Compatibility With Commonly Used Intravenous Fluids: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit. Blood pressure should be monitored during and after completion of the infusion or IV injections. Some labetalol side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Metabolic Disorders: Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8 of 100 patients; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency. nehi.info alfuzosin
Diabetes patients - Trandate tablets may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine. Do not suddenly stop using Trandate without first checking with your doctor. Suddenly stopping Trandate may result in chest pain or temporary symptoms such as shaking, sweating, headache, irregular heartbeat, and general unwell feeling. If your doctor decides that you should stop using Trandate, your dosage should be reduced over a period of 1 to 2 weeks and you should be carefully monitored. Caution should be exercised when labetalol HCl tablets are administered to a nursing woman.
HCl and a molecular weight of 364. Beta 2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure. Both the alpha-and beta-blocking actions of orally administered labetalol HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl consistently, in dose-related fashion, blunted increases in exercise-induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol HCl dosing. Dizziness; indigestion; lightheadedness; nausea; stuffy nose; temporary tingling of the scalp; unusual tiredness.
How should I take Trandate labetalol? The absolute bioavailability of labetalol is increased when administered with food. Cardiovascular: Hypotension, and rarely, syncope, bradycardia, heart block.
Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur. Clinical Laboratory Tests: Among patients dosed with TRANDATE Tablets, there have been reversible increases of serum transaminases in 4% of patients tested and, more rarely, reversible increases in blood urea. Yellow No. 6 100- and 300-mg tablets only hydroxypropyl methylcellulose, lactose, magnesium stearate, pregelatinized corn starch, sodium benzoate 200-mg tablet only talc 100-mg tablet only and titanium dioxide. General: Impaired Hepatic Function: Trandate Injection should be used with caution in patients with impaired hepatic function since metabolism of the drug may be diminished. Trandate tablets may cause drowsiness, dizziness, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Trandate tablets with caution. Gastrointestinal System: Nausea in 13, vomiting in 4, dyspepsia and taste distortion in 1 each. This type of antagonism can be observed when cocaine is administered to animals under the influence of general anesthetics, which enhance the effects of GABA-A in the CNS. Due to the alpha 1-receptor blocking activity of labetalol HCl, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension can occur. During dosing with IV labetalol HCl, the contribution of the postural component should be considered when positioning the patient for treatment, and the patient should not be allowed to move to an erect position unmonitored until his ability to do so is established. Tell the doctor if you notice symptoms in your newborn. This medication passes into breast milk, and the effect on a nursing infant is unknown. Consult your doctor before breastfeeding. Hematologic: Agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura. You may have a lot of hair loss 1 to 3 months after severe physical or emotional stress. Your hair usually will grow back within a few months. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol HCl during investigational use and extensive foreign marketing experience. Beta-adrenergic receptor blocking agents aka beta-blockers in general should not be used in patients with overt congestive heart failure CHF. Sympathetic stimulation may be important in maintaining the hemodynamic function in these patients, thus beta-blockade can worsen the heart failure. LL 400” on one side and blank on the other.
Your medicine comes as round, orange film-coated tablets. Labetalol has been used to treat in women. It is important to control for the health of the mother and unborn baby. This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use. Liver and Biliary System: Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests. To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position. Potential Adverse Effects: In addition, other adverse effects not listed above have been reported with other beta-adrenergic blocking agents. Keep this medicine out of the sight and reach of children. Diabetes patients - Trandate tablets may hide signs of low blood sugar, such as a rapid heartbeat. Be sure to watch for other signs of low blood sugar. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your vision change; give you a headache, chills, or tremors; or make you more hungry. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery. Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Angina pectoris has not been reported upon labetalol HCl discontinuation. However, hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. geodon
HCl caused further dose-related decreases in blood pressure. No. 2 aluminum lake. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol HCl. If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Check with your doctor or pharmacist if you are not sure. Trandate is to be used only by the patient for whom it is prescribed. Do not share it with other people. If angina markedly worsens or acute coronary insufficiency develops, therapy with Trandate Tablets should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with Trandate Tablets abruptly in patients being treated for hypertension. Do not take more Trandate than you should. Do not skip doses or stop taking labetalol without first talking to your doctor. Stopping suddenly may make your condition worse. Scalp tingling may occur as your body adjusts to Trandate. Rate of infusion: The rate of infusion of the diluted solution may be adjusted according to the blood pressure response, at the discretion of the physician. Pharmacokinetics and Metabolism: Labetalol HCl is completely absorbed from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The relative bioavailability of labetalol HCl tablets compared to an oral solution is 100%. The absolute bioavailability fraction of drug reaching systemic circulation of labetalol when compared to an intravenous infusion is 25%; this is due to extensive “first-pass” metabolism. If the patient has laboratory evidence of liver injury or jaundice, labetalol should be stopped and not restarted. Labetalol belongs to a family of medicines known as betablockers. Impaired Hepatic Function: Labetalol HCl tablets should be used with caution in patients with impaired hepatic function since metabolism of the drug may be diminished.
Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Trandate tablets while you are pregnant. Trandate tablets are found in breast milk. If you are or will be breast-feeding while you use Trandate tablets, check with your doctor. Discuss any possible risks to your baby. Labetalol HCl Tablets, USP 300 mg are available as round, blue, film-coated tablets debossed with “ WATSON 607” on one side and plain on the other side. They are supplied in bottles of 100, 500, 1000. AU second and third trimester UK, US: This drug should be used during pregnancy only if the benefit outweighs the risk. Manufactured by Faulding Puerto Rico, Inc. Pharmacodynamics: The capacity of labetalol HCl to block alpha receptors in man has been demonstrated by attenuation of the pressor effect of phenylephrine and by a significant reduction of the pressor response caused by immersing the hand in ice-cold water “cold-pressor test”. Labetalol HCl's beta 1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta 2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure. Both the alpha- and beta-blocking actions of orally administered labetalol HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl consistently, in dose-related fashion, blunted increases in exercise-induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol HCl dosing. Use Trandate tablets with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness, lightheadedness, or fainting. Since the full antihypertensive effect of labetalol HCl is usually seen within the first 1 to 3 hours of the initial dose or dose increment, the assurance of a lack of an exaggerated hypotensive response can be clinically established in the office setting. The antihypertensive effects of continued dosing can be measured at subsequent visits, approximately 12 hours after a dose, to determine whether further titration is necessary. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Laboratory Test Interactions: The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid when measured by fluorimetric or photometric methods. This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Central Nervous System: Reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on psychometrics. This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your with you, and share the list with your doctor and pharmacist. cheapest oxytrol purchase now pharmacy
Ask your pharmacist about using those products safely. It is not known whether labetalol will harm an unborn baby. Labetalol may cause heart or lung problems in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while taking labetalol. Either of two methods of administration of Trandate Injection may be used: a repeated IV injection, or b slow continuous infusion. Side Effects List Trandate side effects by likelihood and severity. DOSAGE MUST BE INDIVIDUALIZED. The recommended initial dosage is 100 mg twice daily whether used alone or added to a diuretic regimen. If needed, the total daily dose may be given in three divided doses. Important: The opinions expressed in WebMD User-generated content areas like communities, reviews, ratings, blogs, or WebMD Answers are solely those of the User, who may or may not have medical or scientific training. These opinions do not represent the opinions of WebMD. User-generated content areas are not reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other reason except for compliance with our Terms and Conditions. Patients should always be kept in a supine position during the period of IV drug administration. A substantial fall in blood pressure on standing should be expected in these patients. The patient's ability to tolerate an upright position should be established before permitting any ambulation, such as using toilet facilities. Drinking alcohol can further lower your blood pressure and may increase certain side effects of labetalol. Results of this survey indicate that the type, severity, and incidence of adverse effects were comparable to those cited above. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. Figure 1. Because prazosin is selective for inhibiting α 1 adrenergic receptors, it will lower arterial blood pressure by blocking postsynaptic α 1 receptors on arterial smooth muscle.
Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life. L-type Ca channels, and b “local anesthetic” effects on vascular smooth muscle resulting in vasodilation. Cocaine also does not typically produce an increase in heart rate under general anesthesia. This drug may rarely cause serious rarely fatal disease. Perinatal and neonatal distress bradycardia, hypotension, respiratory depression, hypoglycemia, hypothermia has been rarely reported. Initiation of Dosing With TRANDATE Tablets: Subsequent oral dosing with TRANDATE Tablets should begin when it has been established that the supine diastolic blood pressure has begun to rise. The recommended initial dose is 200 mg, followed in 6 to 12 hours by an additional dose of 200 or 400 mg, depending on the blood pressure response. The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables. Dizziness; indigestion; lightheadedness; nausea; pain, swelling, or redness at the injection site; stuffy nose; temporary tingling of the scalp; unusual tiredness. It works by blocking the action of certain natural chemicals in your body such as on the and vessels. Single oral doses of labetalol HCl administered to patients with coronary artery disease had no significant effect on sinus rate, intraventricular conduction, or QRS duration. The atrioventricular A-V conduction time was modestly prolonged in two of seven patients. In another study, IV labetalol HCl slightly prolonged A-V nodal conduction time and atrial effective refractory period with only small changes in heart rate. The effects on A-V nodal refractoriness were inconsistent. If you miss a dose of Trandate tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. Severe allergic reactions rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness; chest pain; dark urine; decreased sexual ability; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes eg, depression; muscle pain or tenderness; pale stools; persistent cough; persistent loss of appetite; right upper stomach pain; severe or persistent dizziness; shortness of breath; swelling of the hands or feet; unexplained or sudden weight gain; unusual bruising or bleeding; weakness; wheezing; vision changes; yellowing of the skin or eyes. Labetalol is not approved for use by anyone younger than 18 years old. It also widens the arteries in the body. If cardiac failure continues despite adequate digitalization and diuretic, therapy with Trandate Injection should be withdrawn gradually, if possible. Major Surgery: Do not routinely withdraw chronic beta blocker therapy prior to surgery. Carvedilol, specifically, is indicated for use with these agents in the treatment of mild to severe heart failure of ischemic or cardiomyopathic origin. There is also increasing evidence that the addition of a beta-blocker to standard therapy can improve morbidity and mortality in patients with advanced heart failure, although it is uncertain whether effectiveness varies significantly with the different agents. Data from one meta-analysis study suggest a greater reduction of mortality risk for nonselective beta-blockers than for beta-1 selective agents. target brand generic alavert
Since the half-life of this drug is 5 to 8 hours, steady-state blood levels in the face of a constant rate of infusion would not be reached during the usual infusion time period; the infusion should be continued until a satisfactory response is obtained and should then be stopped and the oral formulation should be started. Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first. The opinions expressed in WebMD User-generated content areas like communities, reviews, ratings, or blogs are solely those of the User, who may or may not have medical or scientific training. These opinions do not represent the opinions of WebMD. User-generated content areas are not reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other reason except for compliance with our Terms and Conditions. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended. When patients being treated with labetalol have a positive urine test for amphetamine using these techniques, confirmation should be made by using more specific methods, such as a gas chromatographic-mass spectrometer technique. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. Should side effects principally nausea or dizziness occur with these doses administered twice daily, the same total daily dose administered three times daily may improve tolerability and facilitate further titration. Titration increments should not exceed 200 mg twice daily. The injection solution is intended for IV use in hospitalized patients. Information for Patients: As with all drugs with beta-blocking activity, certain advice to patients being treated with labetalol HCl is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. While no incident of the abrupt withdrawal phenomenon exacerbation of angina pectoris has been reported with labetalol HCl, dosing with Trandate Tablets should not be interrupted or discontinued without a physician's advice. Food and Drug Administration. WebMD does not endorse any specific product, service, or treatment. Do not consider WebMD User-generated content as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare provider because of something you have read on WebMD. You should always speak with your doctor before you start, stop, or change any prescribed part of your care plan or treatment. WebMD understands that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified health care provider. If you think you may have a medical emergency, call your doctor or dial 911 immediately. Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type. Zimmerman, 1985. In addition prazosin has no effect on the presynaptic α 2 receptors in sympathetic nerve endings that innervate the heart. As a result, any changes in sympathetic tone to the heart are minimized due to activation of negative feedback. In contrast, the blood pressure lowering effects of non-selective alpha blockers, such as phentolamine, are associated with a marked reflex tachycardia due to blunting of inhibitory presynaptic α 2 feedback that suppresses the release of norepinephrine when synaptic levels of the neurotransmitter rise. As with all drugs with beta-blocking activity, certain advice to patients being treated with labetalol HCl is warranted. While no incident of the abrupt withdrawal phenomenon exacerbation of angina pectoris has been reported with labetalol HCl, dosing with TRANDATE Tablets should not be interrupted or discontinued without a physician's advice.
Labetalol HCl produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, presumably through a mixture of its alpha- and beta-blocking effects. Hemodynamic effects are variable, with small, nonsignificant changes in cardiac output seen in some studies but not others, and small decreases in total peripheral resistance. Elevated plasma renins are reduced. Pheochromocytoma: Labetalol HCl has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol HCl to patients with pheochromocytoma. Keep this leaflet. You may need to read it again. While in the hospital, the dosage of the tablets may be increased at 1 day intervals to achieve the desired blood pressure reduction. This drug may reduce flow to your hands and feet, causing them to feel cold. may worsen this effect. Dress warmly and avoid use. Store at room temperature away from moisture and heat. Due to the alpha 1-receptor blocking activity of labetalol HCl, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension 2% including rare instances of syncope, can occur. Following oral administration, when postural hypotension has occurred, it has been transient and is uncommon when the recommended starting dose and titration increments are closely followed see . Symptomatic postural hypotension is most likely to occur 2 to 4 hours after a dose, especially following the use of large initial doses or upon large changes in dose. hydroxyzine
For these reasons, FAERS case reports cannot be used to calculate incidence or estimates of risk for a particular product or compare risks between products. What brand names are available for labetalol? Laboratory Tests: Routine laboratory tests are ordinarily not required before or after IV labetalol HCl. In patients with concomitant illnesses, such as impaired renal function, appropriate tests should be done to monitor these conditions. Labetalol HCl Tablets, USP 100 mg are available as round, beige, film-coated tablets debossed with “ WATSON 605” on one side and scored on the other side. They are supplied in bottles of 100, 500, 1000. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist. Store in a dry place below 25oC. AU: Contraindicated during the first trimester of pregnancy. Hair styling and products. Pulling your hair back too tightly or wearing tight braids or ponytails can cause hair loss. You may lose hair around the edge of the hairline, especially around the face and forehead. Using curling irons or dyes a lot can also result in hair loss. Hair usually grows back when you stop doing these things. The starting dose is 50 mg twice a day. If cardiac failure continues despite adequate digitalization and diuretic, therapy with labetalol HCl tablets should be withdrawn gradually, if possible. Losing a lot of more than 100 hairs a day can be caused by inherited factors, disease, stress, medicines, injury, aging, or care. If you need surgery, tell the surgeon ahead of time that you are using labetalol. Use in children: Labetalol should not be given to children. The rate of infusion of the diluted solution may be adjusted according to the blood pressure response, at the discretion of the physician. Labetalol HCl is a white or off-white crystalline powder, soluble in water.
DOSAGE MUST BE INDIVIDUALIZED. The most common cause of is genetics-you inherit the tendency to lose hair from either or both of your parents. This is called male-pattern or female-pattern hair loss. What should I discuss with my healthcare provider before taking Trandate labetalol? Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required. Tablets Product Information for details. Certain of the side effects increased with increasing oral dose, as shown in the following table that depicts the entire US therapeutic trials data base for adverse reactions that are clearly or possibly dose related. If cardiac failure continues despite adequate digitalization and diuretic, therapy with Trandate Tablets should be withdrawn gradually, if possible. cytotec online prescription
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Body as a Whole: Fever. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication not have serious side effects. Use Trandate with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness, lightheadedness, or fainting.
R' stereoisomer, makes up 25% of racemic labetalol. Steady-state plasma levels of labetalol during repetitive dosing are reached by about the third day of dosing. In patients with decreased hepatic or renal function, the elimination half-life of labetalol is not altered; however, the relative bioavailability in hepatically impaired patients is increased due to decreased "first-pass" metabolism. Do I need a prescription for labetalol? This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects.
When a diuretic is added, an additive antihypertensive effect can be expected. In some cases this may necessitate a labetalol HCl dosage adjustment. As with most antihypertensive drugs, optimal dosages of labetalol HCl tablets are usually lower in patients also receiving a diuretic. Labetalol can pass into breast milk in small amounts. Tell your doctor if you are breast-feeding. Most adverse effects are mild and transient and occur early in the course of treatment. In controlled clinical trials of 3 to 4 months' duration, discontinuation of Trandate Tablets due to one or more adverse effects was required in 7% of all patients. In these same trials, other agents with solely beta-blocking activity used in the control groups led to discontinuation in 8% to 10% of patients, and a centrally acting alpha-agonist led to discontinuation in 30% of patients.
Central and Peripheral Nervous Systems: Paresthesia, most frequently described as scalp tingling. In most cases, it was mild and transient and usually occurred at the beginning of treatment. Our Trandate labetalol Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. IV administration, respectively. Beta 2-agonist activity has been demonstrated in animals with minimal beta 1-agonist ISA activity detected. In animals, at doses greater than those required for alpha- or beta-adrenergic blockade, a membrane stabilizing effect has been demonstrated.