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»	Drug Reactions and Interactions
	»	Cytochrome P450 Enzymes
	»	Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
	»	Acute Generalized Exanthematous Pustulosis (AGEP)
	»	Neutrophilic Eccrine Hidradenitis (NEH)
	»	Anticoagulant-Induced Skin Necrosis
	»	Erythema Multiforme
	»	Stevens–Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)
»	References

Drug Reactions and Interactions

Cytochrome P450 Enzymes (Table 7-11)

Major drug-metabolizing enzymes that are most predominant in the liver but can also be found in other organs (i.e., intestine, lung)
Drug interaction involving p450 enzymes typically occur from one of two processes: enzyme inhibition or enzyme induction
Enzyme inhibition: competition with another drug for the enzyme-binding site
Enzyme induction: drug stimulates synthesis of more enzyme protein, enhancing metabolizing capacity of the enzyme
Different isoforms: CYP2D6, CYP3A4 (most abundant cytochrome enzymes in humans and involved in many clinically important drug interactions), CYP1A2, CYP2C9, CYP2E1, CYP2C19
Many drugs are substrates (metabolized by specific p450 isoenzyme) but unable to inhibit or induce the p450 enzymes

Table 7-11 Cytochrome p450 Drugs
	Cytochrome p450 Substrates		3A4 Inducers	3A4 Inhibitors
	Anti-arrhythmics Digoxin Quinidine Amiodarone Antibiotics Erythromycin Clarithromycin Rifampin Anticonvulsants Phenytoin Carbamazepine Ethosuximide Antidepressants Amitryptaline Doxepin Sertraline Imipramine Antihistamines Fexofenadine Terfenadine Astemizole	Calcium Channel Blocker (CCB) Nifedipine Diltiazem Verapamil Felodipine Immunosuppressants Tacrolimus Cyclosporine Dapsone Cyclophosphamide Protease Inhibitors Indinavir Ritonavir Saquinavir Statins Atorvastatin Lovastatin Simvastatin Miscellaneous Glyburide Pimozide Theophylline Warfarin	Anticonvulsants Phenytoin Phenobarbital Carbamazepine Anti-TB drugs Isoniazid Rifampin HIV antivirals Ritonavir Miscellaneous Propranolol St. John’s Wort Omeprazole Griseofulvin	Antidepressants Fluoxetine Paroxetine Sertraline Azole Antifungals Ketoconazole Itraconazole Fluconazole Antibiotics Erythromycin Clarithromycin Ciprofloxacin Metronidazole CCBs Verapamil Nifedipine Diltiazem Miscellaneous Cimetidine Cyclosporine Quinine Grapefruit Juice Warfarin Protease Inhibitors Ritonavir
	Warfarin + phenobarbital/rifampin/phenytoin → decreased levels of warfarin
	Warfarin + cimetidine/erythromycin/itraconazole/ketoconazole → increased levels of warfarin
	Cyclosporine + itraconazole → increased levels of cyclosporine

Table 7-12 Drug Reactions
	Reaction	Culprit drugs
	Acneiform lesions	Corticosteroids, androgenic steroids, phenytoin, INH, lithium, halogens, (bromides, iodides), epidermal growth factor receptor inhibitors (EGFRI) such as erlotinib, cetuximab, gefitinib
	Acral erythema (erythrodysesthesia)	Doxorubicin, daunorubicin, 5-fluorouracil, cytarabine, docetaxel, methotrexate (MTX)
	Acral sclerosis	Bleomycin
	AGEP (acute generalized exanthematous pustulosis)	β-lactam antibiotics, macrolides, calcium channel blockers (i.e., diltiazem), chloroquine, terbinafine
	Alopecia	Alkylating agents (i.e., cyclophosphamide), anthracyclines (doxorubicin, daunarubicin), taxanes (paclitaxel, docetaxel), vincristine, vinblastine, actinomycin-D, etoposide
	Autoimmune hepatitis	Minocycline (MCN)
	Bullous pemphigoid	Furosemide, PCN, captopril, β-blockers, sulfonamides, terbinafine, penicillamine
	Dermatomyositis-like eruption	Hydroxyurea, penicillamine, statins
	Eccrine squamous syringometaplasia	Cytarabine, cyclosphosphamide, paclitaxel, docetaxel, busulfan, carmustine
	Elastosis perforans serpiginosa (EPS)	D-penicillamine
	Erythema nodosum	OCPs, antibiotics (sulfonamides, tetracyclines), NSAIDs
	Extravasation reaction (ulcer, chemical cellulitis)	Anthracyclines (doxorubicin/daunorubicin), actinomycin-D, docetaxel, paclitaxel, vinblastine, vincristine, etoposide, 5-fluorouracil (5-FU)
	Fixed drug eruption (FDE)	NSAIDS (naproxen), sulfonamides, TCNs, acetaminophen, aspirin, OCP, phenolphthalein, pseudoephedrine (non-pigmenting variant), barbiturates
	Flag sign (of chemo)	MTX (horizontal hyperpigmented bands of hair alternating w/ normal color)
	Gingival hyperplasia	Phenytoin, cyclosporine, CCBs (i.e., nifedipine, amlodipine)
	Hyperpigmentation	Antimalarials, clofazamine (violet-brown to blue in lesional skin), imipramine, amiodarone (blue-gray), phenothiazines (chlorpromazine, promethazine, prochlorperazine), chemotherapeutics (busulfan, cyclophosphamide, hydroxyurea, dactinomycin, MTX, 5-FU), and minocycline (see below):
		Type 1: blue-black color within scars, + iron (hemosiderin) with Perls stain {MCN pigmentation}
		Type 2: blue-gray color on shins, + melanin (Fontana-Masson stain), + iron (Perls stain) {MCN pigmentation}
		Type 3: generalized “muddy brown” hyperpigmentation in sun-exposed sites (↑ melanin within epidermis, no iron deposition)
	Hypersensitivity syndrome	Aromatic anticonvulsants (phenytoin, phenobarbital, carbamazepine, lamotrigine, oxcarbazepine), sulfonamides, allopurinol, dapsone, gold, olanzapine, saquinavir
	Hypertrichosis	Cyclosporine, phenytoin, minoxidil, danazol, anabolic steroids
	Inflamed AKs	5-fluorouracil, capecitabine, pentostatin
	Inflamed SCC	Fludarabine
	Inflamed SKs	Cytarabine, docetaxel
	Leg ulcers	Hydroxyurea
	Leukocytoclastic vasculitis	Antibiotics (especially β-lactam antibiotics), NSAIDs, diuretics
	Lichenoid eruption	Penicillamine, gold, hydrochlorothiazide (HCTZ), furosemide, β-blockers (propanolol, labetalol), ACEI (captopril, enalapril), chlorpromazine, antimalarials (chloroquine, hydroxychloroquine, quinacrine), quinidine
	Linear IgA bullous dermatosis (LABD)	Vancomycin, β-lactam antibiotics, NSAIDs, captopril, phenytoin, sulfonamides, furosemide, amiodarone, lithium
	Localized hyperpigmentation	Flagellate hyperpigmentation: bleomycin
		Supravenous serpentine hyperpigmentation: 5-FU
		Sun-exposed hyperpigmentation: daunorubicin, 5-FU, MTX
		Mucosal: busulfan, cyclophosphamide, 5-FU, hydroxyurea, doxorubicin
		Occluded areas: thiotepa, ifosfamide, topical carmustine, docetaxel, cisplatin
	Lupus	SCLE: HCTZ, griseofulvin, terbinafine, CCBs
	Lupus	SLE: hydralazine, procainamide, isoniazid, MCN, phenytoin, penicillamine
	Melanonychia	Chemotherapeutics (melphalan, hydroxyurea, bleomycin, capecitabine, doxorubicin), lamuvidine, MCN, zidovudine (AZT)
	Mucositis	Cyclophosphamide, daunorubicin, doxorubicin, MTX (high dose), 5-FU
	Neutrophilic eccrine hidradenitis	Doxorubicin, daunorubicin, cytarabine, 5-FU, MTX, bleomycin, cyclosphosphamide, busulfan, taxanes
	Onycholysis	Paclitaxel, docetaxel, etoposide, retinoids, doxorubicin, captopril
	Onycholysis	Photo-onycholysis: TCN, OCPs, fluoroquinolones, psoralens
	Orange-red body fluid	Rifampin
	Pemphigus vulgaris	Thiol drugs (penicillamine, captopril, lisinopril, piroxicam, gold sodium thiomalate), penicillins, cephalosporines, quinolones, rifampicin, phenylbutazone, propranolol, carbamazepine
	Penile ulcers	Foscarnet
	Photosensitivity (includes allergic and toxic reactions)	Griseofulvin, NSAIDs, phenothiazines, sulfonamides, thiazides, dapsone, MTX, hydroxyurea, 5-FU, fluoroquinolones, TCNs, furosemide, diltiazem, isotretinoin, imipramine, chlorpromazine, phenothiazines
	Pseudoporphyria	NSAIDs (naproxen, piroxicam), nalidixic acid, furosemide, HCTZ, isotretinoin, TCNs, sulfonamides
	Pseudotumor cerebri	TCN, isotretinoin
	Pseudoxanthoma elasticum (PXE)	Penicillamine
	Psoriasis (induce/worsen)	Terbinafine, NSAIDs, antimalarials, ACEI, lithium, β-blockers
	Pulmonary fibrosis	MTX, bleomycin, busulfan, amiodarone, gold, penicillamine
	Radiation recall	Doxorubicin, daunorubicin, paclitaxel, docetaxel, MTX, actinomycin-D, capecitabine, gemcitabine, bleomycin
	Raynaud’s phenomenon	Combination of bleomycin and vinblastine
	Sweet’s syndrome	Granulocyte colony-stimulating factor (GCSF), carbamazepine, trimethoprim-sulfamethoxazole (TMP-SMZ)
	Toxic epidermal necrolysis (TEN)	Allopurinol, PCNs, anticonvulsants (carbamazepine, lamotrigine, phenytoin), sulfonamides, antiretrovirals, barbiturates, NSAIDs