therapy

SERENDIPITY STRIKES AGAIN - TWO ACCIDENTAL FINDS

Pizotifen relieves pruritus in polycythaemia vera A woman with polycythaemia vera oblained complete relierrrom pruritus when given pizolifen for her migraine. Pruritus returned when the drug was withdrawn. This led to a small clinical study . Generalised pruritus oCcurs in 25-50 % of those with IXllycythaemia and no clearly defined cause nor treatment has so far been found. 15 patients with polycythaemia were treated in a crossover study with 1 D-day courses ofpizolifen O.5mg lid and placebo.

separated by a 4-day washout. To reduce the placebo effect no reference wa.~ made specifically to the pruritus. In a pretreatment questionnaire, 9 of the 15 patients included pruritus as one of their symptoms and of these, 6 obtained relief from pru ritus: 2 complele, 4 good. Five patients suffered drowsiness which was transient in all but one. The relief of pruritus was not related to concentrations of conjugated bile acids (cholestyramine has previously been reported to be

effective in relief of pruritus in this disease, implying a link to bile acids). The mechanism by which pizotifen works remains unknown, but it would be of interest 10 increase the pizotifen dose and give il for a longer period in those 3 who failed to respond, sinCt: in migraine prophylaxis, individual tailoring of dosage is requi red . FitzsjmmoRS, EJ. eta!. : British Medical Journal 28 ) : 217(25 Jul 1981)

The pain of sickle cell crisis may be alleviated with isoxsuprine An IV infusion of isoxsuprine was given to ward offpremature birth in a 23-year-Old woman undergoing a sickle cell cris is. Surprisingly, a lthough the drug was intended purely as a uterine relaxant, the woman also experienced prompt and complete relief of the pain associated with the sickle cell crisis. This accidental discovery led to a pilot study into the beneficial effects that this

drug might have in crisis management. 24 patients with either homozygous sickle cell anaemia or microdrepanocytic anaem ia (sickle cell I fS·thalassaemia) were studied during 34 crisis episodes. Results were compared to their known histories of previous episodes using conventional therapy.

lsoxsuprine was given in one of 4 methods and doses: 1M isoxsuprine 5-IOmg(I .5mg/ kg) with or without IV infusion of

dextrose 5 96 or dextran 1M followed by rapid IV infusion (I mg/ min); 1M + IV followed by slow IV infusion{O.I­O.3mg/ min); 1M + slow IV infusion. Of 34 episodes, 80% responded within 5 hours, and 4096 within 2 hours. Two cases

(8 .3 %) were considered failures. Narcotics were required in only 2 cases, far less than with conventional treatment. Three relapses occurred, but responded to another regimen of isoxsuprine. About half the cases (the less complicated) needed only a few hours to a few days hospitalisation, while even complicated cases needed no more than 8 days (compared with 10- 1 5 days previously). Side effects (tachycardia of an

extra 15.20 beats/min, palpitations, som nolence) were more prevalent with high dose IV adm ini~t ration. Simultaneous IV infusion of dextrose or dextran seemed to offer some protection from side effects. It was noted that the beneficial effect of

isox~uprine became apparent just as the side effects became strongest. In sickle cell crisis capillary vessels are blocked by Ihe rigid s ickle cells; blood now and oxygen delivery become impaired, causing multiple, small infarcts and extensive pain. 'Conventional' treatment is purely symptomatic and consists of hydration,

dextrans, alkalinisation, and powerful analgesicsl narcotics. The mechanism of action of isoX5uprine is difficult to assess, because of the multiple pharmacological properties of the drug.

I ~oxsuprine dilates deep peripheral vessels, stimulates the myocardium and decreases blood viscosity. Which of Ih~ properti~ is responsible for the alleviation of s ickle cell c risi~ must be determined by furt her research, although it wou ld seem likely that the

prompt pain relief(ofien within half an hour) might well be att ributed to local vasodilation. Psomadaki$. C. et al.: Angiology 32: 249 (Apr t 98 1)

8 INPHAflMA 12 Sep 1981 0IS6 .210Jf81 /~ '2 ·0008 $00.50 /0 IO AD1S Press