DDInter336 DDInter853
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a nonsteroidal anti-inflammatory drug (NSAID) which is known for its decreased risk of causing gastrointestinal bleeding compared to other NSAIDS. It is used to manage symptoms of various types of arthritis pain and in familial adenomatous polyposis (FAP) to reduce precancerous polyps in the colon. It is marketed by Pfizer under the brand name Celebrex, and was initially granted FDA approval in 1998. Interestingly, selective COX-2 inhibitors (especially celecoxib), have been evaluated as potential cancer chemopreventive and therapeutic drugs in clinical trials for a variety of malignancies.
Haloperidol is a high potency first-generation (typical) antipsychotic and one of the most frequently used antipsychotic medications used worldwide. While haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain, it exerts its antipsychotic effect through its strong antagonism of the dopamine receptor (mainly D2), particularly within the mesolimbic and mesocortical systems of the brain. Haloperidol is indicated for the treatment of the manifestations of several psychotic disorders including schizophrenia, acute psychosis, Tourette syndrome, and other severe behavioural states. It is also used off-label for the management of chorea associated with Huntington's disease and for the treatment of intractable hiccups as it is a potent antiemetic. Dopamine-antagonizing medications such as haloperidol are though to improve psychotic symptoms and states that are caused by an over-production of dopamine, such as schizophrenia, which is theorized to be caused by a hyperdopaminergic state within the limbic system of the brain. Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the "positive" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class of drugs is also limited by the development of movement disorders induced by dopamine-blockade such as drug-induced parkinsonism, akathisia, dystonia, tardive dyskinesia, as well as other side effects including sedation, weight gain, and prolactin changes. While there are limited high-quality studies comparing haloperidol to lower-potency first-generation antipsychotics such as , , , and , haloperidol typically demonstrates the least amount of side effects within this class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).[A180613, A180616, A180625] These other low‐potency antipsychotics are limited by their lower affinity for dopamine receptors, which requires a higher dose to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension. Interestingly, in vivo pharmacogenetic studies have demonstrated that the metabolism of haloperidol may be modulated by genetically determined polymorphic _CYP2D6_ activity. However, these findings contradict the findings from studies in vitro with human liver microsomes and from drug interaction studies in vivo. Inter-ethnic and pharmacogenetic differences in haloperidol metabolism may possibly explain these observations. First-generation antipsychotic drugs have largely been replaced with second- and third-generation (atypical) antipsychotics such as , , , , , and . However, haloperidol use remains widespread and is considered the benchmark for comparison in trials of the newer generation antipsychotics. The efficacy of haloperidol was first established in controlled trials in the 1960s.
Celecoxib {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Hyperglycaemia
Hyperglycaemia {u} (Side Effect) is caused by {v} (Compound) Haloperidol
Celecoxib {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Moclobemide
Moclobemide {u} (Compound) resembles {v} (Compound) Haloperidol
Celecoxib {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Loperamide
Loperamide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Hyperglycaemia
Hyperglycaemia {u} (Side Effect) is caused by {v} (Compound) Droperidol
Droperidol {u} (Compound) resembles {v} (Compound) Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Sweating increased
Sweating increased {u} (Side Effect) is caused by {v} (Compound) Cetirizine
Cetirizine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Dry mouth
Dry mouth {u} (Side Effect) is caused by {v} (Compound) Loperamide
Loperamide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Confusional state
Confusional state {u} (Side Effect) is caused by {v} (Compound) Moclobemide
Moclobemide {u} (Compound) resembles {v} (Compound) Haloperidol
Celecoxib {u} (Compound) causes {v} (Side Effect) Hepatobiliary disease
Hepatobiliary disease {u} (Side Effect) is caused by {v} (Compound) Metronidazole
Metronidazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Haloperidol
Celecoxib {u} (Compound) resembles {v} (Compound) Sulfaphenazole
Sulfaphenazole {u} (Compound) binds {v} (Gene) CYP2D6
CYP2D6 {u} (Gene) is bound by {v} (Compound) Haloperidol
Celecoxib (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Haloperidol (Compound)
Celecoxib (Compound) causes Hyperglycaemia (Side Effect) and Hyperglycaemia (Side Effect) is caused by Haloperidol (Compound)
Celecoxib (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Moclobemide (Compound) and Moclobemide (Compound) resembles Haloperidol (Compound)
Celecoxib (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Loperamide (Compound) and Loperamide may cause a moderate interaction that could exacerbate diseases when taken with Haloperidol
Celecoxib (Compound) causes Hyperglycaemia (Side Effect) and Hyperglycaemia (Side Effect) is caused by Droperidol (Compound) and Droperidol (Compound) resembles Haloperidol (Compound)
Celecoxib (Compound) causes Sweating increased (Side Effect) and Sweating increased (Side Effect) is caused by Cetirizine (Compound) and Cetirizine may cause a moderate interaction that could exacerbate diseases when taken with Haloperidol
Celecoxib (Compound) causes Dry mouth (Side Effect) and Dry mouth (Side Effect) is caused by Loperamide (Compound) and Loperamide may cause a moderate interaction that could exacerbate diseases when taken with Haloperidol
Celecoxib (Compound) causes Confusional state (Side Effect) and Confusional state (Side Effect) is caused by Moclobemide (Compound) and Moclobemide (Compound) resembles Haloperidol (Compound)
Celecoxib (Compound) causes Hepatobiliary disease (Side Effect) and Hepatobiliary disease (Side Effect) is caused by Metronidazole (Compound) and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Haloperidol
Celecoxib (Compound) resembles Sulfaphenazole (Compound) and Sulfaphenazole (Compound) binds CYP2D6 (Gene) and CYP2D6 (Gene) is bound by Haloperidol (Compound)