DDInter1008 DDInter410
Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[A181802,T116] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981. At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[A188054,A188057] These effects combined with waning efficacy led to its eventual replacement by triazole agents, [fluconazole], [itraconazole], [voriconazole], and [posaconazole]. Ketoconazole and its predecessor [clotrimazole] continue
Clomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical &beta;-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H<sub>1</sub> receptors, &alpha;<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Clomipramine may be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1A2
CYP1A2 {u} (Gene) is bound by {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Pruritus
Pruritus {u} (Side Effect) is caused by {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1A2
CYP1A2 {u} (Gene) is bound by {v} (Compound) Thioridazine
Thioridazine {u} (Compound) resembles {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Adinazolam
Adinazolam {u} (Compound) resembles {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Pruritus
Pruritus {u} (Side Effect) is caused by {v} (Compound) Trimipramine
Trimipramine {u} (Compound) resembles {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Anaphylactoid reaction
Anaphylactoid reaction {u} (Side Effect) is caused by {v} (Compound) Prochlorperazine
Prochlorperazine {u} (Compound) resembles {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Seborrhoeic dermatitis
Seborrhoeic dermatitis {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} Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Menstrual disorder
Menstrual disorder {u} (Side Effect) is caused by {v} (Compound) Thalidomide
Thalidomide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Clomipramine
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Clomipramine
Ketoconazole {u} (Compound) causes {v} (Side Effect) Epistaxis
Epistaxis {u} (Side Effect) is caused by {v} (Compound) Tiotropium
Tiotropium {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Clomipramine
Ketoconazole (Compound) binds CYP1A2 (Gene) and CYP1A2 (Gene) is bound by Clomipramine (Compound)
Ketoconazole (Compound) causes Pruritus (Side Effect) and Pruritus (Side Effect) is caused by Clomipramine (Compound)
Ketoconazole (Compound) binds CYP1A2 (Gene) and CYP1A2 (Gene) is bound by Thioridazine (Compound) and Thioridazine (Compound) resembles Clomipramine (Compound)
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Adinazolam (Compound) and Adinazolam (Compound) resembles Clomipramine (Compound)
Ketoconazole (Compound) causes Pruritus (Side Effect) and Pruritus (Side Effect) is caused by Trimipramine (Compound) and Trimipramine (Compound) resembles Clomipramine (Compound)
Ketoconazole (Compound) causes Anaphylactoid reaction (Side Effect) and Anaphylactoid reaction (Side Effect) is caused by Prochlorperazine (Compound) and Prochlorperazine (Compound) resembles Clomipramine (Compound)
Ketoconazole (Compound) causes Seborrhoeic dermatitis (Side Effect) and Seborrhoeic dermatitis (Side Effect) is caused by Metronidazole (Compound) and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Clomipramine
Ketoconazole (Compound) causes Menstrual disorder (Side Effect) and Menstrual disorder (Side Effect) is caused by Thalidomide (Compound) and Thalidomide may cause a moderate interaction that could exacerbate diseases when taken with Clomipramine
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Clomipramine (Compound)
Ketoconazole (Compound) causes Epistaxis (Side Effect) and Epistaxis (Side Effect) is caused by Tiotropium (Compound) and Tiotropium may cause a moderate interaction that could exacerbate diseases when taken with Clomipramine