Why Are Medications Administered in Different Forms?
Medications are available and delivered in various forms, including liquids, pills, injections, IV drips, inhalants, and suppositories, to name a few. But what makes one option, otherwise known as a delivery system, better than another?
Paul Beninger, professor of public health and community medicine at Tufts University School of Medicine, now retired, spent his career working at the Food and Drug Administration in the early years of HIV, and then in pharmacovigilance in positions with Merck & Company and Genzyme. After transitioning to academia, he taught a course on pharmacoepidemiology for students in the Master of Public Health Program.
When it comes to providing medication to patients, Beninger said the first step is to think about the destination.
“Every single organ system, or group of organs that work together to perform a function like digestion, has a preferred cadre of drugs,” Beninger said. “The systems also have preferred routes of administration to get to that organ system.”
Clinicians need to determine what symptoms or issues are in need of treatment before deciding how urgently a medication needs to be delivered.
“You’ve got a whole spectrum of delivery systems, from the easiest, which is taking the medicine orally, to the most difficult, which can involve direct injection into the heart, spine, bone, or brain,” Beninger said.
Finding Alternate Routes
Although oral delivery is generally the easiest option, the enteral route, which runs from mouth to anus, isn’t always an accessible or feasible pathway. Factors such as the hostile environment of the stomach, which can break down a medication too quickly, or issues with the gastrointestinal tract’s function—or lack thereof—can make this route a poor option.
“When I was an intern at Los Angeles County Hospital, I had a patient with fairly significant tuberculosis,” Beninger said. “The upper gastrointestinal tract was not working at all, so giving oral drugs—which make up about 90% of TB medications—wasn’t possible. So I asked a senior resident physician about administering the drugs per rectum.”
The resident’s response? “Great idea, figure it out.”
So, Beninger worked with the hospital’s pharmacist who created a formulation of the medication that could be delivered via suppository. “There are a small number of drugs routinely given that way, but for those that aren’t, they require a special preparation, which isn’t commercial,” he said.
“Pharmacists have the authority to prepare what they call compounded drugs,” Beninger said. “When they go to pharmacy school, they learn specific skills —which have taken hundreds of years to develop in the field—to be able to create and deliver drugs for specific scenarios, and in many cases that don’t have preservatives in them.”
In prescription medications, preservatives work much like they do in foods. They extend the shelf life of drugs by preventing oxidation of active ingredients, which can diminish potency. They also maintain colors, keep drugs shelf stable, and prevent the growth of bacterial or fungal contaminants in water-based solutions, such as nasal sprays.
But for some patients, these preservatives can cause irritation, inflammation, or allergic reactions, which is why for some treatments a clinician may seek to use a drug formulation that is preservative-free.
Minimizing Risk and Adverse Reactions
Another major question clinicians ask themselves when determining the optimal path for a medication to be administered: What is the risk-benefit in delivering a medication in a specific way?
For instance, in almost all cases an anesthesiologist would choose to deliver a local anesthetic via injection directly at the site rather than putting the patient under general anesthesia for an open wound that simply requires sutures. Another example is during open-heart surgery, a cardiac surgeon would opt to deliver an urgently needed drug with an injection directly into the heart, rather than intravenously, which would require a trip through the bloodstream and dilute the drug before reaching the heart.
Beninger spent much of his career working in pharmacovigilance, which includes detection, evaluation, communication, mitigation, and prevention of adverse side effects associated with taking medications. He prefers to think of side effects as off-target effects, as opposed to the intended, on-target effects.
For example, the important on-target effects of specific doses of members of the statin family of HMG-CoA reductase inhibitors help to lower LDL cholesterol and, in turn, reduce the risk of heart attacks and strokes. Off-target effects, on the other hand, are undesirable effects of this family of medications, which in the case of statins can include muscle aches and pains and digestive issues.
“For many routes of administration, a drug will make its way to many parts of the body and have lots of effects, which means that the clinician needs to be attentive to all of the potential effects."
- Paul Beninger, professor of public health and community medicine at Tufts University School of Medicine
A drug in its oral formation, whether tablet, capsule or liquid, may have different off-target reactions than from an injectable formulation, say in the case of GLP-1 drugs, so delivery methods must be studied both before and after a drug receives federal approval from the FDA.
“For many routes of administration, a drug will make its way to many parts of the body and have lots of effects, which means that the clinician needs to be attentive to all of the potential effects,” Beninger said. “Something is only identified as a ‘side effect’ because it’s not the original, intended effect that’s being studying.”
When a new drug is being developed and advances to human testing, early trials often involve participants receiving gradually increasing doses so researchers can observe and document the first signs of intended effect and any potential off-target or adverse effects. This establishes the lower limit of the therapeutic window.
After that lower threshold is established, research is typically continued until it is clear no additional desired effect is achieved, and an unwanted effect—or off-target effect—can be seen. This establishes the upper limit of the therapeutic window. Further studies use doses in this window to obtain the optimal balance of therapeutic benefit and potential toxicity.
“After a new drug is approved by FDA, it’s important to follow patients who take the drug and to collect this information systematically,” Beninger said. “In this way, less frequent and rare off-target effects can be identified, published, and reported to the FDA for eventual updating of the safety profile in the new drug’s prescribing information.”
Routes of Drug Administration
There are at least 21 routes of drug administration, from inhalation—think liquid sprays or dry powders for asthma—to parenterals, like insulin for injection, which bypass the digestive system’s metabolism for rapid effect. To learn more about the ways in which someone might receive a drug, visit the National Library of Medicine.