The Pharmacology and Clinical Effectiveness of Phenothiazines and Related Drugs for Managing Chemotherapy-induced Emesis

Wampler, Galen L.

doi:10.2165/00003495-198300251-00005

Cited by 77 publications

(26 citation statements)

References 29 publications

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“…The phenothiazines are a group of potent pharmacological agents with neuroleptic, antiemetic, antihistaminic, anticholinergic, and sedative activities (1,14). Their main pharmacological effect is determined by variations in the chemical structure of the side chain at position 10 of the phenothiazine ring.…”

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confidence: 99%

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Activity of phenothiazines against medically important yeasts

Eilam¹,

Polacheck²,

Ben-Gigi³

et al. 1987

Antimicrob Agents Chemother

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Two phenothiazine compounds, trifluoperazine and chlorpromazlnej inhibited growth in vitro of the five niost common pathogenic yeasts, with MICs ranging from 10 to 40 uLg/ml. Daily intraperitoneal injections of trifluoperazine (4 to 7 mg/kg of body weight) increased the survival of mice experimentally infected with Candida albicans or Cryptococcus neoformans. The potential use of these drugs against fungal meningitis is discussed.The increasing occurrence of mycoses caused by opportunistic systemic infections (2, 3, 7) and the lack of effective and safe drugs (8) led to the search for new antifungal drugs with low toxicity. In previous studies in our laboratory, we investigated the effects and the mechanism of action of compounds from the phenothiazine group on the yeast Saccharomyces cerevisiae (4-6). It was found that trifluoperazine (TFP) and chlorpromazine (CPZ) cause a quick and massive K+ efflux leading to membrane hyperpolarization, Ca2' influx, and inhibition of the plasma membrane H+-ATPase. The results led to the suggestion that these substances, which are currently used as tranquilizers and in antipsychotic therapy (1), may be used as drugs against pathogenic yeasts in systemic infections. Since the phenothiazines accumulate in the central nervous system (1, 2), these drugs may be specifically effective against fungal meningitis and encephalitis. In the present study, we investigate the activity of TFP and CPZ against five medically important yeasts.The yeasts used in the experiments were isolated from clinical specimens taken from different body sites of patients before treatment. Only one isolate per patient was studied. The yeasts were identified to the species level by current conventional methods (11). The isolates were maintained on Sabouraud dextrose agar until tested. In each in vitro experiment, at least five isolates of each species were tested. The mice used for in vivo experiments were Sabra white female mice 20 to 25 g in weight, and each experiment was repeated three times.MICs were determined by the agar dilution method as described previously (10), with the exception that HEPES buffer (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid; 20 mM, pH 7.2) was included in the agar medium. For examining the pH effect, plates with acidic pH values were prepared by the addition of MES (4-morpholineethanesulfonic acid) at the required pH.For the susceptibility test by the broth dilution method, yeast suspensions were prepared from overnight growth on Sabouraud dextrose agar at 30TC and added, at a density of 5 X 105 cells per ml, to test tubes each containing 10 ml of yeast nitrogen base (YNB) broth supplemented with glucose (100 mM), HEPES buffer (20 mM, pH 7.2), and the required concentration of the drug being tested. The loosely capped test tubes were incubated at 30°C in a shaker. Every 2 h, the * Corresponding author. optical densities at 530 nm were determined. MIC,b) was the concentration of the drug at which the increase in the optical density at 530 nm after 8 h was less than 20% of t...

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“…It was recently suggested that phenothiazines such as CPZ, TFP, and others may be given to cancer patients to reduce the chemotherapy-induced emesis (14). It would be beneficial to determine whether these drugs, when administered as antiemetics, also have prophylactic effects in fungal infections, which are common in cancer patients (2).…”

mentioning

confidence: 99%

Activity of phenothiazines against medically important yeasts

Eilam¹,

Polacheck²,

Ben-Gigi³

et al. 1987

Antimicrob Agents Chemother

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“…Before the advent of the 5-HT3-receptor antagonists, available antiemetic agents included phenothiazines, 83 substituted benzamides, 84,85 antihistamines, 86 butyrophenones, 87 corticosteroids, [88][89][90] benzodiazepines, 91,92 and cannabinoids. 93,94 Most drugs used to prevent chemotherapy-induced emesis are classified as dopamine antagonists, serotonin antagonists, and other antagonists.…”

Section: Other Non-5-ht3-receptor Antagonist Antiemeticsmentioning

confidence: 99%

Antiemesis

Ettinger¹,

Armstrong²,

Barbour³

et al. 2009

J Natl Compr Canc Netw

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“…age, gender, history of alcohol use) [8,9]. Before the advent of serotonin type 3 (5-HT 3 ) receptor antagonists, available antiemetic agents included phenothiazines [10], substituted benzamides [11,12], antihistamines [13], butyrophenones [14], corticosteroids [15,16], benzodiazepines [17,18], and cannabinoids [19]. Development of the 5-HT 3 receptor antagonists (i.e.…”

Section: Introductionmentioning

confidence: 99%

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

Vincenzi

Frezza

Silletta

et al. 2016

CBN

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Background Despite the efficacy of prophylaxis with serotonin type 3 (5-HT 3 ) receptor antagonists, nausea and vomiting are still among the most common chemotherapy-induced toxicities. The aim of this study was to evaluate the efficacy of adding aprepitant in patients with chemotherapy-induced nausea and vomiting (CINV) refractory to prophylaxis with 5-HT 3 receptor antagonists and dexamethasone. Patients and Methods Between January 2008 and November 2010, 51 patients (median age 59 years) with a variety of malignancies (breast cancer: 23; lung cancer: 12; sarcoma: 6; ovarian cancer: 3; other: 7) were enrolled. All patients were refractory to antiemetic therapy according to ASCO guidelines and developed at least grade 2 nausea and/or vomiting after the first chemotherapy course. Aprepitant was given at 125 mg on day 1 and 80 mg on days 2-3. Patients also received a single dose of palonosetron 250 µg on day 1 plus dexamethasone 12-20 mg at a constant dose. Results After addition of aprepitant, the number of patients with grade 3/4 nausea decreased from 31 (61%) to 4 (8%), and those with grade 2 nausea from 20 (39%) to 6 (12%) [both p<0.0001]. All patients received aprepitant for more then two courses (range 3-8) and efficacy was maintained during all chemotherapy cycles. Conclusions This study showed that aprepitant was effective as salvage therapy in patients with CINV refractory to prophylaxis with 5-HT 3 receptor antagonists and dexamethasone following platinum-or nonplatinum-based chemotherapy, and that the efficacy of aprepitant persists over multiple cycles.

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The Pharmacology and Clinical Effectiveness of Phenothiazines and Related Drugs for Managing Chemotherapy-induced Emesis

Cited by 77 publications

References 29 publications

Activity of phenothiazines against medically important yeasts

Activity of phenothiazines against medically important yeasts

Antiemesis

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

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