Therapeutic local effect

Aerosolized DNase (dornase) is a therapeutic protein designed for alveoli delivery to achieve local effects in the deep lung. Aerosolized DNase is formulated as a pulmonary dosage form, targeted for deep-lung delivery to reduce opportunistic infections due to the increased viscosity of mucus in the lung that affects respiratory function in patients with cystic fibrosis. 

It is clear that to exert a toxic effect a compound must come into contact with the biological system under consideration. It may exert a local effect at the site of administration on initial exposure, but it must penetrate the organism in order to have a systemic effect. The most common means of entry for toxic compounds are via the gastrointestinal tract and the lungs, although in certain circumstances, absorption through the skin may be an important route. Therapeutic agents may also enter the body by other routes such as injection. 

Solutions (lavages) and foams are liquid preparations. The foams differ from the solutions in the presence of a suitable propellant, in the formulation, and the type of container, a pressurized delivery device. Plasma concentration profiles obtained after solution administration are characterized by a burst effect followed by a rapid decrease below therapeutic levels, due to the low residence time of the formulation in the vaginal cavity. Such preparations are designed to achieve a local effect particularly in case of inflammations or infections caused by bacteria or yeasts (anaerobic bacteria or Candida species). Nonoxynol-9 (N-9) foam is used as a contraceptive and against sexually transmitted diseases [19]. 

I 6 Wu YX, Johnson T Herdeg C, et al, Stent-based local delivery of therapeutic adenovirus effectively reduces neointimal proliferation in porcine coronaries, Di Yi Jun Yi Da Xue Xue Bao 2003 23(12) 1263-1265. 

The permanent positive charge of QTA influences distribution in vivo and prevents passage of blood-brain barrier and blood-cerebrospinal fluid barrier [30, 31]. Myolitic QTA are muscarinic receptor antagonists but allow a better therapeutic index as they are insoluble in lipids and thus poorly systemically absorbed (e.g. bioavailability of A-butyl-scopolamine after oral intake <1 % [30]). Therefore, spasmolytic activity in the GIT (by, e.g. cimetropium, butropium or /V-butyl-scopolamine, Fig. 1), respiratory tract (ipratropium, Fig. 1) and overactive bladder (trospium, Fig. 1) appears as the primary local effect whereas systemic side effects are markedly minimized or absent [32-34],... 

Bees have been used therapeutically in some animal populations for treatment of a variety of disorders. A recent study examined the effects of bee stings on sows with hypogalactia syndrome postpartum. Complications expected from this type of therapy are primarily local effects as well as more systemic hemorrhagic effects. 

Parenteral administration is the primary route of testing delivery for nucleic acid therapeutics irrespective of whether systemic or local effects are desired. However, to some extent, pulmonary and oral routes are also investigated as potential routes for local targeting to treat cystic fibrosis or colonic tissue (171-173). For nonparenteral delivery, the use of pharmaceutical excipients in the formulation is critical. In addition, the production costs of nucleic acid therapeutic-containing drug delivery systems should be minimized. Even for intravenously or subcutaneously injected nucleic acid-based therapeutics, the use of protective carriers is most likely necessary, and advantageous as compared to injection of the naked RNA or DNA. Carriers can be divided into viral or... 

Sulfasalazine is a pro-drug that is not active in its ingested form. It is broken down by colonic bacteria into 5-aminosalicylic acid (5-ASA mesalamine) and sulfapyridine. Some controversy exists regarding which of these two products are responsible for the activity of azulfidine. 5-Aminosalicylic acid, however, is known to have a therapeutic benefit, although it is not clear whether sulfapyridine adds any further benefit. In the colon, the products created by the breakdown of sulfasalazine work as anti-inflammatory agents for treating colon inflammation. The beneficiai effect of sulfasalazine is believed to result from a local effect on the bowel, although there also may be a beneficial systemic immune-suppressant effect. Sulfasalazine was approved in 1950. 

Not much is known about the biopharmaceutics of nasal preparations with a local effect. Dosing is done on a therapeutic result basis. What is known is that bioavailabiUty and residence time are influenced by ... 

Preparations for cutaneous (or dermal) application may be used for local treatment as well as for transdermal administration with a systemic effect. The chapter focuses on preparations with a local effect and on design of formulation and method of preparation of those prepared in pharmacies. The interaction between skin, active substance and base, the anatomy of the skin and biopharmaceutical aspects of cutaneous preparations are discussed as well as the therapeutic effect of the base. Because of the important role of the pharmacist in prescription assessment some recommendations for the communication with the physician are given. One aspect is how to proceed with a request for the mixing of two licensed medicines or for the addition of an active substance or an excipient to a licensed product. The formulation design is generally following the several phases of the multicomponent preparations. Based on the... 

In order to induce a toxic effect, local or systemic, the causative material must first come into contact with an exposed body surface these are the routes of exposure. In normal circumstances, and depending on the nature of the material, the practical routes of exposure are by swallowing, inhalation, and skin and eye contact. In addition, and for therapeutic purposes, it may be necessary to consider intramuscular, intravenous, and subcutaneous injections as routes of adininistration. 

P-D-Arabinofuranosylcytosine [147-94-4] (ara-C, 16), C H N O, reportedly has had significant therapeutic effects in patients with localized herpes zoster, herpes eye infections, and herpes encephaUtis (33), although several negative results have also been reported (34) (Fig. 2). Ara-C, also known as cytarabine, is quite toxic and is only recommended for very severe viral infections. It is rapidly deaminated in humans to the relatively inactive ara-U Ara-C is converted in the cell to the 5 -monophosphate by deoxycytidine kinase, followed by formation of the corresponding di- and triphosphate. The triphosphate has been shown to inhibit DNA polymerase. 

Procainamide. Procainamide hydrochloride is a ben2amide, synthesized to prolong the therapeutic effects of the local anesthetic procaine [59-46-1] (13) (see Anesthetics). The dmg is effective in a wide range of supraventricular and ventricular arrhythmias (14). 

Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Local anaesthetics are more consistently effective than other therapies, but their use is controversial. High concentrations are needed for therapeutic benefit, but this also increases the amount crossing the blood brain barrier and entering the brain producing unwanted effects. Topical administration to the airways can reduce this. 

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