An overview on the use of granisetron in the treatment of emesis associated with cytostatic chemotherapy.

The clinical research programme with granisetron has involved a total of 1,229 patients, 982 receiving granisetron, 233 receiving currently available combination regimens and 14 receiving placebo. The true efficacy of granisetron was evaluated in a placebo-controlled trial with granisetron given prophylactically and being available as rescue medication in the placebo group. Granisetron produced a complete anti-emetic response in 92.9% of patients and was effective as intervention for the emesis experienced by the patients in the placebo group. Dose-finding studies have confirmed the wide therapeutic margin with four-fold increases in dose producing comparable results. In patients receiving high-dose cisplatin chemotherapy, two out of every three patients responded to a single prophylactic dose; which demonstrates granisetron's long duration of action (greater than 24 h). Additional granisetron also demonstrated benefit if the initial dose failed or delayed-onset emesis occurred. These results are also seen with other emetogenic regimens. Granisetron produces a greater degree of control than the anti-emetic combinations of metoclopramide/dexamethasone or dexamethasone/chlorpromazine. The side-effect profile in volunteers was favourable. The profile in patients is more difficult to define due to the range of potent drugs which cancer chemotherapy patients receive. Headache and constipation were the most common effects with granisetron, although the former was treatable with simple analgesics and the latter thought to be related to higher doses and subsided spontaneously. The future is promising, with the possible introduction of a fixed 3 mg i.v. dose administered over 5 min followed by oral maintenance therapy if and when required.

Postural changes in rib cage and abdominal volume-motion coefficients and their effect on the calibration of a respiratory inductance plethysmograph.

Volume-motion coefficients were determined for the rib cage and abdomen in normal human subjects in upright, supine, and semirecumbent postures by the isovolume calibration technique of Konno and Mead (J Appl Physiol 1967; 22:407-422, using the respiratory inductive plethysmograph (RIP) to measure displacements of rib cage and abdominal walls. Volume motion coefficients changed systematically with posture; those for the rib cage were smallest in the upright posture, and for the abdomen, greatest in the upright posture. These volume motion coefficients were then used to estimate tidal volume during resting breathing in the different postures, and compared with estimates of tidal volume derived from calibration by the change in posture technique reported by Sackner and coworkers (American Review of Respiratory Disease 1980; 122:867-871). Estimates of tidal volume derived from RIP signals using both calibration techniques were compared with independently measured spirometric volume changes. Errors in tidal volume averaged 6% with the isovolume technique and 9 to 23% with the change in posture technique (depending upon whether the calibrating postures were upright, supine or semirecumbent supine). The larger errors with the change in posture calibration method are attributable to both the change in volume motion coefficients with posture and the change in distribution of tidal volume between rib cage and abdomen compartments with change in posture.

Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction.

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.