Mianserin

/SIGNS AND SYMPTOMS/ Although cardiac arrhythmias with mianserin use are unusual, life-threatening ventricular arrhythmias including polymorphous ventricular tachycardia following an over dose with an unknown amount of mianserin were associated with serum therapeutic concentration 20 to 50 times the therapeutic value. The therapeutic concentration of mianserin (plus desmethylmianserin) is 100 ng/ml and serious toxicity has been associated with concentrations above 500 mg/ml.

/CASE REPORTS/ Four cases are described in which the drug mianserin was implicated in the development of leucopenia. In one case this was accompanied by fatal aplastic anaemia. In a second, generalized bone marrow depression occurred, although leucopenia was the only clinically significant manifestation. Mianserin may depress bone marrow function and haematological surveillance is appropriate for patients taking this drug.

/CASE REPORTS/ An acute episode of symptomatic sinus bradycardia, occurred in a 50-year-old female patient after she had been given a single therapeutic dose of mianserin. Heart rate was corrected by atropine injection. Re-administration of mianserin resulted in the recurrence of bradycardia. Further examination showed no cardiac abnormalities. This case is the first report of conduction defect in a patient given therapeutic doses of mianserin.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

LD50 Mouse (male) oral 365 mg/kg /Mianserin hydrochloride/

LD50 Mouse (female) oral 390 mg/kg /Mianserin hydrochloride/

LD50 Mouse (male) iv 32.5 mg/kg /Mianserin hydrochloride/

LD50 Mouse (female) iv 31.0 mg/kg /Mianserin hydrochloride/

Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.

A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake.

Absorbed following oral administration.

A pharmacokinetic study with mianserin HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin HCl in 1 hr, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 hr following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 L/hr (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 L, the steady-state volume of distribution 242 +/- 171 L and the elimination half-life 33 +/- 5 hr. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng/mL and for the tablets 54 +/- 5 ng /mL; mean peak time for the solution was 1.1 +/- 0.2 hr and for the tablets 1.4 +/- 0.2 hr. The mean absorption half-life for the solution was 0.43 +/- 0.13 hr and for the tablets 0.39 +/- 0.11 hr.

We studied mianserin kinetics after a single (60 mg) dose in eight inpatients suffering from depression. There was a considerable interpatient variability in plasma levels. Mean peak plasma levels (+/- SEM) were 114 +/- 26 ng/ml and were reached between 1 and 3 hr. The decline of mianserin levels in plasma was biphasic. The mean elimination t 1/2 was 21.6 +/- 3.1 hr and ranged from 10.7 to 40.8 hr. The estimated first-pass loss ranged from 26% to 48% (mean, 37%) and was lower than that reported for tertiary amine tricyclic antidepressants. The mean apparent volume of distribution (15.7 +/- 2.2 L/kg; 9.7 to 28.8 L/kg) was in the range of that for imipramine but somewhat lower than for maprotiline. Apparent total body clearance ranged from 0.33 to 0.81 L/hr/kg (mean +/- SEM, 0.52 +/- 0.05 L/hr/kg) and was of the order of that after maprotiline. Our results indicate that mianserin kinetics are in most respects similar to those of tertiary amine tricyclic antidepressants (e.g., imipramine) and the tetracyclic maprotiline.