China
Africa
Explore chapters and articles related to this topic
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Venlafaxine is a mixed serotonin and noradrenaline reup-take inhibitor used as a first-line treatment of depressive disorders (Holliday and Benfield 1995). After oral administration, venlafaxine undergoes extensive first-pass metabolism by the liver to two minor, less active metabolites, namely, N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine, and a major metabolite, O-desmethylvenlafaxine, which is an active metabolite with antidepressant activity comparable with the parent drug (Figure 3.17) (Ellingrod and Perry 1994). Venlafaxine is converted by CYP2D6 to its active metabolite O-desmethylvenlafaxine, while its N-demethylation is catalyzed by CYP3A4, 2C19, and 2C9 (Fogelman et al. 1999; Otton et al. 1996).
Drug interactions
Published in Alan Weiss, The Electroconvulsive Therapy Workbook, 2018
Venlafaxine is an antidepressant that is seroton-ergic at low doses, recruiting noradrenaline pathways at higher doses. There have been a number of case reports on its use with ECT and two randomised controlled trials. Bernardo, Navarro, Salva, Arrufat and Baeza (2000) randomised 18 patients into bilateral ECT with a tricyclic antidepressant (imipramine 150 mg to 300 mg a day or clomipramine 150 mg to 250 mg a day) or bilateral ECT with venlafaxine 150 mg a day. No patients had prolonged or spontaneous seizures outside of the treatment session and there were no statistically significant differences in mean seizure length, blood pressure or electrocardiogram. These findings were in contrast to another study, where higher doses of venlafaxine were used ranging from 150 mg to 375 mg, which reported increased episodes of asystole and hypotension (Gonzalez et al., 2002). Similar concerns were raised in a large, prospective randomised placebo-controlled trial of 319 patients randomised into RUL or BT ECT alone, with nortriptyline achieving therapeutic blood levels of 100-120 ng/ml or with venlafaxine up to 225 mg a day (Sackeim et al., 2009). Neither group demonstrated any difference in the number of adverse events or serious adverse events. The nortriptyline group showed improvement on all measures of cognitive adverse events except auto-biographical memory, while the venlafaxine group measures were basically unchanged or worse.
Information on level of drugs into breastmilk
Published in Wendy Jones, Breastfeeding and Medication, 2018
In some hospitals babies exposed to venlafaxine in pregnancy are monitored carefully in the first few days after delivery. It may be beneficial for the mother to be taught hand expression before delivery in order that she can stimulate her supply and ensure her baby receives breastmilk via a syringe/cup if breastfeeding is difficult.
Seizure in venlafaxine overdose: a 10-year retrospective review of the California poison control system
Published in Clinical Toxicology, 2020
Kathy T. Vo, Andrew J. Merriman, Ralph C. Wang
Venlafaxine is an antidepressant medication that blocks the reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine. At low doses (e.g., 75–150 mg/day) it acts on serotonergic transmission; at moderate doses (>150 mg/day), it acts on serotonergic and noradrenergic systems; and at high doses (>225 mg/day), it affects serotonergic, noradrenergic, and dopaminergic neurotransmission [15]. These neurotransmitters play an important role in seizure genesis. An animal study investigated proconvulsant effects of high doses of venlafaxine and speculated that the blockage of reuptake of dopamine by venlafaxine can exacerbate D1 postsynaptic dopaminergic receptor effects, thereby promoting a proconvulsant effect [16]. Despite this, a majority of our overdosed patients had a single seizure and the two patients who had the greatest number of seizures (five) ingested 1500 mg and 2250 mg, respectively. One patient who ingested the largest amount, 15 grams, only had two documented seizures.
Developments in the discovery and design of intranasal antidepressants
Published in Expert Opinion on Drug Discovery, 2020
Małgorzata Panek, Paweł Kawalec, Andrzej Pilc, Władysław Lasoń
The effectiveness of drug transport from the nose to the brain can be measured by mathematical parameters such as the drug targeting index (DTI), direct transport percentage (DTP), or drug targeting efficiency (DTE). Hague et al. compared the pharmacokinetic and pharmacodynamic properties of venlafaxine administered as an intravenous solution, intranasal solution, and intranasal venlafaxine-loaded chitosan nanoparticles to evaluate brain-targeting efficiency of the drug. Oral administration of venlafaxine is limited by a slow onset of action, low bioavailability, and short elimination half-life. Therefore, the intranasal administration and novel drug formulation based on chitosan nanoparticles were examined as a potential way to obtain effective therapeutic concentrations in the brain. The best brain uptake of the drug was observed in the case of venlafaxine administered intranasally in combination with chitosan nanoparticles (DTE = 508.59; DTP = 80.34) [23]. Similar difficulties were observed in the case of an oral administration of another antidepressant, namely, buspirone hydrochloride [24]. Khan et al. developed a nasal formulation, Bus-chitosan, consisting of buspirone hydrochloride, chitosan hydrochloride, and hydroxypropyl β‐cyclodextrin. They showed that in comparison with other formulations, Bus-chitosan had a higher DTP and DTI. These findings confirmed that intranasal administration of a drug in the form of nanoparticles allows a better access of molecules to the brain and their higher brain concentrations [24].
Cytogenotoxic effects of venlafaxine hydrochloride on cultured human peripheral blood lymphocytes
Published in Drug and Chemical Toxicology, 2020
Selim Ayabaktı, Ayşe Yavuz Kocaman
Venlafaxine hydrochloride (venlafaxine) is one of the most widely used active antidepressant drugs worldwide (Metcalfe et al.2010). It was first approved by the United States Food and Drug Administration (FDA) in 1993 as an immediate-release tablet formulation (Effexor) for the treatment of major depressive disorder. Finally, Effexor XR was approved in 1999 as an extended-release capsule for the treatment of generalized anxiety disorder, prevention of recurrence and relapse in major depressive disorder, social anxiety disorder and panic disorder (FDA 2008). It has also been used successfully for a chronic headache (Diamond 1995), fibromyalgia (Sayar et al.2003), and neuropathic pain (Sumpton and Moulin 2001). In addition to these, it benefits in hot flashes associated with the menopause or hormone therapy (Barlow 2000). The immediate-release and extended-release forms of venlafaxine are both available as brand and generic formulations.