A medication that is administered subcutaneously is __________.

Other routes

Other routes of administration have been reported such as intra-arterial administration using the femoral artery [16] or the carotid artery [34], intrathymic injection [4], intraspinal injection [35], intrathecal injection [36] or intracardiac injection [8].

The dosing and treatment of newborn mice provides special problems not only because of their size or but also because the dam is apt to reject or cannibalize neonates that have been handled. Subcutaneous injections can be made over the neck and shoulders using a less than 30G × 5/16 inch needle. Up to 0.1 mL (depending on the age of the infant mice) may be administered orally using a piece of plastic tubing inserted over a needle [15, 37]. Direct injection into the stomach of infant mice can be made through the abdominal wall [38]. Intravenous injection into infant mice has also been reported [15, 39, 40].

5.30.5.4 Route of Administration

Routes of administration for developmental immunotoxicants may include oral gavage, drinking water, intratracheal, dosed feed, or intraperitoneal injection of the test article. In the evaluation of DIT, it is important to insure that the offspring are indeed exposed to the xenobiotic. While exposure cannot be specifically controlled in utero (placental transfer is a function of the chemical being tested), offspring can be exposed to xenobiotics either through lactational exposure or through direct dosing. If existing data on the xenobiotic indicate that lactational exposure does not occur, then direct dosing in preweaning pups is necessary to assure exposure throughout the treatment protocol (Holsapple et al. 2004). The selection of administration routes should be based on the relevant exposure in humans as well as pharmacokinetic considerations.

Parenteral Anesthesia

Parenteral Administration

Parenteral routes of administration include the subcutaneous, intramuscular, and intravenous routes. For these routes to be viable, a medication must be water-soluble or in suspension. The intravenous route of administration bypasses the ab-sorption step, resulting in 100% bioavailability. Another advantage is the rapid onset of action. These routes of drug administration may not always be viable because of inconvenience and cost. Also, the drug's adverse effects are not reduced compared with the effects after oral administration. Other disadvantages with parenteral routes are patient discomfort, the need for sterile conditions, and potential risks to health care practitioners from blood-borne pathogens. In some cases, however, these routes of administration may be the only way to achieve therapeutic concentrations at the target tissues, such as with some anti-infective agents and in emergency situations with asthmatic patients.

18.3.1.3 Other nonoral routes

Other nonoral routes of administration include nasal, buccal, pulmonary, ocular, and transdermal drug delivery. Nonoral routes of administration are usually exploited to overcome disadvantages associated with oral administration, such as acidic pH of the stomach and proteolytic degradation. Transdermal administration overcomes the disadvantages of both peroral and parenteral administration. Transdermal administration bypasses the first-pass metabolism and noninvasive route of administration. Transdermal administration of proteins presents a challenge of penetration because of low lipophilicity and large size of protein and peptide drugs (Deb et al., 2019a). Pulmonary delivery reduces the systemic side effect and achieves high local concentration.

9.5.5 Therapeutic Inhalation Aerosols

Different routes of administration may be used to achieve either systemic or local delivery of proteins and peptides. For small therapeutic molecules, various routes for drug administration are parenteral (intravenous, intramuscular, and subcutaneous), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal. However, the routes of administration for proteins and peptides are limited because of their large size and structure. Active ingredients administered via a delivery system are only successful if they are delivered in a timely manner direct to the site of disease, with ease and convenience to the patient and the assurance of a quality product. Advances in drug formulation and inhalation device design are creating new opportunities for inhaled drug delivery as an alternative to oral and parenteral delivery methods. Much of the interest in pulmonary delivery of systemic drug therapies is focused on chronic diseases and refractory conditions—aliments that require frequent drug administration for a specific period of time. The role of device design and development in defining and driving emerging opportunities in this area cannot be overstated. Inhalation aerosols are a system of finely divided liquid or solid particles dispersed in and surrounded by a gas (fine suspensions or dispersions of solid particles in a gas), intended to deliver drugs into the respiratory tract and both the central and peripheral zones of the lung. There, significant retention and systemic absorption of the active component occur, by inhalation or by breathing, using different pulmonary drug deliveries (Fig. 9.3).

There are two types of inhalation aerosols, one that allows the deposition of drug to lungs for systemic effects, and the other whose site of action is primarily localized in the lung. Therapeutic inhalation aerosols are mainly used in the management of patients with obstructive lung disease. In the recent past, drug aerosol delivery devices for inhalable peptides and proteins are garnering increasing interest for the treatment of systemic and respiratory diseases. These include diabetes and therapies for asthma and chronic obstructive pulmonary disease (COPD). This advanced technology was initially applied to the systemic delivery of large molecules, such as insulin, IFN-β, or α1 proteinase inhibitor. The first clinical investigation of systemic insulin delivery via the lung took place in the 1920s, and the interest in this route increased considerably in recent years with advances in formulation and recombinant technology. The protein for inhalation currently available on the market is DNase, but a growing number of proteins and peptides are under various phases of clinical trials. Other proteins and peptides in Phase III trials include leuprolide and IFN-γ.

Other Routes

Other routes of administration may be used to increase the level of antibacterial drug in areas in which diffusion following parenteral administration of the drug may be limited and when high local levels are required. These include intraarticular, intrapleural, and subconjunctival injection. Nonirritant preparations should be used with strict aseptic technique. In most cases these treatments should be supported by parenteral treatment.

Intramammary infusion of drugs is dealt with in Chapter 20. Intratracheal administration of antibiotics has its advocates for the treatment of pneumonia in cattle. In theory, this could result in higher levels of antibiotics at the site of infection, although with many pneumonias diffusion through the affected lung must be minimal. The antibiotics are administered in sterile physiologic saline equivalent to 2 mL/kg body weight. An extensive study has shown variation in absorption and persistence between antibiotics administered by this route, compared with parenteral administration, but has concluded that there is no potentially useful advantage to its use.

The local administration of antibiotics may not always be the preferred route despite historical precedence. For example, in the treatment of the genital tract, it has been shown that parenteral administration of antibiotics achieves tissue concentrations of drug in all areas of the genital tract, whereas intrauterine infusion results in comparable concentrations only in the endometrium and uterine secretions. Local and/or parenteral administration may be indicated in different cases of genital tract infection.

Routes of Fluid Administration

Two routes of administration are commonly used in horses: oral and intravenous. Although horses do appear to absorb some fluid following enema administration, this is typically not the most effective route for hydration. All routes of fluid administration have attendant benefits and risks.

Administration of fluids orally typically necessitates passage of a stomach tube. Depending on the animal, sedation may be necessary. Passage of the stomach tube can result in trauma to the nasal passages and the esophagus, although serious complications are uncommon. Oral fluids may be particularly beneficial when hydration of the gastrointestinal tract is needed. The volume administered is often limited to 6 to 8 L at one time, but the tube can be left in place for repeated fluid administration. Administration of oral fluids is typically much more cost effective than giving intravenous fluids, and oral fluids are more effective at rehydrating the gastrointestinal tract. Oral fluids cannot be used if the horse has an esophageal obstruction or is producing significant volumes of gastric reflux. Oral fluids require absorption and may be less appropriate for the critically hypovolemic horse.

Intravenous fluid administration necessitates placement of an indwelling intravenous catheter. Infections and thrombosis at the catheter site can arise and may be more common outside the hospital setting, where monitoring may be less intensive. Intravenous fluids are more ideal for the critically ill patient in need of rapid volume replacement, and are needed in horses with esophageal obstruction and in those with intestinal ileus or other conditions that result in gastric reflux.

Routes of Administration and Toxicokinetics

The routes of administration include ingestion by swallowing capsules or “bombing” (the powder is swallowed after being wrapped in a cigarette paper), and nasal insufflation (“snorting”), more specifically by “keying” (a key is dipped in the powder and then insufflated) as well as the less frequently reported gingival and sublingual delivery, intravenous and intramuscular injection, and rectal administration (dissolved in an enema or within gelatine capsules) (Schifano et al., 2011; Valente et al., 2014).

When insufflated (snorted), 20–75 mg of mephedrone elicits a rapid onset of effects within a few minutes, followed by the onset of expected effects in less than 30 min. The rapid comedown usually lasts less than 2 h. Oral doses on average are higher than the snorting ones, and vary from 150 to 250 mg. The peak of effects is reached within 45 min after ingestion, lasting almost 4–5 h. Some consumers assumed mephedrone both by insufflation and by oral ingestion in combination in order to obtain both rapid and long-lasting effects. Users report that rectal administration requires lower doses (100 mg on average) than the oral ones and is characterized by faster onset. Intravenous administration is not frequent but has a faster onset of stimulation, with a peak in 10–15 min after injection, and effects lasting for less than 30 min; doses are one-half or two-thirds of the oral ones. Bingeing and mixing routes of administration in a single session is frequent and is made in order to achieve faster onset and long-lasting effects (Schifano et al., 2011).

The synthetic cathinones, such as mephedrone, after absorption undergo phase I metabolism, that is, a reduction of the β-keto group to alcohol catalyzed by liver microsomal enzymes, producing cathine and NE (Valente et al., 2014).

Meyer, Wilhelm, Peters, and Maurer (2010) examined the metabolite pattern after oral administration of the drug to Wistar rats and identified normephedrone, nor-dihydromephedrone, hydroxytolyl-mephedrone, and nor-hydroxytolyl-mephedrone in rat urine, and 4-carboxy-dihydromephedrone in a human urine sample. They also postulated that mephedrone was metabolized via N-demethylation to the primary amine, reduction of the keto moiety to an alcohol, and oxidation of the tolyl portion to the respective alcohol in both rodents and humans. This is followed by a final N-dealkylation process before renal excretion (Coppola & Mondola, 2012).

Pedersen, Reitzel, Johansen, and Linnet (2013), using cDNA-expressed cytochrome P450 (CYP) enzymes and human liver microsomal preparations, found that CYP2D6 was the main enzyme responsible for the in vitro Phase I metabolism of mephedrone.

Rapid bingeing, which is common among mephedrone users to sustain its psychoactive action, is likely to reflect its rapid metabolism in humans (Schifano et al., 2011; Winstock et al., 2011).

Intranasal Vaccines

Alternative routes of administration have been used to improve the protective immune responses at the very places in the body that certain viruses and bacteria are likely to target. Intranasal vaccines can induce protective immunity in the respiratory tract where the viruses attack.8 By either slowing the rate of uptake of the antigens (eg, intranasal vaccines are taken into the body more slowly than injectable vaccines, thus reducing the risk of allergic reaction) or by administering the vaccine viruses to an area of the body that they do not typically grow in (thus reducing the disease-causing effects of some of the strains of live vaccine viruses), the side effects of the vaccine will be reduced. Intranasal administration is easy and acceptable to both humans and animals.

Avirulent intranasal vaccines could be given via the nostrils using special applicators. The cells lining the upper respiratory tract (nasal passages, throat, trachea) would then be coated by the vaccine and the virus would subsequently replicate in these cells. These viruses (and/or bacteria) will be attacked by the immune cells present in the respiratory tract, inducing a protective immune response that tends to remain within or near the respiratory tract.

If an animal received an intranasal vaccine, the lining of its respiratory tract would be coated with protective antibodies. Hundreds of memory cells, primed to recognize the antigens contained on the invading respiratory viruses, will be included in the regional, respiratory-system lymph nodes [194]. When the invading viruses and bacteria reach the respiratory tract, these antibodies and memory cells would react and eliminate them. This response is much more rapid than that produced by an injectable vaccine. This is because the resultant immune defenses are located in the same region as the invading pathogens. The invading viruses will not get the opportunity to damage many cells in this case. Moreover, clinical signs of disease should not occur or, if they do, they should be very mild.

There are advantages and disadvantages for intranasal vaccination [195]. The advantages are:

Improved patient compliance [196].

Improved penetration of (lipophilic) low molecular weight drugs through the nasal mucosa [197].

Due to large absorption surface and high vascularization, rapid absorption and fast onset of action is expected.

Avoidance of the gastrointestinal tract environmental conditions (chemical and enzymatic degradation of drugs) and the hepatic first-pass metabolism.

Direct delivery of vaccine to the lymphatic tissue [198].

Induction of a secretory immune response at distant mucosal site [198].

Because the uptake of viral antigen into the body is slower in intranasal vaccination, allergic reactions are less likely to happen.

The disadvantages are:

Mild upper respiratory tract infection could be induced. This is characterized by watery nasal and ocular discharge, sneezing, and even coughing. However, this is usually self limiting and very mild.

They are generally only effective against respiratory pathogens.

Intranasal vaccines needed every year.

Severe liver damage and even death of the animal could be caused by an accidental injection of the intranasal Bordetella vaccines [194].

Penetration to the brain through the olfactory region may be caused by nasally administered substances, including toxins and attenuated microorganisms.9 For some vaccines and drugs targeting neurological diseases, such direct nose-to-brain transport may be advantageous but raises concerns about potential adverse effects when the brain is not the target organ.8