Route of Administration

Time Required: 
10 minutes

Learning Outcomes:

  • to know the different routes available for managing acute pain
  • to describe the benefits / disadvantages of the respective routes

Route of Administration

The choice of route of administration for a drug should be based on an appreciation of factors that influence its systemic absorption. This determines the rate of onset, peak effect and duration of action of the drug. Changes in the systemic absorption rate may necessitate adjustment in the dose or time interval between repeated drug doses. Systemic absorption depends on the drug's water and lipid solubility, blood flow to the site of absorption and the surface area available for absorption.

Oral administration

The oralroute of administration is the most widely used route and most acceptable for the patient. The oral route should always be the first considered route and alternatives to this route only sought if specific problems prevent this route being utilised. These include:

  • emesis because of irritation of the gastrointestinal mucosa by the drug;
  • destruction by digestive enzymes or acidic gastric fluid;
  • irregularities in absorption in the presence of food or other drugs;
  • drugs may be metabolised by enzymes or bacteria in the gastrointestinal tract before systemic absorption can occur;
  • absorption of opioids may be reduced by the delay in gastric emptying that follows surgery. This has the dual disadvantage of non-absorption initially, followed by the possibility of a large dose being absorbed when gastrointestinal function resumes.

The effect of orally administered drugs is largely dependent on the rate of absorption from the gastrointestinal tract. The principal site of absorption is the small intestine where there is a large surface area.

First-pass metabolism

Drugs absorbed from the gastrointestinal tract enter the portal venous blood and thus pass through the liver before entering the systemic circulation for delivery to the receptors. This is known as the first-pass hepatic metabolism and explains the reason for large differences between effective oral and intravenous doses in drugs that undergo extensive hepatic extraction and metabolism.

Oral transmucosal administration

The sublingual or buccal routeoffers some theoretical advantages for drug administration. Absorption occurs directly into the systemic circulation as there is no first pass metabolism. Thus this route of administration permits rapid onset of drug effect since it by-passes the liver. However, few drugs utilise this route, buprenorphine is the most commonly used – it is rapidly absorbed and has a long duration of action (6 h) but is associated with a high incidence of side effects (namely nausea, vomiting and sedation).

Transdermal administration

Transdermal administration of drugs provides sustained therapeutic plasma concentrations of the drug and decreases the likelihood of loss of therapeutic efficacy owing to peaks and troughs associated with conventional intramuscular injections. There is a low incidence of side-effects due to the small fluctuations in plasma concentrations of drugs used and this contributes to high patient compliance.

Rectal administration

The rectal route is a useful alternative to oral administration of analgesia, particularly if severe pain is accompanied by nausea and vomiting. Drugs administered into the proximal rectum are subjected to first-pass metabolism. However, drugs administered from a low rectal site reach the general circulation without first passing through the liver. The unpredictability of this route is largely explained by whether the drug passes through the liver or not. The slow and sometimes erratic absorption means that this route is not the ideal route for management of those in acute pain but is better suited for maintaining analgesia. Additionally, some drugs can cause irritation of the rectal mucosa. Informed consent must be sought prior to administration of any rectal preparation especially if given during general anaesthesia.

Parenteral administration

Parenteral administration may be required to ensure absorption of the active form of the drug and may be the only suitable route of administration. Sub-cutaneous, intramuscular (IM), intravenous (IV), epidural and intrathecal routes are commonly used.

Systemic absorption after IM injection is usually more rapid and predictable than after oral administration. A disadvantage of this route is that the dose maybe too large (side effects) or too small (no pain relief). In addition, the injections are painful and the onset of pain relief is delayed while the drug is absorbed. Furthermore, absorption varies considerably depending on the IM site e.g. deltoid versus gluteus maximus. The rate of absorption is limited by the surface area of the absorbing capillary membrane and by the solubility of the drug in interstitial fluid.The presence of hepatic or renal disease, the extremes of age and the presence of other drug therapy may also explain the large variations in the blood levels and rates of absorption of opioids after intramuscular injection. Any condition that reduces peripheral blood flow can impair drug uptake and thus, reduced body temperature, hypovolaemia and hypotension will all result in lowered uptake from injection sites. If the patient is shocked and is peripherally vasoconstricted then a depot of the drug can build up in the muscle only to be released when the patient has been resuscitated and vasodilation occurs. This is less important if only one intramuscular injection has been given but if several have been administered, this could cause problems as several doses of the drug are absorbed into the general circulation at once. Furthermore, hypothermia and hypothyroidism may both lead to a reduction in metabolism causing an increased sensitivity to drugs.

This method of analgesia may be associated with peaks and troughs in effect. One way of overcoming this problem is to administer the analgesic on a regular 4-hourly basis, however, the patient then requires repeated injections. Furthermore, many have questioned the ethics of patients receiving painful IM injections when they have an IV line insitu. Additionally, repeated IM injections of analgesics have also been associated with fever as a result of tissue injury secondary to drug administration or hypersensitivity.  

The desired concentration of drug in the blood can be achieved more rapidly and precisely by the IV route of administration which circumvents any physiological factors that limit systemic absorption by other routes. However, whilst intravenous injection brings more rapid pain relief than other methods, they should only be administered in areas which have a high staff to patient ratio and where staff have received specific training as they are inherently dangerous if the patient is left unsupervised for even a short period.

Knowledge Level: 
Pain Condition: 
Professional Issues: 
Care Setting: