P1: JZZ 0521618134c07 CB1006/Lane 521 61813 November 28, 2005 16:25 Therapeutics Pregnancy cat.: Side effects: Monitoring: Notes: 111 B antibiotic-associated colitis (rarely) none poor gram (−) activity neuromuscular blocking properties may enhance other neuromuscular agents good anaerobic coverage Sadick NS Systemic Antibacterial Agents In: Wolverton SE ed., ed Comprehensive Dermatologic Drug Therapy Philadelphia: W B Saunders Co 2001: p 28 Ray WA, Murray KT, Meredith S et al Oral erythromycin and the risk of sudden death from cardiac causes N Engl J Med 2004; 351: 1089–1096 Yee CL, Duffy C, Gerbino PG et al Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin Pediatr Infect Dis J 2002; 21: 525–529 P1: JZZ 0521618134c07 112 CB1006/Lane 521 61813 November 28, 2005 16:25 Pocket Guide for Cutaneous Medicine and Surgery Topical Antimicrobials Bacitracin r inhibits bacterial cell wall synthesis – inhibits peptidoglycan synthesis r gram (+): S aureus, S pneumoniae, Neisseria, H influenzae, T pallidum r gram (−): minimal coverage r SE: contact sensitization, rare anaphylaxis Mupirocin (Bactroban) r inhibits bacterial RNA and protein synthesis (isoleucyl tDNA synthetase) r gram (+): Staphylococci (MRSA), Streptococci r gram (−): some gram (−) cocci r SE: local irritant r does not cross-react with other topical antimicrobials r renal toxicity when used on large denuded areas r uncommon contact sensitization Neomycin r inhibits protein synthesis (binds 30S subunit) r gram (+): good coverage vs S aureus (weak for Strep) r gram (−): yes r SE: ototoxic and nephrotoxic; contact sensitization; virtually always used in combination Polymyxin B r antibacterial via surface detergent-like mechanisms r gram (+): no activity r gram (−): Proteus, Pseudomonas, Serratia r SE: rare contact sensitization Spann CT et al Topical antibacterial agents for wound care: A primer Dermatol Surg 2003; 29: 620–626 P1: JZZ 0521618134c07 CB1006/Lane 521 61813 November 28, 2005 16:25 Therapeutics 113 Systemic Antifungals Terbinafine (allylamine) Mechanism: inhibits squalene epoxidase (↑squalene and impairs ergosterol synthesis) Metabolism: hepatic (80%); fecal (20%) −15 metabolites Excretion: renal Dosing: 250 mg po qd (12 wks – toenails; wks – fingernails) 125 mg po qd (20–40 kg) 62.5 mg po qd (90%) no need to renal dose for single dose multiple drug interactions (cytochrome P-450) minimal CYP 3A4 inhibition at doses g without liver disease/ethanol use and then repeat at intervals test dose of 5–10 mg qd (CBC, LFTs week later) may divide dose q12 hr × doses for nausea may supplement folate mg po qD for nausea antidote for overdose: folinic acid unaffected by food intake in adults interacts with weak acids (probenecid, salicylate, sulfonamide) ↓ renal function increases risk of hepatic and hematologic toxicity P1: JZZ 0521618134c07 120 CB1006/Lane 521 61813 November 28, 2005 16:25 Pocket Guide for Cutaneous Medicine and Surgery Roenigk Classification of Liver Biopsies Grade Histology Action I Normal; mild fatty infiltration Fatty infiltration (mod to severe) Fibrosis (mild) May continue II IIIA IIIB IV May continue May continue but need liver biopsy after mo Fibrosis (moderate to severe) Discontinue Cirrhosis Discontinue Callen JP, Kulp-Shorten CL, Wolverton SE Methotrexate In: Wolverton SE ed Comprehensive Dermatologic Drug Therapy Philadelphia: W B Saunders Co 2001: p 147 Zachariae H Liver biopsies and methotrexate: A time for reconsideration? J Amer Acad Dermatol 2000; 42: 531–534 P1: JZZ 0521618134c07 122 CB1006/Lane 521 61813 November 28, 2005 16:25 Pocket Guide for Cutaneous Medicine and Surgery Systemic Immunomodulators Azathioprine (Imuran) Mechanism: inhibits DNA/RNA synthesis/repair alters T and B-cell function, decreases number of Langerhans cells/APCs Metabolism: i anabolized by HGPRT → active 6-thioguanine ii catabolized by thiopurine methyltransferase iii catabolized by xanthine oxidase (XO) Excretion: Negligible (virtually completely metabolized) Dosing (TPMT): High (>19 U) → ≤2.5 mg/kg/day Medium (13.7–19 U) → ≤1.5 mg/kg/day Low (5–13.7 U) → ≤0.5 mg/kg/day T-cell function Metabolism: hepatic Excretion: hepatic; renal (10–20%) Dosing: 1–3 mg/kg/day (50–200 mg/day) (single am dose) Pregnancy cat.: C Side effects: carcinogenic (including bladder carcinoma) hemorrhagic cystitis Monitoring: WBC (caution if