The effects of drugs on wound healing–‐part II. Specific classes of drugs and their effect on healing wounds

Abstract

Classes of drugs in wound healingDrugs can inhibit or assist wound healing. The effect of a speci®c drug depends on its mechanism of action, dosage, route, and administration in relation to the speci®c phase of wound healing. A discussion of the major classes of drugs that impact wound healing follows, with Tables 1±8 summarizing the effects of major classes of drugs. Generic and trade names used in this paper are summarized in Table 9. Table 1 lists the effects of anti-in¯ammatory agents on wound healing. Anti-in¯ammatory agents CorticosteroidsCorticosteroids affect almost every phase of wound healing because of their inhibitory effect on gene expression in various cells. The in¯ammatory phase of wound healing is affected as corticosteroids inhibit prostaglandin synthesis. 1±4 The recruitment and phagocytic properties of neutrophils 5 and macrophages 6 are decreased causing delayed removal of bacteria and foreign bodies. 7 Lymphocyte recruitment and antibody formation by B lymphocytes is reduced. 2 The antimitotic activity 8 causes decreased epithelial regeneration 4 and granulation tissue formation 4,9 affecting the tissue formation phase. A thinned epidermis occurs due to a reduced rate of keratinocyte proliferation and an increased rate of differentiation. 9,10 Granulation tissue formation is reduced due to decreased ®broblast proliferation, 9 resulting in less collagen, 11 proteoglycans, and glycosaminoglycans. 12±14 A decreased oxygen and reduced nutrient supply 14 may result from steroid-induced vasoconstriction caused by the inhibition of the potent vasodilator prostaglandin E 2 (PGE 2 ) 15 and by the enhanced smooth muscle contraction of vessel walls. 14 As the number of macrophages in the tissue is decreased under the in¯uence of steroids, cytokine stimulation provided by macrophages for normal ®broplasia and angiogenesis is diminished. 6 The tissue remodeling phase is affected by decreased collagen and ground substance synthesis. Decreased numbers of ®broblasts are seen and wound contraction is reduced. 16 Steroid atrophy leads to a thinned dermis and the development of striae 17 (Fig. 1). Interestingly, corticosteroids also decrease collagen degradation by decreasing collagenase production. 18 The most pronounced effects are noted when steroids are administered during the early in¯ammatory phase. 19±21 The suppression of macrophage-orchestrated events by steroids in early in¯ammation is thought to play a role. 22 While oral doses of prednisone (above 10 mg per day) adversely affect wound healing during the ®rst 3 days, high-dose prednisone (at or above 40 mg per day) is needed to effect ®broplasia and collagen remodeling during subsequent days. 21 Inhibition of wound contracture in open wounds occurs regardless of the timing of corticosteroid administration. 20 Steroids affect cells by altering gene expression after they cross cell membranes, bind to cytoplasmic receptors, and translocate into the nucleus. 23,24 The degree of inhibition of gene expression is related to the potency of the steroid. 2...

Canadian Rheumatology Association Recommendations for the Pharmacological Management of Rheumatoid Arthritis with Traditional and Biologic Disease-modifying Antirheumatic Drugs: Part II Safety

“…I. Perioperative Care -Understanding potential perioperative risks in patients with RA Patients with RA are commonly treated with immunosuppressive medications including corticosteroids, methotrexate (MTX), and/or biologic DMARD, which may increase their risk of perioperative infections or affect wound healing. Stopping therapy, however, may result in a flare and impede recovery from surgery 10,11,12 . The balance of these risks needs to be considered when deciding if treatment should be suspended in the perioperative period, and if so, when therapy should be withheld and restarted.…”

Aspectos celulares da cicatrização

“…10 As principais citocinas envolvidas nessa fase são: fator de necrose tumoral (TNF-α), interleucina (IL-1), PDGF e TGF-β produzidas pelos fibroblastos, além das produzidas pelas células epiteliais como EGF e TGF-b. 33 A reepitelização, que é o recobrimento da ferida por novo epitélio e consiste tanto na migração quanto na proliferação dos queratinócitos a partir da periferia da lesão, também ocorre durante a fase proliferativa. Esses eventos são regulados por três principais agentes: fatores de crescimento, integrinas e metaloproteases.…”

Multiple Anticoagulant Use Increases Wound Complications Following Resection of Lower Extremity Soft Tissue Sarcomas

“…Warfarin inhibits the synthesis of vitamin K factors II, VII, IX and X, and thus prevents fibrin deposition which occurs in the proliferative and maturational phases of the wound cascade. Moreover, warfarin is a vitamin K antagonist, which is an essential vitamin in the clotting phase of wound healing [7]. Heparin, in combination with anti-thrombin, inhibits factors IX, X, Xa, XI, and XII in the coagulation cascade.…”

“…Heparin, in combination with anti-thrombin, inhibits factors IX, X, Xa, XI, and XII in the coagulation cascade. Both warfarin and heparin are thought to affect wound healing by inhibiting the formation of fibrin [7,28,29]. ASA irreversibly inhibits platelet aggregation and reduces the inflammation in wounds mediated by the metabolites of arachidonic acid [7,30].…”

“…ASA irreversibly inhibits platelet aggregation and reduces the inflammation in wounds mediated by the metabolites of arachidonic acid [7,30]. Although the biochemical interaction of these medications differ, they have each been shown to impact wound healing such that there is an increased risk of infection, time to heal, development of hematoma, and wound dehiscence when administered [7,10,11].…”