Routes of Opioid Administration

Unlike nonopioid analgesics, which are primarily given orally, opioid analgesics are administered using a variety of routes. The availability of more concentrated dosage forms, controlled release oral opioid preparations, and transdermal opioid preparations are among the most important recent innovations in opioid analgesia treatment. Due to their long duration of action, these preparations lessen the severity of pain that may be experienced at the end of dose effectiveness and often allows the patient to sleep through the night. For example, MS Contin, Oramorph-SR, and OxyContin provide 8 to 12 hours of analgesia with a single dose. Kadian and Avinza are controlled release morphine preparations that may provide pain relief for 12 to 24 hours, respectively, with a single dose.

Oral administration - Giving an opioid analgesic orally is the most common route of administration, and is the preferred route of administration whenever possible. Enteric-coated tablets and controlled release or sustained release forms of opioids delay the drug from dissolving quickly in the stomach and are slower to be absorbed. Liquid preparations of opioids are absorbed more rapidly than solid tablets. Oral opioids, such as morphine, hydromorphone, hydrocodone and oxycodone, can be used for acute or chronic pain. There is no ceiling dose limit on single opioid drugs unless the adverse effects of excessive sedation or respiratory depression occur. The onset of pain relief is not as rapid as opioids that are given intravenously.
Sublingual and buccal administration – When a drug is given sublingually, it is placed under the tongue. Buccal administration refers to placing a tablet between the teeth and the mucous membranes of the cheek. Opioids given via these routes are absorbed rapidly.
Rectal administration – This route may be used for patients who cannot swallow or when intravenous sites are not available. There are many suppository combinations available.
Subcutaneous administration - When a drug is given subcutaneously, it is absorbed beneath the skin into the connective tissue or into fat under the dermis. Drug solubility and vasoconstriction of blood vessels may cause delays in drug absorption when an opioid is given subcutaneously. However, the subcutaneous route can provide rapid pain relief without requiring intravenous access.
Intramuscular administration – When this route is used, the drug is injected into a muscle, most often the deltoid or vastus lateralis muscles. Giving analgesics by the intramuscular route is not recommended for pain management, because intramuscular injections are often painful and drug absorption is variable and unpredictable.
Intravenous administration – When this route is used, the drug is given directly into a vein where it immediately enters the systemic circulation. Almost all opioids can be given by the intravenous route. An intravenous bolus provides the most rapid onset of pain relief. For a patient with severe acute pain or exacerbated cancer pain, repeated intravenous boluses may be used to titrate the analgesic to concentrations that provide effective pain relief, followed by a maintenance infusion if necessary. Intravenous drug administration should always be done slowly to minimize adverse effects. Extreme caution is needed in administering a continuous infusion of opioids to opioid "naive" patients*, either as a sole infusion or in combination with patient controlled analgesia (PCA) bolus doses. Intravenous opioid administration requires skilled nursing and pharmacy support and requires an infusion pump for continuous or patient controlled administration.
Transdermal administration – When the transdermal route is used, the opioid is absorbed through the surface of the skin. Fentanyl is available in a transdermal drug delivery system that provides continuous opioid administration without pumps or needles. Transdermal fentanyl may be given to patients with chronic pain who can benefit from continuous opioid administration. Transdermal fentanyl has a long duration of action and can be used in patients who cannot take medications orally. Transdermal opioids are contraindicated for use in acute post-operative pain or in opioid naive patients, due to the risk of respiratory depression. Transdermal fentanyl has a slow onset of action and the side effects of respiratory depression and sedation may not be quickly reversible. It is difficult to titrate an optimum dose, requiring additional short acting oral opioids to manage breakthrough pain. Adherence of the patch to the skin may be problematic for some patients.

Instant Feedback:
Transdermal fentanyl is not used for patients who have acute postoperative pain or for opioid naïve patients.

Intraspinal (epidural and intrathecal) administration – Intraspinal administration refers to the administration of medications into the spaces or potential spaces surrounding the spinal cord. Intrathecal catheters to manage acute pain are most often used for anesthesia or for giving a single bolus dose of an analgesic. A long term epidural catheter can also be inserted and tunneled subcutaneously for intermittent bolus dosing or for continuous infusion via an external pump. This form of opioid administration is used to control pain following a variety of surgical procedures, for other painful procedures, and for cancer pain. The two opioids most commonly used via this route are morphine and fentanyl. The patient who is having any intraspinal opioid treatment must be managed by a skilled healthcare team that is familiar with the benefits and risks of this type of therapy.

Instant Feedback:
Intramuscular administration of opioid analgesics should be avoided.

Other administration routes – Opioids may also be given via the intra-arterial route (injected directly into an artery), intraperitoneal route, (injected into the large surface lining of the abdominal cavity), pulmonary (using the large surface area of the pulmonary epithelium and mucous membranes), and cutaneous (applying drugs topically to the mucous membranes of the conjunctiva of the eyes, the nasopharynx, oropharynx, vagina, colon, urethra, and urinary bladder) routes for local effects.

Patient controlled analgesia - Patient controlled analgesia (PCA) is a technique in which the patient controls the amount of analgesia he or she receives. PCA provides the important advantage of relieving pain as it begins, and minimizes the delays that can lead to pain exacerbation. When a patient feels pain, he or she pushes a button that releases a pre-set dose of opioid to be delivered into his or her intravenous line. The medication is delivered as long as the lockout interval (a predetermined time between doses) has not been exceeded. PCA is most often used for the intravenous administration of opioid analgesics for severe acute pain, such as following a major surgical procedure. Short and long-term management of cancer pain by PCA has also been shown to be safe and effective.

*opioid "naive" patients are individuals who have not previously received opioid drugs and now, due often to trauma or surgery, receive regular daily doses of opioids.