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202 ADVERSE DRUG REACTIONS

202 ADVERSE DRUG REACTIONS
Harrison’s Manual of Medicine

202

ADVERSE DRUG REACTIONS

Bibliography

Adverse drug reactions are among the most frequent problems encountered clinically and represent a common cause for hospitalization. They occur most frequent in pts receiving multiple drugs and are caused by

1.
Errors in self-administration of prescribed drugs (quite common in the elderly).

2.
Exaggeration of intended pharmacologic effect (e.g., hypotension in a pt given antihypertensive drugs).

3.
Concomitant administration of drugs with synergistic effects (e.g., aspirin and warfarin).

4.
Cytotoxic reactions (e.g., hepatic necrosis due to acetaminophen).

5.
Immunologic mechanisms (e.g., quinidine-induced thrombocytopenia, hydralazine-induced SLE).

6.
Genetically determined enzymatic defects (e.g., primaquine-induced hemolytic anemia in G6PD deficiency).

7.
Idiosyncratic reactions (e.g., chloramphenicol-induced aplastic anemia).
RECOGNITION   History is of prime importance. Consider (1) nonprescription drugs and topical agents as potential offenders; (2) previous reaction to identical drugs; (3) temporal association between drug administration and development of clinical manifestations; (4) subsidence of manifestations when the agent is discontinued or reduced in dose; (5) recurrence of manifestations with cautious readministration (for less hazardous reactions); (6) rare: (a) biochemical abnormalities, e.g., red cell G6PD deficiency as cause of drug-induced hemolytic anemia, (b) abnormal serum antibody in pts with agranulocytosis, thrombocytopenia, hemolytic anemia.
Table 202-1 lists a number of clinical manifestations of adverse effects of drugs. It is not designed to be complete or exhaustive.

Table 202-1

Clinical Manifestations of Adverse Reactions to Drugs

MULTISYSTEM MANIFESTATIONS

Anaphylaxis
Cephalosporins
Dextran
Insulin
Iodinated drugs or contrast media
Lidocaine
Penicillins
Procaine
Angioedema
ACE inhibitors
Drug-induced lupus erythematosus
Cephalosporins
Hydralazine
Iodides
Isoniazid
Methyldopa
Phenytoin
Procainamide
Quinidine
Sulfonamides
Thiouracil
Fever
Aminosalicylic acid
Amphotericin B
Antihistamines
Penicillins
Hyperpyrexia
Antipsychotics
Serum sickness
Aspirin
Penicillins
Propylthiouracil
Sulfonamides
ENDOCRINE MANIFESTATIONS

Addisonian-like syndrome
Busulfan
Ketoconazole
Galactorrhea (may also cause amenorrhea)
Methyldopa
Phenothiazines
Tricyclic antidepressants
Gynecomastia
Calcium channel antagonists
Digitalis
Estrogens
Griseofulvin
Isoniazid
Methyldopa
Phenytoin
Spironolactone
Testosterone
Sexual dysfunction
Beta blockers
Clonidine
Diuretics
Guanethidine
Lithium
Major tranquilizers
Methyldopa
Oral contraceptives
Sedatives
Thyroid function tests, disorders of
Acetazolamide
Amiodarone
Chlorpropamide
Clofibrate
Colestipol and nicotinic acid
Gold salts
Iodides
Lithium
Oral contraceptives
Phenothiazines
Phenylbutazone
Phenytoin
Sulfonamides
Tolbutamide
METABOLIC MANIFESTATIONS

Hyperbilirubinemia
Rifampin
Hypercalcemia
Antacids with absorbable alkali
Thiazides
Vitamin D
Hyperglycemia
Chlorthalidone
Diazoxide
Encainide
Ethacrynic acid
Furosemide
Glucocorticoids
Growth hormone
Oral contraceptives
Thiazides
Hypoglycemia
Insulin
Oral hypoglycemics
Quinine
Hyperkalemia
ACE inhibitors
Amiloride
Cytotoxics
Digitalis overdose
Heparin
Lithium
Potassium preparations including salt substitute
Potassium salts of drugs
Spironolactone
Succinylcholine
Triamterene
Hypokalemia
Alkali-induced alkalosis
Amphotericin B
Diuretics
Gentamicin
Insulin
Laxative abuse
Mineralocorticoids, some glucocorticoids
Osmotic diuretics
Sympathomimetics
Tetracycline
Theophylline
Vitamin B12
Hyperuricemia
Aspirin
Cytotoxics
Ethacrynic acid
Furosemide
Hyperalimentation
Thiazides
Hyponatremia

1.
Dilutional
Carbamazepine
Chlorpropamide
Cyclophosphamide
Diuretics
Vincristine

2.
Salt wasting
Diuretics
Enemas
Mannitol
Metabolic acidosis
Acetazolamide
Paraldehyde
Salicylates
Spironolactone
DERMATOLOGIC MANIFESTATIONS

Acne
Anabolic and androgenic steroids
Bromides
Glucocorticoids
Iodides
Isoniazid
Oral contraceptives
Alopecia
Cytotoxics
Ethionamide
Heparin
Oral contraceptives (withdrawal)
Eczema
Captopril
Cream and lotion perservatives
Lanolin
Topical antihistamines
Topical antimicrobials
Topical local anesthetics
Erythema multiforme or Steven Johnson syndrome
Barbiturates
Chlorpropamide
Codeine
Penicillins
Phenylbutazone
Phenytoin
Salicylates
Sulfonamides
Sulfones
Tetracyclines
Thiazides
Erythema nodosum
Oral contraceptives
Penicillins
Sulfonamides
Exfoliative dermatitis
Barbiturates
Gold salts
Penicillins
Phenylbutazone
Phenytoin
Quinidine
Sulfonamides
Fixed drug eruptions
Barbiturates
Captopril
Phenylbutazone
Quinine
Salicylates
Sulfonamides
Hyperpigmentation
Bleomycin
Busulfan
Chloroquine and other antimalarials
Corticotropin
Cyclophosphamide
Gold salts
Hypervitaminosis A
Oral contraceptives
Phenothiazines
Lichenoid eruptions
Aminosalicylic acid
Antimalarials
Chlorpropamide
Gold salts
Methyldopa
Phenothiazines
Photodermatitis
Captopril
Chlordiazepoxide
Furosemide
Griseofulvin
Nalidixic acid
Oral contraceptives
Phenothiazines
Sulfonamides
Sulfonylureas
Tetracyclines, particularly demeclocycline
Thiazides
Purpura (see also thrombocytopenia)
Allopurinol
Ampicillin
Aspirin
Glucocorticoids
Rashes (nonspecific)
Allopurinol
Ampicillin
Barbiturates
Indapamide
Methyldopa
Phenytoin
Skin necrosis
Warfarin
Toxic epidermal necrolysis (bullous)
Allopurinol
Barbiturates
Bromides
Iodides
Nalidixic acid
Penicillins
Phenylbutazone
Phenytoin
Sulfonamides
Urticaria
Aspirin
Barbiturates
Captopril
Enalapril
Penicillins
Sulfonamides
HEMATOLOGIC MANIFESTATIONS

Agranulocytosis (see also Pancytopenia)
Captopril
Carbimazole
Chloramphenicol
Cytotoxics
Gold salts
Indomethacin
Methimazole
Oxyphenbutazone
Phenothiazines
Phenylbutazone
Propylthiouracil
Sulfonamides
Tolbutamide
Tricyclic antidepressants
Clotting abnormalities/hypothrombinemia
Cefamandole
Cefoperazone
Moxalactam
Eosinophilia
Aminosalicylic acid
Chlorpropamide
Erythromycin estolate
Imipramine
L-Tryptophan
Methotrexate
Nitrofurantoin
Procarbazine
Sulfonamides
Hemolytic anemia
Aminosalicylic acid
Cephalosporins
Chlorpromazine
Dapsone
Insulin
Isoniazid
Levodopa
Mefenamic acid
Melphalan
Methyldopa
Penicillins
Phenacetin
Procainamide
Quinidine
Rifampin
Sulfonamides
Hemolytic anemias in G6PD deficiency
See Table 58-3
Leukocytosis
Glucocorticoids
Lithium
Lymphadenopathy
Phenytoin
Primidone
Megaloblastic anemia
Folate antagonists
Nitrous oxide
Oral contraceptives
Phenobarbital
Phenytoin
Primidone
Triamterene
Trimethroprim
Pancytopenia (aplastic anemia)
Carbamazepine
Chloramphenicol
Cytotoxics
Gold salts
Mephenytoin
Phenylbutazone
Phenytoin
Quinacrine
Sulfonamides
Trimethadione
Zidovudine (AZT)
Pure red cell aplasia
Azathioprine
Chlorpropamide
Isoniazid
Phenytoin
Thrombocytopenia (see also Pancytopenia)
Acetazolamine
Aspirin
Carbamazepine
Carbenicillin
Chlorpropamide
Chlorthalidone
Furosemide
Gold salts
Heparin
Indomethacin
Isoniazid
Methyldopa
Moxalactam
Phenylbutazone
Phenytoin and other hydantoins
Quinidine
Quinine
Thiazides
Ticarcillin
CARDIOVASCULAR MANIFESTATIONS

Angina exacerbation
Alpha blockers
Beta blocker withdrawal
Ergotamine
Excessive thyroxine
Hydralazine
Methysergide
Minoxidil
Nifedipine
Oxytocin
Vasopressin
Arrhythmias
Adriamycin
Antiarrhythmic drugs
Atropine
Anticholinesterases
Beta blockers
Digitalis
Emetine
Lithium
Phenothiazines
Sympathomimetics
Thyroid hormone
Tricyclic antidepressants
Verapamil
AV block
Clonidine
Methyldopa
Verapamil
Cardiomyopathy
Adriamycin
Daunorubicin
Emetine
Lithium
Phenothiazines
Sulfonamides
Sympathomimetics
Fluid retention or congestive heart failure
Beta blockers
Calcium antagonists
Estrogens
Indomethacin
Mannitol
Minoxidil
Phenylbutazone
Steroids
Hypotension
Calcium antagonists
Citrated blood
Diuretics
Levodopa
Morphine
Nitroglycerin
Phenothiazines
Protamine
Quinidine
Hypertension
Clonidine withdrawal
Corticotropin
Cyclosporine
Glucocorticoids
Monoamine oxidase inhibitors with sympathomimetics
NSAIDs
Oral contraceptives
Sympathomimetics
Tricyclic antidepressants with sympathomimetics
Pericarditis
Emetine
Hydralazine
Methysergide
Procainamide
Thromboembolism
Oral contraceptives
RESPIRATORY MANIFESTATIONS

Airway obstruction
Beta blockers
Cephalosporins
Cholinergic drugs
NSAIDs
Penicillins
Pentazocine
Streptomycin
Tartrazine (drugs with yellow dye)
Cough
ACE inhibitors
Pulmonary edema
Contrast media
Heroin
Methadone
Propoxyphene
Pulmonary infiltrates
Acyclovir
Amiodarone
Azathioprine
Bleomycin
Busulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Melphalan
Methotrexate
Methysergide
Mitomycin C
Nitrofurantoin
Procarbazine
Sulfonamides
GASTROINTESTINAL MANIFESTATIONS

Cholestatic jaundice
Anabolic steroids
Androgens
Chlorpropamide
Erythromycin estolate
Gold salts
Methimazole
Nitrofurantoin
Oral contraceptives
Phenothiazines
Constipation or ileus
Aluminum hydroxide
Barium sulfate
Calcium carbonate
Ferrous sulfate
Ion exchange resins
Opiates
Phenothiazines
Tricyclic antidepressants
Verapamil
Diarrhea or colitis
Antibiotics (broad-spectrum)
Colchicine
Digitalis
Magnesium in antacids
Methyldopa
Diffuse hepatocellular damage
Acetaminophen (paracetamol)
Allopurinol
Aminosalicylic acid
Dapsone
Erythromycin estolate
Ethionamide
Glyburide
Halothane
Isoniazid
Ketoconazole
Methimazole
Methotrexate
Methoxyflurane
Methyldopa
Monoamine oxidase inhibitors
Niacin
Nifedipine
Nitrofurantoin
Phenytoin
Propoxyphene
Propylthiouracil
Pyridium
Rifampin
Salicylates
Sodium valproate
Sulfonamides
Tetracyclines
Verapamil
Zidovudine (AZT)
Intestinal ulceration
Solid KCl preparations
Malabsorption
Aminosalicylic acid
Antibiotics (broad-spectrum)
Cholestyramine
Colchicine
Colestipol
Cytotoxics
Neomycin
Phenobarbital
Phenytoin
Nausea or vomiting
Digitalis
Estrogens
Ferrous sulfate
Levodopa
Opiates
Potassium chloride
Tetracyclines
Theophylline
Oral conditions

1.
Gingival hyperplasia
Calcium antagonists
Cyclosporine
Phenytoin

2.
Salivary gland swelling
Bretylium
Clonidine
Guanethidine
Iodides
Phenylbutazone

3.
Taste disturbances
Biguanides
Captopril
Griseofulvin
Lithium
Metronidazole
Penicillamine
Rifampin

4.
Ulceration
Aspirin
Cytotoxics
Gentian violet
Isoproterenol (sublingual)
Pancreatin
Pancreatitis
Azathioprine
Ethacrynic acid
Furosemide
Glucocorticoids
Opiates
Oral contraceptives
Sulfonamides
Thiazides
Peptic ulceration or hemorrhage
Aspirin
Ethacrynic acid
Glucocoricoids
NSAIDs
RENAL/URINARY MANIFESTATIONS

Bladder dysfunction
Anticholinergics
Disopyramide
Monoamine oxidase inhibitors
Tricyclic antidepressants
Calculi
Acetazolamide
Vitamin D
Concentrating defect with polyuria (or nephrogenic diabetes insipidus)
Demeclocycline
Lithium
Methoxyflurane
Vitamin D
Hemorrhagic cystitis
Cyclophosphamide
Interstitial nephritis
Allopurinol
Furosemide
Penicillins, esp. methicillin
Phenindione
Sulfonamides
Thiazides
Nephropathies
Due to analgesics (e.g., phenacetin)
Nephrotic syndrome
Captopril
Gold salts
Penicillamine
Phenindione
Probenecid
Obstructive uropathy
Extrarenal: methysergide
Intrarenal: cytotoxics
Renal dysfunction
Cyclosporine
NSAIDS
Triamterene
Renal tubular acidosis
Acetazolamide
Amphotericin B
Degraded tetracycline
Tubular necrosis
Aminoglycosides
Amphotericin B
Colistin
Cyclosporine
Methoxyflurane
Polymyxins
Radioiodinated contrast medium
Sulfonamides
Tetracyclines
NEUROLOGIC MANIFESTATIONS

Exacerbation of myasthenia
Aminoglycosides
Polymyxins
Extrapyramidal effects
Butyrophenones, e.g., haloperidol
Levodopa
Methyldopa
Metoclopramide
Oral contraceptives
Phenothiazines
Tricyclic antidepressants
Headache
Ergotamine (withdrawal)
Glyceryl trinitrate
Hydralazine
Indomethacin
Peripheral neuropathy
Amiodarone
Chloramphenicol
Chloroquine
Chlorpropamide
Clofibrate
Demeclocycline
Disopyramide
Ethambutol
Ethionamide
Glutethimide
Hydralazine
Isoniazid
Methysergide
Metronidazole
Nalidixic acid
Nitrofurantoin
Phenytoin
Polymyxin, colistin
Procarbazine
Streptomycin
Tolbutamide
Tricyclic antidepressants
Vincristine
Pseudotumor cerebri (or intracranial hypertension)
Amiodarone
Glucocorticoids, mineralocorticoids
Hypervitaminosis A
Oral contraceptives
Tetracyclines
Seizures
Amphetamines
Analeptics
Isoniazid
Lidocaine
Lithium
Nalidixic acid
Penicillins
Phenothiazines
Physostigmine
Theophylline
Tricyclic antidepressants
Vincristine
Stroke
Oral contraceptives
OCULAR MANIFESTATIONS

Cataracts
Busulfan
Chlorambucil
Glucocorticoids
Phenothiazines
Color vision alteration
Barbiturates
Digitalis
Methaqualone
Streptomycin
Thiazides
Corneal edema
Oral contraceptives
Corneal opacities
Chloroquine
Indomethacin
Vitamin D
Glaucoma
Mydriatics
Sympathomimetics
Optic neuritis
Aminosalicylic acid
Chloramphenicol
Ethambutol
Isoniazid
Penicillamine
Phenothiazines
Phenylbutazone
Quinine
Streptomycin
Retinopathy
Chloroquine
Phenothiazines
EAR MANIFESTATIONS

Deafness
Aminoglycosides
Aspirin
Bleomycin
Chloroquine
Erythromycin
Ethacrynic acid
Furosemide
Nortriptyline
Quinine
Vestibular disorders
Aminoglycosides
Quinine
MUSCULOSKELETAL MANIFESTATIONS

Bone disorders

1.
Osteoporosis
Glucocorticoids
Heparin

2.
Osteomalacia
Aluminum hydroxide
Anticonvulsants
Glutethimide
Myopathy or myalgia
Amphotericin B
Chloroquine
Clofibrate
Glucocorticoids
Oral contraceptives
Myositis
Gemfibrozil
Lovastatin
PSYCHIATRIC MANIFESTATIONS

Delirious or confusional states
Amantadine
Aminophylline
Anticholinergics
Antidepressants
Cimetidine
Digitalis
Glucocorticoids
Isoniazid
Levodopa
Methyldopa
Penicillins
Phenothiazines
Sedatives and hypnotics
Depression
Amphetamine withdrawal
Beta blockers
Centrally acting antihypertensives (reserpine, methyldopa, clonidine)
Glucocorticoids
Levodopa
Drowsiness
Antihistamines
Anxiolytic drugs
Clonidine
Major tranquilizers
Methyldopa
Tricyclic antidepressants
Hallucinatory states
Amantadine
Beta blockers
Levodopa
Meperidine
Narcotics
Pentazocine
Tricyclic antidepressants
Hypomania, mania, or excited reactions
Glucocorticoids
Levodopa
Monoamine oxidase inhibitors
Sympathomimetics
Tricyclic antidepressants
Schizophrenic-like or paranoid reactions
Amphetamines
Bromides
Glucocorticoids
Levodopa
Lysergic acid
Monoamine oxidase inhibitors
Tricyclic antidepressants
Sleep disturbances
Anorexiants
Levodopa
Monoamine oxidase inhibitors
Sympathomimetics

SOURCE: Adapted from AJJ Wood: HPIM-15, pp. 432–436.

Bibliography

For a more detailed discussion, see Wood AJJ: Adverse Reactions to Drugs, Chap. 71, p. 430, in HPIM-15.

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