Systemic effects topical route

Drugs have been administered nasally for several years both for topical and systemic effect. Topical administration includes agents for the treatment of nasal congestion, rhinitis, sinusitis, and related allergic and other chronic conditions. Various medications include corticosteroids, antihistaminics, anticholinergics, and vasoconstrictors. The focus in recent years has been on the use of nasal route for systemic drug delivery. 

The drugs can be administered by a variety of routes, either locally or administered orally and by injection. To produce local effects, drugs are applied topically to the skin or mucous membranes. To produce systemic effects drugs are administered orally, rectally, parenterally or by inhalation route. 

Selectivity of action is based on several factors. Some drugs stimulate either muscarinic receptors or nicotinic receptors selectively. Some agents stimulate nicotinic receptors at neuromuscular junctions preferentially and have less effect on nicotinic receptors in ganglia. Organ selectivity can also be achieved by using appropriate routes of administration ("pharmacokinetic selectivity"). For example, muscarinic stimulants can be administered topically to the surface of the eye to modify ocular function while minimizing systemic effects. 

The topical route is the most common method to administer a medication to the eye. Introducing the drag directly to the conjunctival sac localizes drag effects, facilitates drag entiy that is otherwise hard to achieve with systemic delivery and avoids first-pass metabolism. The physiological factors affecting topical drag delivery and the approaches under development to optimize this type of delivery are described in detail below. 

In 1951-1952, Sulzberger et al. showed that systemically - but not topically -applied cortisone acetate was effective in the treatment of eczema and other der-matitides, whereas hydrocortisone was effective with both routes of administration [8,9]. Because the topical route promised a relative freedom from troublesome systemic side effects (e.g., salt retention). Schering recognized the need for an effective synthesis of the latter. 

DOT CLASSIFICATION Forbidden SAFETY PROFILE A human poison by ingestion and possibly other routes. Poison experimentally by ingestion, intraperitoneal, intravenous, subcutaneous, and parenteral routes. Human central nervous system effects by ingestion and possibly other routes general anesthesia, hallucinations or distorted perceptions, and convulsions. An eye irritant. A widely abused, controlled substance. Abuse leads to habituation or addiction. In medicine, it is used as a local narcotic anesthetic applied topically to mucous membranes. The free base is soluble... 

Moderately toxic by subcutaneous route. Human systemic effects by ingestion dyspnea, nausea, other gastrointestinal effects. Experimental reproductive effects. Mutation data reported. A strong irritant due to its oxidizing properties. Used in production of drugs of abuse, as a topical antibacterial agent, and a chemical reagent. 

Systemic steroids are also the cause of numerous negligence claims.These drugs have side effects that can result in serious injury, even death, and consequently must be used conservatively. Systemically administered drugs, with their risk of systemic complications, should not be used if a topical route of administration suffices, and practitioners must be prepared to justify the selection of a systemic route of administration when complications result and a topical route of administration initially was not used. Whenever systemic steroids are prescribed, practitioners must warn patients of side effects, monitor patients adequately so that preventable injuries can be detected, and document the care rendered. 

The percutaneous (transdermal or topical) route for systemic drug delivery is used infrequently for pediatric patients. Medications are typically applied to the skin for their local effect. In the future, this route may be used more frequently for systemic effects as more transdermal systems are developed for drug delivery. 

It is important to note that although aerosolization of antibiotic therapy has resulted in significantly higher sputum concentrations, systemic treatment is clearly more effective than this topical route of delivery. This suggests that factors other than sputum concentrations are important in the overall efficacy of therapy. 

Other routes of administration arc theoretically possible such as rectal route (rectal capsules and rectal suppositories) for drugs having systemic effects such a.s sedatives, tranquilizers, and analgesics topical route (patchs) for drug absorption (hormones or nicotine) into the systemic circulation parenteral route (administration of parenteral suspensions or implantation of compressed pellets). 

Editor s notes In this chapter adverse effects and reactions that arise from the oral or parenteral administration of corticosteroids (glucocorticoids and mineralocorti-coids) are covered in the section on systemic administration. Other routes of administration are dealt with in the sections after that inhalation and nasal administration are dealt with in Chapter 16, topical administration to the skin in Chapter 14, and ocular administration in Chapter 47. 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

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