Systemic Therapies

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

They also are important portals for systemic therapy. However, many variables can influence dmg dissolution and absorption ia these areas, including rate of gastric emptying, intestinal motility, mass and pH of intestinal contents, and condition of the absorbiag surfaces (15—17). These variables, ia turn, can be affected by the patient s disease, posture, and eating habits, and even by such aspects of the treatment as the timing of doses (11). 

Oral mucosal membranes provide a port for systemic therapy as weU. Nitroglycerin sublingual tablets (Nitrostat) abort acute mgina attacks methyl-testosterone [58-18-4] buccal tablets (Android 5) are indicated for testosterone [58-22-0] replacement therapy (39) md nicotine [54-11-5] gum (Nicorette) aids in smoking cessation. 

No ocular products for systemic therapy are commercially available, but research is under way on ocular systems for the systemic deUvery of therapeutic agents such as insulin (53). 

When treating acne vulgaris, topical and systemic therapies (if indicated) are initiated 2 to 4 weeks prior to peeling. Topical antibiotics and benzoyl peroxide based products can be used daily and discontinued 1 or 2 days prior to peeling. However, unless a deeper peel is desired, retinoids should be discontinued 7-10 days prior to salicylic acid peeling. Broad-spectrum sunscreens (UVA and UVB) should be worn daily (see Photo damage. Sunscreen section). 

Systemic therapy for acne includes antibiotics, isotretinoin and hormones (Tables 11.8 and 11.9). Oral treatment is indicated in cases of 1) moderate and severe acne 2) acne with tendency to scars development and 3) psychological distress related to acne. 

Topical analgesics sometimes are used for mild pain or as an adjunct to systemic therapy. There are limited data to support the use of salicylate-containing rubefacients (e.g., methyl salicylate and trolamine salicylate) or other counterirritants (e.g., menthol, camphor, and methyl nicotinate) in OA.32 See Chap. 57 for more information on these products when used for musculoskeletal disorders. 

Topical antibiotic drops are preferred. Consider subconjunctival antibiotics if compliance is a concern. Systemic therapy is useful in cases of systemic infection (e.g., gonorrhea) or if the sclera is infected. Reserve ointments for minor cases or adjunctive nighttime therapy.19... 

Compare and contrast the treatment modalities for psoriasis, including topical and systemic therapies and phototherapy. 

Pustular psoriasis may be localized or generalized and may be an acute emergency requiring systemic therapy. Generalized pustular psoriasis is characterized by disseminated deep-red erythematous areas and pustules, which may merge to become "lakes of pus."... 

Erythrodermic psoriasis is a generalized, life-threatening condition that presents with erythema, desquamation, and edema, and may require life support measures as well as systemic therapy. 

Management of patients with psoriasis generally involves both nonpharmacologic and pharmacologic therapies. Pharmacologic alternatives for plaque psoriasis include topical treatments, phototherapy, photochemotherapy, and systemic therapies alone (orally or by injection). The choice of treatment is usually dictated by the severity of disease.15-17 In some cases, a combination of treatment options may be preferred. Topical therapies can be used in patients with limited or mild... 

Several UVB and systemic therapy combinations have shown efficacy. These include UVB with acitretin (ReUVB) and UVB with methotrexate, and will be discussed later. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Sulfasalazine has variable efficacy and is of limited potency. However, its side-effect profile is better than other systemic therapies and it is sometimes tried as an initial systemic agent for moderate to severe psoriasis. Usual doses are 2 to 4 g/day in divided doses.10... 

Kormeili T, Lowe NJ, Yamauchi PS. Psoriasis immunopathogenesis and evolving immunomodulators and systemic therapies United States experiences. Br J Dermatol 2004 151 3-15. 

Systemic therapy is used to prevent bleeding associated with surgery, childbirth, and dental extractions and to treat bleeding... 

Since dermatophyte hyphae seldom penetrate into the living layers of the skin, instead remaining in the stratum corneum, most infections can be treated with topical antifungals. Infections covering large areas of the body or infections involving nails or hair may require systemic therapy. Patients with chronic infections or infections that do not respond to topical therapy are also candidates for systemic therapy. 

Determine which patient populations may benefit from adjuvant systemic therapy for... 

Neoadjuvant chemotherapy is appropriate for patients with locally advanced or inflammatory breast cancer, followed by local therapy and further adjuvant systemic therapy. 

The use of preoperative systemic therapy is gaining favor in both early-stage and locally advanced breast cancers. This approach to therapy, referred to as neoadjuvant or primary systemic therapy, most often consists of chemotherapy but in special circumstances also may include hormonal therapy (e.g., in inoperable patients with significant comorbidities). The advantages of preoperative systemic therapy include... 

Radiation is an important modality in the treatment of symptomatic metastatic disease. The most common indication for treatment with radiation therapy is painful bone metastases or other localized sites of disease refractory to systemic therapy. Radiation therapy gives significant pain relief to approximately 90% of patients who are treated for painful bone metastases. Radiation is also an important modality in the palliative treatment of metastatic brain lesions and spinal cord lesions, which respond poorly to systemic therapy, as well as eye or orbit lesions and other sites where significant accumulation of tumor cells occurs. Skin and/or lymph node metastases confined to the chest wall area also may be treated with radiation therapy for palliation (e.g., open wounds or painful lesions). 

Kelly H, Goldberg RM. Systemic therapy for metastatic colorectal cancer Current options, current evidence. J Clin Oncol 2005 10 4553-4560. 

Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. New Engl J Med 2005 352 476-487. 

---