Anxiolytics MAOIs

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Monoamine Oxidase inhibitors (MAOis). Developed in the 1950s, the MAOIs were the first class of antidepressants. Subsequently, in the 1960s, the MAOis were also found to be effective anxiolytics. Unlike benzodiazepines and barbiturates, the MAOis are not addictive however, their onset of action is delayed not by minutes or hours but by 3 weeks or more. 

Tricyclic Antidepressants (TCAs). The TCAs were also introduced in the 1950s, and some were discovered to be effective anxiolytics in the 1960s. For example, early studies pioneered by Donald Klein and his colleagues indicated that imipra-mine (Tofranil) effectively relieved panic attacks. Like the MAOIs, the TCAs are not addictive but also require over 3 weeks to begin to achieve significant therapeutic benefit for anxiety. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

It became obvious, however, that psychostimulants were not effective in situations of lowered arousal resulting from mood depression. In the 1950s, antidepressants such as the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) became recognized as more effective in treating depression. The differentiation between arousal and mood thus became clearer. It is through the action of drugs that sedate and thus reduce anxiety versus those drugs that do not sedate but are anxiolytic that the basic concepts of anxiety have forcibly to be reconsidered. This inevitably led to the need for a reconceptualization of psychotropic modes of action in relation to psychiatric disorders. 

Available evidence indicates that systematic desensitization and in vivo exposure are the most effective treatment methods available. Pharmacological treatment has not been well investigated, but studies involving antidepressants suggest that TCAs and MAOIs are ineffective ( 85, 86 and 87). In addition, three studies suggest that sedative-hypnotic anxiolytics may undermine the behavioral treatment of specific phobias (88, 89 and 90). In another study, volunteers with animal phobias were exposed to their phobic object 1.5 hours after administration of either tolamolol, diazepam, or placebo in a double-blind crossover design. Tolamolol abolished the stress-induced tachycardia but had no beneficial behavioral or subjective effects ( 91). 

Tea Tree (Melaleuca alternifolia) Uses Rx of superficial wounds (bacterial, viral, fungal, insect bites, minor burns, cold sores, acne Action Broad-spectrum antibiotic activity against E. coli, S. aureus, C. albicans Available forms Topical creams, lotions, oint, oil apply topically PRN Notes/SE Ataxia, contact dermatitis, D, drowsiness, GI mucosal irritation Interactions Effects OF drugs that affect histamine release EMS effects of Benadryl Valerian (Valeriana officinalis) Uses Anxiolytic, antispasmodic, dys-menorrheal, restlessness, sedative Action Inhibits uptake stimulates release of GABA, which T GABA concentration extracellularly causes sedation Available forms Ext 400-900 mg PO 30 min < hs, tea 2-3 g (1 tsp of crude herb) qid, PRN, tine 3-5 mL (1/2-1 tsp) (1 5 ratio) PO qid, PRN Efficacy Probably effective sedative (reduces sleep latency) Notes/SE GI upset, HA, insomnia, N/V, palpitations, restlessness, vision changes Interactions T Effects OF barbiturates, benzodiazepines, opiates, EtOH, catnip, hops, kavakava, passion flower, skullcap effects OF MAOIs, phenytoin, warfarin EMS T Effects of benzodiazepines and opiates abruptly D/C may cause withdrawal symptoms... 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

ANAESTHETICS-GENERAL 2. ANTICANCER AND IMMUNOMODULATING DRUGS -IL-2 3. ANTIDEPRESSANTS - MAOIs 4. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS 5. ANTI-PSYCHOTICS 6. ANXIOLYTICS AND HYPNOTICS... 

BACLOFEN, TIZANIDINE 1. ANAESTHETICS - general 2. ANTICANCER AND IMMUNOMODULATING DRUGS - IL-2 3. ANTIDEPRESSANTS - MAOIs 4. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS 5. ANTI-PSYCHOTICS 6. ANXIOLYTICS AND HYPNOTICS 7. BETA-BLOCKERS 8. CALCIUM CHANNEL BLOCKERS 9. DIURETICS 10. NITRATES 11. PERIPHERAL VASODILATORS-moxisylyte (thymoxamine) 12. POTASSIUM CHANNEL ACTIVATORS t hypotensive effect Additive hypotensive effect. Tizanidine also has a negative chronotropic effect and may cause additive bradycardia with beta-blockers and calcium channel blockers Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

Although the BZs show a robust anxiolytic effect, many of the clinical trials were conducted before the currently used divisions between specific anxiety disorders became available (4). As a result, knowledge of their efficacy in discrete anxiety disorders is incomplete. In clinical practice (48) BZs are widely used for GAD and as prophylactics in situational anxiety, with diazepam (l)historically being the most popular choice. Others in common use are chlordiazepoxide (2), clorazepate (3), lorazepam (4), alprazolam (5), oxazepam (6), bromazepam (7), and clonazepam (8) Response rates are high and the onset of therapeutic effect is immediate. This is an important contrast to the MAOIs, TCAs, and SSRIs, where an anxiolytic effect is not seen for several weeks. Although not specifically approved for this disorder. BZs are also effective in social phobia, with clonazepam (49) showing a superior response rate to that of alprazolam (50). Alprazolam and clonazepam are the only BZs approved for the treatment of panic disor-... 

The metabolic profile of anxiolytic agents has important ramifications for their clinical use. This section discusses the metabolism of the benzodiazepinesand buspirone in some detail. The metabolism of the SSRIs, TCAs, and MAOIs is covered in the chapter on antidepressants. 

The behavioral despair model forces rats or mice to swim in a narrow cylinder of water from which they cannot escape and they ultimately adopt a characteristic posture of immobility.HI Immobility was reduced by MAOI, TCA and by new drugs like mianserin and nomifensin, as well as by ECT, REM sleep deprivation and an enriched environment. Anxiolytics did not affect immobility, neuroleptics enhanced it, and psychostimulants reduced it but at doses also causing motor stimulation. 

The anxiolytic effects of MAOIs/TCAs are believed to be mediated by three main mechanisms ... 

Furthermore, evidence from animal studies shows that MAOIs/TCAs, like benzodiazepines, decrease the firing rate of noradrenergic neurons - a phenomenon that may explain their anxiolytic capacity. 

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