treatment with corticosteroids, also occurs with thiazide diuretics.

Certain broad-spectrum antibiotics lead to the overgrowth of intestinal bacteria and a severe pseudomembranous enterocolitis.

Gingival hyperplasia is a characteristic side effect of chronic treatment with the anticonvulsant diphenylhydantoin.

Liver:

The single most common cause of jaundice is probably drug toxicity.

In most causes this jaundice is cholestatic - that is, the type resembling biliary obstruction.

Representative drugs producing this condition are the phenothiazines, other tranquilizers, anabolic steroids, and oral contraceptives.

Jaundice also accompanies the hepatitis produced by such drugs as halothane, isoniazid, and propylthiouracil.

Chronic hepatitis, fibrosis, and cirrhosis may all result from drug reactions.

Nervous System:

Cerebrovascular accidents complicate the use of anticoagulants and oral contraceptives.

Convulsive seizures are occasionally produced by phenothiazines and certain other psychotropic agents.

Extrapyramidal dysfunction , notably tardive dyskinesia, is a feared complication of chronic treatment with phenothiazines and other tranquilizing agents, particularly since it is often not reversible upon discontinuation of the medication.

Peripheral neuropathy is one of the more common adverse reactions to drugs, as with the chemotherapeutic agent vincristine and antimalarial chloroquine.

A particularly distressing form of this complication is the eighth nerve deafness caused by the streptomycin.

Skin: Drug related cutaneous lesions: click here

The cutaneous manifestations of the drug reactions run the entire gamut of dermatologic disease, from acne to a fatal exfoliative dermatitis.

Long-term corticosteroid treatment, leading to the development of Cushing’s syndrome, is classically associated with acene.

Among the most common drug reactions is urticaria ("hives"), a hypersensitivity response to agents such as penicillin, sulfonamides, and barbiturates.

Fixed drug eruptions can be troublesome.

Alopecia may be produced by chemotherapeutic agents.

Erythema nodosum, caused by such drugs as penicillin and sulfonamides, is unpleasant but reverses upon discontinuation of the offending drugs.

By contrast, a number of drugs, including penicillin, sulfonamides, hydantoins, and phenylbutazone, cause serious and occasionally life-threatening exfoliative dermatitis, toxic epidermal necrolysis, and the Stevens-Johnson syndrome.

Heart:

The most common cardiac complications of drug therapy relate to the pharmacologic actions of the particular agents.

Arrhythmias are associated with the administration of drugs as diverse as digitalis, propranolol, procainamide, and thyroxin.

Congestive heart failure may be precipitated by drugs that increase blood volume (e.g. corticosteroids) or by intravenous fluid overload.

A toxic dose-related cardiomyopathy results from chemotherapy with doxorubicin (Adriamycin).

Metabolic Effect:

Certain drugs, when used injudiciously, cause electrolyte imbalances, particularly hyponatremia, hypokalemia, and metabolic acidosis.

Overdosage with vitamin D or treatment with thiazide diuretics can cause hypercalcemia.

Acute episodes of hepatic porphyria are precipitated by barbiturates, hydantoins, and sulfonamides.

Although alcohol is not considered a therapeutic agent, it is a potent stimulator of delta-aminolevulinic acid synthetase, and therefore also precipitates acute hepatic porphyria.

Hyperuricemia and associated urate nephropathy complicate the treatment of cancer with therapeutic agents.

Blood:

Aplastic anemia is associated with a variety of drugs on rare occasions.

It is an essential complication of chloramphenicol treatment.

Depression of specific bone marrow precursors by antineoplastic agents, sulfonamides, and barbiturates causes agranulocytosis and thrombocytopenia.

Immune hemolytic anemia complicates treatment with penicillin, quinidine, and the cephalosporins.

In persons with a genetic deficiency of glucose-6-phosphate dehydrogenase, nitrofurans and sulfonamides cause a nonimmune hemolytic anemia.

Folic acid antagonists, such as methotrexate and diphenylhydantoin, can induce a megaloblastic anemia.

Lungs:

An important complication of treating cancer with certain chemotherapeutic agents, such as bleomycin, busulfan, cyclophosphamide, and methotrexate, is an acute toxic alveolitis, which can progress to interstitial pulmonary fibrosis.

Similar reactions can follow the administration of other types of drugs, such as the antiarrhythmic agent amiodarone and the antibiotic nitrofurantoin.

Asthma is precipitated by nonsteroidal anti-inflammatory medications (aspirin, indomethacin) and the beta-adrenergic blocker propranolol.

Pulmonary infections are complication of treatment with corticosteroids and other immunosuppressive drugs.

Kidney:

Renal damage is a limiting factor in the use of a number of antibiotics, including such antibacterial drugs as gentamicin and kanamycin and the antifungal agent amphotericin B.

These drugs produce acute tubular necrosis and, therefore, acute renal failure.

A nephrotic syndrome results from the administration of some drugs (gold salts for rheumatoid arthritis, tolbutamide for diabetes, penicillamine for Wilson’s disease, trimethadione for seizures).

Analgesic abuse is associated with chronic interstitial nephritis and papillary necrosis.

Female Reproductive Tract:

- Iatrogenic Drug Injury- Oral contraceptives: click here

- Other Drugs:

The use of diethylstilbesterol by pregnant women is of historical interest. Although the women themselves suffered no appreciable untoward effects, years later their daughters develop vaginal adenosis and adenocarcinoma.

Drugs given to pregnant women may be potent teratogens. (Eg. Congenital anomalies following maternal ingestion of thalidomide).

Musculoskeletal Effects:

Myopathies and muscle weakness are well recognized as side effects of treatment with corticosteroids, chloroquine, and a number of other unrelated drugs.

A serious complication of corticosteroid administration is osteoporosis.

Long-term use of these steroids in children retards bone growth.

Immunologic Syndromes:

Several deaths occur every year because of severe anaphylactic reactions to penicillin.

Individuals who become sensitized to a variety of other drugs can also exhibit anaphylactic reactions.

Penicillin is the single most common cause of serum sickness, although other antibiotics and drugs, such as propylthiouracil and barbiturates, can also cause this syndrome. The same drugs, presumably acting by similar mechanisms, produce vasculitis.

A lupus-like syndrome, characterized by antinuclear antibodies, fever, muscle and joint pain, and in some cases rash and lymphadenopathy, results from the chronic administration of a number of drugs, including hydralazine, procainamide, penicillin, and hydantoins. Symptoms are generally reversible upon discontinuation of the medication.