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Drugs represent a significant environmental hazard.
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:
Drug
related lesions of the Gastrointestinal tract: click here
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.
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.
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