[Drug administration routes for the hand and wrist].
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Drug Administration Routes↗
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The effects of dose, route of administration, drug scheduling and MDR-1 gene transfer on the genotoxicity of etoposide in bone marrow.
We have used the bone marrow micronucleus assay (BMMN) as a measure of clastogenicity, in response to etoposide exposure in murine bone marrow. Oral delivery of etoposide resulted in a reduced number of micronucleated polychromatic erythrocytes (MPE) relative to the same dose delivered intraperitoneally (P < 0.001). Daily fractionation of the oral schedule of etoposide led to a more than six-fold increase in cumulative MPE frequency over that observed with the same total, unfractionated dose, with the potency of the response increasing with serial exposure (r = 0.79). Retrovirally-mediated expression of MDR1 in murine bone marrow resulted in partial protection against the clastogenic activity of etoposide relative to mock transduced control mice. The model system developed has indicated a variety of factors able to influence the genotoxicity of etoposide. It should now be possible to further exploit this model in order to define other factors governing haemopoietic sensitivity to etoposide.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Controlled-release drugs: administration routes and formulations].
The notion of controlled release has been known since the 1930s, but was not significantly developed until the 1970s. At that time, Alza introduced the concept of a "therapeutic system" and proposed new pharmaceutic formulations. Over time, the idea became one of controlled drug delivery and today concerns not only one rate of release but also the site of release of the active substance. We present here definitions, fundamentals and advantages and disadvantages of currently marketed systems and provide examples illustrating oral, transdermal and respiratory delivery systems. Current research is also examined.
Chemistry, Pharmaceutical↗
[Wrong drug administration route - misunderstanding physician-nurse].
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Aged↗
[Drug administration routes].
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Administration, Oral↗
Symptom control in advanced cancer: important drugs and routes of administration.
Aggressive symptom control is a vital component of palliative medicine. Frequently both physicians and patients focus on pain control, forgetting the broader issues of symptom control. Pain and other symptoms are inextricably linked. Common symptoms include constipation, nausea and vomiting, insomnia, anorexia, weight loss, and cough. All oncologists should be familiar with the indications, doses, and unwanted effects of drugs commonly indicated for symptom control. This article will discuss some drugs presently available to achieve good symptom control. At the correct dose and dosing schedule, these agents can have a significant impact on quality of life. As in all areas of medicine, it is best to know the benefits and unwanted effects of a few drugs, rather than randomly prescribing different agents for similar clinical situations. This is rational prescribing. While the list presented here is not exhaustive, it does reflect core drugs currently available in the United States.
Drug Administration Routes↗
[Routes for drug administration during cardiopulmonary resuscitation].
Selecting a route for drug administration during CPR requires consideration of the speed with which access can be obtained, the technical difficulties involved in performing the procedure, the associated risk of complications, delays in drug delivery to the central circulation, and the duration of effective drug levels following injection. The peripheral venous route is the safest method, and drug delivery can be enhanced by a fluid bolus after injection of the medication. The circulation time is shortest after central venous injection, but there is some risk of complications. The femoral route is associated with a high incidence of unsuccessful catherization. The endotracheal tube provides an accessible route for administration of most drugs, but peak concentrations are lower than those obtained by other routes. While the results are almost the same as an intravenous injection, the intraosseous route is currently underrepresented in clinical practice. This method must not only be considered in pediatric patients, but in adult patients as well.
Adult↗
Opioid pharmacotherapy in the management of cancer pain: a survey of strategies used by pain physicians for the selection of analgesic drugs and routes of administration.
BACKGROUND: This survey documents the strategies used by pain control physicians in the selection of opioid drugs and routes of administration in the management of inpatients referred to a cancer pain service. METHODS: The following approaches were prospectively evaluated during the treatment of 100 consecutive inpatients: 1) the influence of the evaluation of the goals of care on decision making, 2) selection of opioid drugs, 3) indications for changing opioid drugs and the frequency with which this strategy is used, and 4) selection of route of administration. RESULTS: Eighty of the 100 patients underwent a total of 182 changes in drug, route, or both drug and route before discharge or death. The major reasons for change were to improve the convenience of treatment regimen in the setting of adequate pain relief (31.4%), diminish side effects in the setting of controlled pain (25.0%), reduce the invasiveness of therapy in the setting of controlled pain (19.3%), and simultaneously improve pain control and reduce opioid toxicity (17.7%). When opioid toxicity was the reason for change, physicians changed the opioid drug in 71% of cases and the route in 29%. When convenience or invasiveness were targeted, the physicians changed the route in 61% of cases and the opioid in 39%. Forty-four patients required one or more change in the opioid, and 20 required 2 or more changes (range, 2-6 changes). At the time of discharge (n = 82), morphine was more commonly selected than hydromorphone or fentanyl (39% vs. 23% vs. 17%) and the routes of administration were oral (57%), transdermal (18%), intravenous (18%), subcutaneous (5%), and intraspinal (4%). Therapeutic changes were associated with improvement in physician-recorded pain intensity and a lower prevalence of cognitive impairment, hallucinations, nausea and vomiting, and myoclonus among patients who were discharged from the hospital. CONCLUSIONS: These data illustrate the application of strategies for selections of opioid drugs and their route of administration that are recommended in current guidelines for the management of cancer pain.
Adult↗
Routes of drug administration, differential affiliation, and lifestyle stability among cocaine and opiate users: implications to HIV prevention.
Types of drugs used and routes of administration were assessed, and correlations to social affiliation, HIV status, and lifestyle stability were explored among 672 street-recruited drug users in Baltimore. Participants reported 63 patterns of drug use, which were categorized into five groups: (1) only sniff heroin; (2) smoke crack and may snort cocaine; (3) sniff heroin and smoke crack; (4) inject heroin and cocaine; and (5) inject heroin and cocaine, smoke crack, and may snort heroin. Social network analysis revealed that heroin sniffers and crack smokers both tended to associate with those with similar drug use patterns. High symptoms of drug dependence were observed among heroin users irrespective of mode of administration. Injectors reported higher rates of hospitalization compared to noninjectors even after adjusting for HIV status. Implications to HIV prevention and drug use transitions are discussed.
Adult↗
A new route of drug administration: intrauterine delivery of insulin and calcitonin.
High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-release fashion. We report here on the absorption and the systemic biological effect of two peptides, insulin and calcitonin, after instillation into the uterus of the rat. Intrauterine delivery was compared to subcutaneous injections in intact and ovariectomized rats. In addition, we describe results of a preliminary study on calcitonin absorption from controlled-release matrices inserted in the rat uterus. The amount and duration of the hypoglycemic and the hypocalcemic effects induced by intrauterine delivery of insulin and calcitonin, respectively, were equivalent to those obtained after subcutaneous injections. The results were similar in intact and ovariectomized rats. It is concluded that the intrauterine administration of both insulin and calcitonin is bioequivalent to subcutaneous injection. The therapy of a number of clinically important diseases could benefit from this discovery.
Absorption↗
Anal submucosal injection: a new route for drug administration in pelvic malignancies. III. Misonidazole distribution in serum, uterus and vagina: an experimental study.
The anal and oral administration routes were compared in 40 rats to study the distribution of misonidazole (MIS), a radiation sensitizer, in the serum, uterus and vagina. 14C-labelled MIS was administered in a dose of 0.2 ml water/100 g body weight containing 1 microCi MIS. The dose was given orally in 20 rats and was injected in the anal submucosa in another 20 rats. Animals were then sacrificed after 15, 30, 60 or 120 min or after 24 h. Serum samples was taken at the time of sacrifice; organs were dissected and radioactivity was determined in each by the internal standard method. The study has shown that the highest drug concentration in uterus and vagina relative to serum was achieved by the anal submucosal route. They showed a drug concentration of 10 and 8 times, respectively, of the serum level after 15 min in contrast to oral administration, which in the same period of time produced a drug concentration of 1/5 and 1/4 the serum level. The anal route thus offers an adequate channel for MIS administration to promote radiation responsiveness in cancer of uterus and vagina.
Administration, Oral↗
[Drug administration via the endobronchial route. Possibilities of drug administration in emergency medicine].
For cardiopulmonary resuscitation, the endobronchial route represents a good means of administering drugs with a systemic effect, such as adrenaline and atropine, even without a venous line. Via this route, however, higher doses are needed (2.5 times as much as those normally given intravenously). In order to produce a larger surface area within the bronchio-alveolar space and thus speed up absorption, the drugs are diluted in 5-10 ml solvent (isotonic saline solution or distilled water). For endobronchial administration of a drug, various techniques are employed, for example, simply injecting it into the upper end of the (endotracheal) tube, puncture of the tube the use of an application probe introduced into the endobronchial tube, aspiration or venacaval catheter, or the EDGAR tube with an injection needle incorporated within the tube wall. After injection, the diluted medication is distributed into the tiny branches of the bronchial tree by repeated hyperventilation. Despite the need for an adequate alternative to the venous route in the field of cardiopulmonary resuscitation, we still have very few reliable facts about the endobronchial application technique.
Administration, Inhalation↗
[Technic and administration routes of drugs].
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Drug Administration Routes↗
[Antibiotic levels in the lacrimal fluid and liquid ocular media in various routes of drug administration].
Rabbit experiments (n = 273) and examinations of the lacrimal fluid and aqueous humor of the eye, carried out in 165 patients after antibiotic administration via various routes, have revealed that antibiotics (gentamycin, ampicillin, benzylpenicillin) do not penetrate into the liquid media of the eye or lacrimal fluid after intramuscular injections. These drugs appear in these fluids only after subconjunctival injections; the therapeutic concentration in the lacrimal fluid persists for an hour, that in the anterior chamber fluid for 30-45 min.
Adolescent↗
Sex and racial differences in pharmacological response: effect of route of administration and drug delivery system on pharmacokinetics.
Mechanistic investigations into the physiological and biochemical differences between patients have only recently begun to help explain what was previously categorized as "intersubject variability." Additional factors, including the particular drug formulation or delivery system, have been implicated in observed sex-based and race-based differences in pharmacokinetic response. Drug absorption following intramuscular injection can be highly variable if the injection is mistakenly placed in the overlying tissues, a situation that is more likely to occur in women than men. Slower gastric emptying in women can significantly delay the onset of effectiveness of enteric-coated dosage forms, and differences in gastric pH can affect the drug solubility and dissolution rate. Slower drug release rates designed into many extended release dosage forms interact with the differential locations and populations of intestinal and hepatic transporters and metabolizing enzymes to cause significant sex-based and race-based differences in plasma drug concentrations. Increased efforts to identify and understand the interplay of an individual's physiological makeup, dietary intake, environment, and the drug products he or she uses are needed to be able to provide optimal drug therapy regimens to each patient.
Biological Availability↗
The inhalation of drugs: advantages and problems.
Inhalation is a very old method of drug delivery, and in the 20th century it became a mainstay of respiratory care, known as aerosol therapy. Use of inhaled epinephrine for relief of asthma was reported as early as 1929, in England. An early version of a dry powder inhaler (DPI) was the Aerohalor, used to administer penicillin dust to treat respiratory infections. In the 1950s, the Wright nebulizer was the precursor of the modern hand-held jet-venturi nebulizer. In 1956, the first metered-dose inhaler (MDI) was approved for clinical use, followed by the SpinHaler DPI for cromolyn sodium in 1971. The scientific basis for aerosol therapy developed relatively late, following the 1974 Sugarloaf Conference on the scientific basis of respiratory therapy. Early data on the drug-delivery efficiency of the common aerosol delivery devices (MDI, DPI, and nebulizer) showed lung deposition of approximately 10-15% of the total, nominal dose. Despite problems with low lung deposition with all of the early devices, evidence accumulated that supported the advantages of the inhalation route over other drug-administration routes. Inhaled drugs are localized to the target organ, which generally allows for a lower dose than is necessary with systemic delivery (oral or injection), and thus fewer and less severe adverse effects. The 3 types of aerosol device (MDI, DPI, and nebulizer) can be clinically equivalent. It may be necessary to increase the number of MDI puffs to achieve results equivalent to the larger nominal dose from a nebulizer. Design and lung-deposition improvement of MDIs, DPIs, and nebulizers are exemplified by the new hydrofluoroalkane-propelled MDI formulation of beclomethasone, the metered-dose liquid-spray Respimat, and the DPI system of the Spiros. Differences among aerosol delivery devices create challenges to patient use and caregiver instruction. Potential improvements in aerosol delivery include better standardization of function and patient use, greater reliability, and reduction of drug loss.
Administration, Inhalation↗
Changes in route of drug administration among continuing heroin users: outcomes 1 year after intake to treatment.
This study investigates the type and extent of changes in route of drug administration among heroin users after treatment: whether injectors move to other routes of use; whether changes in route for one drug influence routes used for other drugs; and associations between changes in route of administration and other substance use outcomes. The sample comprised 641 heroin users recruited to 54 UK treatment programmes. At intake, the main routes of heroin use were injecting (61%) and "chasing the dragon" (37%). After 1 year, 81% of those using heroin took it by the same route as at intake, while 19% reported a change, with 14% switching from injecting to chasing. Changes from injecting to chasing were associated with improvements in other substance use behaviours. Changes in route represent an important aspect of drug-taking behaviours. Interventions to prevent the change to injecting should be developed and offered to noninjectors. "Reverse transitions" (from injecting to chasing) may represent a useful intermediate treatment goal for drug injectors who cannot achieve abstinence.
Administration, Inhalation↗
Anaphylactoid reactions to vitamin K.
Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966--1999) and EMBASE (1971--1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition. The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69 %) had a reaction defined as anaphylactoid, with 24 fatalities (18 %) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5 mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18 %), with 1 fatality (3 %) attributed to the drug. The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the solubilizing vehicle or immune-mediated processes. We conclude that use of intravenous vitamin K should be limited to patients with serious hemorrhage due to a coagulopathy that is secondary to a relative or absolute deficiency of vitamin K.
Adverse Drug Reaction Reporting Systems↗