Introduction - Uppsala Monitoring Centre

(Crofton, 2009). Asthma, pancytopenia, aplastic anaemia, haemolytic anaemia,
Stevens-Johnson syndrome, peripheral neuritis, encephalopathy, neuromuscular
block, anosmia and loss of concentration were all discovered after 1957 suggesting
that they might be very rare. Fiedler’s myocarditis was probably a single case
(Chatterjee & Thakre, 1958). The case series prior to 1948 seem to have been
effective in discovering the commoner ADRs.
Of those ADR mentioned in SED 2000:
Stevens-Johnson Syndrome. The original description was given in 1922
(Stevens and Johnson, 1922) George Orwell probably suffered it as an ADR to
Streptomycin in 1947. There was a single case published in 1982 (Sarker et al.,
1982) A case of toxic erythema with generalising follicular pustules with a positive
rechallenge appeared in 1981 (Shimoto & Aoki, 1981).
Anosmia. A survey of 300 patients found 8 cases of anosmia and 13 cases of
hyposmia, but all but two had had anosmia before streptomycin (Kereković &
Curkević, 1971) an allusion to 5 case of olfactory disturbance was made in 2003
(Welge-Luessen & Wolfensberaed, 2003).
Haemolytic anaemia. A single case of immune haemolytic anaemia and renal
failure was reported in 1977 (Martinez-L et al., 1977) and a similar case in 1962
(Nachman et al., 1962).
Peripheral neuritis. First reported in 1971 (Herishahy & Tauste, 1971).
The small number of patients involved in these late reported cases suggests that
they are rare and that their discovery probably resulted from the large number of
patients treated over the years. Most of the ADRs were discovered via individual
reports or small case series and the MRC Trial added little to our knowledge of the
ADRs. In the USA where they had started with individual cases and case series the
dramatic improvements meant that controlled studies would be unethical, but the
dramatic improvement only became clear after a controlled study had started and
since there was sufficient drug available to treat patients the placebo control study
was unethical and was stopped. The situation was different in the UK as there was
insufficient drug to treat all the patients so a placebo group was ethical (Green,
1954). Streptomycin was more vestibule-toxic than dihydrostreptomycin, but this
was frequently reversible. Di-hydrostreptomycin was more cochleo-toxic and the
resulting deafness was nearly always permanent. The advent of streptomycin made
little difference to the already declining death rate of tuberculosis (McKeown, 1976).
Discussion on Part Two
First we will take a look at the amount of knowledge that we have on single
representative ADR for each marker drug.