And selective serotonin receptor inhibitors

Pharmacological treatment of OSA is an elusive concept. A number of selective serotonin receptor inhibitors (SSRIs) and other medications were tried and found to be ineffective. SSRIs and analogous medication have been anecdotally reported to help REM-related OSA, but no study systematically confirmed this claim. Two studies showed positive effect of mirtazapine [33, 34], a tetracyclic non-SSRI antidepressant, on OSA, but further research on a bigger sample is necessary. On the other hand, one should be aware of a muscle relaxation property of some commonly used medications such as benzodiazepines (BZDs), which may result in a worsening of OSA. Assisted nasal ventilation is commonly used in patients with both hypercapnic and non-hypercapnic CSA. The administration of oxygen is observed to ameliorate the frequency of both the central and obstructive events in patients with a predomi-... 

With respect to a specific and common clinical problem, advice to withdraw hypnotic medication should follow a careful evaluation of self-reported sleep patterns, psychological factors and psychosocial status. Ambulant monitoring can be helpful in patients who have encountered severe problems in effecting withdrawal. A careful psychiatric assessment should be made to ascertain whether the patient has clinically significant anxiety and/or depression. Both should be treated with a selective serotonin receptor inhibitor (SSRI) before withdrawal from the hypnotic is attempted. An optimal tapering schedule should be discussed with the patient some will attempt a rapid withdrawal over less than 8 weeks and others will require much longer. This is particularly so if previous attempts to withdraw have been unsuccessful. Carers, family and friends should be mobilized to help in withdrawal, should the patient wish this. Substitution of zolpidem may facilitate withdrawal but should be kept as a reserve strategy. 

Dexamethasone has been nsed successfully in the management of chemotherapy-indnced and postoperative nansea and vomiting, either as a single agent or in combination with selective serotonin receptor inhibitors (SSRIs). For chemotherapy-indnced nansea and vomiting, dexamethasone has demonstrated efficacy in the prevention of both cisplatin-indnced acnte emesis" and delayed nansea and... 

NVP nausea and vomiting of pregnancy PONV postoperative nausea and vomiting RINV radiation-induced nausea and vomiting SSRI selective serotonin receptor inhibitor... 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

Monaca, C., Boutrel, B., Hen, R., Hamon, M. Adrien, J. (2003). 5-HTia/b receptor-mediated effects of the selective serotonin reuptake inhibitor citalopram, on sleep studies in 5-HTia and 5-HTib knockout mice. Neuropharmacology 28, 850-6. 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

Some failures will be due to the presence of variants in drug handling. Patients who are rapid acetylators of isoniazid have a slower antituberculous response than slow acetylators (Evans and Clarke, 1961). Asthmatics who do not respond well to (32-agonist bronchodilators may have fewer functioning p2-adrenergic receptors (Drysdale et al., 2000). Variations in the synthesis or structure of the serotonin transporter protein, which is involved in selective reuptake of serotonin by presynaptic neurons, may explain why some patients with depressive disorders respond to selective serotonin reuptake inhibitors and others do not (Steimer et al., 2001). 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

A few cases have been reported of exacerbation of HPPD by risperidone (Risperdal) (Abraham and Mamen 1996). The exact reason for this is uncertain, but the fact that risperidone and LSD both act at 5-HT2 receptors is probably causative. Also, two cases have been reported of an exacerbation of HPPD by selective serotonin reuptake inhibitors (Markel et al. 1994). 

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

A life-threatening condition, when selective serotonin reuptake inhibitors (SSRIs) and 5-hydroxytryptamine receptor agonists (triptans) are used together. However, many other drugs have been implicated (see below). Signs and symptoms of serotonin syndrome include the following ... 

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