Olanzapine

Brand Canonpharma

In stock 758 Items

Available since: 2019-09-19

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Clinical Pharmacology

Pharmacotherapeutic group: antipsychotic (neuroleptic)

ATX code: N05AH03

Pharmacological properties

Pharmacodynamics
Olanzapine is an antipsychotic (neuroleptic) with a broad pharmacological spectrum of effects on a number of receptor systems. The affinity of olanzapine to serotonin 5-NT was established.₂a / s, 5NTz, 5NTb; dopamine D_b D2, Dz, D4, D₅; Muscarinic M1.5; adrenergic alpha1 and histamine Hi receptors. In animal experiments, the presence of olanzapine antagonism with respect to 5HT, dopamine and cholinergic receptors was detected. In vitro and in vivo, olanzapine has a more pronounced affinity and activity for serotonin 5HT2 receptors, compared to dopamine D2 receptors. Olanzapine reduces the conditioned defensive reflex (a test that characterizes antipsychotic activity) at doses lower than the doses that cause catalepsy (a disorder reflecting a side effect on motor function). Unlike other neuroleptics, olanzapine enhances the anti-anxiety effect during an "anxiolytic" test.
Olanzapine provides a statistically significant reduction of both productive (delusions, hallucinations, etc.) and negative disorders.
Pharmacokinetics
Absorption and bioavailability: after oral administration, olanzapine is well absorbed and its maximum concentration (C_max) in plasma is achieved in 5-8 hours. The absorption of olanzapine does not depend on food intake. The concentration of olanzapine in plasma varies linearly and proportionally to the dose.
Distribution: at a plasma concentration of 7 to 1000 ng / ml, about 93% of olanzapine binds to proteins, mainly albumin and alpha-acid glycoprotein. The major circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the blood-brain barrier.
Metabolism: olanzapine is metabolized in the liver as a result of conjugation and oxidation. CYP1A2 and CYP2D6 isoenzymes of cytochrome P450 are involved in the formation of N-desmethyl and 2-hydroxymethyl olanzapine metabolites. CYP2D6 cytochrome P450 isoenzyme activity does not affect the level of olanzapine metabolism. Both metabolites in animal studies had significantly less pronounced pharmacological activity in vivo than olanzapine. The main pharmacological activity of the drug is due to the starting material, olanzapine, the activity of its metabolites is less pronounced.
Excretion: when administered orally, the average half-life (T1 / 2) is 33 hours. Plasma clearance of olanzapine is 26 l / h.
The pharmacokinetic parameters of olanzapine vary depending on smoking, gender and age.

Indications

Schizophrenia in adults. Olanzapine Canon is indicated for the treatment of exacerbations, supportive and long-term anti-relapse therapy of patients with schizophrenia.
Bipolar affective disorder in adults. The drug Olanzapine Canon in the form of monotherapy or in combination with lithium or valproic acid is indicated for the treatment of acute manic or mixed episodes in bipolar affective disorder with / without psychotic manifestations and with / without rapid phase change. The drug Olanzapine Canon is indicated for the prevention of relapse in patients with bipolar disorder, in whom olanzapine was effective in the treatment of the manic phase.
In combination with fluoxetine, olanzapine canon is indicated for the treatment of depressive conditions associated with bipolar disorder.
Therapeutically Resistant Depression
In combination with fluoxetine, olanzapine canon is indicated for the treatment of therapeutically resistant depression in adult patients (major depressive episodes if there is an ineffective use of two antidepressants with a dose and duration of therapy that are adequate to this episode

Composition

1 tablet, film coated, 5 mg contains:
active ingredient: olanzapine 5 mg;
excipients: hyprolose (hydroxypropylcellulose) low-substituted 2.5 mg, calcium hydrogen phosphate 40 mg, croscarmellose sodium 1 mg, mannitol 50.5 mg, magnesium stearate 1 mg;
film coating composition: opadry II yellow 3 mg, including: polyvinyl alcohol 1.2 mg, macrogol (polyethylene glycol) 0.606 mg, talc 0.444 mg, titanium dioxide 0.705 mg, iron dye yellow oxide 0.045 mg

Olanzapine is marketed under different brands and generic names, and comes in different dosage forms:

Brand name	Manufacturer	Country	Dosage form
Olanzapine	Canonpharma	Russia	pills
Olanzapine	North Star	Russia	pills
Zalasta Q-tab	Krka dd Novo mesto AO	Slovenia	lozenges
Zalasta	Krka dd Novo mesto AO	Slovenia	pills
Zyprexa	Eli lilly	USA	pills
Zyprexa Zydis	Eli lilly	USA	pills

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Dosage and Administration

Orally, regardless of the meal.
The recommended therapeutic dose of olanzapine canon is from 5 mg to 20 mg per day. The daily dose must be selected individually depending on the patient’s clinical condition.
Schizophrenia in adults. The recommended initial dose of the drug Olanzapine Canon is 10 mg once a day.
Acute mania for bipolar disorder in adults. The recommended initial dose of the drug Olanzapine Canon is 15 mg once a day as monotherapy or 10 mg once a day in combination with lithium or valproic acid.
Supportive care for adults with bipolar disorder. The recommended initial dose of the drug Olanzapine Canon is 10 mg once a day. Patients receiving olanzapine canon for the treatment of acute mania are advised to continue maintenance therapy at the same dose.
Depression in the framework of bipolar disorder in adults. Olanzapine Canon in combination with fluoxetine should be administered once a day, in the evening. The initial dose is 5 mg of olanzapine and 20 mg of fluoxetine.
Antidepressant activity was confirmed when using olanzapine in a dose of 6–12 mg (average daily dose — 7.4 mg) and fluoxitin at a dose of 25–30 mg (average daily dose —39.3 mg). If necessary, changes in dosages of both olanzapine and fluoxetine are allowed.
Therapeutic resistant depression. The drug Olanzapine Canon should be administered in combination with fluoxetine 1 time per day, in the evening. The initial dose is 5 mg of olanzapine and 20 mg of fluoxetine. If necessary, changes in dosages of both olanzapine and fluoxetine are allowed.
Special patient groups
In elderly patients, a reduction in the initial dose (up to 5 mg per day) is usually not recommended, but it is possible in patients over 65 years of age with risk factors (see the section "Special Instructions").
Patients with liver and / or kidney diseases are recommended to reduce the initial dose to 5 mg / day. In moderate liver failure (cirrhosis, class A and B according to Child-Pugh hepatocellular insufficiency in patients with liver cirrhosis), the initial dose is 5 mg / day, a further increase in dose with caution is possible.
Women do not require changes in dosage compared with men.
In non-smoking patients, dose adjustment compared to smokers is not required. A reduction in the initial dose may be recommended for patients with a combination of factors (female, elderly, non-smoker) who can slow down the metabolism of olanzapine.

Adverse reactions

Classification of the incidence of side effects (WHO):
very often> 10%
often <10% and> 1%
infrequently <1% and> 0.1%
rarely <0.1% and> 0.01%
very rarely - <0.01% including individual messages

Violations of the blood and lymphatic system
often: eosinophilia;
infrequently: leukopenia, neutropenia;
rarely: thrombocytopenia;
Immune system disorders
very rarely: allergic reactions (anaphylactic shock, angioedema, pruritus, urticaria);
Metabolic disorders
very rarely: development or decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis and diabetic coma, including fatal; after discontinuation of therapy, after 9-12 months of treatment, a decrease in blood glucose concentration is possible;
Metabolic and nutritional disorders
very often: weight gain;
often: increased cholesterol, triglycerides, glycosuria, increased appetite;
A change in glucose concentration from normal fasting values (<5.5b mmol="" l="" to="" elevations=""> 7 mmol / l) is often observed. The change in glucose concentration from borderline values (> 5.5b mmol / l - <7 mmol="" l="" to="" elevated=""> 7 mmol / l) is observed very often;
very rarely: hypertriglyceridemia, hypercholesterolemia; frequency not known: abdominal distension;
Disturbances of the nervous system very often: drowsiness;
often: dizziness, akathisia, parkinsonism, dyskinesia;
infrequently: spasms (more often against the background of a convulsive syndrome in the anamnesis);
very rarely: neuroleptic malignant syndrome, dystonia (including oculogy crisis), tardive dyskinesia, "withdrawal" syndrome (sweating, insomnia, tremor, anxiety, nausea or vomiting);
Heart disorders
infrequently: bradycardia, prolongation of the QT interval;
very rarely: ventricular tachycardia / ventricular fibrillation, sudden death;
Vascular disorders are often: orthostatic hypotension;
very rarely: pulmonary embolism, deep vein thrombosis;
Disorders of the gastrointestinal tract
often: transient anticholinergic effects, including dry mouth, constipation; rarely: pancreatitis;
Disorders of the liver and biliary tract
often: transient increases in liver transferase activity (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), especially in the early period of the study;
rarely: hepatitis (including hepatocellular, hepatocellular, or mixed).
Violations of the skin and subcutaneous tissue
often: skin rash;
infrequently: photosensitivity reactions;
very rarely: alopecia;
Disorders of the musculoskeletal and connective tissue
rarely: rhabdomyolysis;
frequency not known: arthralgia;
Kidney and urinary tract disorders
infrequently: urinary incontinence;
seldom: delayed urination;
Frequency unknown: increased uric acid;
Disorders of the genitals and breast
rarely: priapism.
General disorders and disorders at the site of administration
often: asthenia, fatigue, swelling;
rarely: hypothermia;
frequency not known: fever;
Laboratory and instrumental data
very often: an increase in plasma prolactin concentration, but clinical manifestations (for example, gynecomastia, galactorrhea, and an increase in the mammary glands) are rare. In most patients, prolactin levels spontaneously returned to normal without discontinuing the drug;
often: an increase in the activity of creatine phosphokinase (CPK), total bilirubin;
very rare: increased alkaline phosphatase activity.
Unwanted effects in specific therapeutic groups
A very frequent (> 10%) undesirable effect when using olanzapine in patients with psychosis on the background of dementia is gait disturbance and a fall. Urinary incontinence and pneumonia are common (<10% and> 1%) undesirable effects when using olanzapine in elderly patients with psychosis on the background of dementia.
In patients with psychosis induced by taking the dopamine receptor agonist drug in Parkinson's disease, an increase in the symptoms of parkinsonism is very often observed. Also in this group of patients hallucinations are very often observed. In patients with bipolar mania receiving olanzapine in combination with lithium or valproic acid, very frequent undesirable effects are weight gain, dry mouth, increased appetite, tremors, and frequent speech disorders.
Data on the side effects of the drug according to the results of clinical studies:
In clinical trials, cases of parkinsonism and dystonia in patients taking olanzapine were more frequent, but the difference with the placebo group was not statistically significant.
In patients treated with olanzapine, cases of parkinsonism, akathisia, and dystonia were observed less frequently than in patients who received titrated doses of haloperidol. Due to the lack of such information about the presence of acute and late dyskinesias in the history of patients, it is currently not possible to conclude that olanzapine causes the development of late dyskinesias or other late extrapyramidal syndromes to a lesser extent.
In clinical studies with a duration of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal in approximately 30% of patients with normal baseline prolactin levels. In most of these patients, an increase in prolactin concentration was moderate, and less than 2 times the upper limit of normal. In patients taking olanzapine, disorders of the genital organs and the mammary gland, possibly associated with olanzapine intake (aminorea, breast enlargement, galactorrhea in women, gynecomastia and breast enlargement in men) were rare. Sexual dysfunction, possibly associated with taking olanzapine (erectile dysfunction in men, decreased libido in men and women), was observed frequently.

Contraindications

Hypersensitivity to any of the components of the drug
At risk of developing glaucoma
Angle-closure glaucoma
Under 18 years old (effectiveness and safety not proven)
Breastfeeding period

Drug interactions

The metabolism of olanzapine can be altered by the action of inhibitors or inducers of cytochrome P450 isoenzymes, showing specific activity against the CYP1A2 isoenzyme. The clearance of olanzapine is increased in smoking patients and in patients taking carbamazepine (due to an increase in the activity of the CYP1A2 isoenzyme). Known potential inhibitors of the CYP1A2 isoenzyme can reduce the clearance of olanzapine. Olanzapine is not a potential inhibitor of CYP1A2 isoenzyme activity; therefore, when taking olanzapine, the pharmacokinetics of drugs, such as theophylline, which are mainly metabolized with the participation of the isoenzyme CYP1A2, do not change.
In clinical studies, it was shown that a single dose of olanzapine during therapy with the following drugs is not accompanied by suppression of the metabolism of the following drugs: imipramine or its metabolite desipramine (CYP2D6, CYP3A, CYP1A2), warfarin (CYP2C19), theophylline (CYP1A2), or diafamine diafamine (CYP2C19), theophylline (CYP1A2), or diafamine diazepamum diamepamum or diazepamam diamam. CYP2C19). There are no signs of drug interactions when using olanzapine in combination with lithium preparations or biperiden. Against the background of a stable concentration of olanzapine, there is no change in ethanol pharmacokinetics. However, taking ethanol with olanzapine. may be accompanied by increased pharmacological effects of olanzapine, for example, a sedative effect. A single dose of aluminum - or magnesium-containing antacid or cimetidine does not violate the bioavailability of olanzapine when administered. The simultaneous use of activated carbon reduces the bioavailability of olanzapine when administered orally to 50-60%. Fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in the maximum concentration of olanzapine on average by 16% and a decrease in the clearance of olanzapine on average by 16%. The degree of influence of this factor is significantly inferior to the severity of individual differences in these indicators, so it is usually not recommended to change the dose of olanzapine when it is prescribed in combination with fluoxetine.
Fluvoxamine, an inhibitor of the CYP1A2 isoenzyme, reduces the clearance of olanzapine. The result is an average increase in C_max with fluvoxamine administered by 54% in non-smoking women and 77% in male smokers, the average increase in the area under the pharmacokinetic curve (AUC) of olanzapine is 52% and 108%, respectively. Small doses of olanzapine should be given to patients who are receiving fluvoxamine together.
In vitro studies using human liver microsomes have shown that olanzapine slightly inhibits the formation of valproate glucuronide (the main metabolic pathway of valproic acid). Valproic acid also has little effect on olanzapine metabolism in vitro, so a clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely.
According to in vitro studies using human liver microsomes, olanzapine also demonstrated extremely small potential in suppressing the activity of the following cytochrome P450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A.As with the use of other antipsychotics, when using olanzapine, care should be taken when used with drugs that prolong the QTc interval, as well as affecting the central nervous system.

Pregnancy and Lactation

Pregnancy: due to insufficient experience with olanzapine during pregnancy, the drug Olanzapine Canon should be prescribed during pregnancy only if the potential benefit to the mother greatly exceeds the potential risk to the fetus. Patients should be warned that in the event of the onset or planning of pregnancy during the period of treatment with Olanzapine, Canon must be reported to your doctor. Very rare reports were received that newborns whose mothers took olanzapine in the third trimester of pregnancy, had tremor, muscle hypertension, lethargy, and drowsiness.
Breastfeeding: olanzapine is excreted in breast milk, therefore, during the period of drug therapy with olanzapine canon, breastfeeding should be stopped. The average dosage received by the child (mg / kg) when reaching the equilibrium concentration in the mother is 1.8% of the dose of mother olanzapine (mg / kg).

Special instructions

Clinical improvement may take several days and requires patient monitoring.
Malignant Neuroleptic Syndrome
Malignant neuroleptic syndrome (NNS) (a potentially lethal symptom complex) can develop with any antipsychotic medication, including the drug Olanzapine Canon, however, to date, there is no evidence of a significant association of olanzapine with the development of this condition. Clinical manifestations of neuroleptic malignant syndrome include a significant increase in body temperature, muscle rigidity, changes in mental status and autonomic disorders (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include an increase in creatinine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. Clinical manifestations of a malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms of a malignant neuroleptic syndrome require the discontinuation of all neuroleptics, including the drug Olanzapine Canon.
Late dyskinesia
Treatment with olanzapine is less frequently accompanied by the development of dyskinesia, which requires medical correction than with the use of haloperidol. However, the risk of tardive dyskinesia during long-term neuroleptic therapy should be considered. With the development of signs of tardive dyskinesia, a dose reduction or withdrawal of the drug Olanzapine Canon is recommended. It should be borne in mind that when transferring to the drug Olanzapine Canon, symptoms of tardive dyskinesia may develop as a result of the simultaneous cancellation of previous therapy. Symptoms of tardive dyskinesia may increase or manifest after discontinuation of the drug.
Parkinson's disease
Efficacy when used in Parkinson's disease does not exceed placebo (in order to relieve iatrogenic psychosis). The use of the drug Olanzapine Canon in the treatment of psychosis induced by taking dopamine receptor agonists in Parkinson's disease is not recommended, in these patients there is an increase in symptoms of parkinsonism and hallucination.
Experience in the use of elderly patients with psychosis on the background of dementia
Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including deaths, are observed in elderly patients with psychosis on the background of dementia. In placebo-controlled studies, a higher incidence of cerebrovascular adverse events was observed in patients in the olanzapine group compared with the placebo group.These patients had previous risk factors (cerebrovascular disorders (in history), transient ischemic attack, arterial hypertension, smoking), as well as associated diseases and / or medication associated with time. with cerebrovascular disorders.
The effectiveness of olanzapine in elderly patients with psychosis on the background of dementia has not been established. The main risk factors for increased mortality for this group of patients with olanzapine are age> 80 years, sedation, combined use with benzodiazepines, or the presence of lung disease (for example, pneumonia with or without aspiration). There is not enough data to establish differences in the incidence of cerebrovascular disorders and / or mortality (compared with placebo), and in the risk factors for this group of patients with oral olanzapine and intramuscular injections. The drug Olanzapin Canon is not recommended for the treatment of patients with psychosis on the background of dementia.
Sudden death risk development
Experience with the clinical use of any neuroleptics, including olanzapine, revealed a similar, dose-dependent, twofold increase in the risk of death due to acute heart failure compared with deaths due to acute heart failure in patients not taking antipsychotics.
QT interval length
A clinically significant increase in the QT interval in patients receiving olanzapine was rarely observed in the absence of significant differences with placebo in the incidence of adverse events in the heart. However, as with the use of other antipsychotics, caution is recommended when prescribing Olanzapine Canon in combination with drugs that can prolong the QT interval, especially in elderly patients, with congenital prolongation of the QT interval, with congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.
Postural hypotension
Postural hypotension is rarely observed in elderly patients. As with other antipsychotics, in the case of prescribing the drug Olanzapine Canon, blood pressure control is recommended for patients over 65 years of age.
Thromboembolism
The development of venous thromboembolism during olanzapine therapy is extremely rare. The presence of a causal connection between taking olanzapine and venous thromboembolism has not been established. However, given that patients with schizophrenia often have acquired risk factors for venous thromboembolism, it is necessary to conduct a cumulative assessment of all possible risk factors for the development of this complication, including the immobilization of patients, and to take the necessary preventive measures.
Liver function disorders
In some cases, olanzapine intake, as a rule, in the early stages of therapy is accompanied by a transient, asymptomatic increase in liver transaminases (ACT and ALT) in serum. There are rare cases of hepatitis. In very rare cases, hepatic cholestasis and other mixed liver damage was noted. Special precaution is required when increasing the ACT and / or ALT in serum in patients with liver failure, with limited liver reserve, or in patients receiving treatment with potentially hepatotoxic drugs. In case of an increase in ACT and / or ALT, during treatment with olanzapine, careful monitoring of the patient and, if necessary, a dose reduction of the drug Olanzapine Canon are required. If hepatitis, including hepatocellular, cholestatic or mixed, is detected, Olanzapine Canon should be discontinued.
Hyperglycemia and Diabetes
There is a higher prevalence of diabetes in patients with schizophrenia.As with the use of certain other antipsychotic drugs, hyperglycemia, diabetes mellitus, exacerbation of pre-existing diabetes mellitus, ketoacidosis and diabetic coma were very rarely observed. The cause-effect relationship between antipsychotic drugs and these conditions has not been established. Careful clinical monitoring of patients with diabetes mellitus and patients with risk factors for the development of diabetes is recommended. For all groups of patients, regardless of body mass index, a clinically significant increase in body weight was observed. An increase of 7% or more from the average after a short course of treatment (the average duration was 47 days) was observed very often (22.2%), an increase of 15% or more was frequent (4.2%) and an increase of 25% and more was infrequent (0.8%). In patients receiving longer treatment (at least 48 weeks), an increase of> 7%> 15% and> 25% was very frequent (64.4%, 31.7%, 12.3%, respectively).
Changes in lipid profile
In patients treated with olanzapine, undesirable changes in the lipid spectrum are observed. Recommended lipid profile monitoring and clinical observation.
Epileptic seizures
The drug Olanzapin Canon should be used with caution in patients with epileptic seizures in history or exposed to factors that reduce the threshold of convulsive readiness. In these patients, olanzapine treatment seizures are rare.
Hematologic changes
As with other antipsychotics, caution should be exercised in treating olanzapine in patients with reduced white blood cell count and / or neutrophils in peripheral blood for various reasons; with signs of depression or toxic impairment of bone marrow function under the influence of drugs in history; with inhibition of bone marrow function due to concomitant disease, radiotherapy or chemotherapy in history; with hypereosinophilia or myeloproliferative disease. In clinical studies, the history of olanzapine use in patients with clozapine-dependent neutropenia or agranulocytosis was not accompanied by a recurrence of these disorders. The development of neutropenia was reported mainly in combination therapy with olanzapine and valproic acid.
Anticholinergic activity
Olanzapine therapy is rarely accompanied by anticholinergic side effects. However, clinical experience with olanzapine in patients with comorbidities is limited, so caution is advised when prescribing Olanzapine Canon in patients with clinically significant prostatic hypertrophy, paralytic ileus and similar conditions.
Dopaminergic antagonism
In vitro, olanzapine antagonizes dopamine receptors and, like other antipsychotics, can theoretically suppress the effects of levodopa and dopamine agonists. Total activity against the central nervous system. Given the main effect of olanzapine on the central nervous system, caution should be exercised when using olanzapine in combination with other drugs of central action and alcohol.
Suicide
The risk of a suicidal attempt by patients with schizophrenia and bipolar disorder of the first type is due to these diseases themselves. In this regard, against the background of pharmacotherapy requires careful monitoring of those patients whose risk of suicide is particularly high. When prescribing the drug Olanzapine, Canon should strive to minimize the number of tablets taken by the patient in order to reduce the risk of overdose.
Cancel therapy
In the case of abrupt withdrawal of olanzapine, sweating, insomnia, tremor, nausea and vomiting rarely develop (0.01 - 0.1%).With the abolition of the drug is recommended gradual dose reduction.
Children and teenagers under 18 years old
Olanzapine is not recommended for use in children and adolescents under 18 years of age, due to the lack of sufficient data on efficacy and safety. In short-term studies that were conducted in adolescents 13-17 years old, there was a more significant increase in body weight and changes in the concentration of lipids and prolactin than in similar studies in adults.

Impact on the ability to drive
Patients taking the drug Olanzapine Canon, should be careful when driving and work that requires the speed of psychomotor reactions, since olanzapine can cause drowsiness, dizziness.

Overdosage

Common symptoms: tachycardia, agitation / aggressiveness, articulation disorder, various extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma).
Other clinically significant effects include delirium, convulsions, neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (<2% of overdose cases), cardiac arrest and respiration. The minimum dose for acute overdose with a fatal outcome according to research is 450 mg, the maximum dose for an overdose with a favorable outcome (survival) is 2000 mg.
Treatment: There is no specific antidote for olanzapine. It is not recommended provoking vomiting. Standard overdose procedures (gastric lavage, activated carbon administration) may be indicated. The joint appointment of activated carbon leads to a decrease in the bioavailability of olanzapine when administered to 50-60%. Symptomatic treatment is shown in accordance with the clinical condition and control over the functions of vital organs, including the treatment of arterial hypotension, circulatory disorders and the maintenance of respiratory function. Epinephrine, dopamine and other sympathomimetics, which are beta-adrenoreceptor agonists, should not be used, since stimulation of these receptors may exacerbate hypotension.