Norepinephrine dosing

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

WARNING Fatal Hep liver failure possible do not retreat closely monitor for worsening depression or emergence of suicidality, particularly in ped pts Uses Depression Action Neuronal uptake of serotonin norepinephrine Dose Initial 100 mg PO bid usual 300-600 mg/d in 2 doses Caution [C, ] Contra w/ MAOIs, pimozide, carbamazepine, alprazolam active liver Dz Disp Tabs SE Postural 4- BP allergic Rxns HA, drowsiness, xerostomia, constipation, GI upset, liver... 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

In a third study the time course of the effects of intravenous and intracoronary injections of cysteinyl leukotrienes on metabolic parameters and systemic and coronary hemodynamics was examined in patients with normal coronary arteries [32]. LTD4 (3 nmol, injected into the left coronary artery) induced an early (20 s), transient fall in mean arterial pressure paralleled by rises in heart rate and plasma levels of epinephrine and norepinephrine, all of which had returned to baseline by 10 min. CVR rose at 10 and 15 min and myocardial oxygen extraction at 15 min. Thus, small doses of cysteinyl leukotrienes may induce both an early, transient fall in mean arterial pressure, with secondary sympathoadrenergic activation, and a later increase in small coronary arteriolar resistance. 

PTX caused a dose-dependent release of norepinephrine (NE). The NE release induced by lower concentrations of PTX increased proportionately with increasing Na concentrations, but was not modified by tetrodotoxin. However, the NE-releasing action of higher concentrations of PTX was dependent on external Ca, but not Na . Thus our experimental results suggest that in adrenergic neurons the PTX-induced release of NE by lower concentrations of PTX is brought about by tetrodotoxin-insensitive Na permeability, whereas that induced by higher concentrations is mainly caused by a direct increase of Ca influx into smooth muscle cells. 

Based on the modest ability of the (+)-isomers of MDMA and MBDB to inhibit the reuptake of norepinephrine (NE) into hypothalamic synaptosomes (Steele et al. 1987). it seemed possible that noradrenergic pathways might be involved in the eue. In ano er series of drug discrimination experiments designed to test this hypothesis, the specific NE uptake inhibitor (-)-tomoxctine was tested for stimulus transfer in doses up to 10 mg/kg in MDMA-trained rats. At 5 mg/kg, 67 percent of the animals responded on, the drug lever. However, pretreatment with tomoxetine in six rats trained to discriminate MDMA from saline had no effect on the discrimination of a subsequent dose of MDMA. 

In an attempt to simulate in rats the dosage regimen commonly employed by abusers of amphetamines, METH was administered (10 or 15 mg/kg every 6 hours four to six doses), after which the animals were killed (Koda and Gibb 1971 Koda and Gibb 1973). TH activity and catecholamine con-eentrations were measured in various brain regions and in the adrenal. Neostriatal TH aetivity was depressed in a dose-dependent manner and reaehed its nadir at 36 hours. Dopamine (DA) and norepinephrine concentrations were initially elevated, but then deereased in parallel with TH aetivity. Adrenal TH aetivity was elevated, presumably because of stress assoeiated with the toxie doses of METH. 

In contrast, following a treatment regimen of 20 mg/kg MDMA, there were no significant differences in the density of [3H]mazindol-labeled norepinephrine (NE) uptake sites (fmol/mg protein) in the frontal cerebral cortex between saline-treated (159 17) and MDMA-treated (152 5) animals. With respect to the dose of MDMA, serotonin levels appeared to be more readily decreased (45 percent reduction at 5 mg/kg), while comparable reductions in 5-HlAA levels and serotonin uptake sites were noted only at 10 or 20 mg/kg MDMA. This apparent discrepancy among the three serotonergic markers measured in the present study may relate to effects of lower doses of MDMA on synthetic enzyme activity (i.e., TPH), whereas the effects of higher doses of MDMA in reducing all three markers may relate in part to effects on TPH activity and in part to destruction of serotonin neurons as evidenced by decreases in serotonin uptake sites. 

MDMA produced a dose-related depletion of serotonin without altering the eoncentration of either dopamine or norepinephrine in the monkey brain (table 1). Even the lowest dose of MDMA produced a substantial depletion... 

Dopamine—2.5-20 mcg/kg/min continuous IV infusion. May require doses >10 mcg/kg/min for adequate BP response ° Norepinephrine—start at 4 mcg/min and titrate to desired effect... 

Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin have been used with some success in the treatment of IBS-related pain (Table 18-5). They modulate pain principally through their effect on neurotransmitter reuptake, especially norepinephrine and serotonin. Their helpfulness in functional gastrointestinal disorders seems independent of mood-altering effects normally associated with these agents. Low-dose TCAs (e.g., amitriptyline, desipramine, or doxepin 10 to 25 mg daily) may help patients with IBS who predominantly experience diarrhea or pain. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Norepinephrine is a potent a-adrenergic agent with less pronounced P-adrenergic activity. Doses of 0.01 to 3 mcg/kg per minute can reliably increase blood pressure with small changes in heart rate or cardiac index. Norepinephrine is a more potent agent than dopamine in refractory septic shock.24,27-28... 

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