Drugs and Drug Reactions Flashcards
Fixed Drug Eruption
Sulfonamides (#1 cause on genitals)
NSAIDs (esp. naproxen, targets lips)
Tetracyclines (Doxy=genitals)
Pseudoephedrine (cause of non-pigmented)
Stevens-Johnson
- Allopurinol
- Anticonvulsants
- Lamotrigine, carbamazepine, phenytoin, phenobarbital
- Risk highest in first 2 months
- Valproate does not cross-react with others
- Lamotrigine does not cross react w/ aromatics
- Antibiotics (sulfondamides > B-lactams, cephalosporins, minocycline, antifungal)
- NSAIDS
- NNRTIs (Nevirapine, abacavir, efavirenz) - neva efa abracadabra
- Others (contrast medium, dengue, etc.)
Linear IgA bullous dermatosis
VSADCLIP
Vanc (#1)
Sulfa/statin
Amio
Diclofenac
Captopril, gCSF
LI/lasix
IFN-g/IL-2
PCN, phenytoin, puva, piroxicam
Drug-induced pemphigus
ICRAP
Indocin
Captopril
Rifampin
Ampicillin
PCN, Penicillamine.
Bullous pemphigoid
Onycholysis
Taxanes (hemorrhagic and painful)
AGEP
Within days of starting drug
B-lactams
Macrolides
Terbinafine
CCBs
Hydroxychloroquine
Carbamazepine
NSAIDs
Diuretics
Hand-Foot Skin Reaction (HFSR)
Clinically similar to acral erythema variant of TEC but less severe acral dysesthesia and hand swelling; classic feature is prominent hyperkeratotic plaques on areas of friction; Rx: tazorac, 40% urea and efudex (treats hyperkeratosis)
Multi-kinase inhibitors (sorafenib, sunitinib, VEGF inhibitors), capecitabine (pre-cursor to 5-FU)
Exudative hyponychial dermatitis
Combination of docetaxel and capacitabine (for breast cancer)
Lower foot ulcer, dermatomyositis-like
Hydroxyurea
Serpentine supravenous hyperpigmentation
5-FU
Necrosis of psoriatic plaques
MTX
Sticky Skin Syndrome
Doxorubicin + ketoconazole
Sclerodermoid Reaction
Lower extremities most common - taxanes
Flagellate hyperpigmentation
Bleomycin
Shittake mushrooms
Alopecia
Drug-induced alopecia is non-scarring, diffuse, and reversible; two main types:
- Telogen effluvium: delayed (2–4 mos after starting med) diffuse non-scarring alopecia
- Anagen effluvium: rapid (within 2 wks of starting med) diffuse non-scarring alopecia; due to rapid cessation of cell division (mitoses) within hair matrix
Telogen effluvium: Heparin, β-blockers, IFN, lithium, retinoids, OCP
discontinuation, antidepressants, anticonvulsants, ACE inhibitors, colchicine, NSAIDs
Anagen effluvium: Chemotherapy, heavy metals (arsenic, gold, thallium, bismuth)
Gingival hypertrophy
Typically occurs in first year of drug; starts in interdental papillae of the front teeth, on labial side → may progress to involve rest of teeth with multinodular overgrowth of gums; spares edentulous areas; degree of hyperplasia strongly correlated with poor oral hygiene; histology: excess buildup of otherwise normal gum tissue; Rx: strict oral hygiene, drug d/c, surgical removal if all else fails
Phenytoin (most common, 50%) > nifedipine (25%) and cyclosporine (25%)
Less common: other
anticonvulsants, other CCBs,
lithium, amphetamines, OCPs
Corticosteroids
Apremilast (Otezla)
• Phosphodiesterase-4 (PDE-4) inhibitor (blocks IL-
• Used for psoriasis and psoriatic arthritis
• Most common SEs are diarrhea and nausea – resolve on
their own within 4 weeks usually
• Depression and weight loss have also been reported
• Dose halved in patients with severe renal impairment
• No laboratory monitoring required
Tralokinumab (Adbry) IL-13 blocker
Janus Kinase Inhibitors
Tofacitinib
• JAK 1 and 3 inhibitor
• FDA approved for moderate to severe rheumatoid
arthritis (RA) patients who have failed MTX
• Topical and oral have been tested in psoriasis; reports of
oral used in alopecia areata
• Most common SEs: URI, mild headaches, and nausea
• May have ↓hemoglobin and mean neutrophil count, but
usually normalize on treatment
• May have ↑LDL, HDL, CK, TGs, and LFTs
• Tuberculosis reactivation not reported
Ruxolitinib
• JAK 1 and 2 inhibitor
• FDA approved for treatment of intermediate- or high-risk
myelofibrosis
• Topical version tested in psoriasis; reports of oral used in
alopecia areata
• Mainly local SEs
Azathioprine
Important pharmacology points
- TPMT activity is reduced in certain populations, and functional enzyme allele sequencing is available
- ↓activity of TPMT (measured by allele activity) or ↓xanthine oxidase (as a result of allopurinol or febuxostat) → ↑azathioprine levels → ↑risk of life-threatening myelosuppression
- ACE inhibitors, sulfasalazine, and concomitant use of folate antagonists also increases risk of myelosuppression
- Azathioprine may decrease anticoagulant effects of warfarin and reverse neuromuscular blockade
Indications
- FDA approved indications: organ transplantation and severe RA
- Off-label dermatologic uses include atopic dermatitis, chronic actinic dermatitis, Behçet’s disease, bullous pemphigoid, cicatricial pemphigoid, dermatomyositis, oral lichen planus, and pemphigus
Side effects
- Leukopenia, thrombocytopenia, and immunosuppression (correlates with low TPMT activity)
- Squamous cell carcinoma (SCC) and lymphoma (particularly non-Hodgkin’s B-cell lymphoma) with nNo clear evidence of increased risk for dermatologically dosed indications
- Infection (particularly human papilloma virus, herpes simplex, and scabies)
- Teratogenicity
- Hypersensitivity syndrome (usually between first and fourth week of therapy and more common in patients who are receiving concomitant cyclosporine or MTX)
- Gastrointestinal SEs – most common adverse effect of azathioprine – include nausea, vomiting, and diarrhea (often present between first and tenth day of therapy); also gastritis and pancreatitis
- Transaminase elevation and severe hepatocellular toxicity are rare
Cyclosporine
Mechanism of action
- Forms a complex with cyclophilin, which inhibits calcineurin – an intracellular enzyme – which in turn reduces the activity of NFAT-1 (transcribes various cytokines, such as IL-2)
- ↓IL-2 production leads to decreased numbers of CD4 and CD8 cells.
Important pharmacology points
- Cyclosporine should ideally be gradually tapered while an alternative therapy is instituted to prevent flaring
- Maximum dermatologic dose = 5 mg/kg daily and can be used continuously for up to 1 year according to the FDA (2 years for worldwide consensus data)
- Cyclosporine lipid nanoparticles formulation maximum dermatolyte dose = 4 mg/kg
- For obese patients, ideal body weight should be used to calculate starting dose
Indications
- FDA approved for psoriasis
- • Off-label uses include atopic dermatitis, chronic idiopathic urticaria, pyoderma gangrenosum, lichen planus, bullous dermatoses, autoimmune connective tissue diseases, neutrophilic dermatoses, and pityriasis rubra pilaris among others
SEs
- Contraindicated in patients with cutaneous lymphoma (risk of progression)
- Nephrotoxicity and hypertension are the two most notable SEs of cyclosporine, which are dose- and duration-dependent
- Irreversible kidney damage is avoided if patients receive dermatologic doses (2.5–5 mg/kg daily), have dose adjusted when creatinine increases by 30% from baseline, and use cyclosporine for no longer than 1 year
- Hypertension occurs in 27% of psoriasis patients who receive cyclosporine and is thought to be secondary to renal vasoconstriction
- When HTN develops, it can be controlled with medication and is not a contraindication to continuing therapy
- Prescription of choice = CCBs (e.g., nifedipine or isradipine), because they do not alter cyclosporine serum levels
- ↑risk of NMSC in psoriasis patients, particularly when treated >2 years
- Risk of other malignancies, such as lymphoma, is unclear
- Hyperlipidemia not uncommon – dietary changes and ↑ physical activity should be recommended
- Other SEs include: hypertrichosis, gingival hyperplasia, myalgia, paresthesia, tremors, malaise, hyperuricemia (can precipitate gout), hypomagnesemia, and hyperkalemia
Mycophenolate Mofetil
Hydroxyurea
Anti-malarials
TNF-a inhibitors
Ustekinumab
Rituximab
UVA Blockers
New FDA Sunscreen Guidelines
- Only sunscreens that have been shown to block UVA
and UVB can be labeled as “broad spectrum” - Sunscreens can have a label with a numbered SPF up to SPF 50. Higher SPF sunscreens will be labeled as “SPF 50+”
- Only SPF 15+ broad-spectrum sunscreens can claim to reduce risk of skin cancer and slow photoaging
- Elimination of the terms “sweat proof,” “sunblock,” and “water proof”
- Water-resistant sunscreens can claim up to 40 or 80 min of resistance with sweating or swimming
IL-17 Inhibitors
Cases of new- onset inflammatory bowel disease or exacerbation of disease activity occurred during the clinical trials of IL-17 inhibitors. The package inserts for all the interleukin IL-17A inhibitors—, secukinumab, ixekizumab, and brodalumab—advise that these drugs be used with caution in patients with inflammatory bowel disease. The other treatment options listed to do not have a known increased risk for inducing or exacerbating inflammatory bowel disease.
Telangiectasias
SCLE-Like Drug Rxn
Photosensitivity Rxns
Azelaic acid
Lichenoid drug
Most common: HCTZ, β-blockers, ACE inhibitors, antimalarials, gold salts, TNF-α inhibitors, NSAIDs, penicillamine, and quinidine
PD-1 inhibitors (pembrolizumab, nivolumab)
Lichenoid drug eruptions tend to present in older patients without Wickham striae in a photodistribution (B) and with a more eczematous or psoriasiform look (D) with less frequent mucosal involvement
Vesmodigib
BRAF inhibitors
Vemurafenib, dabrafenib
Development of new primary melanomas and atypical nevi has been reported in several series of patients treated with vemurafenib as well as dabrafenib, another selective BRAF inhibitor. Vemurafenib and dabrafenib are approved by the US Food and Drug Administration for the treatment of BRAF V600E metastatic melanoma. Interestingly, the new melanocytic lesions that arise in the setting of BRAF inhibitor treatment are typically BRAF wild type. This may be attributable to paradoxical activation of the MAPK pathway in BRAF wild type melanocytes. Because patients treated with vemurafenib and dabrafenib appear to have an increased risk of developing new melanomas and atypical nevi, in addition to squamous cell carcinomas and keratoacanthomas, thorough evaluations of the skin are recommended at regular intervals.
Drug-induced acne
- Halogens, such as bromide and iodide
- Androgenic hormones
- Adrenocorticotropic hormone (ACTH)
- Corticosteroids
- Isoniazid
- Lithium
- Epidermal growth factor receptor (EGFR) antagonists
- Phenytoin
- Cyclosporine
- Vitamins B2, B6, B12
- Mammalian target of rapamycin (mTOR) inhibitors (sirolimus/tacrolimus)
- MEK inhibitors (trametinib)
- Sorafenib/sunitinib
MEK Inhibitors
Drug-induced acne
Ipilimumab
PD-1 Inhibitors
Pembrolizumab, nivolumab
- Cemiplimab FDA approved for metastatic/nonresectable SCC, BCC
- Melanoma
- The PD-1 inhibitors have been notably associated with the development of bullous pemphigoid, in some cases requiring cessation of the cancer therapy.
Imatinib mesylate
Treatment of HES: (PDGF-FIP1 mutation)
Also used in DFSP (PDGF-COl1A1 mutation)
Imatinib → white discoloration (c-kit inhibition)
5-FU
Imiquimod
Diclofenac
Ingenol Mebutate
Nemolizumab
EGFR inhibitors
Acneiform papulopustular eruptions are commonly associated with epidermal growth factor receptor inhibitor (EGFRi) therapy, particular monoclonal antibodies (incidence of ~76%-90%). Moderate to severe sterile pustular eruptions are reported to be the most common reason for dose reduction, and thus prophylactic treatment is integral to both the dermatologic and oncologic care of this patient population. Moreover, the development of papulopustular reactions portends a better overall prognosis, and thus identifies a cohort who that should continue to receive therapy, as opposed to stopping or dose reducing therapy.
Expert consensus guidelines suggest treatment with prophylactic tetracycline antibiotics (D) for the first two months of EGFR therapy, with reactive treatment with topical steroids. Isotretinoin (C) should be reserved for severe rash at presentation (grade 2 or greater) or if refractory to standard therapy from tetracyclines. Prednisone would be used for severe eruptions only for limited duration, and would not be employed prophylactically.
mTOR inhibitors
Kinase inhibitor
PATEO (PeriArticular Thenar Erythema and Onycholysis)
the characteristic development of dusky erythematous patches on the dorsal aspects of the hands and joints with a sharp cut off sparing the Wallace’s line and associated onycholysis has been termed PATEO (PeriArticular Thenar Erythema and Onycholysis) and is intimately associated with taxane therapy. In particular, docetaxel is often implicated more frequently than paclitaxel. Incidence is ~5% to -10%. While Although the distribution is suggestive of a phototoxic reaction, the mechanism responsible for PATEO has not been fully elucidated.
Hydroquinone
Minocycline Hyperpigmentation
I have SCARS on my SHINS from the SUN
Hydroxychloroquine hyperpigmentation
Hydroxychloroquine is a potential cause of skin pigmentation, especially in patients receiving long-term therapy for conditions such as connective tissue diseases. Pigmentation has been reported on cutaneous surfaces, mucous membranes, and rarely, in nails. The reported etiology includes pigment deposition as well as increased iron in biopsy specimens compared with normal skin. None of the other medications listed are notable for causing pigmentation.
Combo therapies
Talimogene laherparepvec
Injectable oncolytic virus indicated for treatment of unresectable, cutaneous/subQ/nodal recurrent melanomas
Drug-induced Sweet’s Syndrome
Starts 2 weeks after drug
- G-CSF #1
- Antibiotics
- Retinoids
Dx requires:
Typical skin lesions
Typical histopathology
Fevers higher than 38°C (100.4°F)
Temporal relationship between drug ingestion and development of clinical features
Temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids
Eculizumab
Monoclonal antibody complement inhibitor, used for paroxysmal nocturnal hemoglobinuria and hemolytic uremic syndrome. Can increase risk for acute meningococcemia.
Drug-induced sarcoidosis
- IFN-a, ribavirin (hep C patients)
- HAART (HIV patients)
- TNF-a inhibitors, vemurafenib, ipilimumab, alemtuzumab (CD-52, for CLL)
Tetracyclines
Drug-induced psoriasis
- beta-blockers
- lithium
- antimalarial drugs such as (hydroxy)chloroquine
- interferons
- imiquimod
- terbinafine
- tumor necrosis factor-alpha antagonists
- anti-programmed cell death protein 1 immune checkpoint inhibitors.
Drug-induced SLE
Drug-induced systemic lupus erythematosus (DILE) usually is antihistone positive, but certain medications induce p-ANCA positivity (minocycline, methimazole, hydralazine, propylthiouracil). The classic drugs to induce DILE with anti-histone positivity include: methyl-dopa, procainamide, sulfonamides, isoniazid, chlorpromazine, propylthiouracil, and hydralazine (propylthiouracil and hydralazine have been reported to cause both anti-histone or p-ANCA positivity). Of note, the TNF-alpha inhibitors and penicillamine can cause a dsDNA positive DILE.
PUVA
NB-UVB
Extracorporeal photopheresis
PDT
Acyclovir, valacyclovir, famciclovir
Cidofovir
Foscarnet
Other anti-virals
Fluconazole, Itraconazole
Ketoconazole, voriconazole
Allylamines
Griseofulvin
Amphotericin
Other antifungals
Systemic antiparasitics
Topical antiparasitics
Drug induced DM
Drug rash timeline
Butorphanol
Butorphanol is a small molecule opioid pain reliever that has been used to treat refractory pruritus (B), prurigo. It is a mixed κ-opioid agonist/μ-opioid antagonist and is a systemic neuromodulator. It is administered intranasally.
Dupilimumab
Anti-androgens
Lindane
Lindane, an organochloride, is a second-line treatment for refractory lice and has the potential side effect of severe neurologic toxicity, including seizures and death. It should be avoided in patients with a history of seizure disorder. Pyrethrins are pyrethroid extracts from the chrysanthemum flower and should be avoided in patients who are allergic to chrysanthemum or ragweed. Similarly, permethrin, should also be avoided in patients with these allergies because it is a synthetic pyrethrin. The other treatment options can be used for lice and are not contraindicated in this patient.
HIV Drugs
Vemurafenib panniculitis
Vemurafenib-associated panniculitis typically presents with tender nodules on the lower extremities, and can be mistaken for erythema nodosum. Histopathology typically reveals a lobular panniculitis with a neutrophilic infiltrate; however, lymphocytic and mixed infiltrates have also been reported. Median time to occurrence is approximately four weeks after starting therapy. Panniculitis is not a common side effect of dacarbazine, ipilimumab, pembrolizumab, or trametinib, but it can be seen in the setting of combination therapy with MEK inhibitors and BRAF inhibitors.
Erythema Nodosum
Erythema nodosum is usually a reactive process to medications (most commonly oral contraceptive pills, sulphonamides, salicylates, nonsteroidal anti-inflammatories, bromides, iodines), pregnancy, infections (bacterial, fungal, mycobacterial, viral, and parasitic have all been reported), sarcoidosis, Behçet disease, inflammatory bowel disease, tuberculosis, and other autoimmune connective tissue diseases.
