Local drug administration techniques

Finally, application of the suspected substance should produce a response that mimics the action of the transmitter released by nerve stimulation. Furthermore, application of a selective antagonist should block the response. Microiontophoresis, which permits highly localized drug administration, has been a valuable technique in assessing the action of suspected transmitters. Because of the complexity of the CNS, specific pharmacologic antagonism of a synaptic response provides a particularly powerful technique for transmitter identification. 

There are three drug administration techniques which have traditionally been labelled parenteral ("around the gastrointestinal tract"). These techniques involve skin puncture. Thus administration involves risk of infection, pain, and local irritation ... 

After oral administration, drug and metabolite concentrations in blood, urine, and feces can easily be monitored. In contrast, topical application to the skin usually aims at a local treatment. Therefore, the main interest lies in determining the drug level within the skin, in order to evaluate the dermal bioavailability of compounds or assess the bioequivalence between different formulations. In the following sections, appropriate analytical techniques will be presented. 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

When an initially painful intravenous or intramuscular injection must be administered repetitively, patient reluctance develops. Injection pains are usually accompanied by hemorrhage, edema, inflammation, and tissue necrosis." Among the factors responsible for painful injections, the most important are the drug solubility in aqueous medium, the viscosity, the pH and the hypo- or hyperosmotic character of the injected drug solution, the amount of the injected volume, the site of injection, the pain tolerance of the patient, and the technique of administration. Other factors include precipitation of the drug at the injection site, and localized cell lysis. ... 

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