Dermatopharmacology Flashcards

Question

25. A- 46-year-old woman presents to the emergency room with fever and widespread confluent erythematous patches studded with pustules. CMP is normal, and CBC shows only neutrophilia. Which of the following medications is the most likely cause of this patient's eruption? A. TMP-SMX B. Amoxicillin C. Lamotrigine D. Allopurinol E. Phenytoin

Answer 1

Correct choice: B. Amoxicillin Explanation: The stem describes the classic presentation of acute generalized exanthematous pustulosis (AGEP), which is typified by the triad of fever, neutrophilia, and eruption of punctate non-follicular sterile pustules on a background of edematous erythema. It often occurs within 1-2 days of starting the offending drug, which is most often a beta-lactam antibiotic such as amoxicillin. The remaining answer choices are more likely to produce SJS/TEN or DRESS syndrome rather than AGEP.

Answer 2

Correct choice: D. Inhibition of Fas (CD95)-mediated keratinocyte death Explanation: Intravenous immune globulin is useful for inflammatory disorders, including toxic epidermal necrolysis. The dosing of IVIg in toxic epidermal necrolysis is 1 g/kg/day for 3 days. The immunomodulatory effects of IVIg may be exerted through one or more of the following mechanisms: 1) functional blockade of Fc receptors; 2) inhibition of complement-mediated damage; 3) alteration of cytokine and cytokine antagonist profiles; 4) reduction of circulating antibodies via anti-idiotype antibodies; 5) neutralization of toxins that trigger autoantibody production. In toxic epidermal necrolysis, IVIg is believed to block Fas (CD95)-mediated keratinocyte death by inhibiting Fas-Fas ligand interactions. 1 – IVIg leads to inhibition of complement-mediated damage. 2 – IVIg leads to a reduction of circulating antibodies via anti-idiotype antibodies. 3 – IVIg leads to neutralization of toxins that trigger autoantibody production. 5 – IVIg leads to functional inhibition of Fas-Fas ligand interactions. c

Answer 3

Correct choice: A. FK506 binding protein Explanation: Tacrolimus and pimecrolimus are non-steroidal calcineurin inhibitors that act as anti- inflammatory medications. In dermatology, they are most commonly used in topical preparations. These medications form complexes with FK506 binding protein, which inhibits calcineurin activity. A key regulatory step in the activation of T cells is the activation of calcineurin via calmodulin. Tacrolimus does not complex with the other listed proteins.

Answer 4

Correct choice: A. Alitretinoin Explanation: Alitretinoin is the only retinoid that binds all retinoic acid receptors (RAR) and retinoid X receptors (RXR). This question probes the examinee’s knowledge of the receptor affinities of retinoids. Alitretinoin (9-cis-RA, choice 1) is a first-generation retinoid that binds all RAR and RXR and is used in treatment of Kaposi sarcoma. Tretinoin (all-trans-RA, choice 2) is another first-generation retinoid that binds all RAR but not RXR. Adapalene (choice 3) and tazarotene (choice 4) are third-generation retinoids that preferentially bind RAR-β/γ over RAR-α, but do not bind RXR. Bexarotene (choice 5) is third generation and binds RXR rather than RAR; it is used to treat cutaneous T-cell lymphoma.

Answer 5

Correct choice: E. trimethoprim Explanation: There is an increased risk of myelosuppression when methotrexate is coadministered with drugs that inhibit folic acid metabolism ie. trimethoprim, sulfonamides, and dapsone. The other medications do not affect folic acid metabolism. Folinic acid (leukovorin) is given to treat methotrexate-induced myelosuppression.

Answer 6

Correct choice: A. levofloxacin Explanation: Levofloxacin. Levofloxacin is not associated with photosensitivity/photo-onycholysis, which is a result of UVA exposure. Lomefloxacin is associated with highest risk of photosensitivity/ photo-onycholysis.The remaining answer choices are associated with photosensitivity. Lomefloxacin is associated with highest risk of photosensitivity/photo-onycholysis.

Answer 7

Correct choice: E. Rifampin Explanation: Theoretically, decreased enterohepatic absorption of hormones due to altered gut flora could decrease contraceptive efficacy. However, this theory has not been borne out in studies. Only rifampin, which is a potent hepatic microenzyme inducer, has been definitively shown to reduce contraceptive efficacy.

Answer 8

Correct choice: E. Hyperkalemia Explanation: Well-documented adverse effects and toxicities of cyclosporine include renal impairment, hypertension, elevated triglycerides, hyperkalemia, hypomagnesemia, hepatotoxicity, hypertrichosis, and long-term increased risk of malignancy. The other answer choices listed are incorrect.

Answer 9

Correct choice: D. Concomittant administration of cimetidine has been shown to decrease the risk of methemoglobinemia Explanation: Cimetidine has been shown to provide some protection against methemoglobin formation. Dapsone and sulfapyridine exert their anti-inflammatory actions by inhibiting the myeloperoxidase activity and chemotactic abilities of polymorphonuclear leukocytes. Dapsone hypersenstivity syndrome is characterized by eosinophilia, as well as a severe mononucleosis-like reaction, including fever, erythroderma, hepatitis, and even death. Sulfapyridine has a similar but often less severe side effect profile.

Answer 10

Correct choice: D. Is a Toll-like receptor 7 agonist Explanation: Topical 5-FU blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, thus interfering with the synthesis of DNA and RNA. Normal side effects during treatment include pruritus and burning at the site of application. It is a treatment option for patients with multiple AKs within an area. It is not recommended during pregnancy. Imiquimod is a Toll-like receptor 7 agonist and is another treatment option for actinic keratosis.

Answer 11

Correct choice: B. It binds tubulin Explanation: Podophyllin is a crude cytotoxic extract from the May apple (Mandrake) plant. It is antimitotic, arresting cells in metaphase (not prophase) by binding to the protein tubulin. It may be teratogenic and should not be used in pregnancy. It is typically used to treat warts, particularly condyloma.

Answer 12

Correct choice: D. Alefacept Explanation: Alefacept is a soluble form of LFA-3 that blocks the immunologic synapse between CD2 on the T cell and LFA-3 on the antigen presenting cell. Furthermore, alefacept targets CD2+ activated T cells for apoptosis. Etanercept and infliximab are TNF-alpha inhibitors. Efalizumab binds to the CD11a subunit of lymphocyte function-associated antigen 1 and acts as an immunosuppressant by inhibiting lymphocyte activation and cell migration out of blood vessels into tissues. Efalizumab was associated with fatal brain infections and was withdrawn from the market in 2009.

Answer 13

Correct choice: D. Methylprednisolone Explanation: Of the corticosteroids listed, the steroid with the lowest mineralocorticoid activity is methylprednisolone. Mineralocorticoids act on the kidney to decrease the rate of sodium excretion (with accompanying retention of water). Triamcinolone, dexamethasone, and betamethasone also have low mineralcorticoid activity. The other answer choices have higher mineralcorticoid activity.

Answer 14

Correct choice: E. 7 Explanation: Imiquimod acts on toll like receptor 7. It can be used in the treatment of warts, actinic keratosis, superficial basal cell carcinomas, and squamous cell carcinomas in-situ. It also up- regulates TNF alpha, IFN gamma and alpha, and IL-12. Imiquimod does not act on the other Toll-like receptors.

Answer 15

Correct choice: E. Redness and desquamation of the palms and soles Explanation: Redness and desquamation of the palms and soles. This chemotherapy-induced acral erythema or hand-foot reaction is common among those taking sorafenib. Sorafenib is a chemotherapy drug. Common side effects include anemia, alopecia, hand-foot synrome, pruritus, erythema, fatigue, hypertension, GI upset, thrombocytopenia. Hypertrichosis can occur secondary to cyclosporine, Q-T prolongation can be seen with pimozide used for delusions of parsitosis and excessive amounts of lidocaine. Cystitis is characteristic of cyclophosphamide.

Answer 16

Correct choice: A. Erythromycin Explanation: Macrolide antibiotics inhibit RNA-dependent protein synthesis by binding to the 50s ribosomal subunit, and include erythromycin and azithromycin. Tetracyclines inhibit RNA- dependent protein synthesis by binding to the bacterial 30s ribosomal subunit. TMP-SMX inhibits bacterial folic acid synthesis. Benzoyl peroxide is a bactericidal agent with direct oxidizing effects. Azeleic acid is a dicarboxylic acid that inhibits tyrosinase; the mechanism of action against P. acnes is not completely understood.

Answer 17

Correct choice: E. Hydroxyurea Explanation: The image depicts the heliotrope sign of dermatomyositis. Hydroxyurea is a cytotoxic chemotherapeutic agent used for myelodysplasia. The adverse cutaneous effects due to hydroxyurea include leg ulcers, hyperpigmentation of the skin and nails, a lichen planus-like eruption, lupus erythematosus, and a dermatomyositis-like eruption.

Answer 18

Correct choice: E. Ketoconazole Explanation: Ketoconazole can cause rare fulminant hepatitis, gynecomastia, and impotence. It inhibits CYP 450 and is a triazole and a keratinophilic. c

Answer 19

Correct choice: E. Etanercept Explanation: Etanercept is a fusion protein TNF-receptor that that binds to TNFα and decreases its role in disorders involving excess inflammation, including autoimmune diseases such as ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and, potentially, in a variety of other disorders mediated by excess TNFα. Infliximab and Adalimumab are monoclonal antibodies that bind TNF. Risankizumab is a monoclonal antibody targeting IL-23A. Apremilast is a phosphodiesterase-4 inhibitor which inhibits spontaneous production of TNF.

Answer 20

Correct choice: E. Symblepharon Explanation: This man has Stevens-Johnson syndrome (SJS) secondary to allopurinol. Symblepharon is the most common complication. As such, it is essential that patients with SJS undergo formal ophthalmologic evaluation early and often. The other remaining answer choices are potential complications from SJS, but symblepharon is most common.

Answer 21

Correct choice: A. Cytoplasm Explanation: Both androgen and corticosteroid receptors localize to the cytoplasm. Estrogen receptors are found in the nucleus. Progesterone receptors are distributed in both the nucleus and the cytoplasm. The other listed answers are not the correct loction of the corticosteroid receptor.

Answer 22

Correct choice: D. Interleukin-10 Explanation: Psoriasis is generally described as a TH1 autoimmune disease where IL-12/IFN- gamma pathway is dominant. IL-10 is the prototype of TH2 and calcipotriene application results in increased levels of IL-10, thus decreasing TH1 disease. Calcipotriene does not increase the levels of the other listed cytokines.

Answer 23

Correct choice: A. Secukinumab Explanation: Brodalumab binds to the interleukin-17 receptor while ixekizumab and secukinumab target IL-17. Ustekinumab targets Il12/23 and adalimumab targets TNF- alpha. Apremilast is a PDE4 inhibitor.

Answer 24

Correct choice: D. Capecitabine Explanation: At present, the pathogenesis of pyogenic granulomas is unknown. Reported triggers include antecedent trauma, pregnancy and certain drugs, including acitretin, HIV protease inhibitors, EGFR inhibitors, docetaxel, capecitabine and rituximab.

Answer 25

Correct choice: D. Anti-SSA (Ro) Explanation: The stem describes the clinico-path findings of subacute cutaneous lupus erythematosus (SCLE), which can be native or drug-induced. When caused by a medication, HCTZ is an extremely common culprit. Both native and drug-induced SCLE are associated with Anti-SSA (Ro) antibodies most commonly. Anti-histone antibodies are classically present in cases of drug- induced systemic lupus erythematosus (SLE). Anti-dsDNA and Smith are typically present in native SLE. Lastly, Anti-SSB (La) antibodies may be present in both native or drug-induced SCLE, although less commonly than Anti-SSA (Ro).

Answer 26

Correct choice: D. 50-75% Explanation: Drug hypersensitivity syndrome is characterized by fever, skin eruption and internal organ involvement. Drugs associated with drug hypersensitivity syndrome include sulfonamindes, dapsone, anticonvulsants (carbamezapine, phenobarbitol, lamotrigine), anti-retrovirals (ritonovir, nevirapine) and minocycline. In one study, over 70% of patients had abnormal liver enzymes. The other answers do not accurately present the percentage of patients with DHS to develop liver abnormalities.

Answer 27

Correct choice: A. Bradykinins Explanation: Bradykinins are responsible for angiotensin converting enzyme inhibitor-induced angioedema. The remaining answer choices are not associated with ACE inhibitor-induced angioedema.

Answer 28

Correct choice: D. Ipilimumab Explanation: A recent study in the New England Journal of Medicine reported an increase in survival of patients with stage III and stage IV melanoma with a immunologic therapy agent named ipilimumab. The survival was increased from 6 months to 10 months (P < 0.001). All the other medicines are not used to treat melanoma; they are used to treat psoriasis, among other disease.

Answer 29

Correct choice: D. Oxybenzone Explanation: Oxybenzone (as well as Meroxyl XL, titanium dioxide, and zinc oxide) blocks both UVA and UVB. Avobenzone and meradimate block only UVA, whereas PABA and octocrylene block only UVB.

Answer 30

Correct choice: A. Epidermal growth factor receptor (EGFR) inhibitor Explanation: Epidermal growth factor receptor (EGFR) inhibitors cause a variety of cutaneous adverse reactions including paronychia, papulopustular (acneiform) eruption, photosensitivity, skin fragility, and hair changes. TNF inhibitors may be associated with injection site reactions and paradoxical psoriasiform eruptions. Smoothened inhibitors are associated with muscle spasm, alopecia, and dysgeusia. BRAF inhibitors are associated with maculopapular eruptions, photosensitivity, seborrheic dermatitis-like eruptions, keratosis pilaris-like eruptions and squamoproliferative growths. PD-1 inhibitors are associated with maculopapular eruption, pruritus, lichenoid eruption, and vitiligo.

Answer 31

Correct choice: E. Warfarin, carbamazepine, or methylprednisolone Explanation: Erythromycin inhibits the hepatic cytochrome P450 system and can increase serum levels and potential toxicities of carbamazepine, theophylline, warfarin, digoxin, and methylprednisolone.

Answer 32

Correct choice: A. Sweet's syndrome Explanation: Sweet's syndrome, or acute febrile neutrophilic dermatoses, is often associated with AML and G-CSF. Histologically, there is marked dermal edema with a prominent infiltrate composed of neutrophils with leukocytoclasia. There is an absence of extensive vascular damage.

Answer 33

Correct choice: E. 50x Explanation: Etretinate is 50x more lipophilic than acitretin, with increased storage in adipose tissue. The highly lipid soluble etretinate lasts several years in the fatty tissues, and in the presence of ethanol, acitretin is re-esterified to etretinate.

Answer 34

Correct choice: C. Clonidine Explanation: Menopausal flushing occurs at menopause or perimenstrual when estrogen levels are low. Pharmacologic menopause may be caused by drugs, including danazol, tamoxifen, clomiphene citrate, decapeptyl, leuprolide, and 4-hydroxyandrostenedione. Treatment is with oral estrogen replacement or clonidine hydrochloride 0.05mg bid. Nadolol is an effective treatment of emotional flushing. The other options can cause flushing.

Answer 35

Correct choice: C. Cytarabine Explanation: Cytarabine, used for the treatment of acute myelogenous leukemia, can cause a rare reaction of inflammation of existing seborrheic keratoses. The other answer choices have not been reported to produce a reaction of inflammation of existing seborrheic keratoses.

Answer 36

Correct choice: E. Decreased magnesium Explanation: Cyclosporine use is associated with decreased serum magnesium levels. Thus, magnesium levels should be monitored and magnesium supplementation given as needed for patients taking cyclosporine. Cyclosporine is associated with several potential adverse effects, including: nephrotoxicity, reversible hypertension, gingival hyperplasia, hyperlipidemia, paresthesias, hypertrichosis, and increased serum levels of potassium and uric acid.

Answer 37

Correct choice: E. Acitretin Explanation: This HIV-positive patient has psoriasis requiring systemic therapy. Of the options listed, only acitretin is non-immunosuppressive and thus should be the first systemic therapy in this case. The remaining answer choices are less ideal in this HIV-positive patient considering that they are immunosuppressive.

Answer 38

Correct choice: C. muscle spasms Explanation: Muscle spasms are the most common side effect and cause the most patients to discontinue vismodegib.

Answer 39

Correct choice: B. 7-21 days Explanation: Extensive oral erosions coupled with widespread epidermal detachment is highly concerning for Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), which is a severe cutaneous adverse reaction that is almost always drug-related. The most common offending drugs include: antibiotics (especially sulfonamides and penicillins), allopurinol, anticonvulsants (often lamotrigine, carbamazepine, or phenytoin), barbiturates, NSAIDs, and anti-retrovirals. For SJS/ TEN, the typical onset of eruption after drug ingestion is 7-21 days (although it can be up to 60 days for anticonvulsants). Hours to 2 days is typical for acute generalized exathematous pustulosis (AGEP). Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome usually occurs 21-56 days after medication exposure. Lichenoid drug eruptions and drug-induced pemphigus may occur several weeks or months after drug initiation.

Answer 40

Correct choice: C. TNF-alpha Explanation: Thalidomide inhibits TNFa expression. TNFa is the primary mediator of acute inflammation, fever, and hepatic production of acute phase reactants. Thalidomide does not regulate the other cytokines listed above.

Answer 41

Correct choice: A. Lymphokine production Explanation: Tacrolimus and pimecrolimus are topical macrolide immunomodulators that inhibit lymphokine or cytokine production via binding to macrophilin. This complex inhibits calcineurin, a phosphatase involved in the activation of NF-AT. This suppresses the production of IL-2 and IFN- gamma (TH1 cytokines) as well as IL-4, 5 and 13 (TH2 cytokines). In addition, they decrease the expression of IgE receptors on Langerhans cells and reduce mast cell degranulation. Topical macrolides do not interfere with antigen production, prostaglandin secretion and neutrophil/ lymphocyte migration.

Answer 42

Correct choice: E. Azithromycin Explanation: SCLE most commonly presents as psoriatic or annular/polycyclic erythematous scaly patches and plaques in a photo distribution. The condition is often drug induced with many traditional culprits but Azithromycin is not one. All of the other choices have been implicated in drug-induced subacute cutaneous lupus erythematosus.

Answer 43

Correct choice: E. Chlorpromazine Explanation: Chlorpromazine is associated with blue-gray pigmentation on sun-exposed areas and is not associated with photoonycholysis. Quinolones, tetracyclines, psoralens and quinine can cause photoonycholysis.

Answer 44

Correct choice: B- BRAF inhibitor Monotherapy with BRAF inhibitor have been associated with hyperkeratotic papules,verruca,keratoacanthomas , SCC in up to 30 % of patients. Combination therapy with MEK inhibitor have drastically reduced this side effect.

Answer 45

Correct choice: C. The patient has been compliant with 5-FU treatment and the appearance of inflammation, erythema and erosions are expected. Compliance is a key feature in treatment with 5-FU. Erythema, inflammation and erosion must develop and is considered a sign of successful treatment.

Answer 46

Correct choice: B. 5-fluorouracil Explanation: 5-fluorouracil can be an effective treatment for benign familial pempigus or Hailey- Hailey disease, having induced remission of the disease in a subset of patients after 6 months to a year of tapered treatment.

Answer 47

Correct choice: B. Apremilast Explanation: Apremilast should be strongly considered in this patient. He is at risk for infections due to his occupation (especially tuberculosis) and HIV+ status. Ustekinumab and infliximab may put the patient at higher risk for infection, including tuberculosis. Prednisone and cyclosporine are not good long term management options. Apremliast theoretically does not put the patient at higher risk of infection due to its mechanism (PDE4 inhibition).

Answer 48

Correct choice: C. Pre-medicate with acetaminophen 1 g by mouth, diphenhydramine 25 mg by mouth, and allow the injection to reach room temperature prior to injection Explanation: Premedication and allowing the medication to reach room temperature reduce injection site reactions. The remaining choices are not the next most reasonable steps for injection site reaction on ixekizumab.

Answer 49

Correct choice: B. IL-23 blockade Explanation: Tildrakizumab-asmn is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

Answer 50

Correct choice: A. Sunitinib Explanation: Sunitinib is a tyrosine kinase inhibitor for VEGFR and PDGFR in GI stromal tumors, pancreatic neuroendocrine tumors, and renal cell cancers. While it is generally a well tolerated chemotherapeutic agent, it can have dermatologic side effects, such as yellowing of the skin. Vemurafenib is a BRAF inhibitor, which can cause warty keratoses and new SCC/KAs. Pembrolizumab is a PD1 inibitor, which can cause autoimmune, vitiligo-like, and lichenoid reactions. Cetuximab is an EGFR inihibitor, which can cause an acneiform rash. Imatinib is a tyrosine kinase inhibitor, which can cause periorbital edema and hypopigmented/depigmented eruptions.

Answer 51

Correct choice: C. Diclofenac Explanation: Diclofenac topical may provide anti-inflammatory action for pruritic and inflamed Darier disease. The remaining choices are incorrect. Reference: J Am Acad Dermatol. 2014 Apr;70(4):e89-e90. doi: 10.1016/j.jaad.2013.11.033. Improvement of Darier disease with diclofenac sodium 3% gel. Millán-Parrilla F1, Rodrigo-Nicolás B2, Molés-Poveda P2, Armengot-Carbó M2, Quecedo-Estébanez E2, Gimeno-Carpio E2.

Answer 52

Correct choice: A. Monoclonal antibody to IL-4 receptor Explanation: Dupilumab has been studied for atopic dermatitis and binds to the IL-4R alpha. This modulates signaling of IL-4 and IL-13. Mepolizumab is an IL-5 inhibitor. Several humanized monoclonal antibodies to IL-13, including anrukinzumab, lebrikizumab and tralokinumab, are currently under clinical evaluation.

Answer 53

Correct choice: B. Vasoconstriction Explanation: Oxymetazoline HCl 1% works via vasoconstriction of cutaneous vessels in patients with rosacea. The medication is an alpha 1A adrenoceptor agonist. Vasodilation is the opposite effect we want in patients with rosacea. Pulsed dye laser aims via destruction of cutaneous vessels. Ivermectin is a topical and systemic agent that is anti-parasitic and used to treat rosacea. Several antibiotics - both by mouth and by topical application - work to reduce inflammation in the skin of patients with rosacea. https://doi.org/10.1016/j.jaad.2018.01.027.

Answer 54

Correct choice: D. Discuss starting nicotinamide and acitretin with the patient Explanation: Evidence suggests that in high risk populations with many non-melanoma skin cancers nicotinamide and acitretin may reduce the development of new non-melanoma skin cancers along with photoprotection and close surveillance. The remaining choices are either dangerous to the patient or inappopriate medical care. TCA peels can be used on certain parts of the body for patients who have failed photodynamic therapy and/or 5-fluorouracil or imiquimod but the strength is not 50% - you could use 35% TCA with Jessner's on the face and TCA 25% on the neck, chest, arms, hands, legs, and feet with close attention to the depth of the peel on the extremities, neck, and chest.

Answer 55

Correct choice: A. Terbinafine Explanation: Terbinafine is a fungicidal medication used for onychomycosis that can cause dysgeusia, or metallic taste. The other medications listed do not cause dysgeusia.

Answer 56

Correct choice: D. Methotrexate Explanation: Although not all costs were factored, one 2015 study found that methotrexate and cyclosporine had the most favorable monthly costs (number needed to treat to achieve PASI 75) for treatment of psoriasis. Infliximab and ustekinumab were the most expensive treatment options for psoriasis.

Answer 57

Correct choice: C. Doxycycline Explanation: Doxycycline is a tetracycline antibiotic which inhibits protein synthesis by binding to the 30S ribosomal subunit. It is effective against both gram-positive and gram-negative infections. Retapamulin is incorrect as it blocks the 50S ribosomal subunit. Amoxicillin/Clavulanate blocks bacterial cell wall synthesis by binding the transpeptidase/penicillin binding proteins and is enhanced by clavulanic acid binding beta-lactamase. Mupirocin blocks t-RNA synthetase. Levofloxacin blocks DNA Gyrase/topoisomerase II.

Answer 58

Correct choice: D. Tildrakizumab Explanation: Tildrakizumab would be an ideal first-line agent in this patient given her co- morbidities (IBD, depression, and FHx of MS), but significant psoriatic burden. Tildrakizumab (Ilumya) is an human antibody directed against the p19 subunit of IL-23. IL-23 inhibitors are not contraindicated in depression, IBD, or in patients with a family history of MS. Apremilast and Brodalumab are incorrect due to the patient's history of depression. Etanercept is incorrect because of the direct family history of multiple sclerosis, which is contraindicated in TNF-a inhibitors. Ixekizumab and Brodalumab are incorrect due to the patient's history of inflammatory bowel disease, which is contraindicated in IL-17 inhibitors.

Answer 59

Correct choice: A. The creatinine should be rechecked in 2 weeks and then the patient reassessed. Explanation: Cyclosporine is highly effective in most patients with severe chronic plaque-type psoriasis. Doses start at 2.5 to 4mg/kg/day and can go as high as 5.5mg/kg/day. Renal impairment may occur and is often reversible. If the creatinine increases 30% or greater from baseline, it should be repeated in 2 weeks to verify the increase is persistent and then the dose should be reduced by 25% and the patient followed closely.

Answer 60

Correct choice: C. Sunitinib Explanation: Sunitinib is reported to cause yellow skin discoloration. This question checks the examinee’s knowledge of targeted cancer therapy-related skin reactions. Although all of the answer choices have been reported to cause multiple cutaneous effects, some reactions are more closely linked to particular agents and thus more likely to be tested. Sunitinib (choice 3) is a multikinase inhibitor that can cause a characteristic yellow discoloration of the skin. Dasatinib (choice 1), another multikinase inhibitor, is associated with Sweet syndrome, panniculitis, and urticaria, among other cutaneous side effects. The BRAF inhibitors, dabrafenib (choice 2) and vemurafenib (choice 5), are well known to induce keratoacanthomas and squamous cell carcinomas, an effect ameliorated by combination with a MEK inhibitor. Sorafenib (choice 4) is another multikinase inhibitor that can also cause yellow skin discoloration, but less frequently than sunitinib.

Answer 61

Correct choice: C. Gastrointestinal distress Explanation: This patient has sporotrichosis. Sporotrichosis is mainly an occupational disease of farmers, gardeners, and horticulturists. Persons who handle thorny plants, sphagnum moss, or baled hay are at increased risk. Outbreaks have occurred in nursery workers who handled sphagnum moss, rose gardeners, children playing on baled hay, and greenhouse workers who handled bayberry thorns contaminated by the fungus. Classic treatment is with oral potassium iodide for 3-4 weeks. The most recognized side effect of treatment is gastrointestinal distress. Thyroid function tests should be performed during treatment as suppression can occur.

Answer 62

Correct choice: A. IL-17A monoclonal antibody Explanation: Ixekizumab and Secukinumab are both IL-17A monoclonal antibodies. B describes Brodalumab which is an IgG2 against the IL-17 receptor; therefore it inhibits pan-IL-17, including A, A/F, E, F, and C receptors C describes apremilast which blocks PDE4, resulting in ↑ cAMP levels which inhibits production of proinflammatory cytokines. D describes ustekinumab which is an IgGκ against the p40 subunit of IL-12 & IL-23. E describes Etanercept, Adalimumab, Infliximab, Golimumab, and Certolizumab which are TNFa inhibitors.

Answer 63

Correct choice: C. IL-23 blockade Explanation: Risankizumab-rzaa is a humanised immunoglobulin G1 (IgG1) mAb, which selectively binds to IL-23 cytokine and blocks its interaction with the IL-23 receptor. Naturally occurring in the human body, the IL-23 cytokine is responsible for inflammatory and immune responses. IL-17, IL-12/23, PDE-4, and TNF alpha blockade describe the mechanisms of action for other medications used in the treatment of psoriasis and other conditions.

Answer 64

Correct choice: C. Methotrexate Explanation: The correct answer is B, methotrexate. The current recommendation to possibly decrease the risk of anti-drug antibodies (if desired) in the treatment of psoriasis is the concomitant use of methotrexate. The other medications listed have not been shown to decrease anti-drug antibodies to biologics used in psoriasis.

Answer 65

Correct choice: E. Conjunctivitis Explanation: Dupilumab does induce conjunctivities in a subset of patients using the medication, which is FDA approved to treat atopic dermatitis.

Answer 66

Correct choice: E. Ustekinumab Explanation: Ustekinumab is an injection given every 3 months as maintenance therapy for the indication of psoriasis. The remaining choices are incorrect as they are given every week (etanercept), every two weeks (adalimumab), every month (ixekizumab), and every two months (guselkumab) as maintenance therapy - these responses do not represent the longest interval that would reduce needle phobia experience.

Answer 67

Correct choice: B. Edema of the face and hands may be seen Explanation: This patient has acute generalized exanthematous pustulosis (AGEP). AGEP is a severe cutaneous adverse reaction that typically develops 1-3 days after starting the offending drug. In addition to the rapid appearance of widespread, sterile, non-follicular pustules, edema of the face and hands may be seen. AGEP is most often caused by beta-lactam antibiotics, making piperacillin- tazobactam a more likely culprit than vancomycin. Fever and neutrophilia (not eosinophilia) are characteristic of AGEP. Drug withdrawal and supportive care are the mainstays of treatment.

Answer 68

Correct choice: A. Folic acid supplementation Explanation: Isotretinoin (ISO) is a first-generation retinoid discovered in 1952 and approved by the FDA for the treatment of nodulocystic acne in 1982. The anti-inflammatory properties of ISO have found its use in disorders other than acne. ISO can create psychiatric problems, including depression and suicidal ideation. These neuropsychiatric problems are very similar to disorders secondary to hyperhomocysteinemia (HHcy), vitamin B12, and folic acid (vitamin B9) deficiencies. Given that previous literature suggested folate supplementation improved the efficacy of traditional antidepressant medications, clinicians may wish to consider folate supplementation for patients with depression or possible depressive symptoms, such as acne patients with genetic susceptibility.

Answer 69

Correct choice: A. Propranolol Explanation: Terbinafine is a potent inhibitor of CYP2D6 and therefore could cause bradycardia when given with beta blockers, such as propranolol. Given this property, it can also cause oversedation when given with some SSRIs, such as doxepin. Metformin, glipizide, lisinopril, and aspirin do not have contraindications with terbinafine use.

Answer 70

Correct choice: D. Etanercept Explanation: This woman has Stevens-Johnson syndrome (SJS) secondary to lamotrigine. The treatment of SJS/TEN is controversial and variable given the paucity of high-quality data. Nevertheless, publications exist that support the use of various immunomodulators, including etanercept, prednisone, IVIG, and cyclosporine. Etanercept is the only one of these options that is pregnancy category B, indicating animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Prednisone, IVIG, and cyclosporine are all pregnancy category C (animal studies show a fetal risk and there are no adequate human studies) and therefore carry a theoretically increased fetal risk compared to etanercept. Rituximab is not used in the treatment of SJS/TEN, and is also pregnancy category C.

Answer 71

Correct choice: B. Captopril Explanation: The stem and image describes a patient with a lichenoid drug eruption. Captopril is an ACE inhibitor which is classic cause for lichenoid drug eruptions. Other medications causing lichenoid eruptions include HCTZ, antimalarials, NSAIDS, gold, and D-penicillamine. Doxycycline can cause fixed drug eruptions and phototoxic reactions. Topical clobetasol causes an acneiform eruption. Hydralazine causes an SLE-like rash. Penicillin is classic for morbilliform eruptions and Linear IgA dermatosis.

Answer 72

Correct choice: C. Low dose naltrexone Explanation: Low dose naltrexone can improve the inflammation of lichen planopilaris. The remaining choices are dangerous or inappropriate for the management of lichen planopilaris.

Answer 73

Correct choice: E. Erlotinib Explanation: Erlotinib is an EGFR inhibitor known for its efficacy in the treatment of NSCLC and pancreatic cancers. It has been reported to cause eyelash trichomegaly. Imatinib, Infliximab, Vismodegib, and Pembrolizumab have not been reported to cause trichomegaly.

Answer 74

Correct choice: C. Zidovudine Explanation: The pigmented nail streaks are a known side effect of zidovudine. Nail pigmentation can be drug induced. This includes: -Brown or black transverse and/or longitudinal bands — which can be due to melanonychia (melanocytes stimulation) from zidovudine, psoralens (PUVA), hydroxyurea and other chemotherapy drugs -Yellow transverse pigmentation — which can be due to tetracyclines -Bluish grey pigmentation of the nail bed that does not move outwards— which can be due to minocycline -Brownish discolouration of the nail bed — which can be due to antimalarial drugs (hydroxychloroquine and chloroquine) .

Answer 75

Correct choice: D. Suicidal ideation and completion Explanation: The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis. The remaining choices are incorrect as they do not represent the black box warning for brodalumab.

Answer 76

Correct choice: E. Sirolimus Explanation: Sirolimus (rapamycin) is an mTOR inhibitor which causes the downregulation of the PI3K/AKT signaling pathway. It can be efficacious for complex vascular malformations including lymphatic malformations and the Kasabach-Merritt phenomenon. Sirolimus has also been shown to have a reduced risk of SCC development in transplant patients. It can, however, cause drug induced acne. Cyclosporine, Azathioprine, Prednisone, and Mycophenolate all increase SCC risk.

Answer 77

Correct choice: D. Apremilast Explanation: Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increased intracellular cyclic adenosine monophosphate (cAMP) levels. The specific mechanism(s) by which crisaborole exerts its therapeutic action for the treatment of atopic dermatitis is not well defined.

Answer 78

Correct choice: E. Coccidioidomycosis Explanation: Yearly screening IgG and IgM serum testing for coccidioidomycosis should be performed in addition to yearly PPD or Quantiferon Gold test for tuberculosis screening for patient populations in endemic areas such as Arizona. The remaining choices are incorrect.

Answer 79

►D Doxorubicin when given with retinoids or ketoconazole may lead to sticky skin. A dermatomyositis-like reaction and leg ulcers may be seen with hydroxyurea. Epidermal growth factor receptors such as erlotinib and cetuximab can produce papulopustular eruptions. Capillary leak syndrome is seen with interleukins.

Answer 80

►A Various vehicles are used for different clinical situations. Ointments are water in oil emulsions. Creams are oil in water emulsion. Gels are semisolid emulsion in alcohol base . Lotions/Solutions are powder in water (some oil). Foams are liquid and/or solid materials in a gaseous medium.

Answer 81

►E Adverse effects from dapsone are both pharmacologic and idiosyncratic and include hemolytic anemia, methemoglobinemia, agranulocytosis, hypersensitivity syndrome and neuropathy. Of these, the first two are pharmacologic and anticipated, to some degree, in most patients treated with dapsone. However, the magnitude of toxicity varies greatly among individuals on the drug. Methemoglobinemia is the formation of methemoglobin in the blood, which has a decreased oxygen-carrying capacity compared with hemoglobin and can result in cyanosis. The reaction is related to the N-hydroxy metabolites of dapsone, which are potent oxidants. G6PD-deficient individuals are more susceptible to oxidative stresses, including those from dapsone metabolites, and a baseline G6PD level is recommended prior to initiation of dapsone therapy. Vitamin E (800 IU/day) has been suggested to provide a small amount of protection against methemoglobinemia and hemolysis, however, the clinical benefit of this strategy is unclear.

Answer 82

►D Co-administration of erythromycin with the antihistamines terfenedine and astemizole or the gastrointestinal promobility agent cisapride increases the risk of torsade de pointes and is contraindicated. These drugs are no longer available in the US.

Answer 83

►D Fomiversen (Vitraene) represents a new class of therapeutic agents known as antisense drugs. It is indicated for the treatment of CMV retinitis in patients with AIDS. The most common adverse effects are ocular inflammation and increases in intraocular pressure.

Answer 84

►A Cyclophosphamide is a cell-cycle nonspecific agent, which produces DNA cross-linkages at any point in the cell cycle. Methotrexate, azaithioprine, and hydroxyurea are S -phase specific cytotoxic agents. 5-fluorouracil is a cell-cycle specific pyrimidine antagonist.

Answer 85

►E All of the following drugs cause pseudoporphyria except ampicillin. Dapsone, tetracycline, amiodarone, NSAIDs, and nalidixic acid.

Answer 86

►C The Wolff-Chaifkoff effect, which is the inhibition of thyroid hormone synthesis from excess iodides which block organic iodides from binding in the thyroid, can be observed in patients on potassium iodide therapy. In patients with normal thyroid function, autoregulatory mechanisms allow for appropriate escape from this effect. In patients with impaired autoregulatory mechanisms, the Wolff-Chaikoff effect can lead to hypothyroidism.

Answer 87

►E Doxepin, a tricyclic antidepressant, has H1 and H2 antihistamine activity.

Answer 88

►B Adverse effects of oral retinoid therapy: Cutaneous: Xerosis, palmoplantar digital desquamation, retinoid dermatitis, photosensitivity, pyogenic granulomas, stickiness sensation, Staph aureus infxns Hair: Teolgen effluvian, abnormal hair texture, dryness Nails: Fragility with nail softening, paronychia, onycholysis Occular: Dry eyes w/visual blurriness, Blepharoconjunctivitis, Photophobia Oral: Cheilitis, dry mouth, sore mouth and tongue Nasal: Nasal mucosal dryness, decreased mucous secretion, epistaxis Musculoskeletal: Arthralgias, myalgias, fatigue and muscle weakness, tendinitis Neurological: Headache, mild depression Gatrointestinal: N/V/D, adb pain

Answer 89

►E Technically, 35 mg/kg is considered the safe and average amount recommended. However, maximum amount of lidocaine has been reported to be 55 mg/kg. Tumescent anesthesia is a method where dilute lidocaine is injected into subcutaneous fat for the liposuction procedure.

Answer 90

►C Finasteride, a type II 5 alpha reductase inhibitor, given as a 1mg tablet daily, is effective in preventing further hair loss and in increasing the hair counts to the point of cosmetically appreciatable results in men ages 18 to 41 with mild to moderate hair loss at the vertex, in the anterior midscalp, and the frontal region.

Answer 91

A Precipitated sulfur 6% can be used for the treatment of scabies in pregnant women. Scabies can be in bedding and in clothes and should be washed in hot water after the patient is treated.

Answer 92

►A Women that have unwanted facial hair can use eflornithine and is also known as Vaniqa. It is applied to the skin for the reduction of unwanted facial hair. It inhibits ornithine decarboxylase located in the root of the hair follicle.

Answer 93

►E Ketoconazole causes rare fulminant hepatitis risk, gynecomastia, and impotence. It inhibits CYP 450 and is a triazole and a keratinophilic.

Answer 94

►E Phenophalein is an ingredient in laxatives and causes fixed drug eruption. Anticonvulsants, Isoniazid, hydralazine, minocycline, procainamide, penicilline, and D-penicillamine all cause SLE- like eruption.

Answer 95

►A Ciclopirox chelates polyvalent cations resulting in the inhibition of metal dependent enzymes that degrade peroxides in the fungal cell wall.

Answer 96

►A Griseofulvin has been reported as a potential exacerbator of acute intermittent porphyria, and thus is contraindicated in patients with a history of porphyria.

Answer 97

►E Hydrochlorothiazide causes a lichenoid eruption. Beta-lactam antibiotics, macrolide antibiotics, Mercury, and cephalosporins all have been known to cause AGEP.

Answer 98

►B Lichen-planus-like (lichenoid) drug eruptions have been reported with: antimalarials, B-blockers, captopril, gold, penicillamine, HCTZ, NSAIDs. Lichenoid drug reactions are often photodistributed.

Answer 99

►C When live attenuated varicella vaccine is given to healthy adults, it protects even individuals who never had serconversion or whose antibody levels were undetectable from severe varicella zoster viral disease.

Answer 100

►D Of the corticosteroids listed, the steroid with the lowest mineralcorticoid activity is methylprednisolone. Minerocorticoids act on the kidney to decrease the rate of sodium excretion (with accompanying retention of water). Triamcinolone, dexamethasone, and betamethasone also have low mineralcorticoid activity.

Answer 101

►B Cetirizine is a second-generation H1 antihistamine that is a low sedation metabolite of hydroxyzine.

Answer 102

►A Nitritoid reaction is after a gold injection that causes acute flushing, dizziness, hypotension, and fainting. Gold is used in treat severe lupus erythematosus and psoriatic arthritis. The most common reaction is mucocutaneous side effects such as stomatitis, cheilitis and li chen planus like eruptions and pityriasis rosea like eruptions.

Answer 103

►E Medications that alter the lipid composition of the epidermis and stratum corneum may impair the normal barrier function of the skin. Cholesterol lowering medications like HMG-CoA reductase inhibitors and niacin may cause xerosis through this mechanism.

Answer 104

►A Halobetasol propionate cream 0.05% is a superpotent Class 1 topical steroid. Triamcinolone acetonide ointment 0.1% and hydrocortisone valerate ointment 0.2% are medium potency class 4 topical steroids. Fluocinolone acetonide cream 0.025% is a medium potency class 4 topical steroid. Mometasone furoate ointment 0.1% is a high potency class 2 topical steroid.

Answer 105

►E Castellani's paint is a fungicidal and bactericidal agent. It contains boric acid, resorcinol, acetone, water, industrial methylated spirit, magenta, and phenol. Magenta may stain clothing and skin while phenol may be toxic in children.

Answer 106

►A Absorption through the scrotum is about 42 times greater than the ventral forearm. Although less, other occluded sites such as the axilla have increased percutaneous absorption. The palms and soles have the least due to the thick stratum corneum.

Answer 107

►E Imiquimod acts on toll like receptor 7. It can be used in the treatment of warts, actinic keratosis, superficial basal cell carcinomas and squamous cell carcinomas in-situ. It also up-regulates TNF alpha, IFN gamma and alpha and IL-12.

Answer 108

►C Drug hypersensitivity syndrome is characterized by fever, skin eruption and internal organ involvement. Drugs associated with drug hypersensitivity syndrome include sulfonamindes, dapsone, anticonvulsants (carbamezapine, phenobarbitol, lamotrigine), anti-retrovirals (ritonovir, nevirapine) and minocycline. Approximately 50% of patients will have abnormal liver enzymes.

Answer 109

►D All of the above drugs are pregnancy category B except efalizumab which is category C.

Answer 110

►A Patients on methotrexate with renal disease and on NSAIDs and TMP/SMX with no folate supplementation are at a great risk for pancytopenia. Leukovorin is given under conditions of methotrexate induced myelosuppression.

Answer 111

►D IVIG is used to treat several diseases including graft versus host disease, connective tissue disease, and autoimmune bullous dermatoses. Adverse effects include infusion reactions (headache, flushing, chills, myalgia, wheezing, Tachycardia, lower back pain, nausea, or hypotension). Anaphylaxis occurs rarely. Disseminated intravascular coagulation, transient neutropenia, and aseptic meningitis syndrome has been reported. Cutaneous adverse effects include eczematous eruptions and alopecia. c

Answer 112

►C The Wolff-Chaikoff effect is the inhibition of thyroid hormone synthesis from excess iodides which block organic iodides from binding in the thyroid. In patients with normal thyroid function, autoregulatory mechanisms allow for escape from this effect. In patients with impaired autoregulatory mechanisms, the Wolff-Chaikoff effect can lead to hypothyroidism. Thyroid function should be evaluated and monitored with patients started on potassium iodide.

Answer 113

►D This patient has minocyclin-induced hyperpigmentation. Hyperpigmentation is one of the most commonly observed side effects of minocycline and occurs regardless of dosage or treatment duration (although most often seen in patients after long-term treatment with the drug). Three distributions can be seen: Type I (blue-black pigmentation in sites of inflammation/scars), Type II (blue-black pigmentation on the anterior lower legs, and Type III (muddy brown diffuse pigmentation on normal, sun-exposed skin). This patient has Type II pigmentation.

Answer 114

►A Spironolactone is an antiandrogenic potassium sparing diuretic. It can be used for women with adult acne that is recalcitrant to treatment. Although it is not first line, it helps to block androgens that cause acne in the jawline. Spironolactone has a black box warning against patient with a personal history of breast cancer or family history of breast cancer.

Answer 115

►A Bexarotene can cause a central hypothyroidism with low TSH and T4. You must titrate the levothyroxine dose to the free T4 as it is a central hypothyroidism which is defined as insufficient TSH to stimulate an otherwise normal thyroid gland.

Answer 116

►C Isotretinoin, acitretin, and bexarotene are water-soluble, with very little lipid deposition. Etretinate is 50 times more lipophilic than acitretin, with increased storage in adipose tissue.

Answer 117

►C Many medications are associated with acneiform eruptions, including halogens (bromide and iodide), androgenic hormones such as testosterone, ACTH, corticosteroids, isoniazid (INH), lithium, phenytoin, and vitamins B2, B6 and B12.

Answer 118

►C Peak vulnerability to thalidomide occurs between days 21 to 36 of gestation, during which only a single dose will cause birth defects to occur. Birth defects associated with thalidomide include phocomelia (underdevelopment of arms and legs, the most common birth defect), ear malformation, and gastrointestinal and urogenital defects.

Answer 119

►D Drug/Specific enzyme inhibited Tacrolimus - Calcineurin Methotrexate - Dihydrofolate reductase Mycophenolate mofetil - Inosine monophosphate dyhydogenase Acyclovir - DNA Polymerase Terbinafine - Squalene epoxidase

Answer 120

►D Systemic retinoids, indinavir and capecitabine have all been describe to cause pyogenic granulomas.

Answer 121

►A Alefacept is given intramuscularly.

Answer 122

►A Bleomycin is an antibiotic that induces single strand breaks in the DNA. Reactions to bleomycin include flagellae hyperpigmentation, acral sclerosis with Reynaud's, penile calcification, and a morbilliform eruption. Etreinate is stored in the lipid for years and can be re-esterified to acitretin after ETOH. It should not be used for women that are wanting to get pregnant because it can be stored in the fat for years.

Answer 123

►A Etreinate is stored in the lipid for years and can be re-esterified to acitretin after ETOH. It should not be used for women that are wanting to get pregnant because it can be stored in the fat fo r years.

Answer 124

►B Thiopurine methyltransferase is one of three enzymes that metabolize azathioprine along with xanthine oxidase and HGPRT. Decreased activity of TPMT leads to heightened metabolism by HGPRT into the active 6-thioguanine. This may lead to increased toxicity including bone marrow suppression.

Answer 125

►D The use of cefaclor has been associated with an increased incidence of serum sickness in children.

Answer 126

►C Methotrexate is an antimetabolite that can be used for psoriasis and immunobullous diseases. At a cumulative dose at or above 4.0 grams can risk inducing liver fibrosis and cirrhosis. The liver biopsy is the gold standard diagnostic test.

Answer 127

►E Cetuximab is a chimeric anti-epidermal growth factor receptor antibody that is FDA approved to treat advanced colorectal cancer. Acneiform eruptions have been reported to occur in up to 1/3 of patients.

Answer 128

►B Neutrophilic eccrine hidradenitis most commonly occurs in the setting of a patient with acute myelogenous leukemia being treated with cytarabine. Clinical manifestations include tender, erythematous macules, papules and plaques on the trunk, neck and extremities which resolve within a few days. Histologically, this drug eruption is defined by the presence of dense neutrophilic infiltrate within and around eccrine glands, with necrosis of eccrine epithelial cells.

Answer 129

►D Grapefruit juice is an inhibitor of CYP3A4 at the intestinal mucosal membrane. The intestinal CYP3A4 is involved in "first pass" metabolism - thus with inhibition of this enzyme in the gut, less cyclosporine is metabolized, allowing for greater absorption of cyclosporine. Saquinivir also can be affected by this "first pass" inhibition by grapefruit juice.

Answer 130

►E None of the above statements are true. Dapsone and sulfapyridine exert their anti-inflammatory actions by inhibiting the myeloperoxidase activity and chemotactic abilities of polymorphonuclear leukocytes. Dapsone hypersenstivity syndrome is characterized by eosinophilia, as well as a severe mononucleosis-like reaction, including fever, erythroderma, hepatitis, and even death. Sulfapyridine has a similar but often less severe side effect profile. Cimetidine has been shown to provide some protection against methemoglobin formation.

Answer 131

►A Bexarotene is excreted via hepatobiliary excretion. The others are excreted in bile and urine.

Answer 132

►B The estolate form of erythromycin has been associated with cholestatic hepatitis.

Answer 133

►D Long-term therapy with oral corticosteroids can result in numerous adverse effects, including elevated risks of glaucoma, cataracts, hypertension, diabetes, osteoporosis, adrenal axis suppression, and aseptic bone necrosis. Alternate-day dosing or oral corticosteroids lowers the rate of adrenal axis suppression. It is hypothesized that during the off day, cell mediated immunity, white blood cells subset levels, and potassium excretion are normalized while the anti-inflammatory benefits of the drug persist. Alternate-day corticosteroid therapy should be employed once adequate disease control has been attained with daily dosing. Of note, the risk of cataracts, osteoporosis, and other adverse effects of long-term corticosteroid use are not minimized with alternate-day dosing.

Answer 134

►C Both azaithioprine and mycophenolate mofetil directly interfere with purine synthesis.

Answer 135

►B The form of erythromycin that most likely causes jaundice is estolate.

Answer 136

►A Glucocorticoids alter the balance of circulating leukocytes, causing an increase in the number of polymorphonuclear leukocytes and diminishing the numbers of lymphocytes, eosinophils, and monocytes.

Answer 137

►A Foscarnet is a non-competitive inhibitor of viral DNA polymerase. It does not require phosphorylation and can be used for acyclovir recalcitrant disease.

Answer 138

►A Azathioprine is a purine analog which is used to treat multiple inflammatory disorders, including autoimmune bullous disease, vasculitis, and severe dermatitis. A hypersensitivity syndrome with fever and shock can occur at around 14 days.

Answer 139

►A Despite low therapeutic responses of advanced cancers to retinoids, these drugs appear to have a promising role in chemoprevention. Patients with oral leukoplakia, actinic keratoses, arsenic keratoses, and Bowen's disease can benefit from retinoid therapy.

Answer 140

►C Physical blockers reflect and scatter UV rays, whereas chemical sunscreens absorb UV light and convert the absorbed energy into longer lower energy wavelengths. Menthyl anthranilate is a UVA blocker. Padimate O, a PABA derivative, is a UVB blocker. Photoallergy has been reported with increasing frequency to benzophenones. Allergic contact allergy can occur with PABA and its derivatives, which can cross react with azodyes, aniline, procaine, benzocaine, paraphenylenediamine, and sulfonamides.

Answer 141

►A A cream is a semisolid emulsion of oil in water that contains a preservative to prevent overgrowth of microorganisms. A gel is a semisolid transparent, nongreasy emulsion. A lotion is a liquid vehicle that is aqueous or alcohol-based that may contain a salt in solution. An ointment is a semisolid grease/oil, sometimes also containing powder, but little or now water; usually there is no preservative needed. A paste is an ointment with a high proportion of powder that gives it a stiff consistency.

Answer 142

►C Although post menopausal women are at greatest risk for fractures from steroid therapy (they have the weakest bones to begin with), it is young men who have the most dramatic decrease in bone density. Young men have the highest bone density on average and therefore will show the greatest change with steroid therapy. Trabecular bone (ribs, vertebrae) are more affected than cortical bones (long bones) due to higher metabolic rate of the former. Also, most demineralization occurs during the first 6-12 months of therapy. This highlights the fact that even young men who are not traditionaly at risk for fractures, need prophylaxis for osteoporosis while on systemic steroids.

Answer 143

►C Demeclocycline and doxycycline are the most phototoxic of all the tetracyclines.

Answer 144

►B Cimetidine and vitamin E can reduces the formation of methemoglobin, thereby increasing tolerance to dapsone which can lead to methemoglobinemia. Azathioprine can cause hepatitis, lymphoproliferative malignancy, infections, and hypersensitivity syndrome. Cyclosporine can lead to renal dysfunction, hypertension, and ginvigal hyperplasia. Rifampin can cause decreased effectiveness of oral contraceptives.

Answer 145

►A Fixed drug eruptions occur 30 mintues to 8 hours after ingestion of offending agent. After rechallenge with the same agent, the fixed drug eruption will recur. Potential causes of a fixed drug eruption include analgesics, sulfonamides, barbituates, pseudoephedrine and anticonvulsants. Pseudoephedrine causes non-pigmented fixed drug as shown in the photo.

Answer 146

►D Acitretin is an synthetic retinoid with affinity to the retinoic acid receptor (RAR). It can modulate the proliferation and differentiation of epidermal keratinocytes. The concurrent injestion of ethanol and alcohol increases the formation of etretinate. Unlike acitretin, etretinate is more lipophilic and accumulates in the fat. It therefore has a much longer elimination half -life, estiimated at 120 days.

Answer 147

►A Permethrin is a pyrethroid compound that disables sodium transport channels in the nerve cell membrane of the parasite, leading to paralysis. It is used in scabies infections.

Answer 148

►B Clofazamine can induce red-brown hyperpigmentation within skin lesions of patients with Hansen's disease (I.e. leprosy).

Answer 149

►E Castellani's paint was named after Sir Aldo Castellani and contains resorcinol, acetone, magenta, phenol, boric acid, industrial methylated spirit, and water. It is fungicidal and bactericidal with local anesthetic effects. It has been used to treat inflammatory tinea cruris, leg ulcers, and acute paronychia.

Answer 150

►A Fluoroquinolones inhibit DNA gyrase and is effective against Mycobacterium species, gramnegative infections and is contraindicated during pregnancy and in children because of evidence of its deposition in cartilage leading to impaired cartilage formation

Answer 151

►A Itracaonazole acts by inhibiting 14 alpha demethylase that blocks the conversion of lanosterol to ergosterol. It is highly lipophilic and has a affinity for cytochrome p450.

Answer 152

►A Tetracyclines bind the bacterial at the 30S ribosomal subunit. There is a risk of photosensitivity with this class of drug. Demeclocycline has the highest risk of photosensitivity.

Answer 153

►A Thiabendazole inhibits fumarate reductase, a helminth-specific enzyme. It is used to treat creeping eruption or cutaneous larva migrans and larva currens.

Answer 154

►A The answer is betamethasone is the longest acting systemic corticosteroid. The half life is 36 -54 hours. Methylprednisolone, prednisone, prednisolone, triamcinolone are intermediate acting and hydrocortisone is short acting with a half life of 8-12 hours.

Answer 155

►E Concomitant allopurinol use, which inhibits xanthine oxidase, can lead to excess toxic purine analogs via increased metabolism of azaithioprine via the HGPRT pathway, causing bone marrow suppression.

Answer 156

►A Mesna or sodium 2-mercptoethanesulfonate, has been used to reduce bladder toxicity from cyclophosphamide.

Answer 157

►A Leukovorin, or folinic acid, is able to bypass dihydrofolate reductase in the cell division pathway. It is administered under conditions of methotrexate-induced myelosuppression. Leukovorin is also available as an oral form, and may be administered as a continual part of methotrexate therapy, instead of folic acid. It is now believed that neither folic acid nor folinic acid inhibit the efficacy of methotrexateï¿½s antipsoriatic actions.

Answer 158

►A Cromolyn sodium blocks mast cell degranulation and is used for controlling diarrhea in mastocytosis.

Answer 159

►E Drugs associated with drug-induced SLE include minocycline, hydralazine, procainamide, isonaizid, penicillamine, and anti-convulsants.

Answer 160

►A Anti-histone Ab is most specific for drug-induced lupus. In addition to minocycline, hydralazine, procainamide, isonaizid (INH), penicillamine and anti-convulsants have been associated with drug- induced lupus-like syndrome.

Answer 161

►C Polsen et. al. reported a 29% incidence of sticky skin in patients treated with high dose ketoconazole and doxorubicin for prostate cancer. Other medications reported to cause this include etretinate and tretinoin. Polsen JA, Cohen PR, Sella: Acquired cutaneous adherence in patients with androgen-independent prostate cancer receiving ketoconazole and doxorubicin: medication-induced sticky skin. J Am Acad Dermatol: 32 (4):571-5 1995

Answer 162

►A All of the above medications are involved in the pathophysiology of pseudo-PCT except for penicillin. Patients with pseudo-PCT have normal porphyrin profile.

Answer 163

►E The most relevant drug interactions in dermatology involve the hepatic biotransformation pathways catalyzed by the cytochrome P-450 isoenzymes from the subfamilies CYP3A3/4. Drugs that induce CYP3A enzymes may decrease levels of drugs which act as substrates for CYP3A. CYP3A inhibitors may increase levels and cause toxicity of drugs metabolized by cytochrome P-450. Terbinafine is not metabolized by cytochrome P-450, but inhibits CYP2D6mediated metabolism. Tobacco induces P-450 enzymes.

Answer 164

►C Side effects of psoralen with ultraviolet A light (PUVA) include side effects which are due to phototoxic effects including pruritus, photoonycholysis, friction blisters, ankle edema and hypertrichosis. In addition, there are adverse effects from methoxypsoralen including gastrointestinal and neurologic effects, hepatotoxicity and exanthems. Neutropenia is not a described side effect of PUVA.

Answer 165

►B Cimetidine and vitamin E have both been known to provide prophylaxis against methemoglobin formation. G6PD-deficient individuals are at greater risk of hematologic toxicity from dapsone.

Answer 166

►A Tetracyclines inhibit protein synthesis by binding to the 30S ribosomal subunit. It is effective agains both gram positive and gram negative organisms and mycoplasma infections

Answer 167

►B Ketoconazole and itraconazole require an acidic environment. Fluconazole, however, does not require an acidic environment and can work safely and effectively in patients taking antacids, which can raise gastric pH levels.

Answer 168

►A Sulisobenzone is a benzophenone, a UVA blocker. The others are UVB blockers. Padimate A is a PABA derivative.

Answer 169

►C Staphylococcus aureus colonization tends to correlate with isotretinoin-induced reduction in sebum production and may lead to infections. This complication may possibly be prevented with pulsed intranasal mupirocen therapy. There has been a report of staphylococcus endocarditis in a patient with underlying aortic insufficiency.

Answer 170

►C The laboratory abnormalities associated with cyclosporine are decreased magnesium, increased potassium, and increased uric acid. Renal function and blood pressure must also be monitored closely in patients using cyclosporine.

Answer 171

►A Acyclovir is a guanosine analog. It is preferentially phosphorylated by viral thymidine kinase. It inhibits viral DNA polymerase, halting viral DNA synthesis by chain termination. Rapid intravenous infusion of acyclovir has been associated with a reverisble obstructive nephropathy.

Answer 172

►D The hypersensivity reaction associated with abacavir usually resolves with cessation of the drug, however upon rechallenge the reaction can be life-threatening.

Answer 173

►E All of the following are cutaneous side effects reported with zidovudine, a nucleoside HIV reverse transcriptase inhibitor. Periungal/paronychial eruptions resulting in pyogenic granulomalike lesions have also been reported with other HIV medications, including indinavir and lamivudine.

Answer 174

►D Imiquimod is an immune response modifier that acts via the toll like receptor 7. It induces cytokines including interferon alpha, interleukins 1, 5, 6, 8, 10, and tumor necrosis factor. It has been used to treat Erythroplasia of Queyrat, superficial basal cell carcinomas, actinic keratoses, extramammary Paget‟s disease, and warts.

Answer 175

►A Clindamycin is particularly effective against anaerobic and gram-positive organisms, particularly those causing deep tissue infections. It works by binding to the 50S ribosomal subunit thereby inhibiting protein synthesis. Macrolide antibiotics such as erythromycin also work by this mechanism. Fluoroquinolones block DNA gyrase. Tetracyclines inhibit the 30S subunit of ribosomes. Penicillin blocks transpeptidation of the bacterial cell wall.

Answer 176

►B Terbinafine is an allylamine antifungal that is fungicidal. It works via noncompetitive inhibition of squalene epoxydation. Amphotericin is also fungicidal. The azoles are fungistatic and inhibit 14-alpha-demthylase to prevent ergosterol synthesis. Griseofulvin disrupts microtubule formation.

Answer 177

►C Ketoconazole has been shown to be the strongest inhibitor of cytochrome p450 (CYP) 3A4. Itraconazole is an inhibitor of CYP 3A4, whereas fluconazole inhibites CYP 2C9 sign ificantly more than minimal inhibitory role of CYP 3A4. Terbinafine inhibits CYP 2D6. c

Answer 178

►E Pigmented incontinence is usually prominent in a fixed drug eruption; yet occasionally, fixed drug reactions do not result in long-lasting hyperpigmentation. The so-called nonpigmented fixed drug eruption is distictive. Pseudoephedrine hydrochloride is by far the most common cause.

Answer 179

►B Alefacept is a human LFA-3/IgG fusion protein, which blocks LFA-3 on antigen presenting cells from interacting with CD-2 on T-cells, preventing T-cell stimulation. Alefacept also eliminates activated memory-effector T-cells, so weekly CD4 T-cell counts are required.

Answer 180

►D Cimetidine is an H2 antihistamine that has suppressor T-cell inhibitory activity, by competitively blocking their H2 receptors. Immunomodulatory effects are useful for treating mucocutaneous candidiasis, verruca vulgaris, and condyloma acuminata.

Answer 181

►A Denileukin difitox (brand name Ontak) is approved for the treatment of cutaneous T-cell lymphoma. Denileukin difitox is a fusion protein composed from a portion of IL-2 with diphtheria toxin. The chemotherapy is taken up by cells expressing high-affinity IL-2 receptors. Capillary leak syndrome presenting with hypotension, edema, pleural effusions, and weight gain caused by fluid retention has been reported in patients receiving denileukin difitox.

Answer 182

►A Penicillins, cephalosporins, carbapenems, and vancomycin work on the cell wall. Quinolones inhibit DNA gyrase. Tetracyclines and aminoglycosides work at the 30 S ribosomal subunit.

Answer 183

►A Dapsone is a lipid-soluble sulfone drug that is used widely in dermatology in a variety of conditions including dermatitis herpetiformis, leprosy, and neutrophilic dermatoses. Adverse effects from dapsone are both pharmacologic and idiosyncratic and include hemolytic anemia, methemoglobinemia, agranulocytosis, hypersensitivity syndrome and neuropathy. Of these, the first two are pharmacologic and anticipated, to some degree, in most patients treated with dapsone. However, the magnitude of toxicity varies greatly among individuals on the drug. Methemoglobinemia is the formation of methemoglobin in the blood, which has a decreased oxygen-carrying capacity compared with hemoglobin and can result in cyanosis. The reaction is related to the N-hydroxy metabolites of dapsone, which are potent oxidants. G6PD-deficient individuals are more susceptible to oxidative stresses, including those from dapsone metabolites, and a baseline G6PD level is recommended prior to initiation of dapsone therapy. In the event of emergent methemoglobinemia, oral methylene blue (100-300 mg/day) can be used to decrease methemoglobin levels. However, if the patient is G6PD deficient, this strategy is ineffective.

Answer 184

►B Neutrophilic eccrine hidradenitis occurs in neutropenic patients with malignancies, usually acute myelogenous leukemia. Cytarabine is the most commonly associated medication.

Answer 185

►E Etretinate is 50x more lipophilic than acitretin with increased storage in adipose tissue. The highly lipid soluble etretinate lasts several years in the fatty tissues, in the presence of ethanol and acitretin is re-esterified to etretinate.

Answer 186

►A Cyclophosphamide disrupts DNA cross linkage. It is the treatment of choice for Wegener's and there is a risk for hemorrhagic cystitis. In up to 40% of patients there is a risk for transitional cell bladder cancer.

Answer 187

►C Podophyllin is a crude cytotoxic extract from the May apple plant. It is antimitotic, arresting cells in metaphase (not telophase) by binding to the protein tubulin. It may be teratogenic and should not be used in pregnancy.

Answer 188

►E Category X drugs include: acitretin, etretinate, estrogens, finasteride, 5-fluorouracil, flutamide, isotretinoin, methotrexate, stanozolol, thalidomide, and tazarotene.

Answer 189

►B The most likely diagnosis is neutrophilic eccrine hidradenititis. Cytarabine is the usual offending agent.

Answer 190

►B Bladder toxicity is due to the acrolein metabolite of cyclophosphamide. Hemorrhagic cystitis is associated with the increased risk of transitional cell carcinoma of the bladder. Mesna has been used to reduce the toxic effect. The risk of cystitis is avoided by adequate fluid intake, frequent voiding, and careful screening for hematuria.

Answer 191

►A The most common cause of fixed drug eruption is tetracyclines. There is also a risk of brown discoloration of the teeth and delayed bone growth it should not be used in children in less than 9 years old.

Answer 192

►A Hydroxyurea is a cytotoxic agent that is used to treat psoriasis, scleromyxedema, and Sweet's syndrome. Poikiloderma of the dorsal hands with a band-like distribution over the fingers and toes, diffuse hyperpigmentation, and leg ulcers upon withdrawal of the medication have been described. Radiation recall, acral erythema and dermatomyositis like reactions are other rare side effects.

Answer 193

►A Calcipotriene is relatively unstable and inactivated by acidic pH, ie with ammonium lactate and salicylic acid. The other statements are true. Psoriasis is classically a TH1 disease and this medicine upregulates TH2 cytokines it is commonly used to treat this condition. It has mild anti inflammatory properties via its inhibition of NF-kB. It also inhibits cell proliferation and induces cell differentiation.

Answer 194

►A The patient has infectious mononucleosis and is developing a morbilliform eruption from treatment with ampicillin. It affects teenagers and young adults. They also develop malaise, headache, pharyngitis, hepatosplenomegaly and fevers.

Answer 195

►E First-generation retinoids are tretinoin (all-trans RA) and isotretinoin (13-cis RA). Secondgeneration synthetic retinoids are etretinate, which was replaced by its metabolite acitretin. Third-generation (polyaromatic retinoids) include the arotinoids, tazarotene, adapalene, and bexarotene.

Answer 196

►A A fixed drug eruption is a single or multiple oval or annular erythematous patches that arise as a result of exposure to a systemic medication. Repeat exposure to the offending drug can cause reappearance of the lesions in the same location. Tetracycline is the most common cause of fixed drug eruption.

Answer 197

►B Medications that can precipitate acute attacks in variegate porphyria include barbiturates, estrogen, griseofulvin, sulfonamides and ethanol. Ketoconazole can produce impotence and gynecomastia by interfering with androgen synthesis. Ketoconazole inhibits cytochrome (CYP) P450 and most concerning, can rarely cause fulminant hepatitis. Griseofulvin induces CYP P450, not inhibits it. Terbinafine is fungicidal along with amphotericin B. Ketoconazole is fungistatic.

Answer 198

►C Keratinocyte differentiation is enhanced by retinoids with increased filaggrin production, increased keratohyalin granules, keratin filaments, and Odland body secretion of lipids. Retinoids directly inhibit ornithine decarboxylase and therefore lessen inflammatory hyperplasia.

Answer 199

►E Methotrexate is a S-phase specific antimetabolite which competitively and irreversibly blocks dihydrofolate reductase from catalyzing the formation of tetrahydrofolate, an important cofactor in thymidylate and purine synthesis. Tetracyclines, phenytoin, phenothiazines, chloramphenicol, NSAIDs, salicylates, and sulfonamides can all increase methotrexate levels by displacement of plasma proteins. Acetaminophen is safe for concurrent use with methotrexate.

Answer 200

►E Exogenous ochronosis has been reported with prolonged use of high concentration hydroquinone. On pathology, a characteristic ochre colored deposit is noted between the collagen bundles.

Answer 201

►A Polidocanol is a detergent type of sclera agent and can have a disulfiram like reaction. It also has a very rare risk of anaphylaxis. Sodium morrhuate is also a detergent sclera agent and has the highest risk of anaphylaxis.

Answer 202

►B Thalidomide was introduced in the late 1950's as a "safe" sleeping aide. It readily penetrates the CNS, where it exerts a hyposedative effect comparable with barbiturates. By far, the most common adverse effect from thalidomide is sedation, which in many patients may require that primarily night-time doses be utilized.

Answer 203

►C The t 1/2 of isotretinoin is 20 hours. The other answers list the t 1/2 times of various retinoids.

Answer 204

►B The patient presents with blue-gray discoloration in sun-exposed areas. The most likely offending agent is amiodarone. Blue-gray discoloration from minocycline usually occurs on legs. Chloroquine usually causes blue-gray discoloration in the sclerae, teeth, buccal mucosa, nail beds, and pretibial areas. Quinacrine causes yellow discoloration of skin and conjunctiva. Clofazamine usually causes a red-brown discoloration.

Answer 205

►A Erythema Nodosum Leprosum is a type 2 reaction of leprosy. It most commmonly ocurrs in lepromatous leprosy. Clinically, it presents as painful nodules and is associated with fever, malaise, anorexia, and arthralgias. The treatment of choice is thalidomide.

Answer 206

►C Risk of retinopathy is greatest with chloroquine and does not exist for quinacrine.

Answer 207

►E Etretinate has a prolonged half-life of 80-160 days. The levels may persist up to 3 years in the body. Acitretin can be converted to etretinate in the presence of ethanol.

Answer 208

►C Bleomycin use has been associated with Raynaud's phenomenon occurring in digits treated with intralesional therapy for periungual and plantar warts.

Answer 209

►D Chloramphenicol is the treatment of choice for pregnant patients with Rocky Mountain Spotted Fever. In non-pregnant patients, the treatment of choice is Doxycycline.

Answer 210

►D Allopurinol inhibits xanthine oxidase, an enzyme that catabolizes azathioprine. In patients concurrently taking bothe medications, the allopurinol shunts more 6-MP from the xanthine oxidase catabolic pathway to the hypoxanthine-guanine phosphoribosyltransferase(HGPRT)anabolic pathway, creating an excess of purine analogs. This in turn may lead to to excessive immunosuppression and risk of pancytopenia.

Answer 211

►B Ivermectin (Stromectol) is an anti-helminthic agent currently FDA-approved for the treatment of strongyloides and onchocerciasis. Several publications have reported efficacy of this agent in the treatment of scabies and head lice. Due to its low rate of adverse effects, its high rate of effectiveness, and its ease of administration, some authors consider this agent to be the treatment of choice for scabies and head lice. The mechanism of action of ivermectin is blockade of glutamate- gated, chloride ion channels, with adverse effects on nerve and muscle resulting in paralysis and death of the helminth or mite. The drug has a very low affinity for mammalian chloride channels resulting in its relatively low toxicity. Adverse effects are rare and have been associated with accidental intoxication. It should be avoided when there is compromise of the blood-brain-barrier. Ivermectin is pregnancy category C. There are virtually no associated drug interactions with oral ivermectin therapy.

Answer 212

►D Bexarotene targets RXR receptors. It is used in the treatment of mycosis fungoides refractory to conventional therapy. Side effects include central hypothyroidism and hyperlipidemia. These should be treated with synthroid, lipitor, and fenofibrate.

Answer 213

►E Rifampin is an antibiotic used frequently for M. leprae and M. tuberculosis. It is the only drug bactericidal to M. leprae. Its mechanism of action is by inhibiting RNA synthesis by inhibiting DNA-dependent RNA polymerase. Penicillin G inhibits bacterial cell wall synthesis by blocking the transpeptidation step. Cephalosporins have a similar mechanism of action, possessing a betalactam ring. Tetracycline inhibits protein synthesis by binding and inhibiting the 30S ribosome while the fluoroquinolone family inhibits DNA gyrase.

Answer 214

►C Wegener granulomatosis is an idiopathic disorder characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomerulonephritis, and a variable degree of small-vessel vasculitis. Testing for c-ANCA is 90% sensitive for the diagnosis when the presentation is classic. Cyclophosphamide has been used very effectively and now is the usual drug of choice for induction of remission.

Answer 215

►D Glucocorticoids play a diverse role in the human body. They modulate transcription of specific genes that lead to an increase or decrease in the levels of specific proteins, ie they decrease transcription of AP-1 and NF-kB. All the other statements are true. Side effects include osteoporosis, hyperglycemia, hypertension, poor wound healing, peptic ulcers, Cushingoid features, and muscle weakness.

Answer 216

►A The most common side effect of azathioprine (Imuran) is bone marrow suppresion (Pancytopenia). It is a rare adverse event resulting from excessive immunosuppression by azathioprine. To prevent catastrophic bone marrow failure, regular complete blood counts should be checked.

Answer 217

►A Systemic corticosteroids are commonly used in dermatology. Short acting steroids, cortisone and hydrocortisone, have the greatest mineralocorticoid activity, while cortisone has the lowest glucocorticoid activity. Intermediate and long-acting steroids, methylprednisolone, triamcinolone, dexamethasone, and betamethasone, have virtually no mineralocorticoid activity. Dexamethasone and betamethasone have the highest glucocorticoid activity.

Answer 218

►B Drugs that simultaneously inhibit the folate metabolic pathway, such as NSAIDS, dapsone, or trimethoprim-sulfamethoxazole, can increase hematologic toxicity when combined with methotrexate.

Answer 219

►A Stanozolol and Danazol are synthetic derivatives of testosterone with anabolic properties. It is a potent fibrinolytic activity used in the treatment of cryofibrinogenemia, lipodermatosclerosis, and livedoid vasculitis.

Answer 220

►E Malathion, an organophosphate cholinesterase inhibitor used to treat scabies and head lice, is flammable.

Answer 221

►E Mycophenolate mofetil (cellcept), a purine analog, blocks de novo purine synthesis by inhibiting the enzyme inosine monophosphate dehydrogenase.

Answer 222

►A Hydroxyurea is a S-phase specific cytotoxic agent which inhibits ribonucleotide reductase, an enzyme responsible for converting ribonucleotides to deoxyribonucleotides in DNA synthesis. Anemia, hepatitis, and renal toxicity are associated adverse effects. Fluoroquinolones inhibit DNA gyrase. Methotrexate inhibits dihydrofolate reductase. Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase. Acyclovir utitilizes thymidine kinase to interrupt viral replication.

Answer 223

►D Thiabendazole inhibits fumarate reductase, a helminth-specific enzyme. It is used to treat creeping eruption or cutaneous larva migrans and larva currens. Ivermectin blocks glutamategated chloride ion channels, and is used to treat strongyloidiasis, onchocerciasis, and Norwegian scabies. Lindane is an organochloride which blocks neural transmission, and is effective against scabies, pubic lice, head lice, and body lice. Permethrin disables sodium transport channels in the nerve cell membrane of the parasite. Cidofovir is an antiviral nucleotide analogue.

Answer 224

►A Chlorambucil is a nitrogen mustard derivative that is used as a steroid sparing agent in vasculitis, Behcet\'s disease, dermatomyositis, and sarcoidosis. In children with nephritic syndrome or adults with a seizure history, it can cause generalized tonic-clonic seizures.

Answer 225

►B Oral contraceptives decrease free testosterone levels by increasing the production of sex hormone binding globulin (SHBG).

Answer 226

►B The constellation of adverse effects is most closely associated with hydroxyurea.

Answer 227

►E Renal failure may prolong the half-life of most tetracyclines except doxycycline. Doxycycline is excreted via the GI tract, unlike the other tetracyclines.

Answer 228

►E All agents listed are associated with fixed drug eruptions, however, pseudoephedrine hydrochloride is the one most commonly associated with non-pigmenting fixed drug eruptions.

Answer 229

►D Topical nitrogen mustard, or mechlorethamine, is an antineoplastic agent which works via alkylation thereby inhibiting DNA synthesis. Allergic contact dermatitis occurs in two-thirds of patients who are treated with topical nitrogen mustard in aqueous solution, but occurs in less than 5% of patients treated with the ointment based preparation. c

Answer 230

►C The recommended period for contraception after acitretin therapy is three years. Isotretinoin, acitretin and bexarotene are water soluble with very little lipid deposition. It is un -detecable in the serum after one month of stopping therapy.

Answer 231

►B Systemic retinoids like acitretin have been used in the chemoprophylaxis of skin cancers. Several studies have suggested a beneficial effect of retinoids with lowered incidences of skin cancer. However, following cessation of the retinoids, the incidence normalizes.

Answer 232

►A Valacyclovir is a prodrug of acyclovir and is used in acute HSV 1 and 2 infections. It is converted in first pass through gastrointestinal tract and liver to acyclovir. It is probably better for zoster than acyclovir. It is not approved in immunosuppressed patients.

Answer 233

►D All of the above inhibit the folic acid metabolic pathway, and can lead to hematologic toxicity when combined with methotrexate.

Answer 234

►C Podophyllotoxin, also known as podofilox or Condolox, is a anti-mitotic agent that reversibly binds tubulin, arresting cells in metaphase. It is used topically to treat genital warts. Podophyllin, which has the same mechanism of action, contains kaempero and quercetin which are potent mutagens. Both are derived from the May Apple plant. Cantharin, an antiviral agent derived from the Blister beetle, is a phosphodiesterase inhibitior.

Answer 235

►C Three types of ocular adverse effects may develop from antimalarials: corneal deposits, neuromuscular eye toxicity and retinopathy. Only retinopathy is potentially irreversible. It is recommended that a patient be evaluated for retinopathy at baseline, then every 6 months by an ophthamologist. Testing visual acuity, visual fields and performing a funduscopic examination are considered acceptable for screening purposes.

Answer 236

►D True retinopathy is associated with "bull's eye" pigment deposition, central scotoma, and diminished visual acuity. Chloroquine is at greatest risk of causing retinopathy. Quinacrine is not associated with the risk of retinopathy.

Answer 237

►A The most common presentation of the neuropathy from thalidomide is a mild proximal muscle weakness with symmetric painful paresthesias of the distal extremities with accompanying lower limb sensory loss. Hypothyroidism is a rarely reported adverse effect.

Answer 238

►C Dapsone inhibits the neutrophil halide-myeloperoxidase system which results in an impaired respiratory burst and subsequent tissue damage.

Answer 239

►A Bexarotene is a third generation retinoid. Other include arotinoid, tazarotene, adapalene, and bexarotene that selectively act on specific receptors. Bexarotene has been shown to caus e reversible hypothyroidism.

Answer 240

►B The benzophenones, oxybenzone and dioxybenzone, have the broadest absorption spectrum of the chemical sunscreens, with UVB and UVA II range. Methyl anthranilate absorbs UVA II, and octyl salicylate, and padimate O are UVB-absorbing chemicals. Titanium dioxide is not a chemical absorber, it is a physical blocker.

Answer 241

►D Drug penetration varies depending on body site and thickness of stratum corneum. An important consideration in topical therapy is that abnormal skin may have an altered (increased, decreased, or absent) stratum corneum, thus changing the body site's barrier function. Regional penetration of topical therapy is ranked from highest penetration to less penetration as following: Mucous membrane > scrotum > eyelids > face > chest and back > upper arms and legs > dorsal hands and feet > palms and soles > nails

Answer 242

►C Genital ulcers have been reported as a complication of foscarnet therapy.

Answer 243

►B The risk of pseudotumor cerebri is increased in patients on isotretinoin and a tetracycline.

Answer 244

►C Eythromycin inhibits the hepatic cytochrome P450 system and can increase serum levels and potential toxicities of carbamazapene, theophylline, warfarin, digoxin, methylprednisolone.

Answer 245

►A Terbinafine block ergosterol synthesis early in the synthetic pathway by inhibitins squalene epoxidase. Squalene then accumulates within fungal cells and discupts cell membranes. At standard dosaging, it is believed to be fungicidal. The other choices are fungistatic.

Answer 246

►E Antacids decrease the absorption of fluoroquinolones and should be taken at least 2 hours after the drug. Tetracycline absorption is impaired by the ingestion of dairy products, calcium, and iron or zinc salts. Minocycline and doxycycline absorption may be impaired by the ingestion of those products; they may be taken on an empty stomach or with food. Thus, all of the statements are false.

Answer 247

►A Macrolides inhibit the 50S ribosomal subunit during protein synthesis. Arthyromycin and clarithromycin are effective in the treatment of gram-negative soft-tissue infections. Erythromycin is effective against acne, pyodermas, erythrasma, and pitted keratolysis.

Answer 248

►C procollagen 3 testing. Procollagen 3 has been shown to be a sensitive marker for methotrexate induced liver fibrosis. Procollagen 1 is a marker for AFX.

Answer 249

►A Amiodarone can cause slate gray hyperpigmentation in photo-exposed areas. Histologically, there are yellow-brown granules are seen in macrophages in the dermis.

Answer 250

►C Foscarnet does not require phosphorylaton for antiviral activity. Therefore, it is achieved against viruses resistant to acyclovir, famcyclovir, or gancyclovir on the basis of altered-kinase activities.

Answer 251

►B Valacyclovir has been associated with severe and even fatal cases of thrombotic thrombocytopenic purpura / HUS syndrome in AIDS and transplant patients taking high doses.

Answer 252

►D Long term use of oral corticosteroids has been shown to decrease bone mineral density (BMD). This decrease in BMD leads to an increased risk for fractures. It was originally thought that Vitamin A analogues such as isotretinoin and acitretin may also increase the risk of fracture but in a large case-controlled study published in the May 2010 Archives illustrates that risk of fracture is not associated with Vitamin A analogues. Vitamin A analogues have been associated with hyperostosis.

Answer 253

►B The Mazzotti reaction is characterized by urticaria, fever, chills, sweats, abdominal pain, arthralgias, and lymphadenopathy. Hypotension and tachycardia may also be present, and the reaction can be life threatening. Mazzotti reactions are most often associated with the administration of diethylcarbamazine for the treatment of onchocerciasis, but may be seen during treatment with other anti-helminthics, such as suramin. The pathogenesis of Mazzotti reactions is thought to be consequent to abrupt release of parasitic antigens during cell death, prompting an intense inflammatory cascade. Currently, ivermectin is the treatment of choice for onchocerciasis, which has a lower incidence of associated Mazzotti reactions (approximately 10%).

Answer 254

►A Rifampin has been shown to decrease the efficacy of oral contraceptives. It is an inducer of cytochrome p450 which increases the metabolism of hormones thereby decreasing the efficacy of oral contraceptives. There is no clear decrease in oral contraceptive efficacy with concomitant use of ampicillin, ciprofloxacin, clarithromycin, doxycyline, metronidzole, ofloxacin, or tetracycline.

Answer 255

►A Erythromycin estolate is contraindicated in pregnancy because of the risk of cholestatic hepatitis. Other forms of erythromycin are safer for use in pregnancy. Tetracyclines are category D and estrogens are category X. NSAIDS may promote persistent fetal circulation or oligohydramnios.

Answer 256

►B Mucocutaneous side effects, which are more common with injectable gold, include stomatitis, cheilitis, lichen planus-like eruptions, and pityriasis rosea-like eruptions.

Answer 257

►D Rituximab is an anti-CD20 monoclonal antibody. CD20 is a B-cell marker and is used to treat Non- Hodgkins B-cell lymphoma. It is also approved for the treatment of rheumatoid arthritis.

Answer 258

►C Foscarnet has been reported to cause penile erosions.

Answer 259

►A Colchicine is an alkaloid with antimitotic activity that is used in dermatology for its effects on neutrophils. The most common side effect from colchicine use is gastrointestinal distress with abdominal cramping and watery diarrhea.

Answer 260

►A Thalidomide is the drug of choice for erythema nodosum leprosum. It is known for its uses in HIV associated mucosal ulceration and apthous stomatitis, chronic cutaneous lupus erythematosus and chronic GVHD.

Answer 261

►D Cyclosporine binds to cyclophilin, an intracellular immunophilin, and inhibits the activity of calcineurin phosphatase, which is then unable to dephosphorylate NFAT. Guidelines limit the use of cyclosporine in the US to one year. Cyclosporine is an effective treatment for psoriatic arthritis, alone or in combination with methotrexate. Cyclosporine inhibits the activation of T cells, NK cells, and antigen presenting cells. And cyclosporine has shown some efficacy in histamine resistant chronic urticaria.

Answer 262

►B All of the listed medications have been reported to cause nail hyperpigmentation, but the addition of oral hyperpigmented macules and trichomegaly (lengthened anagen phase of the eyelashes). AZT can also cause bone marrow suppression with subsequent anemia and granulocytopenia.

Answer 263

►D CMV is most susceptible to cidofovir, ganciclovir, and valganciclovir. HSV-1 and HSV-2 are more susceptible to acyclovir and famciclovir. Foscarnet can be used to treat resistant strains of CMV, HSV-1 and HSV-2.

Answer 264

►B The most common electrolyte abnormalities associated with cyclosporin A are hyperkalemia, hyperuricemia, and hypomagnesemia.

Answer 265

►E Hydroxyurea has been associated with poikiloderma of the dorsal hands with a band-like distribution of the fingers and toes. It has also been associated with diffuse hyperpigmentation, and with leg ulcers upon withdrawal.

Answer 266

►A All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers.

Answer 267

►C Melanonychia occurring simultaneously on several nails is most likely to be due to minocycline therapy. Blue-black pigmentation may be present in nails, skin, scars and sclerae.

Answer 268

►D All of the above are side effects of bleomycin except serpentine supravenous hyperpigmentation. This is a side-effect of 5-fluorouracil.

Answer 269

►D Azelaic Acid is pregnancy category B. The other choices are in less safe pregnancy categories. Epinephrine is category C, Benzoyl peroxide is category C, and Methotrexate and Isotretinoin are category X.

Answer 270

►A NSAIDS (including ibuprofen) and Azathiprine have been associated with IUD failure. The other listed medications are all pregnancy category B and should be safe for use in this patient.

Answer 271

►C Drugs are category C if risk to the human fetus cannot be ruled out, studies are lacking, or animal studies are equivocal. Drugs for which risk to the human fetus has been demonstrated are pregnancy category D.

Answer 272

►E Acute generalized exanthematous pustulosis (AGEP) has been associated with beta-lactam antibiotics, macrolide antibiotics, cephalosporins, and mercury.

Answer 273

►B The half-life of isotretinoin is 20 hours. The half lives of bexarotene, acitretin, etretinate are 7 hours, 50 hours, 120 days respectively.

Answer 274

►D Cefazolin, cephradrine, cephalexin are all first generation cephalosporin. The correct answer is cefaclor, which is a second generation cephalosporin. Cefotaxime is a 3rd generation cephalosporin.

Answer 275

►A Quinacrine frequently produces a yellow discoloration of the sclera and skin, especially over the dorsal hands and feet. Minocycline and hydroxychloroquine can cause bluish-gray hyperpigmentation. Terbinafine and prednisone are not associated with alteration of cutaneous pigmentation.

Answer 276

►E Anticonvulsant hypersensitivity syndrome (also drug rash with eosinophilia and systemic symptoms (DRESS0 and dilantin hypersensitivity syndrome) presents with cutaneous eruption accompanied by fever, facial edema, lymphadenopathy, leukocytosis and hepatitis. Cross reactivity is present in all aromatic anticonvulsants including phenytoin, carbamazepine and phenobarbitol. There is no cross reaction with valproic acid.

Answer 277

►A Isotretinoin, acitretin, and bexarotene are water-soluble, with very little lipid deposition. Watersoluble retinoids are undetectable in the serum 1 month after stopping therapy. Etretinate is 50 times more lipophilic than acitretin. It can last several years in fatty tissues.

Answer 278

►E This patient is most likely taking metronidazole for acute diarrhea secondary to giardella. Metronidazole causes antabuse-like reactions with ingestion of alcohol.

Answer 279

►A For cold urticaria, the antihistamine that is first generation is cyproheptadine. First generation antihistamine have the side effect of sedation, increased appetite, dry mouth, and constipation.

Answer 280

►E Linear IgA dermatosis can be due to vancomycin, lithium, amiodarone, captopril, and penicillin. Actinomycin D can cause folliculitis.

Answer 281

►E SCLE-like reaction are known to occur most likely from glyburide, griseofulvin, captopril, hydrochlorothiazide, penicillamine, piroxicam, and terbinafine.

Answer 282

►C Erythromycin inhibits the cytochrome P-450 system, which may result in increased levels of digoxin, among many other drugs.

Answer 283

►E Bexarotene has been shown to cause reversible hypothyroidism, not hyperthyroidism. Systemic retinoids have been shown to cause diffuse interstitial skeletal hyperostosis, premature epiphyseal closure, and pseudotumor cerebri (risk increased with concommitant use of tetracyclines).

Answer 284

►D Cidofovir is a nucleotide analogue antiviral agent. It does not require phosphorylation by virus, but is converted by host cell kinases to a diphosphate.

Answer 285

►B Acyclovir relies upon the fact that thymidine kinase is produced at a higher rate in herpes infected cells than in noninfected cells. It is a guanosine analog that is preferentially phosphorylated by viral thymidine kinase which then inhibits viral DNA polymerase, thus halting viral DNA synthesis by chain termination. Acyclovir does not inhibit viral RNA polymerase or boost immune destruction of infected cells. It is not a non-competitive inhibitor of viral DNA polymerase at the pyrophosphate binding site â€“ this mechanism of action is that of Foscarnet, also an antiviral active against HSV.

Answer 286

►D Thio-TEPA is an alkylating agent used in a variety of cancers. It can cause pruritus, urticaria, angioedema, and hyperpigmentation localized to occluded areas. Generalized Addisonian- hyperpigmentation may be caused by busulfan. Hyperpigmentation of the teeth with discoloration of the gingival margins is associated with cyclophosphamide. Intense flushing of the skin is usually seen with dacarbazine and carmustine. Alternating colors of hair, representing the "flag sign," can be seen with methotrexate.

Answer 287

►A Toxic epidermal necrolysis is a life threatening drug eruption characterized by widespread epidermal necrosis. The exact etiology of the keratinocyte necrosis has not been fully elucidated. However, FasL (FasL and Fas are able to trigger apoptosis) has been shown to be upregulated in TEN. There is also drug induced increased secretion of granulysin from cytotoxic T cells, and NK cells.

Answer 288

►D Sedation is a very common side effect of treatment with thalidomide. It is additive with other sedatives, such as alcohol and barbiturates.

Answer 289

►E Cefaclor has been associated with an increased incidence of serum sickness in children; the other drugs have not.

Answer 290

►B Isotretinoin is a oral retinoid that helps with nodulocystic acne. When isotretinoin is combined with tetracycline there is an increased risk for pseudotumor cerebri. It should not be used together or in patients with a history of pseudotumor cerebri that has been diagnosed by a neurologist. Pseudotumor cerebri can be diagnosed by measuring the in traocular pressure, in which it will be elevated.

Answer 291

►C Alternate-day corticosteroid dosing regimens does not decrease the risks of posterior subcapsular cataracts, osteoporosis, and possibly osteonecrosis.

Answer 292

►A Valacyclovir is a prodrug of acyclovir, and has enhanced bioavailability and converts rapidly and completely to acyclovir. Severe and even fatal cases of thrombotic thrombocytopenia purpura/ hemolytic uremic syndrome have been reported in AIDS and transplant patients taking high doses of valacyclovir.

Answer 293

►D The half-life of isotretinoin is 20 hours.

Answer 294

►A Rifampin has been shown to reduce the efficacy of oral contraceptives and should not be used in conjunction with them. All other antibiotics such as ampicillin, ciprofloxacin, clarithromycin, tetracyclines, metronidazole, doxycyline and minocycline all do not change the efficacy of oral contraceptives.

Answer 295

►D All of the above choices have been implicated in drug-induced subacute cutaneous lupus erythematosus.

Answer 296

►B Acquired brachial dyschromatosis is a condition described as asymptomatic, gray-brown patches with geographic borders, occasionally interspersed with hypopigmented macules, on the dorsum of the forearms, mostly bilaterally and seen in middle aged women. Epidermal atrophy, basal layer hyperpigmentation, elastosis and angiectases were histopathologic features. An association with Civatte's poikiloderma as well as hypertension and/or antihypertensive drugs, especially ACE- inhibitors, is suggested.

Answer 297

►E Terbinafine inhibits squalene epoxidase and blocks the biosynthesis of ergosterol, a sterol essential to the integrity of fungal cell membranes. Itraconazole inhibits 14-alpha-demethylase, blocking lanosterol conversion to ergosterol. Griseofulvin disrupts microtubule mitotic spindle formation causing metaphase arrest. Ketoconazole has a mechanism of action similar to itraconazole. Fluconazole also inhibits 14-alpha-demethylase, not squalene epoxidase.

Answer 298

►A Dapsone is used in the treatment of dermatitis herpetiformis. Contraindications include severe cardiovascular disease, marked renal insufficiency, and sulfonamide allergy. Patients need to be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This is common among blacks and Asians.

Answer 299

►A Foscarnet is a noncompetitive inhibitor of viral DNA polymerase at the pyrophosphate b inding site. It does not require phosphorylaton for antiviral activity and therefore active against viruses resistant to acyclovir, famciclovir or ganciclovir.

Answer 300

►A Indinavir is a protease inhibitor used for the treatment of HIV. The protease enzyme is responible for the final assembly of new viral proteins. The protease inhibitors, particularly indinavir, have been associated with lipodystrophy, which manifests as abnormal fatty deposits known as the \"buffalo hump\" and \"protease pouch.\"

Answer 301

►B Minocycline, which is widely used in the treatment of acne, often without adequate supervision, may induce arthritis and livedo vasculitis associated with anti-MPO (pANCA). (O Elkayam. Ann Rheum Dis. 1996) Isoniazid most often causes drug-induced lupus associated with anti-histone antibodies. Penicillamine and TNF-inhibitors are associated with anti-dsDNA antibodies. Griseofulvin can exacerbate lupus but is most often associated with drug-induced SCLE and anti- Ro antibodies.

Answer 302

►E Tetracyclines, phenytoin, phenothiazines, chloramphenicol, NSAIDs, salicylates, and sulfonamides, among other drugs, can all increase methotrexate levels by displacement of plasma proteins.

Answer 303

►D Tetracycline has been associated with onycholysis and photo-onycholysis. Chloroquine may cause a blue-brown discoloration of the nail bed and retinoids are associated with paronychia.

Answer 304

►A Sorafenib is a small-molecule multi-kinase inhibitor used in the treatment of renal cell cancer and hepatocellular cancer. Notably it inhibits Raf kinase, which functions in the Ras signaling pathway, in addition to blocking VEGFR-2, VEGFR-3, FLT3, and PDGFRb signaling. Reports of hand and foot syndrome have been noted, characterized by acral erythema and paresthesias. This side effect seems to resolve rapidly after discontinuation of treatment.

Answer 305

►A Bleomycin damages DNA by binding to the M and the G2 phase It is effective in treatment of HPV and it associated with Raynaud's phenomenon occurring in digits treated with intralesional therapy for periungual and plantar warts.

Answer 306

►C Mycophenolate mofetil is a lymphocyte selective immunosuppressive agent that inhibits de novo purine synthesis. Specifically, it depletes guanosine nucleotides by inhibiting inosine monophosphate dehydrogenase. The most commonly reported side effects are GI and are dosedependent. Fluoroquinolones, rifampin, and metronidazole have been shown to decrease the bioavailability of mycophenolate mofetil, which may result in lower circulating levels. Medications that result in elevated concentrations of mycophenolate mofetil include salicylates and probenecid. There is also a possibility of reduced concentration of nevirapine when coadministered with mycophenolate mofetil. It is currently classified as FDA pregnancy category D. Azathioprine can be toxic in individuals with TPMT deficiency, not mycophenolate mofetil.

Answer 307

►D Carbamezapine, phenytoin, and phenobarbital are known to cross-react with one another.

Answer 308

►C In contrast to tetracycline staining of the teeth, which occurs in childhood and produces a brown discoloration along the gingival third, minocycline stains the permanent teeth in adults, with a gray- green discoloration of the mid-portion of the tooth.

Answer 309

►A Dapsone is used to treat a wide variety of dermatoses, including dermatitis herpetiformis, bullous SLE, erythema elevatum diunitum, Sweet\'s syndrome, and others. The anti-inflammtory effect of this medication is most effective against neutrophils because of inhibition of myeloperoxidase activity and chemotactic abilities.

Answer 310

►C Cimetidine competitively inhibits dihydrotestosterone at the androgen receptor site and can exhibit anti-androgen effects.

Answer 311

►A Patients on dapsone and sulfapyridine can experience hemolytic anemia and methemoglobinemia. It is dose related and occur with varying degrees within all individuals. Oral methylene blue is used in emergency situations to lower methemoglobin levels.

Answer 312

►B Lichenoid drug reaction and lichen planus are best distinguished clinically. However, there are clues to lichenoid drug, including parakeratosis and eosinophils. The presence of parakeratosis has been shown to be more sensitive than eosinophils in the diagnosis of lichenoid drug reaction.

Answer 313

►A Minocycline is least phototoxic. Demeclocycline and doxycycline are the most phototoxic of all the tetracyclines. Onycholysis can accompany tetracycline-induced phototoxicity.

Answer 314

►E Terbinafine and Naftifine work by way of inhibiting ergosterol synthesis by blocking squalene epoxidation (B&C). Itraconazole works by inhibiting ergosterol synthesis by blocking Lanosterol 14-alpha demthylase. c

Answer 315

►A First generation synthetic retinoids include tretinoin and isotretinoin. Second generation synthetic retinoids are etretinate and acitretin. Tazarotene, adapalene, and bexarotene are third generation.

Answer 316

►A Methylene blue is reduced in the presence of NADPH and diaphorase II to leukomethylene blue, which then reduces methemoglobin (Fe3+) to hemoglobin (Fe2+)

Answer 317

►B Periungual pyogenic granulomas and painful paronychial eruptions have been reported in association with various anti-HIV medications including, indinavir, zidovudine, and lamivudine.

Answer 318

►B This patient has anticonvulsant hypersensitivity syndrome most likely resulting from a deficiency of epoxide hydroxylase. Slow acetylators are also predisposed to this condition after being given sulfonamides. Renal failure is a risk factor with allopurinol administration. Recent vaccination and thyroid disease are not known risk factors.

Answer 319

►A This patient presents with a surgical wound infection unresponsive to cephalexin. This is likely secondary to community acquired MRSA infection. Doxycycline is the best choice for community acquired MRSA infection. Bactrim, not listed, is another option. Amoxicillin, Azithromycin, and Ciprofloxacin are not typically used to treat MRSA infections as resistance is high with these medications. Polymixin B is a topical antibiotic with anti-pseudomonal properties.

Answer 320

►A Patients that are on dapsone can experience motor peripheral neuropathy. They can also experience hemolytic anemia and methemoglobinemia.

Answer 321

►E Mucous membranes have the highest absorption of topical medicines. Percutaneous absorption, from highest to lowest, is as follows: mucous membrane > scrotum > eyelids > face > chest and back > upper extremity > lower extremity > acral.

Answer 322

►B Terbinafine, an allylamine, interferes with ergosterol synthesis by inhibiting squalene epoxidase. The azoles inhibit 14-a demethylase. Nystatin is a polyene which binds irreversibly to membran e sterols, resulting in a permeability shift. Ciclopirox does not appear to affect sterol biosynthesis but instead interferes with cell respiratory processes.

Answer 323

►A Rifampin inhibits RNA synthesis by inhibiting DNA dependent RNA polymerase. It is effective in tuberculosis and atypical mycobacterial infections. It is also effective in cutaneous leishmaniasis and rhinoscleroma.

Answer 324

►A Category C means that risk to the human fetus cannot be ruled out, studies are lacking; animal studies are equivocal.

Answer 325

►E Cimetidine, an H2 antihistamine, also competitively inhibits dihydrotestosterone at the androgen receptor site, with resultant antiandrogen side effects including gynecomastia, impotence, and loss of libido.

Answer 326

►A Terfenadine is an anti-histamine that was one of the first nonsedating antihistamines. It is no longer available in the USA because of its propensity to cause life-threatening cardiac arrhythmias. The problem is worsen by interaction with macrolide antibiotics and imidazole antifungals.

Answer 327

►A Anti-oxidants are thought to be protective against photoinjury by neutralizing oxygen radicals. Vitamin C, Vitamin E, tea polyphenois, and silymarin are all anti-oxidants.

Answer 328

►D Mucocutaneous side effects of gold include stomatitis, cheilitis, lichen planus- like eruptions, and pityriasis rosea-like eruptions.

Answer 329

►E Probenicid is co-administered with penicillin to prolong its half-life through decreased renal tubular secretion when higher blood levels are warranted.

Answer 330

►D Mycophenolate mofetil binds with Fe preparations preventing its absorption. Oral iron supplements markedly reduce absorption of mycophenolate mofetil (CellCept®). It is recommended that iron be taken four to six hours before, or two hours after mycophenolate mofetil.

Answer 331

►A The most common drugs that have been known to cause a skin reaction is ampicillin, Penicillin G, Cephalosporins, and Heparin. All the other drugs have a very low incidence of drug reaction and do not have a high incidence of a rash.

Answer 332

►A Rifampin inhibits RNA synthesis by blocking DNA-dependent RNA polymerase. It is effective in tuberculosis and atypical mycobacterial infections. It is the only drug that is bactericidal to Mycobacterium leprae. Cutaneous leishmaniasis and rhinoscleroma also respond to rifampin.

Answer 333

►B A sunscreen SPF is based on using it at a concentration of 2 mg/cm2 which is about 1 ounce or 30 grams for the entire average sized body. It also is about 3-5 grams for the head and neck.

Answer 334

►E Rituximab (brand name Rituxan) is a monoclonal antibody is approved for the treatment of CD20 non-Hodgkin‟s lymphoma. Rituximab is a monoclonal antibody directed against B lymphocytes which are CD20.

Answer 335

►E Craford et al. reviewed the available literature examining the efficacy of systemic anti -fungals and performed a meta-analysis. Pooled analysis of cure rates at 11 and 12 months suggested that terbinafine was more effective than itraconazole.

Answer 336

►A Voriconazole can cause photosensitivity and accelerated photoaging. Is a triazole antifungal medication that is generally used to treat serious, invasive fungal infections. These are generally seen in patients who are immunocompromised, and include invasive candidiasis, invasive aspergillosis, and certain emerging fungal infection.

Answer 337

►A Griseofulvin disrupts microtubule mitotic spindle formation causing metaphase arrest. It is effective against dermatophytes but not yeast. It is resistant to Trichophyton.

Answer 338

►B Voriconazole blocks ergosterol synthesis by inhibiting 14-alpha-demethylase. Side effects include visual disturbances in 30%, headaches, nausea, vomiting, fever, and peripheral edema.

Answer 339

►C Isotretinoin is thought to cause congenital defects by interfering with neural crest development. The most likely congenital defect is cranial synostosis.

Answer 340

►E Malathion is an organophosphate cholinesterase inhibitor.

Answer 341

►A The tetracycline family of antibiotics are bacteriostatic and act by inhibiting protein synthesis. Each member of the family may cause photosensitivity, but demeclocycline is the most photosensitizing.

Answer 342

►A Patients on potassium iodide can experience the Wolff- Chaikoff effect. It can impair autoregulatory mechanisms and lead to hypothyroidism. TSH should be checked a month after therapy is initiated. It competes with organic iodides from binding to thyroid.

Answer 343

►C Efalizumab is pregnancy category C. The other drugs listed are pregnancy category B.

Answer 344

►C Exogenous ochronosis is an uncommon complication of irreversible pigmentation due to overuse of topical hydroquinone (1,4 dihydroxybenzene). Hydroquinone acts to by melanocyte pigment production by auto-oxidation of melanin, tyrosinase and phenol oxidases.

Answer 345

►A Cephalosporins resembles the penicillins and possesses a beta lactam ring. It block bacterial cell wall synthesis through inhibition of penicillin binding proteins that catalyze transpeptidation. It treats soft tissue infections that are caused by staphylococci and non-enterococcal streptococci.

Answer 346

►E Itraconazole is a triazole whose mechanism, like the other azoles, is inhibition of cytochrome P450 enzyme lanosterol 14-alpha demethylase, with resultant inhibition of lanosterol conversion to ergosterol. Ergosterol is an essential component of fungal cell membranes. Itraconazole is a weak base, which is highly lipophilic and virtually insoluble in water. It is ionized only at a low pH. Griseofulvin is administered in divided doses for the treatment of tinea capitus. Its absorption is optimized when given with a fatty food. Oral fluconazole is very well absorbed when given orally with over 90% bioavailability. Terbinafine, though highly lipophilic, has 70 to 80% absorption, when administered orally, with a bioavailability not significantly impacted by food intake.

Answer 347

►A Cidofovir is a nucleotide analogue and does not require phosphorylation by virus and is converted by host cell kinases to a diphosphate. It is usually active against CMV isolates that is resistant to ganciclovir and foscarnet.

Answer 348

►C Avobenzone (Parsol 1789) is primarily a UVA blocker. Photostability of avobenzone may be a problem if it is combined with octyl methoxycinnamate. Salicylates, PABA, Padimate O, and cinnamates are primarily UVB blockers.

Answer 349

►A Griseofulvin should not be used in patients that have porphyria. It can exacerbate lupus erythematosus and photoallergy. It is also absorbed by fatty meals. It is not effective in candidiasis.

Answer 350

►A Long term systemic steroid therapy can result in hyperlipidemia, especially Hypertriglyceridemia. Hyperglycemia, not hypoglycemia may occur with steroid therapy. Hypokalemic alkalosis may result from long term steroid use. Uncommonly, hypocalcemia may develop with resultant tetany.

Answer 351

►C A woman should wait one month before trying to conceive after taking isotretinoin to prevent birth defects. After taking acitretin a woman should wait three years before trying to conceive.

Answer 352

►D Drug induced lupus consists of systemic lupus type symptoms with anti-histone antibodies. Common culprit drugs are hydralazine, procainamide, isoniazid, and minocycline. Cessation of the medication usually results in improvement of symptoms. The TNF inhibitors also induce systemic lupus, but this typically is an unmasking of native lupus that is not associated with antihistone antibodies and does not remit with cessation of treatment.

Answer 353

►C The only biologic that is pregnancy category C is efaluzimab. The other biologics are category B. Efaluzimab is a humanized antibody that binds CD11a.

Answer 354

►A Alefacept eliminates activated memory T-cells, so weekly CD4 T-cell counts are recommended.

Answer 355

►B Gemfibrozil generally reduces trygliceride levels to a greater extent than niacin, cholestyramine, and the HMG-CoA reductase inhibitors.

Answer 356

►D Infliximab is infused intravenously.

Answer 357

►A Warfarin can lead to elevated levels of fluoroquinolones by inhibition of CYP 1A2. It should be taken two hours apart from each other. All the others reduce levels of fluoroquinolones except ACE inhibitors.

Answer 358

►C Cyclophosphamide is an alkylating agent that cross links DNA at any point during the cell cycle. Methotrexate, 5-fluorouracil, azathioprine, and hydroxyurea are S-phase specific cytotoxic agents. Methotrexate is a folic acid analog that blocks dihydrofolate reductase. 5-FU is a pyrimidine analog that prevents the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate in DNA synthesis. Azathioprine is a purine analog that is converted into the active metabolite 6- thioguanine bit hypoxanthine guanine phosphoribosyltransferase. Hydroxyurea inhibits ribonucleotide reductase which normally converts ribonucleotides to deoxyribonucleotides in DNA synthesis.

Answer 359

►A Bacitracin is a polypeptide antibiotic produced by the Tracey I stain of Bacillus subtilis. It inhibits bacterial cell wall synthesis by complexing with the carrier protein C55-prenol pyrophosphatase, which is involved in the transfer of polysaccharides, liposaccharides, and peptidoglycans to a growing cell wall.

Answer 360

►D Ketoconazole is known to cause gynecomastia and impotence, by interfering with androgen and glucocorticoid synthesis.

Answer 361

►A Azathioprine is a purine analog that is used as a steroid-sparing agent in a variety of dermatologic inflammatory disorders. Azathioprine is converted into 6-mercaptopurine before being converted into the active metabolite, 6-thioguanine, by the hypoxanthine guanine phosphoribosyltransferase pathway. Other inactive metabolites are produced via xanthine oxidase and thiopurine methyltransferase.

Answer 362

►D The most common side effect of treatment with interferon-alpha is flu-like symptoms of fever, chills, myalgias, headache and arthralgias. Prophylactic administration of non steroidal anti inflammatory medications may alleviate some of these symptoms.

Answer 363

►D All of the listed medications except azeleic acid are pregnancy category X. Azeleic acid is a pregnancy category B medication, meaning that there are controlled human studies that show no risk to fetus but may show risk to animals, or no risk in animals with no human studies conducted.

Answer 364

►D Many authors consider precipitated sulfur to be the drug of choice for the treament of scabies in pregnant women, although there are no published studies for this indication (see Wolverton). Permethrin of note is category B in pregnancy.

Answer 365

►C Both podophyllin and colchicine have antimitotic activity. They bind to tubulin dimers, interfering with mitotic spindle and microtubule assembly.

Answer 366

►B Interferons can cause increased growth of eyelashes. Trichomegaly has been reported after treatment with interferon-alpha in patients with chronic hepatitis, B-cell lymphoma, chronic granulocytic leukemia, and cutaneous melanoma. Trichomegaly has also been reported in associatoin with latanoprost, minoxidil, cyclosporine, phenytoin, psoralen, and penicillamine.

Answer 367

►B Dioxybenzone is one of the benzophenones (as in oxybenzone and sulisobenzone), which are UVA blockers. Amyl p-dimethylaminobenzoate is a UVB blocker. Dibenzoylmethane (avobenzone; Parsol 1789) is a UVA/UVB blocker. Red veterinary petrolatum is a UVA blocker.

Answer 368

►A Tetracycline antibiotics inhibit protein synthesis by binding to the 30S ribosomal subunit. They are effective against gram positive and negative organisms, Mycoplasma, Chlamydia, Rickettsia, and others. Doxycycline, which is excreted by the Gi tract, is the only tetracycline for use in patients with renal failure.

Answer 369

►A Cyclophosphamide is a nitrogen mustard derivative. It is cell-cycle nonspecifc and works by producing DNA cross-linkages at any point in the cell cycle. It is the treatment of choice for Wegener's granulomatosis.

Answer 370

►E Azathioprine has been known to cause SCLE like eruption. Tetracyclines, Barbiturates, NSAIDs,naproxen, sulfonamides, and phenopthalein in laxatives have been known to cause fixed drug eruptions.

Answer 371

►C Itraconazole should be avoided in heart patients due to its black box warning against CHF. Other reported adverse effects from itraconazole include photosensitivity and COPD.

Answer 372

►A Patients that are on azathioprine that have low levels of xanthine oxidase or thiopurine methyltransferase activity (TPMT) and on allopurinol use can have bone marrow suppression. Allopurinol inhibits xanthine oxidase activity or in patients with genetically low TPMT allele activity.

Answer 373

►A Imiquimod is FDA approved for the treatment of actinic keratoses, superficial basal carcinomas, and condyloma acuminate. It is not used to treat infiltrative basal cell carcinomas, squamous cell carcinoma in situ, superficial spreading melanoma, or psoriasis. Off label uses include common warts, molluscum contagiosum, Bowen‟s disease (SCCIS), and keloids.

Answer 374

►E Dihydroxyacetone is the active ingredient in sunless tanning preparations. Upon oxidation it turns orange-brown and binds to the stratum corneum. Rubber accelerators contain mercaptobenthothiazole, carba mix, thiuram mix, or mercapto mix. Shampoos, especially "tear - free" ones, may contain cocamidopropyl betaine. Artificial nails may contain methyl methacrylate or ethyl acrylate. Hair dyes often have paraphenylenediamine.

Answer 375

Correct choice: A. Induces sebaceous gland atrophy Explanation: Azelaic acid is a dicarboxylic acid that has weak activity against P. acnes. It inhibits tyrosinase, and can be helpful in reducing post-inflammatory pigment alteration. Itching, burning, or dryness at the initiation of treatment is not uncommon. It is pregnancy category B. Azeleic acid does not induce sebaceous gland atrophy - this is unique to isotretinoin.

Answer 376

Correct choice: D. Lindane Explanation: This is scabies. Management of a scabies outbreak involves the identification and treatment of individual patients and household contacts with insecticides. Oral antibiotics are required for secondary infection. Careful attention to instructions is essential if scabies is to be cured. The chemical insecticides used to treat scabies are called scabicides. The scabicide is applied to the whole body from the scalp to soles. The usual topical treatment is 5% permethrin cream, left on the entire skin for 8–10 hours. It should be applied under fingernails using a soft brush. Oral ivermectin 200 mcg/kg is convenient, but more expensive than topical permethrin. It may be slightly less effective. It is mainly used for mass treatments in institutions, or in patients unable to use topical therapy. Gamma benzene hexachloride cream is no longer recommended or available due to neurotoxicity; it is also a suspected carcinogen and is no longer marketed in New Zealand. Other proven treatments include: - 0.5% aqueous malathion lotion, left on for 24 hours - 25% benzyl benzoate lotion, applied daily for 3 days. This is irritant, and should not be used in children. - 2–10% precipitated sulphur ointment Treatment should be repeated after 8–10 days after the first application to catch mites that have newly hatched. Crotamiton cream can be used to reduce itch; it is a weak scabicide. Patients with crusted scabies may need repeated oral and topical treatments over several weeks or longer. Contacts must be identified and treated. In addition: -Bed linen, towels and clothing should be laundered after treatment. -Non-washable items should be sealed in a plastic bag and stored for one week. -Rooms should be thoroughly cleaned with normal household products. Fumigation or specialized cleaning is not required. -Carpeted floors and upholstered furniture should be vacuumed.

Answer 377

Correct choice: C. Denileukin difitox Explanation: Cutaneous T-cell lymphoma (CTCL) is a rare non-Hodgkin lymphoma with predominant skin manifestations and a relatively indolent course at early stages, but it can be fatal in advanced settings. In the absence of cure, the goal of therapy for CTCL is to induce long-term remissions without further compromising a patient's immune system or quality of life. Denileukin diftitox (DD) is a fusion protein chemotherapeutic agent used for the treatment of persistent or recurrent CTCL. It binds selectively to the high- and intermediate-affinity interleukin-2 receptor (CD25+) on lymphocytes and is internalized by these cells. Inside the cells, the diphtheria toxin portion of fusion protein is cleaved by proteolytic enzymes, causing cell death. DD produces durable responses and may forestall disease progression. The most frequent and clinically significant adverse effects of DD include: acute infusion reactions, capillary leak syndrome, hypoalbuminemia, visual changes, constitutional symptoms, and hepatobiliary disorders. Many DD- associated adverse effects can be managed effectively without dose reduction or interruption of treatment with prudent use of supportive care measures.

Answer 378

Correct choice: A. Itraconazole Explanation: The correct answer is A. Itraconazole (as well as most of the azoles) is a CYP3A4 inhibitor. Since cyclosporine is metabolized by CYP3A4, itraconazole may cause increased levels of cyclosporine. Griseofulvin induces cytochrome P450 and therefore would decrease cyclosporine levels. Cytochrome P450 Inhibitors * Warfarin * Azoles * Verapamil * Erythromycin * Sex steroids and methylprednisolone * St. John’s wort * Ciprofloxacin * Cimetidine * Cyclosporine * Clarithromycin * Diuretics (furosemide and thiazides) * Danazol * Diltiazem * Grapefruit juice * Protease inhibitors Cytochrome P450 Inducers * Griseofulvin * Rifampin * INH * Propranolol * Phenytoin * Phenobarbital * Carbamazepine * Omeprazole * Retinoids * Tobacco

Answer 379

Correct choice: E. HMG-CoA reductase inhibitors Explanation: Medications that alter the lipid composition of the epidermis and stratum corneum may impair the normal barrier function of the skin. Cholesterol lowering medications like HMG- CoA reductase inhibitors (aka statins) may cause xerosis through this mechanism.

Answer 380

Correct choice: C. Binds IL-17 receptor Explanation: Brodalumab binds to the interleukin-17 receptor and so prevents interleukin 17 (IL-17) from activating the receptor. This mechanism is similar to that of another anti-psoriasis antibody, ixekizumab, which however binds to IL-17 itself.

Answer 381

Correct choice: B. minocycline Explanation: Minocycline does not typically lead to overt phototoxicity but may cause diffuse “muddy brown” hyperpigmentation that is accentuated in sun-exposed areas as well as bluish discoloration of scars (including those due to acne) and normal skin (in particular on the shins). The muddy brown hyperpigmentation presents with increased melanin at the basal layer and within macrophages on histopathology.

Dermatopharmacology Flashcards

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