Læknablaðið : fylgirit - 01.07.1978, Blaðsíða 91

Analgesics.
It appears that a drug must have anti-
inflammatory properties before it can
relieve pain in rheumatoid arthritis. Both
pentazocine (Nuki et al,' 1973) and
paracetamol (Lee et al, 1975 Lee et al,
1976) have been shown to be no more
effective than placebo, even when given
with an anti-inflammatory drug (Nuki et
al, 1973, Lee et al, 1976). Approximately
40 per cent of our patients are prescribed
paracetamol by their family doctor (Lee
et al, 1974b) thus costing the British
Health Service undue expense. Despite
our efforts to indicate to our family
practitioner colleagues there has been no
diminution of the amount of paracetamol
prescribed.
Non-steroidal anti-inflammatory drugs
other than aspirin.
There are now a large number of such
drugs available, and their principal
pharmacological properties are summarised
in Table I. Phenylbutazone and oxyphen-
butazone, one of its two metabolites, have
been used since the early fifties. Their
potential list of side effects is breath
taking, but of particular importance is
bone marrow depression. Agranulocytosis
and thrombocytopenia occur especially in
younger people, and aplastic anaemia in
elderly females (Inman, 1977). There is
no doubt that these drugs are extremely
useful and effective, but risk of bone
marrow depression - albeit slight (1 in
80.000 prescriptions) - indicates that they
should only be used after less toxic
preparations have been tried. We no
longer use these drugs to treat acute gout,
since bone marrow depression occurs in
5 per cent of patients who have received
treatment for less than one week (Fowler,
1972). There seems little to choose
between phenylbutazone and oxyphenbutazone
in terms of clinical efflcacy or toxic
manifestations.
The fenemates were introduced also in
the 1950s. They are anthranilic acid
derivatives, and the most popular one in
the United Kingdom is mefenamic acid.
Parke Davis, the maker of mefenamic
acid claims that it is only a "weak
analgesic", but trials we have recently
done (Lee et al, 1976, Mavrikakis et al
1977) indicate that it is as potent as
indomethacin and other non-steroidal
drugs. Family doctors in Glasgow clearly
have been influenced by adverts, for they
only consider it a "weak analgesic" (Lee
et al, 1974b). Side effects of the fenemates
are relatively common, but most are mild.
Dyspepsia is the more frequent complica-
tion, and diarrhoea a close second.
Rashes have been reported but clear on
discontinuing therapy. Leucopenia,
thrombocytopaenia and Coombs-positive
haemolytic anaemia have also been
described. Perhaps mefanamic acid has
been somewhat underestimated and should
be used more.
Indomethacin is an indole derivative and
continues to be a popular prescription of
patients with rheumatoid arthritis, despite
a high incidence of dyspepsia and cerebral
symptoms. The drug has been accused of
causing peptic ulceration, but a direct
causal relationship has yet to be established.
It is of interest that when probenecid is
given with indomethacin much higher
blood concentrations of the latter drug are
found (Brooks et al, 1974).
It is common for family doctors to
prescribe two or even more non-steroidal
anti-inflammatory drugs at the sametime,
but the studies of Brooks at al (1975) have
clearly shown that when indomethacin and
aspirin are prescribed together their
combined effect is no greater than either
alone.
There are now several propionic acid
derivatives being used as non-steroidal
anti-inflammatory analgesics. Ibuprofen
was introduced in the 1960s by Boots
Drug Company, and this has proved very
popular. It is remarkably free from
side effects, but it is not quite as potent
as indomethacin (Deodhar et al, 1973).
Flurbiprofen will shortly be released in
the United Kingdom, and in our experience
it promises to be more effective than
ibuprofen (Lee et al, 1976). Naproxen
was introduced in the 1970s by Syntex.
It has the benefit that it only requires
twice daily oral administration. Side
effects are mild, but a few patients have
been reported to have developed gastro-
intestinal haemorrhage. Ketoprofen (May
and Baker) is similar to ibuprofen in its
effect and low incidence of side effects
(Lee et al 1976). Fenoprofen has been
89