Core Questions for Understanding Systemic Dermatologic Drugs

Q1.1 What are the simplest definitions of ‘pharmacokinetics’, ‘pharmacodynamics’, and ‘pharmacogenetics’? ( Pg. 1, Table 1.1 )

Q1.3 What are some of the pros and cons to the decision of whether to calculate drug dose on (1) actual body weight, (2) ideal body weight? ( Pg. 3 )

Q1.6 What are several of the most important examples in which drugs inhibit specific enzymes? ( Pg. 6, Table 1.6 )

Q1.7 What are several important examples of active drug and active metabolite relationships? ( Pg. 7, Table 1.9 )

Q1.8 What are several of the most important examples of prodrug and active drug relationships? ( Pg. 8, Table 1.8 )

Q1.10 What are five of the most important basic components that determine percutaneous absorption of topical medications in general? ( Pg. 8 )

Q9.2 Which antibiotic classes have significant alterations in bioavailability because of foods and divalent cations? (Pgs. 73, 75, 78, 81, 82, 84x2, 91, 92)

Q9.5 What are three to four of the mechanisms by which bacteria develop resistance to antibacterial agents? (Pgs. 78, 84, 91, 95, 96)

Q9.8 What are several antibiotic classes with significant antiinflammatory activity, and what are several of the mechanisms for this anti-inflammatory activity? (Pgs. 78, 83x2)

Q10.3 How do the pharmacokinetics of terbinafine, itraconazole, and fluconazole in (1) the sweat, sebum, and stratum corneum, (2) the nails, and (3) the hair influence the option of intermittent/pulse therapy? (Pg. 102x3)

Q10.5 Considering the allylamine mechanism (terbinafine), (1) what enzyme is inhibited, (2) what conversion step is inhibited, and (3) is the net in vitro result fungicidal or fungistatic? (Pg. 103)

Q10.6 Considering the azole mechanism (itraconazole, fluconazole), (1) what enzyme is inhibited, (2) what conversion step is inhibited, and (3) is the net in vitro result fungicidal or fungistatic? (Pg. 103)

Q11.2 What are the two primary steps (one step with two parts) by which acyclovir reaches the form that inhibits viral replication (similar steps for valacyclovir and famciclovir) (Pg. 115, Fig. 11.2 )

Q11.5 Of the three drugs for HHV infections discussed in this chapter, which two are defined as ‘prodrugs’ for another active drug? (Pgs. 119, 121)

Q11.7 How does the bioavailability differ between acyclovir, valacyclovir, and famciclovir? How might this relate to treating varicella-zoster virus (VZV) infections and herpes simplex virus (HSV) infections?) (Pg. 121)

Q13.1 Concerning prednisone and cortisone, what is (1) the active form of each drug, and (2) the enzyme necessary for this conversion, and (3) the effect of severe liver disease on this conversion? (Pgs. 134, 135)

Q13.2 What are ‘physiologic dose’ levels for (1) prednisone, (2) prednisolone, (3) dexamethasone, (4) methylprednisolone, and (5) triamcinolone? ( Table 13.1 , Pg. 151)

Q13.9 Concerning response to physical stressors, which part of the hypothalamic-pituitary-adrenal (HPA) axis is (1) quickest to be suppressed, (2) quickest to recover, and (3) overall most important to stress responsiveness? (Pg. 148)

Q13.10 What are some of the ‘back-up’ mechanisms the body has to minimize the likelihood of CS-induced HPA-axis suppression? (Pg. 149x2)

Q14.1 What are the proposed mechanisms by which methotrexate inhibits inflammatory dermatoses? (Pg. 159x4)

Q14.2 What is the biochemical rationale behind the use of (1) folinic acid, and/or (2) thymidine in patients with acute methotrexate liver toxicity (especially pancytopenia)? (Pg. 159)

Q15.2 What is a general guide for interpretation of the laboratory testing for the genotype for TPMT activity? (Pg. 170)

Q16.1 How do MMF and mycophenolic acid (MPA) relate pharmacologically: (1) prodrug/active drug, or (2) active drug/active metabolite? (Pg. 178)

Q16.5 Concerning the MPA mechanism of action (1) what purine biosynthesis enzyme is inhibited, and (2) why are activated lymphocytes specifically targeted by MPA? (Pg. 179)

Q17.1 What are the differences between the Sandimmune and Neoral versions of cyclosporine (CsA) in their (1) formulation, (2) bioavailability, and (3) consistency of absorption? (Pgs. 187, 188, 195)

Q17.2 Regarding the mechanism of action for CsA, what is (1) the enzyme inhibited, (2) the transcription factor inhibited, and (3) the resultant cytokine alterations? (Pg. 188, Table 17.3 , Fig 17.2 )

Q18.1 What are the most important differences between small molecule drugs (such as apremilast and tofacitinib) and biologics? (Pg. 200)

Q19.2 What are (1) the two major categories of cytotoxic agents, (2) major drug examples of each category, and (3) the mechanism for each category concerning the cell cycle? (Pgs. 210, 211, 214)

Q20.2 What is the overall function of the myeloperoxidase system in neutrophils? (Pg. 225)

Q21.1 What are the proposed mechanisms by which antimalarials work in various dermatoses discussed in this chapter? (Pg. 236)

Q22.2 How much time is needed for complete serum elimination of (1) isotretinoin, (2) acitretin, and (3) bexarotene; what is the role of acitretin re-esterification to etretinate in this issue? (Pgs. 248x2, 254)

Q24.3 What are the proposed mechanisms by which ECP may benefit patients with cutaneous T-cell lymphoma (CTCL)? (Pg. 273)

Q25.2 Concerning biochemistry of ALA/MAL, what (1) is the endpoint of this metabolism, (2) is the photosensitizing porphyrin that accumulates, and (3) what are the differences between ALA and MAL metabolism? (Pg. 281)

Q25.5 Concerning the mechanism of action for ALA and MAL, what are (1) the wavelengths with peak absorption of each product, and (2) the subsequent photochemical and photobiologic reactions? (Pg. 282x2)

Q26.1 What is the rationale strongly supporting the role of TNF-α in the pathogenesis of psoriasis? (Pg. 288)

Q28.1 What is the rationale strongly supporting the role of interleukin [IL]-17 in the pathogenesis of psoriasis? (Pg. 312)

Q28.2 What is the rationale strongly supporting the role of IL-17 in the pathogenesis of psoriatic arthritis? (Pg. 313)

Q28.6 How does the mechanism of action differ for brodalumab compared with secukinumab and ixekizumab? (Pg. 317)

Q29.2 What subunit of IL-23 do IL-23 inhibitors target? (Pg. 321)

Q30.3 Concerning B-cell depletion with rituximab, what is (1) the timing of onset, (2) the average duration of depletion and (3) the timing of recovery? Why are plasma cells spared? (Pg. 331)

Q30.7 In addition to depleting pathogenic B cells, what are two ways rituximab indirectly modifies B and T autoimmunity in pemphigus? (Pg. 333x2)

Q31.4 What is the mechanism of action of dupilumab that allows for blockade of both interleukin (IL)-4 and IL-13 signaling? (Pg. 340)

Q31.9 After omalizumab binds free IgE, what are five subsequent mechanisms of action? (Pg. 343)

Q32.1 How do first- and second-generation antihistamines differ regarding lipophilic properties and anticholinergic effects, and what are the resultant clinical difference? (Pgs. 350, 352)

Q32.3 Concerning chronic urticaria patients, (1) in what percentage are autoantibodies produced, and (2) what two types of autoantibodies are typical of this subgroup? (Pg. 350)

Q32.4 How do H ₁ and H ₂ receptors differ regarding their role in (1) itching, (2) vasodilation, (3) increased vascular permeability, and (4) suppression of T lymphocytes? (Pgs. 350, 351)

Q32.7 What pharmacologic property allows persistence of a therapeutic effect from antihistamines significantly longer than the plasma half-life of a given antihistamine? (Pg. 352)

Q32.10 Which histamine receptors do cimetidine and doxepin inhibit and how do these properties compare with traditional first-generation antihistamines? (Pgs. 355, 356)

Q33.7 Why does aspirin have a paradoxically greater antiplatelet effect at relatively low doses? (Pg. 362)

Q33.8 What are the mechanisms by which pentoxifylline improves various disorders of cutaneous vasculature? (Pg. 364)

Q34.1 What is the difference between an ‘antiandrogen’ and ‘androgen inhibitor’? (Pg. 367)

Q34.4 Concerning spironolactone (1) what are the primary biologic effects, and (2) what is the metabolite that contributes to the majority of the drug’s effects (Pg. 369, 371)

Q36.1 What are the mechanisms by which intravenous immunoglobulin (IVIg) affects (1) antibody (Ab) production, (2) Ab neutralization, (3) the complement system, (4) T-cell activation, (5) immune cell trafficking, and (6) Fas/Fas ligand interaction? (Pg. 398)

Q37.8 What is the mechanism of action for the following drugs: vorinostat, denileukin diftitox, ipilimumab, and etoposide? (Pg. 414, 415x2, 417)

Q40.3 What are some of the properties of biotin which led to its clinical use for hair and nail disorders? (Pg. 447)

Q40.5 What is the mechanism of action for colchicine, and how does this mechanism and other drug properties make the drug well suited for neutrophilic dermatoses? (Pg. 450)

Q40.12 Which cytokines of central importance to inflammation do thalidomide inhibit? (Pg. 458)

Q62.4 What are some of the enzymes involved with the phase I (primarily oxidation) and phase II (conjugation) metabolic steps of drug biotransformation (and which enzymes have polymorphisms)? (Pg. 679, Table 62.2 )

Q62.5 What are several of the mechanisms involved in the pathogenesis of drug-induced liver injury (DILI) are caused by reactive metabolic intermediates? (Pg. 680, Box 62.3 )

Q64.3 What are the primary components of the multistep carcinogenesis model, and what are some applications of this model for chemical, ultraviolet, and viral carcinogenesis? (Pg. 703)

Q64.5 In general, what are the roles of oncogenes and tumor suppressor genes in carcinogenesis? (Pg. 703)

Q64.6 Of the four malignancies with the highest relative risk in organ transplantation settings, which viruses are frequently co-factors for each malignancy? (Pg. 704)

Q65.5 At which stage of pregnancy does organogenesis occur, leading to the highest risk of teratogenicity? (Pg. 712)

Q66.4 Which two cytochrome P-450 (CYP) isoforms are responsible for the greatest amount of drug metabolism (and what are 3–4 other CYP isoforms that also account for the majority of drug interactions)? (Pg. 731)

Q66.5 Which drugs are CYP3A4 inducers? (Pg. 733)

Q66.9 Given the CYP2D6 polymorphism, what are four general terms and abbreviations for different overall rates of drug metabolism? (Pgs. 738x2, 741)

Q66.11 In addition to CYP2D6, which other CYP isoforms have a genetic polymorphism? (Pgs. 738, 739)

Q9.13 What are some practice guidelines for use of systemic antibiotics in chronic inflammatory dermatoses to reduce antimicrobial resistance? (Pg. 84)

Q9.16 Concerning community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, what are (1) several of the best oral antibiotic choices, and (2) several antibiotics with a trend towards increasing resistance? (Pgs. 91x2, 94, 96, 97x4)

Q10.7 Considering all five main systemic antifungal agents in this chapter, which have the most optimal coverage against (1) Candida infections, (2) dermatophytes, (3) non-dermatophyte mold infections, and (4) Pityrosporum infections? (Pgs. 103, 105, 106)

Q10.8 Why did terbinafine and itraconazole largely replace griseofulvin as treatment for dermatophyte onychomycosis? (Pg. 105)

Q11.1 What is the spectrum of dermatologic conditions that human herpes virus (HHV) infections can cause? (Pg. 115, Table 11.1 )

Q11.4 What is the rationale for the use of acyclovir or valacyclovir in patients with recurrent erythema multiforme, and which regimens are most effective? (Pgs. 118, 120)

Q11.6 What advantages does valacyclovir have over acyclovir in treating herpes zoster? (Pgs. 119, 120)

Q11.10 What are the two available vaccines to prevent shingles and how are they different? (Pg. 123)

Q12.1 Concerning ivermectin therapy for scabies, (1) how does ivermectin compare with topical permethrin in success rate, and (2) is ivermectin alone effective treatment for crusted scabies? (Pg. 126x2, 127)

Q12.4 Should ivermectin be utilized differently in immunocompromised patients, including human immunodeficiency virus patients? (Pg. 127)

Q12.7 What are the clinical implications of increasing parasite resistance to ivermectin in treating (1) onchocerciasis, and (2) scabies? (Pg. 128)

Q13.3 What are several cells that systemic corticosteroid (CS) can induce to undergo apoptosis, and the disease states that may logically be successfully treated because of this apoptosis? ( Table 13.2 , Pgs. 136, 139x2)

Q13.5 What are several pros and cons of intramuscular (IM) CS injections versus oral dosing? What are several dermatoses for which IM Kenalog has the best risk:benefit ratio and overall logic of use? ( Table 13.5 , Box 13.4 , Pg. 141)

Q13.6 What are the two key issues that determine the rapidity of systemic CS dose tapering? Which of these two key issues matters primarily when dosing is below ‘physiologic’ dose levels? ( Box 13.8 , Box 13.9 , Table 13.14 , Pgs. 142, 149, 151x2)

Q13.11 What are some general principles (1) to maximize CS safety (z), (2) to taper CS therapy ( Box 13.9 ), and (3) to convert CS to alternate-day dosing ( Table 13.14 )? What two criteria should be met before making this conversation? (Pgs. 51, 154x2)

Q14.4 What are four to five dermatoses for which there is reasonable data concerning safety and efficacy regarding use of methotrexate in children? (Pg. 162, Box 14.1 )

Q14.12 What are the pros and cons of the two common methods of administering weekly dosages of methotrexate, administered either as a single dose or in divided doses over 24 hours? (Pg. 167)

Q15.4 Based on TPMT enzyme levels (phenotype testing), what is the appropriate azathioprine dose in mg/kg/day for a patient with a (1) normal enzyme level, (2) intermediate enzyme level, and (3) low enzyme level? (Pg. 172)

Q16.7 What is the clinical advantage of enteric-coated mycophenolate (mycophenolate sodium)? (Pg. 182)

Q16.13 What is the typical (1) starting dose for mycophenolate (mofetil and sodium formulations), and (2) therapeutically effective dose range for mycophenolate (mofetil and sodium formulations) (Pg. 185)

Q17.3 What are the ‘off-label’ uses of CsA with the greatest literature support? (Pgs. 191,192)

Q17.10 What is the ‘approved’ maximum duration of continuous therapy of CsA for psoriasis patients as published by (1) the United States consensus conference, and (2) the ‘worldwide’ consensus conference? (Pg. 195)

Q18.3 What drugs inhibit phosphodiesterase 4 and for what diseases are these drugs being used for? (Pgs. 200, 201, 202)

Q18.4 What can be expected of apremilast in terms of efficacy for psoriasis and psoriatic arthritis, based on clinical trial results? (Pg. 201x2)

Q18.7 What drugs inhibit the JAK/STAT pathway and for what diseases are these drugs used? (Pg. 203x6)

Q19.1 Concerning cytotoxic drug use in dermatology, what are (1) five to six of the disease categories for which these drugs are used, and (2) the three most important adverse effect categories? (Pg. 209)

Q20.1 What is the role of hydroxylamine metabolites in dapsone toxicities and how does cimetidine alter these effects? (Pg. 224)

Q20.3 Concerning the myeloperoxidase system, (1) what are several additional cells that use this enzyme, and (2) which dapsone-responsive dermatoses involve these cell types? (Pg. 226)

Q20.5 Concerning bullous dermatoses responsive to dapsone, (1) what are several that are immunoglobulin A (IgA) mediated, and (2) what are several other dapsone responsive immunobullous dermatoses? (Pg. 227)

Q20.6 What are several ‘neutrophilic dermatoses’ which typically respond to dapsone? (Pg. 227)

Q21.2 In general, concerning responses of lupus erythematosus to antimalarials, (1) which cutaneous subsets respond well, (2) which cutaneous subsets respond less well, and (3) which systemic features/organ systems respond well? (Pg. 237)

Q21.9 What is the recommended ‘maintenance’ dosage range, with an acceptably low incidence of retinopathy, for antimalarial therapy with hydroxychloroquine or chloroquine therapy? (Pg. 242)

Q21.11 In which important ways does the dosage scheme differ when antimalarial agents are used in porphyria cutanea tarda? (Pg. 243)

Q22.5 How do (1) daily isotretinoin doses and (2) cumulative isotretinoin doses affect the likelihood of significant clinical recurrence of acne vulgaris? (Pg. 250)

Q22.6 How significant is the evidence for a chemopreventative effect of acitretin in (1) solid organ transplantation patients, and (2) other patients with frequent nonmelanoma skin cancer? (Pg. 251)

Q23.10 What is the specific action spectrum of excimer laser? (Pg. 268)

Q23.12 What are the three main indications for UVA-1 phototherapy? (Pgs. 269x2, 270)

Q24.6 What are four prognostic factors for a favorable outcome with ECP in patients with erythrodermic CTCL? (Pg. 274)

Q24.9 Aside from ECP for CTCL, what is the most promising additional dermatologic indication for ECP therapy? (Pg. 276)

Q25.4 Which cells tend to have the greatest accumulation of ALA and MAL with topical application, and how do these sites of greatest absorption relate to conditions treated with PDT? (Pg. 281)

Q25.7 What is the one US Food and Drug Administration (FDA)-approved indication for photodynamic therapy with ALA and MAL? (Pg. 283)

Q25.8 What are the overall pros and cons for treating acne with photodynamic therapy using (1) ALA, (2) MAL, (3) the Blu-U light in the absence of either product? (Pg. 284)

Q25.12 What are the pros and cons (limitations) of chemical and physical sunscreens subsequent to a photodynamic therapy treatment session? (Pg. 286)

Q26.4 How do the maximum PASI-75 rates compare between the four TNF-α inhibitors? (Pgs. 291x2, 293, 295, 297)

Q27.1 Which IL 12/23 inhibitor is currently approved for the treatment of psoriasis and which biologics are in development? (Pg. 303)

Q27.4 What conclusions were drawn from the phase III ustekinumab trials with regard to efficacy? (Pg. 308)

Q27.5 What conclusions can be drawn from the PSUMMIT 1 and 2 studies on the effect of ustekinumab on psoriatic arthritis? (Pg. 308)

Q27.7 How does interleukin [IL]-12/23 inhibitor compare to IL-17 inhibitors in the treatment of psoriasis in terms of Psoriasis Area Severity Index (PASI) score? (Pg. 308)

Q28.7 What step is required prior to prescribing brodalumab and why is this extra step needed? (Pg. 318)

Q29.4 How does the efficacy of IL-23 inhibition alone compare with IL-12/23 inhibition? (Pg. 321)

Q29.5 What conclusions were drawn from the phase III guselkumab trials with regard to efficacy? (Pg. 322)

Q29.7 What conclusions were drawn from the phase III tildrakizumab trials with regard to efficacy? (Pg. 325)

Q29.8 What conclusions were drawn from the phase III risankizumab trials with regard to efficacy? (Pg. 326)

Q29.9 In what other diseases may IL-23 inhibitors may have utility? ( Table 29.4 , Pg. 328)

Q30.1 Rituximab is US Food and Drug Administration (FDA) approved for what dermatologic conditions? What are several categories of dermatoses for which off-label use of rituximab has at least some literature support? (Pg. 331x2)

Q30.12 What are FDA-approved dosing schemes for (1) lymphoma patients, (2) rheumatoid arthritis? (3) granulomatosis with polyangiitis and microscopic polyangiitis and (4) pemphigus vulgaris? (Pg. 336)

Q31.1 For which category of patients with atopic dermatitis is dupilumab US Food and Drug Administration (FDA)-approved? (Pg. 339)

Q31.5 What are two off-label dermatologic conditions in which dupilumab has been of benefit? (Pg. 341)

Q32.9 Which is the most sedating of the ‘low-sedation’ second-generation antihistamines, and how can this be an advantage or disadvantage, depending on clinical circumstances? (Pg. 354)

Q33.2 Which drugs discussed in this chapter have demonstrated efficacy in patients with Raynaud phenomenon? (Pgs. 359, 364x3, 365, Box 33.1 )

Q34.2 For which skin disorders are antiandrogens and androgen inhibitors clinically useful from a mechanistic standpoint? (Pgs. 367, 368)

Q35.3 What is the basis of the tremendous dosing variation between patients receiving doxepin for depression or for pruritus (and how does this relate to doxepin-induced sedation)? (Pg. 386)

Q36.2 What is the likelihood of success and unique risks when using IVIg for patients with severe, recalcitrant dermatomyositis? (Pg. 399)

Q36.3 What is the likelihood of success and unique risks when using IVIg for patients with severe, recalcitrant pemphigus? (Pg. 400)

Q36.5 What is the likelihood of success and unique risks when using IVIg for patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)? (Pg. 401)

Q36.9 What are the most common regimens for IVIg therapy regarding: (1) dosage per kilogram, (2) duration of therapy per cycle, and (3) interval between cycles? (Pg. 404)

Q36.11 Overall, which conditions managed at least in part by dermatologists have the greatest evidence for efficacy of IVIg? (Pg. 404)

Q37.9 What are the indications for dexamethasone in preventing or treating dermatologic adverse events associated with anticancer drugs? (Pgs. 415x3, 416)

Q38.1 What are the US Food and Drug Administration (FDA)-approved indications for vismodegib and sonidegib? (Pg. 422x2)

Q39.4 What are typical doses for (1) calcium, (2) vitamin D, and (3) various bisphosphonates in the prevention and management of corticosteroid-induced osteoporosis? (Pg. 434)

Q39.10 Concerning vitamin D therapy (1) what is the mechanistic role of vitamin D in corticosteroid osteoporosis prevention, and (2) what malignancies are possibly reduced by significant vitamin D intake? (Pg. 444)

Q65.9 What are some of the drugs that present essentially no risk when taken in pregnancy? ( Box 65.1 , Pg. 714)

Q65.10 What are the eight principles for safely using dermatologic drugs in pregnancy and lactation listed in the Summary section? (Pg. 724)

Q67.6 Aside from drug discontinuation, what are several of the appropriate drug choices in treating DRESS? (Pg. 747)

Q67.10 What are several of the most well-documented treatment options for SJS and TEN? (Pg. 751)