Analgesics ROBERT G
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Postgrad Med J: first published as 10.1136/pgmj.60.710.876 on 1 December 1984. Downloaded from Postgraduate Medical Journal (December 1984) 60, 876-880 Analgesics ROBERT G. TWYCROSS M.A., D.M., F.R.C.P. Sir Michael Sobell House, The Churchill Hospital, Headington, Oxford Introduction different mechanisms. Such concepts are almost certainly an oversimplification. Aspirin and related There is no internationally agreed classification of drugs appear to act at several sites in relation to analgesics. The terms mild and strong are not always prostaglandin synthesis, some peripheral and some helpful. Codeine, for example, is usually classed with central (Ferreira, 1981). Morphine also acts both the former which obscures its pharmacological rela- centrally and peripherally, though the major anal- tionship with morphine and other narcotics. More- gesic effect is undoubtedly central. over, there are occasions when morphine (a 'strong analgesic') does not relieve pain which aspirin (a 'mild analgesic') does. Anti-pyretic and narcotic have Analgesics in perspective much in their favour, although nefopam does not fit There is always more to analgesia than analgesics.by copyright. into either category. The basic division into non- The importance of explaining in simple terms the narcotic (non-opioid) and narcotic (opioid) is impor- mechanism(s) underlying the patient's pain should tant. The advent of drugs that have morphine-like not be forgotten. Pain that does not make sense or, (agonist) properties when used alone but act as worse, is seen as a threat is always more intense than antagonists when given after or in association with pain which is understandable. morphine has complicated matters. As agonists and Many drugs affect pain. Some affect it indirectly, agonist-antagonists should not be prescribed concur- for example, antibiotics in cystitis or sinusitis and rently, the classification in Table 1 has much to penicillamine or gold in rheumatoid arthritis. These commend it. drugs act by modifying the pathological process, and It is generally considered that aspirin and non- fall outside the definition of analgesic. Spasmolytics, http://pmj.bmj.com/ steroidal anti-inflammatory drugs (NSAID) act peri- such as baclofen, diazepam (somatic muscle) and pherally and narcotics centrally, that is, within the probanthine (smooth muscle), are another group of central nervous system. Paracetamol (acetamino- pain-modulating drugs. phen) and nefopam also act centrally but via Surgery is a commonly employed measure for the management of acute severe pain (e.g. appendicec- TABLE 1. Classification of analgesics tomy), likewise, radiation therapy and cytotoxic chemotherapy in pain associated with cancer. The Narcotic agonist- use of such measures does not preclude the use of on September 29, 2021 by guest. Protected Narcotic agonists Non-narcotic antagonists analgesics. Best results are often obtained by adopt- Weak Aspirin Weak ing a 'broad spectrum' approach, using two or more Codeine Paracetamol Pentazocine treatments in combination. In some conditions, e.g. Dihydrocodeine Nefopam trigeminal neuralgia, a sequential approach may, Dextropropoxyphene Ethoheptazine however, be appropriate. Strong Strong The use ofanalgesics is best seen as simply one way Morphine Butorphanol of elevating a patient's pain threshold. Analgesics, Diamorphine Buprenorphine including narcotics, do not usually relieve pain caused Pethidine Nalbuphine by degenerative nerve damage (dysaesthetic and Levorphanol Phenazocine stabbing pains). The site ofthe neurological lesion and Methadone the type of pain determine which pharmacological measures are appropriate, if any (Table 2). Postgrad Med J: first published as 10.1136/pgmj.60.710.876 on 1 December 1984. Downloaded from Analgesics 877 Principles of use and forces the patient to be in pain for perhaps 3 out of every 6 hr. Persistent pain requires prophylactic (preventive) therapy TABLE 2. Neuromuscular classification of pain: implications for therapy Analgesics should be given regularly, and prophy- of pain Treatment lactically. The aim is to titrate the dose of the Type analgesic against the patient's pain, gradually in- (1) Muscle spasm Baclofen creasing the dose until the patient is pain-free. The Diazepam next dose is given before the effect of the previous (2) Nociceptive Analgesics one has fully worn off-and therefore before the (3) Nerve compression Analgesics patient may think it necessary (Fig. 1 and 2). In this Corticosteroids way it is possible to erase the memory and fear of Nerve blocks (4) Nerve destruction Psychotropic drugs pain. If a drug ceases to be effective, do not transfer (dysaesthetic) (especially antidepressants) to an alternative ofcomparable efficacy but prescribe peripheral nerve- Narcotics a drug that is definitely stronger. occasionally useful Corticosteroids If a strong analgesic other than morphine is used, cord lesion- Nerve blocks the physician must be familiar with its pharmacol- of no benefit Cordotomy (5) Mixed nerve Treated as mixed 3 and 4 ogy. For example, pethidine (meperidine) is effective compression and destruction (?)Stellate ganglion block for an average of 2-3 hr. Yet it is commonly (partly dysaesthetic) for upper limb pain prescribed every 4 or 6 hr. This is clearly insufficient, PAIN Toxicity by copyright. PD]p -] 1<\ \tl a t t 1 X E A Pain controlled Poor or no control 0 6 12 18 24 AS REQUIRED MEDICATION http://pmj.bmj.com/ FIG. 1. Diagram to illustrate the result of 'as required' morphine sulphate. [Dip= plasma concentration of drug. CONTINUOUS PAIN RELIEF Toxicity on September 29, 2021 by guest. Protected [L]p Pain controlled Poor or no control - 0 4 8 1-2 16 20 24 FOUR HOURLY DRUG REGIMEN FIG. 2. Diagram to illustrate the result of regular 4-hourly morphine sulphate. [D]p =plasma concentration of drug. Postgrad Med J: first published as 10.1136/pgmj.60.710.876 on 1 December 1984. Downloaded from 878 R. G. Twycross Use oral medication whenever possible (2) It may be appropriate to prescribe aspirin in addition to a narcotic, especially in patients with The route of administration is a significant con- bone pain. sideration because it has substantial impact on the It is to patient's way of life. The patient taking oral medica- (3) logical combine analgesics that act via tion is free to move around, travel in a car and, most different mechanisms, for example: aspirin and important, be at home. Injections promote depen- paracetamol; paracetamol and codeine; aspirin and dence on the person administering the Oral morphine. However, it is not always wise from the drug. point of view of patient compliance, nor is it always administration eliminates muscle trauma, and en- therapeutically necessary. ables the patient to maintain control over his own (4) It is pharmacological nonsense to prescribe either drug administration. two weak or two strong narcotics simultaneously. (5) There is sometimes a place for a patient on a Doses should be determined on an individual basis strong narcotic to have another narcotic (weak or The effective analgesic dose varies considerably strong) as a second as required analgesic for occa- from patient to patient. The right dose ofan analgesic sional troublesome pain, though generally patients is that which gives adequate relief for at least 3 and should be advised to take an extra dose of their preferably 4 or more hours. 'Maximum' or 'rec- regular medication if 'breakthrough' pain occurs. ommended' doses, derived mainly from post-opera- (6) If one weak narcotic preparation does not control tive parenteral single-dose studies, are not applicable the pain, do not waste time by prescribing an in cancer. The dose of morphine and other strong alternative; move to something definitely stronger. narcotic agonists can be increased almost indefin- (7) Morphine or an alternative strong narcotic should itely. On the other hand, the non-narcotics, weak be used when non-narcotics and weak narcotics fail narcotic agonists and narcotic agonist-antagonists all to control the pain (Table 3). reach a plateau of maximum effect after 2 or 3 (8) 'Morphine exists to be given, not merely to be upward dose adjustments. Thus, ifthe upper effective withheld.' The severity of the pain determines the dose has been reached with one of these agents, the choice of analgesic, not the doctor's estimate of lifeby copyright. dose should not be increased further but a stronger expectancy-which is often wrong. A patient should drug should be prescribed. not be made to wait in pain until the last days or hours of life. Keep it simple (9) Morphine may be given in a wide range of doses from as little as 5 mg to more than 500 mg. The three basic analgesics are aspirin, codeine and (10) Do not prescribe a narcotic agonist-antagonist, morphine. The rest should be considered alternatives such as pentazocine or buprenorphine, with a narco- of fashion or convenience. Appreciating this helps tic agonist. prevent 'kangarooing' from analgesic to analgesic in (11) Preferably do not prescribe pentazocine, pethi- a deperate search for some drug that will suit the dine or dextromoramide (Palfium). The first is a patient better. If a non-narcotic or weak narcotic weak narcotic by mouth and frequently causeshttp://pmj.bmj.com/ preparation, such as aspirin-codeine or paracetamol- unpleasant mental effects. All three tend to be short- dextropropoxyphene, fails to relieve, it is usually best acting (2-3 hr). to move directly to a small dose of oral morphine (12) Many cancer pains respond better to the sulphate than, for example, to prescribe dihydrocode- concurrent use of an analgesic and a 'co-analgesic' ine. (see Baines, 1984, this issue). It is necessary to be familiar with one or two alternatives for use in Adjuvant medication is often patients who cannot tolerate necessary on September 29, 2021 by guest. Protected the standard preparation. Aspirin has two alterna- Laxatives are almost always tives: paracetamol, which has no anti-inflammatory necessary, especially effect, is one: non-steroidal anti-inflammatory drugs with patients receiving a narcotic.