Local Administration Routes Research Articles

Pharmacology of botulinum neurotoxins

Botulinum toxin type A has long been an important therapy in the treatment of focal dystonias of the head and neck. It has been studied more recently for the treatment of cervical pain, cricopharyngeal dysphagia, and gustatory sweating. Botulinum neurotoxins inhibit exocytosis from selected neurons after injection into specific target areas such as muscles. The localized action of botulinum neurotoxins is an advantage in many disorders, and results from the local route of administration combined with the specific features of the neurotoxin formulation, which varies among different botulinum toxin preparations. This review examines the basic and clinical pharmacology of botulinum neurotoxins as well as the influence of molecular structure, mechanisms, and formulation on the pharmacology. Evidence for additional mechanisms of action beyond the traditional inhibition of acetylcholine release is also considered.

The Use of Topical Tacrolimus (FK506/Protopic) in Cutaneous Manifestations of Autoimmune Diseases

The cutaneous manifestations of autoimmune diseases, including systemic lupus erythematosus, are common and often recalcitrant to treatment. Unfortunately, therapy for lupus and other autoimmune skin diseases has not advanced and relies heavily on the use of oral and topical corticosteroids. Frequently, treatments prove less than ideal, either from toxicity or lack of efficacy. A topical form of the immunomodulating transplant medication, tacrolimus (FK-506, Protopic), has recently been developed and approved for use in treating atopic dermatitis. Its mechanism of action and local route of administration render tacrolimus a potentially attractive novel therapeutic alternative for the treatment of various autoimmune dermatologic conditions. We report our successful experience using this drug in 3 patients with autoimmune dermatologic disease who were referred to a tertiary care subspecialty clinic.

Efficacy of sublingual immunotherapy in asthma and eczema.

Sublingual immunotherapy (SLIT) is the local route of administration of allergen extracts investigated in several controlled clinical trials. In a number of countries, particularly Italy, France and Spain, this has become common in office practice. At variance with subcutaneous immunotherapy, the knowledge of mechanisms of action of SLIT is still at the beginning: some studies, in animal models, provided interesting information: the dendritic cells of oral mucosa act as efficient antigen-presenting cells and produce IL-12, which directs the immune response towards a Th1 profile away from IgE-Th2 profile. Its clinical efficacy (improvement of symptoms and reduction of drug intake) for both asthma and rhinitis has been assessed in detail for the most common allergens: house dust mites, grass pollen, Parietaria, birch pollen and olive tree. SLIT requires further evaluation concerning the treatment of the extrinsic form of atopic dermatitis. The induction of immunologic tolerance rather than immunoreactivity should be worth pursuing due to the immunologic pathway involved in the pathophysiology of atopic dermatitis. The safety profile of SLIT, derived from the clinical trials and postmarketing surveillance studies, turned out to be satisfactory in adults and children. SLIT represents an important step towards an efficacious and safe treatment of patients with allergic respiratory diseases; nevertheless, further studies are necessary to establish it as a viable alternative to subcutaneous immunotherapy.