Drug Interactions between estradiol topical and succinylcholine

The use of estrogens is contraindicated in patients with undiagnosed, abnormal vaginal bleeding. Prolonged (> 1 year), unopposed estrogen use (i.e. estrogen without concomitant progestin therapy) has been associated with a significant, dose-related risk of endometrial carcinoma. The risk may be offset substantially by the addition of a progestin but may not be completely abolished. Prior to initiating estrogen therapy, appropriate diagnostic tests should be performed in patients with abnormal vaginal bleeding to rule out endometrial malignancy. The same applies if recurrent or persistent bleeding develops during estrogen therapy.

Some neuromuscular blocking agents stimulate the release of histamine, which can cause wheezing, bronchospasm, increased bronchial secretions, hypotension, tachycardia, and circulatory collapse. Hypotension may also occur due to ganglionic blockade or as a complication of positive pressure respiration. Tubocurarine appears to be the most potent inducer of histamine, followed by metocurine (no longer commercially available in the U.S.) and succinylcholine. Other agents with varying but lesser degrees of histamine-releasing properties include atracurium, mivacurium, and pancuronium (at excessive dosages). Therapy with these neuromuscular blocking agents should be administered cautiously in patients with clinically significant cardiovascular disease and/or a history of asthma or severe allergic reactions. Certain agents may prolong the QTc interval, especially during general anesthesia in pediatric patients. The initial dosage and rate of administration may need to be reduced, and hemodynamic and respiratory status carefully monitored. Neuromuscular blocking agents that appear to have little or no histamine-inducing effects include cisatracurium, doxacurium, pipecuronium, rocuronium, and vecuronium.

Some neuromuscular blocking agents stimulate the release of histamine, which can cause wheezing, bronchospasm, increased bronchial secretions, hypotension, tachycardia, and circulatory collapse. Hypotension may also occur due to ganglionic blockade or as a complication of positive pressure respiration. Tubocurarine appears to be the most potent inducer of histamine, followed by metocurine (no longer commercially available in the U.S.) and succinylcholine. Other agents with varying but lesser degrees of histamine-releasing properties include atracurium, mivacurium, and pancuronium (at excessive dosages). Therapy with these neuromuscular blocking agents should be administered cautiously in patients with clinically significant cardiovascular disease and/or a history of asthma or severe allergic reactions. Certain agents may prolong the QTc interval, especially during general anesthesia in pediatric patients. The initial dosage and rate of administration may need to be reduced, and hemodynamic and respiratory status carefully monitored. Neuromuscular blocking agents that appear to have little or no histamine-inducing effects include cisatracurium, doxacurium, pipecuronium, rocuronium, and vecuronium.

When treated with an estrogen, patients with breast cancer and bone metastases may develop severe hypercalcemia, in which case the drug should be stopped and measures be taken to reduce serum calcium levels.

The use of succinylcholine is contraindicated in patients after the acute phase of injury following major burns. These patients are more likely to develop significant hyperkalemia which may lead to cardiac arrest. The risk of hyperkalemia typically peaks at about 7 to 10 days after injury.

Some neuromuscular blocking agents stimulate the release of histamine, which can cause wheezing, bronchospasm, increased bronchial secretions, hypotension, tachycardia, and circulatory collapse. Hypotension may also occur due to ganglionic blockade or as a complication of positive pressure respiration. Tubocurarine appears to be the most potent inducer of histamine, followed by metocurine (no longer commercially available in the U.S.) and succinylcholine. Other agents with varying but lesser degrees of histamine-releasing properties include atracurium, mivacurium, and pancuronium (at excessive dosages). Therapy with these neuromuscular blocking agents should be administered cautiously in patients with clinically significant cardiovascular disease and/or a history of asthma or severe allergic reactions. Certain agents may prolong the QTc interval, especially during general anesthesia in pediatric patients. The initial dosage and rate of administration may need to be reduced, and hemodynamic and respiratory status carefully monitored. Neuromuscular blocking agents that appear to have little or no histamine-inducing effects include cisatracurium, doxacurium, pipecuronium, rocuronium, and vecuronium.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The use of succinylcholine is contraindicated in patients with upper motor neuron injury that can be a sequelae of cerebral vasculopathy. The risk of hyperkalemia is increased in these patients.

The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

The use of succinylcholine is contraindicated in patients with a personal or family history of skeletal muscle myopathies. Acute rhabdomyolysis with hyperkalemia followed by ventricular arrhythmias, cardiac arrest, and death have been reported following the administration of succinylcholine in apparently healthy children who were later found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne muscular dystrophy. Immediate treatment of hyperkalemia should be instituted whenever a healthy appearing infant or child develops cardiac arrest with no obvious cause soon after administration of succinylcholine.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The use of succinylcholine is contraindicated in patients with a personal or family history of skeletal muscle myopathies. Acute rhabdomyolysis with hyperkalemia followed by ventricular arrhythmias, cardiac arrest, and death have been reported following the administration of succinylcholine in apparently healthy children who were later found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne muscular dystrophy. Immediate treatment of hyperkalemia should be instituted whenever a healthy appearing infant or child develops cardiac arrest with no obvious cause soon after administration of succinylcholine.

The use of succinylcholine is contraindicated in patients after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury. has been associated with an elevation in potassium levels due to rapid release of potassium from intracellular sites. Therapy with succinylcholine should be administered cautiously in patients with hyperkalemic states such as extensive soft-tissue trauma, burns, chronic abdominal infections, and subarachnoid hemorrhage.

The risk of myocardial infarction and strokes, including those associated with oral contraceptive use and some estrogen use, is increased in patients with hypertension. Moreover, estrogens (and progestogens) may elevate blood pressure and worsen the hypertension, thus compounding the risk. Clinically significant blood pressure increases have been reported during estrogen therapy, particularly in patients receiving high dosages or treated with oral contraceptive combinations having high progestational activity. These effects also increase with duration of therapy and patient age. Therapy with estrogens should be administered cautiously in patients with preexisting hypertension. Some estrogen-based therapies, such as combined hormonal contraceptives, may be contraindicated in patients with uncontrolled hypertension or hypertension with vascular disease. Patients should be monitored for changes in cardiovascular status, and their antihypertensive regimen adjusted or estrogen therapy withdrawn as necessary. In patients requiring contraception, alternative methods should be considered for those who are hypertensive, over age 35, and smoke.

The use of succinylcholine is contraindicated in patients after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury. has been associated with an elevation in potassium levels due to rapid release of potassium from intracellular sites. Therapy with succinylcholine should be administered cautiously in patients with hyperkalemic states such as extensive soft-tissue trauma, burns, chronic abdominal infections, and subarachnoid hemorrhage.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The use of succinylcholine is contraindicated in patients with a personal or family history of malignant hyperthermia. Succinylcholine administration has been associated with acute onset of malignant hyperthermia, especially during the concomitant use of volatile anesthetics. If malignant hyperthermia occurs, anesthesia should be discontinued and supportive measures rendered promptly, including rapid cooling, inhalation of 100% oxygen, control of acidosis, support of circulation, and assurance of adequate urinary output. In addition, intravenous dantrolene sodium is recommended.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The use of succinylcholine is contraindicated in patients with a personal or family history of skeletal muscle myopathies. Acute rhabdomyolysis with hyperkalemia followed by ventricular arrhythmias, cardiac arrest, and death have been reported following the administration of succinylcholine in apparently healthy children who were later found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne muscular dystrophy. Immediate treatment of hyperkalemia should be instituted whenever a healthy appearing infant or child develops cardiac arrest with no obvious cause soon after administration of succinylcholine.

The use of estrogens is generally contraindicated in patients with known or suspected estrogen-dependent neoplasia such as breast and endometrial cancer, since it may stimulate tumor proliferation. High dosages of estrogens may be used for the palliative treatment of inoperable, metastatic breast cancer, but only in appropriately selected men and postmenopausal women.

Neuromuscular blocking agents can cause respiratory depression and paralysis. Therapy with neuromuscular blocking agents should be administered cautiously in patients with pulmonary impairment. Treatment of respiratory paralysis consists of positive-pressure artificial respiration with oxygen and maintenance of a patent airway until the recovery of normal respiration is assured.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The use of exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Close monitoring is recommended when prescribing these agents to patients predisposed to angioedema.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

A two- to four-fold increase in risk of gallbladder disease has been noted in women receiving postmenopausal estrogen therapy. The risk for gallbladder disease may be less for premenopausal women using oral contraceptives containing low-dose estrogens and/or progestins. Therapy with estrogens should be administered cautiously in patients with preexisting gallbladder disease or a history of pregnancy-related cholestasis.

The use of succinylcholine has been associated with an increase in intraocular pressure. Therapy with succinylcholine should be administered cautiously in patients with narrow-angle glaucoma.

The use of succinylcholine may exacerbate bradycardia via vagal stimulation leading to asystole, especially after a second dose. Therapy with succinylcholine should be administered cautiously in patients with bradycardia.

Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.

Estrogens are primarily metabolized by the liver. Use of estrogen therapy is contraindicated in patients with liver dysfunction or disease. Patients with impaired hepatic function may be at increased risk for adverse effects associated with estrogen administration due to decreased drug clearance. Patients with hepatic hemangiomas are at increased risk of exacerbation with use of estrogens. Therapy with estrogens should be administered cautiously in patients with cholestatic jaundice associated with past estrogen use or with pregnancy. In addition, clinicians should be aware that estrogen therapy may affect liver function tests.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Depolarizing agents, including succinylcholine, should be used with caution in patients with known neuromuscular junction disease. The succinylcholine-induced neuromuscular blockade may be prolonged in patients with myasthenia gravis (MG). Care should be exercised when using this agent in patients with existing, previously diagnosed MG.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring.