Rectal and Transdermal Routes of Drug Administration (2005)

FigureIt has been accepted for years that medications can be administered in the rectum. Antiemetics are often prescribed by this route, and anesthesiologists have administered preinduction medications rectally for quite some time. More recently, a rectal gel became available for the treatment of status epilepticus, and many parents of children with seizure disorders have this agent in their homes for emergency use. Although rectal administration is convenient in children who are vomiting or uncooperative, as with every means of drug delivery, there are important considerations. One of the key issues with rectal drug administration is the venous drainage of the rectum. The veins in the upper portion of the rectum (the superior rectal veins) are part of the portal circulation, and agents administered in this portion of the rectum are often transported directly to the liver. If the agent administered this way is subject to a significant first-pass effect, it will be metabolized before a clinical effect is seen, and may be ineffective. On the other hand, the middle and inferior rectal veins drain into the systemic circulation, and agents absorbed in this way are avoiding the first-pass effect. Additionally, there appears to be significant patient-to-patient variability in the rate of absorption. In some children, drug levels peak quickly, almost as if an intravenous bolus had been given, while in others absorption is significantly delayed. Of course, the presence of stool in the rectal vault may interfere with absorption. Other factors help determine the effect of rectally administered medications. Liquid medications can be expelled by the rectum, but if they are retained, they are absorbed rather quickly. Suppositories must liquefy before they can be absorbed, meaning they are absorbed more slowly. The volume of the liquid administered and the concentration of the drug are also important factors. Patients were equally well sedated by 0.25 cc/kg of a 10% methohexital solution and by 0.75 cc/kg of a 2% solution, but peak drug levels were sustained longer in the children who received the 2% solution. This implies that the larger volume was absorbed gradually, leading to a more protracted period of sedation. The rectal contents also can affect drug delivery. If there is stool in the vault or if rectal pH does not favor absorption of the medication in question, then absorption will be slowed. While all of these factors influence the effectiveness of a rectally administered drug, in fact, many medications including benzodiazepines, barbiturates, ketamine, and antiemetics are successfully administered rectally hundreds of times each day. Nonetheless, their impact on an individual patient cannot be predicted with certainty. Peak blood levels achieved by identical per-kilogram doses of medication may be very different. This is the primary problem with rectal administration, especially for emergency physicians. If Johnny needs sedation for an outpatient MRI and his rectally administered sedative does not achieve the desired effect, he will have to come back another day. In the emergency department, the procedure often cannot be delayed or postponed. If Johnny is in status epilepticus and lacks intravenous access, we obviously cannot bring him back tomorrow for another try. Rectal medication has a somewhat circumscribed role in the ED because of several limitations Unreliable rectal absorption also can be potentially dangerous. To be certain of achieving effective serum drug levels, it is often necessary to administer a somewhat higher per-kilogram dose of medication than might be administered intravenously or orally. Suppose that we have given such a dose of medication to little Johnny to sedate him for his procedure, but after waiting a sufficient period of time, we conclude that the rectal medication is not effective. So we bite the bullet, start an IV, and then administer an intravenous sedative. Unknown to us, however, the rectal medication that we gave Johnny is slowly being absorbed, and at some point in the procedure, we notice that Johnny isn't breathing well. Given these limitations, rectal medication has a somewhat circumscribed role in the emergency department. Rectally administered anticonvulsants should be considered for the management of status epilepticus when intravenous access is not available. Rare patients might be appropriate candidates for rectally administered sedatives and antiemetics. In nearly 20 years of pediatric emergency medicine, however, I have only ordered a rectal medication other than acetaminophen a handful of times. Transdermal Administration Even simpler than rectal administration is transdermal administration. After all, what could be easier and safer than placing medication on the skin surface? There is, however, a cautionary tale about the “safety” of cutaneous administration in the sad history of medical misadventures. Many years ago, nurseries washed newborn infants in hexachlorophine soap only to find that the babies' thin skin and large body surface-to-volume ratio allowed so much of the drug to be absorbed that central nervous system toxicity occurred. Of course, it is unlikely that we will prescribe too many medicines that will be spread over the entire skin surface, but like everything else in pediatric practice, the safety and efficacy of transdermally administered drugs is dependent on a host of age-related factors, and a few factors less influenced by the patient's age. The primary issues related to the child's age and developmental level are the thickness of the stratum corneum epidermis and the amount of skin surface to which the medication has been applied in relation to the patient's body surface area. Other factors include the integrity of the skin (broken skin allows access to deeper tissue layers with more rapid absorption), the site of application, the impact of skin flora on the metabolism of the drug, the patient's state of hydration, and the amount of blood flow to his skin (e.g. warmer ambient temperatures result in more blood flow to the skin surface). Finally, the drug delivery system itself plays a role. Factors related to the delivery system include the pH of the drug, its lipid solubility, and the construction of the delivery vehicle.