As explained previously, if they are to have any effect, opioids must come into contact with the opioid receptors of nerve cells. In other words, they must be transported from where they are given, to the nervous system. This can be done in several ways. By mouth, by intramuscular injection and intravenously (continuous opioid infusion, or patient controlled analgesia); by injecting opioids into the spinal fluid or the epidural space; or by other routes

Opioid drugs can be given orally, but unfortunately this route is not practical following surgery or during labour. To begin with, the stomach does not function properly and so drugs are not passed on to the intestines, where they are absorbed. Even when the gut is working normally, absorption is slow and not sufficiently reliable. This is partly because drugs, which are absorbed, pass through the liver first, and it is here where most drugs are either broken down or excreted back into the intestine by the bile (where they can be absorbed again). Swallowing opioids by mouth, therefore, would simply not be effective. Some opioids can be absorbed in the mouth itself, but again this has not been found to be sufficiently reliable in labour.

This is the most common way in which opioid drugs are administered, both during labour and after surgery. The most common sites of injection are the outer side of the thigh or the buttock. The injection is given in a small volume (l-2 ml) by a nurse and is not usually painful. A muscle is chosen because the drug is absorbed into the bloodstream quicker than if it were to be injected just beneath the skin. It takes time for the drug to be absorbed from a muscle and to reach its peak concentration in the bloodstream (and so achieve its maximal effect). For most opioids, this interval is approximately 15-30 minutes.

Once the opioid enters the bloodstream, it is circulated all around the body and leaks out through the finest blood vessels (capillaries) into the various organs and tissues, until it is absorbed back into the bloodstream again. Inevitably, a proportion also passes into the nervous system and comes into contact with a sufficient number of opioid receptors to produce a clinical effect.

The quickest way to relieve pain is to give opioid drugs directly into the bloodstream. Blood circulates completely around the body in less than a minute: so, when an opioid is injected into a vein, the drug reaches the brain within a few seconds. (This is why intravenous anaesthetics work so rapidly.) Accordingly, intravenous opioids take effect within a couple of minutes. The difference in speed of onset between an intramuscular and an intravenous opioid is illustrated in the diagram.

The figure also shows how the peak concentration that is reached in the bloodstream can be much higher following an intravenous injection. It is necessary, therefore, to be more cautious. For this reason, intravenous opioids are usually only given

The desired effect of opioid drugs, of course, is pain relief. In order to achieve this, it is necessary for the opioid to reach a high enough concentration in the bloodstream and to stay within a fairly narrow range for as long as the pain persists. In the case of single injections (either intramuscular or intravenous), the optimum concentration is reached for only a limited period. At other times the concentration is either too low, or too high. In the former case, pain relief will be inadequate; in the latter, there may be unpleasant side effects (which will be described later). To try and overcome these difficulties, various attempts have been made to devise a system that will deliver a more constant, and reliable, opioid blood concentration. Two such developments are worth describing. These are continuous opioid infusion and patient controlled analgesia (PCA).

The first approach has been to try and calculate the opioid dose requirement in advance and then administer it as an intravenous infusion. This means that the drug is 'trickled in' at just the right speed until it is no longer needed. The opioid is carefully prepared beforehand and delivered into a vein in the arm via a special pump. The aim is to maintain the blood concentration within the optimum range . Generally speaking, opioid infusions have found most favour in the management of postoperative pain, and are popular in some centres following caesarean section. Other units feel that the benefits are not all that spectacular and hardly worth the bother. Whether infusions are available or not, depends on the local facilities and the enthusiasm of medical and nursing staff for the technique. They have not been used to any great extent during labour - probably because of the difficulties in determining the dose requirements and the incidence of side effects.

The spinal cord is rich in neurones with opioid receptors. By introducing opioid drugs directly into the fluid surrounding the spinal cord, it is possible to achieve very good pain relief- but with much smaller doses than when given by other routes. This is because they act immediately at the opioid receptors in the spinal cord, instead of having to be delivered there via the bloodstream. Because the dose requirements are lower, and there is less spread to other sites in the brain, some of the side effects associated with opioid drugs are also reduced.

Spinal opioids may be given as a ‘single shot’ technique. Here a very fine needle is introduced into the spinal sac in an area below where the spinal cord ends. A small dose of opioid is injected and the needle is removed. This technique has been used in the past for morphine because its pain relieving effects are long acting (6-12 hours) when given this way. Unfortunately, depression of breathing can potentially occur any time up to 24 hours later, which obligates extra observations. Another reason why morphine has fallen from popularity recently is that he itchiness caused by morphine can be severe and difficult to treat.

Shorter acting opioids like fentanyl and sufentanyl can be used as an alternative to morphine however, they may not provide pain relief for very long. Giving repeated injections into the spinal sac increases the likelihood of causing a spinal headache from leaking cerebrospinal fluid.

In recent times, a technique, which combines a single injection of spinal opioid and an epidural, has gained popularity. This is called a ‘combined spinal epidural’ CSE. The epidural catheter is placed at the same time as the spinal injection and can be used later in labour if further pain relief is needed.

Opioid drugs can also be given epidurally. Although the epidural space is separated from the spinal cord and fluid by a thick membrane (the dura), opioid drugs pass through this barrier fairly easily. The fine epidural catheter remains in the epidural space: this means that additional doses can be given whenever necessary - without requiring any more injections. For these reasons, most centres prefer to use the epidural, as opposed to the spinal, route when opioids are used in the management of postoperative and childbirth pain. When compared with the intramuscular and intravenous routes of injection, the opioid dose requirements are also much less but not to the same extent as when they are given directly into the spinal fluid.

Some drugs, including certain opioids, can be absorbed through the skin and there have been attempts to produce special opioid-containing adhesive patches that can be applied to the skin. This attractive concept has shown some promise in the management of postoperative pain, but is not sufficiently reliable for use in childbirth.