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Weekly UpdatesWhen considering methods of medication administration, one may initially consider the traditional routes: oral, subcutaneous, intramuscular, intravenous, and topical. These routes use traditional medication delivery systems: needles, syringes, fluted paper cups, IV bags, and catheters. It must be noted that these medication delivery systems may not always optimize rapid delivery of the appropriate concentration of medication to the appropriate site, nor do they necessarily minimize local or systemic toxicity.
Medication delivery systems that concentrate medications only where needed and used could reduce the destruction of surrounding tissues while minimizing side effects. The benefits of such systems in the treatment of both acute and chronic conditions are clear. Because research demonstrates that patient adherence is improved when side effects are minimized, it is imperative that drug delivery systems efficiently and precisely deliver medications in a fashion that the patient finds acceptable and tolerable. Patients themselves are demanding drug delivery systems that are convenient, easy to use, and affordable.
Progress in the development of novel drug delivery systems is bringing researchers and clinicians closer to meeting the goals of maximum efficacy with minimal toxicity and inconvenience. This article reviews several of these recent advances in medication delivery, some of which are already in use and some still await clinical implementation.
Intrapulmonary and Endotracheal Routes of Administration
According to current guidelines recommended for the management of cardiac arrest, the American Heart Association has recommended that when intravenous or intraosseous routes cannot be established, endotracheal administration of some resuscitation drugs be used. Medications that can be absorbed through the trachea include lidocaine, epinephrine, atropine, naloxone, and vasopressin (American Heart Association [AHA], 2005). Although the optimal dose of these drugs has yet to be established, two to two and one half times the recommended intravenous dose is used (AHA, 2005).
Recent studies investigated the intrapulmonary route of drug administration. One study suggests that intrapulmonary vancomycin may have efficacy in acute lung injuries, such as meconium aspiration syndrome in neonates (Jeng, Lee, & Soong, 2007). Televancin is also being studied for intrapulmonary use. Because the antibacterial activity is not affected by pulmonary surfactant, further studies of intrapulmonary televancin for use in treating gram-positive respiratory infections are underway (Gotfried et al., 2008).
Implantable Technology for Pain Management
Chronic pain affects as much as one half of the adult population at some point during their lives, and 10% of this population experiences pain that is considered to be disabling. Management of chronic pain can be difficult, and numerous treatment options have been studied. Since Melzack and Wall first outlined their Gate-Control Theory of Pain in 1962, understanding the neuroscience of pain has improved significantly (Chaudhari & Mackenzie, 2007). This has led to the development of implantable neuromodulatory technologies for refractory pain. Neuromodulation seeks to reduce afferent activity within pain pathways by targeted drug delivery into cerebrospinal fluid, allowing drug delivery directly to the neural tissues (Chaudhari & Mackenzie, 2007).
Implantable pumps can deliver analgesic drugs directly to the intrathecal or intracerebroventricular sites. A programmable infusion pump can dispense medication at a preprogrammed rate that is then adjusted based on symptoms. A wide variety of devices exist, spanning the cost range. The intraventricular route has also been used for patients with pain from head and neck cancer. Morphine can be infused into the cerebral ventricles after placement of an Ommaya reservoir or with a continuous infusion pump (Bajwa & Warfield, 2008). There has been relatively little experience with the use of this procedure; however, it has been demonstrated that 50% to 90% of patients obtain excellent initial relief (Bajwa & Warfield, 2008). The use of implantable pumps is not without complications, however, including infection, pharmacological side effects, catheter dislodgment, and malfunction.
Disposable Infusion Pumps
Another novel form of drug delivery is the disposable infusion pump. These have been in clinical use for more than 20 years, and their use has increased dramatically (Skryabina & Dunn, 2006). These devices are predominantly used by ambulatory infusion centers and by home healthcare organizations to deliver such therapies as chemotherapy, antimicrobials, analgesia, and anesthesia. Disposable infusion pumps use the same physical principle as other infusion pumps for delivery of medications: mechanical restriction within the flow path determines the speed of the pressurized fluid. The pressure generated by these pumps is approximately 250 to 600 mm Hg. This can be compared with electric pumps, which generate 5 to 1,200 mm Hg.
There are several types of disposable pumps. One of these is the elastomeric pump. The drug in this pump is contained in an elastomeric membrane that is encased and protected by an outer shell. The force of the stretched elastomer generates the pressure on the fluid (Skryabina & Dunn, 2006). Baxter Healthcare (Deerfield, IL) produces several of these pumps, including the Intermate, the Singleday Infusor, the Multirate Infuser, the PCA Infusor, and the Two Day Infusor. Alaris (Dublin, OH) produces the ReadyMED and Block Medical has the Eclipse.
Spring-powered disposable infusion pumps use positive pressure and are powered by energy stored in a compressed spring (Skryabina & Dunn, 2006). The mechanical parts of this pump are reusable, and the bag with the administration set is for single use. The Sidekick and Paragon (I-Flow Corporation, Lake Forest, CA) are reusable and the Springfusor (Go Medical Industries, Pty, Ltd., Australia) and Beeline (McKinley Medical LLC, Wheat Ridge, CO) are for single use only.
Disposable patient-controlled analgesia pumps are also available. These pumps have an additional fixed-volume reservoir that is used for bolus dosing. The user pushes a button, which forces a valve to open and allows the reservoir to empty. The speed of filling this reservoir is regulated by the pump's flow rate and determines the lockout time. The reservoir is connected to the primary infusion line, which delivers the basal rate (Skryabina & Dunn, 2006).
There are several factors that can affect the accuracy and flow of disposable pumps, including ambient temperature, fluid viscosity, atmospheric pressure, back pressure, partial filling, and storage. The advantages of using disposable pumps include their small size, light weight, simplicity of use, elimination of programming errors, independence from an external power supply, portability, and disposability. Disadvantages include the possibility of inaccurate flow rates, fixed reservoir volume, inability to change flow rate, inability to trace the history of analgesia demand, and the long-term cost (Skryabina & Dunn, 2006).
Another method of pain management, the ON-Q PainBuster Post-Op Pain Relief system by the I-Flow Corporation (Lake Forest, CA), has been used after gynecologic and orthopedic surgery. This device consists of a small balloon with a catheter extension. When delivered with a local anesthetic agent, such as bupivacaine, the device will deliver drug at a continuous rate directly to the surgical wound for as long as 5 days. A point-source catheter or a soaker catheter is available based on the size of the wound. The clinician may choose from an OnDemand system, a Fixed Flow Rate system, or a Select-A-Flow system that can be used to titrate the medication dose externally. This system requires little to no management or intervention by the caregiver or the patient and is completely portable. It has been shown to reduce hospital stays, narcotic use, and overall costs related to postoperative pain (Medscape Medical News, 2002).
Surgically Implanted Medication Delivery
Surgically implanted medication delivery systems are noteworthy for their ease of use. They also improve adherence, a major concern in the pharmacological treatment of individuals with serious psychiatric illnesses (Irani et al., 2004). A subcutaneous surgically implanted medication delivery system inserted under the skin eliminates the need for oral medication, definitively addressing the adherence issue. One system delivers psychoactive medication for as long as 14 months, significantly decreasing the need for adherence checks in this historically difficult population. The implant is biodegradable and does not require a second surgical procedure.
One advantage of this system is that it allows the patient to make decisions during periods of health rather than after periods of exacerbation. An ongoing study of haloperidol implants in schizophrenic patients shows that lower doses, consistent steady-state serum levels, and fewer side effects make this method of delivery more effective (Irani et al., 2004). If the implanted medication needs to be reversed, the implant can simply be removed.
Intranasal Delivery
Intranasal formulation is a remarkable and easy mode of drug delivery. It is a needle-free, patient-friendly route that does not contribute to biohazardous waste (Wermeling, Miller, & Rudy, n.d.). Pharmacokinetically, the absorption rate is so rapid that it results in a faster onset of action compared with oral and intramuscular administration. In addition, hepatic first-pass metabolism is avoided (Wermeling et al., n.d.). (The metabolism of an administered dose of a drug by the liver before it reaches systemic circulation is referred to as the first-pass metabolism.) For many oral drugs, a clinically significant portion of the drug taken is destroyed during first-pass metabolism, requiring a higher oral dose for a given effect (Wynne, Woo, & Olyaei, 2007).
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