Arch Dis Child: first published as 10.1136/adc.62.8.771 on 1 August 1987. Downloaded from

Archives of Disease in Childhood, 1987, 62, 771-772

Giving drugs per rectum for systemic effect

Suppositories were used as early as 1500 BC by the inferior rectal veins. The superior rectal vein drains Egyptians for the local treatment of haemorrhoids through the inferior mesenteric vein into the portal and constipation. These suppositories were made by vein, whereas the inferior and middle rectal veins rolling conical chips of wood or bone in honey in drain directly into the inferior vena cava through the which a drug had been boiled until the solution was internal pudendal and internal iliac veins. There are nearly solid. A thousand years later Hippocrates extensive anastomoses between the rectal veins. described the use of a suppository made of anise, When a drug is taken orally and absorbed from myrrh, goose grease, and honey as a specific relief the gastrointestinal tract, it enters the portal vein for asthma, but it was in Britain in the seventeenth and is metabolised in the liver. If it is one which is century that the word 'suppositorium' was first principally broken down in the liver-for example, used. ' morphine, hydralazine, or propranolol, it does not The Egyptian technique of using inspissated achieve its optimal effect when taken orally. If it is honey was used until the end of the seventeenth given through the rectum however, better absorp- century. Cocoa butter was then used as it liquefied tion and greater systemic effect may be achieved. readily on warming and could be mixed with various The mechanism of rectal absorption is probably ingredients; it quickly formed a hard wax and yet similar to that of the upper part of the gastrointesti- conveniently dissolved in the rectum. It was in nal tract, despite differences in pH, surface area, general use for the next two hundred years, until the and fluid content. The use of surfactants can introduction of water soluble polyethylene glycols. increase the amount of absorption of a drug from

The importance of the base used in the formulation the rectum; they can, however, damage the rectal copyright. of a suppository has been reported over the past 20 mucosa and so their use requires further investiga- years. tion. The effects of different pharmaceutical formu- lations of the suppository may also affect the Acceptability to the patient availability of the drug, and this has been par- ticularly well documented concerning paracetamol.2 Suppositories are commonly used in certain parts of A practical problem with the use of suppositories Europe, but not in the United Kingdom. It is clear is premature expulsion, which may result in from the amount that has been written on the inadequate absorption. http://adc.bmj.com/ subject that the cultural influences of the parent, the child, and the doctor all have an effect on the Specific drugs acceptability of the treatment. Although it is often difficult to get young children to take their medicine Anticonvulsants. A solution of diazepam given by mouth there is no evidence to suggest that rectally is effective for treating convulsions in compliance is improved if suppositories are pre- children, therapeutic plasma concentrations being scribed. obtained within four minutes.3 There is a consider- able delay in the achievement of a therapeutic on September 28, 2021 by guest. Protected Indications for giving drugs through the rectum plasma concentration of diazepam after the use of suppositories, and with the introduction of rectal There are several circumstances under which it may solutions there is no indication to use suppositories. be preferable to give a drug through the rectum as The two major indications for the use of diazepam opposed to intramuscularly or intravenously; these solution rectally in children are by parents at home include circumstances in which the patient is uncon- for children who suffer from either febrile convul- scious; nauseated or vomiting; or if oral intake is sions or recurrent, poorly controlled epilepsy, or by forbidden immediately before operation. First pass a doctor when immediate intravenous access is not elimination in drugs with a high hepatic clearance technically possible. It is preferable to give diaz- may also be avoided in this way. epam intravenously in a paediatric unit or in an accident and emergency department, as therapeutic Absorption from the rectum plasma concentrations are more readily achieved by this route. Although clonazepam can be adminis- The rectum is drained by the superior, middle, and tered rectally, it takes up to 20 minutes for 771 Arch Dis Child: first published as 10.1136/adc.62.8.771 on 1 August 1987. Downloaded from

772 Choonara therapeutic plasma concentrations to be achieved. Other drugs. Theoretically, morphine is an ideal Paraldehyde used to be given rectally in the drug to be given rectally as it is extremely well United States of America, but we now know that absorbed. A pharmacokinetic study following rectal rectal absorption of paraldehyde is considerably morphine (0-15 mg/kg) in propylene glycol, how- slower than if it is given either intramuscularly or ever, showed plasma concentrations that were orally and it is therefore unsuitable for treating inadequate for pain relief.5 Rectal theophylline has epilepsy. Paraldehyde can also irritate the rectum been used for children with asthma, but with the and large intestine when given rectally, and decom- advent of oral slow release theophylline prepara- posed paraldehyde has caused perforation of the tions suppositories have been superseded. There large bowel. It is far safer to administer it as a deep have been several reports of one or more drugs intramuscular injection. given rectally as premedication before operation.5 6 Unfortunately, little data were given on the accept- Antibiotics. Metronidazole suppositories are effec- ability of the rectal compared with the intramuscular tive in reducing the postoperative anaerobic wound route. infections in children with appendicitis.4 The sup- positories are considerably cheaper than the in- References travenous infusion, and pharmacokinetic studies 1Senior N. Review of rectal suppositories. 1. Formulation and manufacture. Pharmnaceutical Journial 1969;203:703-6. have shown that they produce therapeutic plasma 2 de Boer AG, Moolenaar F, de Leede LGJ, Breimer DD. Rectal concentrations. If, however, the child has an in- drug administration: clinical pharmacokinctic considerations. travenous line, it is preferable for the drug to be Clin Pharmacokintet 1982;7:285-311. given intravenously. 3Knudsen FU. Plasma diazcpam in infants aftcr rectal adminis- tration in solution and by suppository. Acta Paediatr Scatid 1977;66:563-7. Paracetamol. Paracetamol is used mainly as an 4Ford WDA, MacKellar A, Richardson CJL. Pre- and postop- antipyretic in children. Although paracetamol sup- erative rectal metronidazole for the prevention of wound positories are not commercially most infection in childhood appendicitis. J Pediatr Surg 1980;15: available, 160-3. hospital pharmacies produce their own. The for- Lindahl S, Olsson AK, Thomson D. Rectal premedication in copyright. mulation of the suppository influences the availabil- childrcn. Use of diazcpam, morphine and hyoscine. Atnaesthesia ity of the paracetamol, and there are few data on the 1981:36:376-9. biovailability of the paracetamol in suppositories in Lindsay WA, Shepherd J. Plasma levels of thiopentone after premedication with rectal suppositories in young children. Br J different hospitals. The major clinical indication for Anaesth 1969-;41:977-84. giving paracetamol rectally is if a child is admitted I A CHOONARA with an acute febrile convulsion, and the paraceta- Department of Paediatrics and mol can be administered before the child wakes up. Child Health, Paracetamol is also useful in suppository form for St James's University Hospital, http://adc.bmj.com/ children who have fevers associated with vomiting. Leeds LS9 7TF on September 28, 2021 by guest. Protected