Rhett J. Drugge, MD

References: The Cutaneous Drug Reactions Database , by Jerome Litt is a generous online resource maintained at Dartmouth by Daniel Collison, M.D.
At the time when excessive publicity is given to side effects, with the implication that the physician neither know nor cares about them, it behooves every practitioner to be extremely familiar with the toxic and allergic effects of drugs of all kinds. These may be cumulative, as in the case of argyria, where continued use of silver compounds leads to a slate gray skin color, or the yellow color of the Atabrine taker, the retinopathy in patient who continue taking chloroquin, and the mercurial pigmentation of the nails in ammoniated mercury ointment users. Hypervitaminosis A, leading to pseudo-tumor cerebri, thinning hair or localized periosteal swelling in small children, is also an example.

Overdosage effects, such as too much anticoagulant producing bleeding into the skin, or a mixture of too much aspirin with Coumadin, leading to a dose-related purpura (usually more than six aspirins per day leads to the rash), are seen. Hair loss as a result of heparin or Coumadin is also seen.

Trigger effects (biotropism) of certain drugs or foods activating a latent herpes simplex infection are seen.

Ecological effects are seen in the destruction of friendly intestinal organisms leading to monilial overgrowth after antibiotic therapy.

Pharmacological effects include a reaction against Triparenal, which produced ichthyotic skin changes with alopecia while reducing serum cholesterol and had to be withdrawn.

The Jarisch-Herxheimer reaction is the sudden destruction of spirochetes by penicillin in early syphilis, which releases allergenic products to which the tissue reacts with fever and rash within 24 hours.

The Schwartzman reaction leads to a hemorrhagic type of reaction to a drug to which the patient has, in an interim, developed antibodies, usually purpura from a barbiturate sleeping pill taken intermittently.

In hepatotoxic effects, phnothiazine derivatives (e.g., thorazine) can produce jaundice imitating biliary obstruction, as can methyltesterone, triacetyloleandomycin and erythromycin estolate, and can produce alteration in the serum oxaloacetic transaminase (SGOT), indicating allergic reaction in the liver in a small percentage of the healthy population. Other drugs can do this also, for example, cararsone, norethandrolone, para-amino-salicylic acid, chrolothiazide, novobiocin, dinitrophenol and isoniazid.

Bone marrow depression notably occurs from chloromycetin, though sulfapyridine, methotrexate, sulfones, antihistamines, butazolidin, gold arsphenamines, griseofulvin, novobiocin, orinase, and tridione also produce it.

Eighth nerve damage can result from streptomycin, kanamycin and colimycin.

Hemolysis can be expected to result from long continued sulfone treatment of dermatitis herpetiformis, although it responds to iron orally. Primaquine, pamaquine, sulfonamides, acetophenetidin, acetanilid, para-amino-salycylic acid, probenecid, aspirin and nitrofurantoin are prone to produce this in some individuals with an inherited susceptibility.

Special Reactions

Fixed Drug Eruption. -- This is usually a persistent purplish erythema that lasts a long time and recurs at the same spot on taking the drug again. Many drugs can cause this, perhaps the most common being phenophthalein and amidopyrine.

Toxic Epidermal Necrosis. -- The sudden onset of widespread severe involvement of the whole skin in an eruption is at first bullous, and later desquamating in sheets and also fatal. Butazolidin, sulfonamides, hydantoin and amtipyrine have reportedly been involved. There may be a greater drug or viral role triggering the event.

Tumor-like Reactions. -- Bromides and iodides produce large granulomatous nodules often of frightening appearance. Arsenic can lead to warty growths on the palms and soles, around the sweat ducts, and even to carcinomas.

Polyneuropathy. -- Large amounts of mercury, usually from the overuse of ointments can produce enzyme changes causing neuropathy, e.g., the salivations of old syphilitics years ago, "mad as a hatter" mercury poisoning seen in hatters, and acrodynia in children. British anti-Lewisite (BAL) helps this.

Pseudotumor Cerebri. -- This is found classically in vitamin A overdoses, but usually headache and diplopia are the earliest signs. Sudden changes in the type of steroid maintenance therapy occasionally result in hypertensive encephalopathy.

Pseudolymphoma. -- Dilantin can cause enlargement of the spleen, liver and lymph nodes, as well as hypertrophy of the gums; hydralazine leads to lupus erythematosus cells in blood and enlarged lymph nodes, liver and spleen.

Para-aminosalicylic acid (PAS) Isoniazid. -- This causes a mononucleosis-like syndrome.

Sulfonamides. -- These drugs can cause Stevens-Johnson syndrome.

Teeth Changes. -- Changes resulting from tetracyclines taken by pregnant women or infants lead to hypoplasia of tooth enamel and staining with yellow fluorescence and a mottled appearance. The permanent teeth can be affected in children, with fibrocystic disease of the pancreas.

Methotrexate. -- Methotrexate can lead to abortion in pregnant women.

Declomycin. -- Any of the tetracyclines can produce photo-onycholysis, and old tetracycline can produce Fanconi's syndrome (failure of the tubules to resorb, with frequent thirst and urination).

Mucous Membrane Lesions. -- Dilantin can produce hypertrophy of the gums and bismuth produces the blue line along the gum margins (like the lead line). Various antibiotics and on occasion vitamin B complex can produce hairy black tongue, and stomatitis can occur from mercury, phenolphthalein and streptomycin. Cheilitis can come from fluoridated toothpastes, as can an ulcerative stomatitis. Diodoquin and codeine produces pruritus ani with regularity, and chloroquin can bleach hair. Lipoiodine can lead to recurrent painful folliculitis of the nostrils.

Drug Fever. -- Drug fever is caused by some drugs, particularly Potaba, sulfonamides, PAS, iodides and thiouracil.

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