Haematological toxicity of drugs used in psychiatry

Flanagan, Robert J.; Dunk, Louisa

doi:10.1002/hup.917

Cited by 193 publications

(174 citation statements)

References 89 publications

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“…Haematological changes such as anaemia are often accompaniments of bone marrow toxicity (Flanagan and Dunk, 2008) among other causes. The lack-of-effect on neutrophil levels indicates that the extract may not have induced any inflammatory process since these cells are usually elevated in the course of inflammations (Formela et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Acute and sub-acute toxicological assessment of the aqueous seed extract of <i>Persea americana</i> Mill (Lauraceae) in rats

Ozolua¹,

Anaka²,

Okpo³

et al. 2010

Afr. J. Trad. Compl. Alt. Med.

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The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD 50 ) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD 50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-tobody weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable. Keywords: Persea americana seed, herbal medicine, safety profile IntroductionThe use of herbal medicines as complements or alternatives to orthodox medicines has been on the increase. The reasons, which have given rise to this trend, include the cheapness, availability and accessibility of these natural medicines. Besides, there has been the erroneous belief that these medicines are free from adverse effects (Larrey, 1994;Ernst, 2005). On the other hand they have been rejected because many of the acclaimed medicinal values have not been scientifically evaluated and their safety profiles uncertain (Ernst, 2005). It is, therefore, pertinent that safety assessments should be conducted on natural products for which certain medicinal uses have been scientifically validated.The fruit of Persea americana Mill of family Lauraceae is eaten in many parts of the world. In recent years, research has focused on various parts of the plants. The fruit in particular has been shown to possess medicinal properties. The edible fruit pulp contains up to 33% oil rich in monounsaturated fatty acids (Ortiz et al., 2004) that are believed to modify the fatty acid contents in cardiac and renal membranes and enhance the absorption of α/β-carotene and lutein (Salazar et al., 2005). The carotenoid content has been reported to play significant role in cancer risk reduction (Lu et al., 2005).Other properties of the oil include wound healing (Nayak et al., 2008) and hepatoprotection (Kawagishi et al., 2001). Proximate analysis has been conducted on the seeds (Olaeta et al., 2007).Other parts of the plant have been reported to possess medicinal properties. The aqueous leaf extract for example has analgesic and anti-inflammatory (Adeyemi et al.,...

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Section: Discussionmentioning

confidence: 99%

Acute and sub-acute toxicological assessment of the aqueous seed extract of <i>Persea americana</i> Mill (Lauraceae) in rats

Ozolua¹,

Anaka²,

Okpo³

et al. 2010

Afr. J. Trad. Compl. Alt. Med.

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“…Trifluoperazine has been shown to induce mitochondrial permeability transition (MPT) and cytochrome c release from the isolated mitochondria (Cruz et al 2010). In patients, antipsychotics have been reported to exert direct toxicities on many organs or cells, including liver and blood cells, in addition to the indirect systemic side effects such as endocrine disturbances, hypotension and seizures (Lader 1999;Flanagan and Dunk 2008). This suggests that the clinical dose of these drugs is high enough to exert cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Perphenazine and trifluoperazine induce mitochondria-mediated cell death in SH-SY5Y cells

Hong

Lee

Shin

et al. 2012

Animal Cells and Systems

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Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

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“…It is postulated that the activation of metabolites of CLZ to electrophilic nitrenium ions may cause idiosyncratic neutropenia/agranulocytosis events through direct binding of these ions to neutrophils, causing cell death by oxidative stress-induced apoptosis, and finally by directly targeting the bone marrow stroma cells [Pirmohamed and Park, 1997;Husain et al 2006;Pereira and Dean, 2006;Flanagan and Dunk, 2008]. However, the precise mechanisms of CLZ-induced leucopenia/ agranulocytosis are still unclear [Guest et al 1998;Coleman, 2001;Rajagopal, 2005].…”

Section: Discussionmentioning

confidence: 99%

Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports

Nunes

Rezende

Morais

et al. 2012

Therapeutic Advances in Psychopharmacology

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Background: Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics. Methods: We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients. Results: Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ. Discussion: It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration.

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Haematological toxicity of drugs used in psychiatry

Cited by 193 publications

References 89 publications

Acute and sub-acute toxicological assessment of the aqueous seed extract of <i>Persea americana</i> Mill (Lauraceae) in rats

Acute and sub-acute toxicological assessment of the aqueous seed extract of <i>Persea americana</i> Mill (Lauraceae) in rats

Perphenazine and trifluoperazine induce mitochondria-mediated cell death in SH-SY5Y cells

Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports

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