Midodrine

It appears possible, although there is no supporting experimental evidence, that the high renal clearance of desglymidodrine (a base) is due to active tubular secretion by the base-secreting system also responsible for the secretion of such drugs as metformin, cimetidine, ranitidine, procainamide, triamterene, flecainide and quinidine. Thus there may be a potential for drug-drug interaction with these drugs.

Midodrine hydrochloride has been used in patients concomitantly treated with salt-retaining steroid therapy (i.e., fludrocortisone acetate), with or without salt supplementation. The potential for supine hypertension should be carefully monitored in these patients and may be minimized by either reducing the dose of fludrocortisone acetate or decreasing the salt intake prior to initiation of treatment with midodrine hydrochloride. Alpha-adrenergic blocking agents, such as prazosin, terazosin and doxazosin, can antagonize the effects of midodrine hydrochloride.

The use of drugs that stimulate alpha-adrenergic receptors (e.g., phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine or dihydroergotamine) may enhance or potentiate the pressor effects of midodrine hydrochloride. Therefore, caution should be used when midodrine hydrochloride is administered concomitantly with agents that cause vasoconstriction.

When administered concomitantly with midodrine hydrochloride, cardiac glycosides may enhance or precipitate bradycardia, A.V. block or arrhythmia.

An episode of transient, severe hypertension occurring within 2 minutes of injection of 1% lidocaine with 1:100,000 U of epinephrine in a patient taking midodrine for orthostatic hypotension /is reported/. /It was/ hypothesize that the patient's autonomic nervous system was dangerously susceptible to the effect of local anesthetic when combined with the vasoactive systemic effect of midodrine. Surgeons should minimize the use of vasoconstrictors in patients treated with midodrine to avoid hypertensive complications.

/SIGNS AND SYMPTOMS/ Symptoms of overdose could include hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention.

/CASE REPORTS/ A 42-year-old female had suffered from repeated syncope. She had vasovagal syncope with convulsions from vasodilatation and cardiac standstill which lasted for 9.8 sec. The 60 degrees head-up tilt test, nitroglycerin injection and isoproterenol infusion provoked vasovagal reaction. Although a beta blocker was not effective in preventing tilt-induced hypotension and bradycardia, midodrine hydrochloride (alpha-1 stimulant) or atropine prevented it. In this patient, insufficient constriction of capacitance vessels might have played an important role in activation of an inhibitory reflex from cardiopulmonary mechanoreceptors which caused hypotension and bradycardia.

/CASE REPORTS/ There are 2 reported cases of overdosage with midodrine hydrochloride, both in young males. One patient ingested midodrine hydrochloride drops, 250 mg, experienced systolic blood pressure greater than 200 mm Hg, was treated with an IV injection of 20 mg of phentolamine and was discharged the same night without any complaints. The other patient ingested 205 mg of midodrine hydrochloride (41 5-mg tablets) and was found lethargic and unable to talk, unresponsive to voice but responsive to painful stimuli, hypertensive and bradycardic. Gastric lavage was performed and the patient recovered fully by the next day without sequelae. The single doses that would be associated with symptoms of overdosage or would be potentially life-threatening are unknown.

/CASE REPORTS/ Midodrine is an alpha-agonist that causes peripheral vasoconstriction, resulting in increased blood pressure. It has been reported to be safe and effective in patients with end stage renal disease (ESRD) and is widely used for hemodialysis-associated hypotension. We report a case report of midodrine-induced ischemia in a patient on hemodialysis and review the literature relating to the safety of midodrine in patients with end stage renal disease.

For more Human Toxicity Excerpts (Complete) data for Midodrine (8 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

midodrine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Midodrine hydrochloride increased the rate of embryo resorption, reduced fetal body weight in rats and rabbits and decreased fetal survival in rabbits when given in doses 13 (rat) and 7 (rabbit) times the maximum human dose based on body surface area (mg/sq m). No teratogenic effects have been observed in studies in rats and rabbits.

Midodrine hydrochloride is contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine hydrochloride should not be used in patients with persistent and excessive supine hypertension.

Recommended general treatment, based on the pharmacology of the drug, includes ... administration of alpha-sympatholytic drugs (e.g., phentolamine).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

LD50 Mouse oral 675 mg/kg

LD50 Rat oral 30 to 50 mg/kg

LD50 Dog oral 125-160 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including midodrine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Midodrine hydrochloride/

MEDICATION

Use (kg; approx.) in Germany (2009): >10

Synthesized from hydroquinone dimethyl ether by Friedel-Crafts acylation with chloroacetyl chloride, amination to the corresponding 2-aminoacetophenone, acylation at the amino function with chloroacetyl chloride, displacement of the chloro by the azido group and finally reduction with, e.g., sodium borohydride and catalytic hydrogenation (Pd/C).