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MIDODRINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Midodrine hydrochloride is a prodrug that is metabolized in the liver to desglymidodrine. This active metabolite is a peripheral alpha-1-adrenergic agonist that causes arterial and venous vasoconstriction.

Specific Substances

    1) Midodrine hydrochloride
    2) CAS 42794-76-3

Available Forms Sources

    A) FORMS
    1) Midodrine is available in the United States in 2.5, 5, and 10 mg tablets (Prod Info midodrine hcl oral tablets, 2006).
    B) USES
    1) Midodrine is used to treat symptomatic orthostatic hypotension of various etiologies (Prod Info midodrine hcl oral tablets, 2006).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Midodrine is used to treat symptomatic orthostatic hypotension of various etiologies.
    B) PHARMACOLOGY: Midodrine forms desglymidodrine, an alpha(1)-agonist, and exerts its action by activating the alpha-adrenergic receptors of the arteriolar and venous vasculature, thus resulting in an increase in vascular tone and elevation of the blood pressure. It has no effect on beta-adrenergic receptors.
    C) TOXICOLOGY: Excessive alpha stimulation can produce hypertension and reflex bradycardia.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Supine and sitting hypertension, paresthesia (including hyperesthesia and scalp paresthesia), pruritus, piloerection, chills, urinary urge, retention, and frequency. OTHER: Reflex bradycardia, associated with dizziness, and syncope; rash; abdominal pain.
    F) WITH POISONING/EXPOSURE
    1) Information on human overdose is limited. Reported effects have included hypertension, bradycardia, and lethargy.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Chills may occur.

Laboratory Monitoring

    A) Monitor vital signs (especially blood pressure and pulse) and obtain an ECG.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. For severe hypertension, nitroprusside or phentolamine are preferred. Labetalol or nitroglycerin are alternatives.
    C) DECONTAMINATION
    1) PREHOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    2) HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) ANTIDOTE
    1) None.
    E) HYPERTENSIVE EPISODE
    1) Mild/moderate asymptomatic hypertension does not usually require treatment. For severe hypertension, nitroprusside or phentolamine are preferred, with nitroglycerin or labetalol as alternatives.
    F) AGITATION
    1) Although no CNS effects have been reported for midodrine at therapeutic doses, toxic doses may have some adverse CNS effects. Agitation may be treated with increasing doses of diazepam or lorazepam.
    G) ENHANCED ELIMINATION
    1) The active metabolite, desglymidodrine is dialyzable. No data on midodrine is available.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: An adult with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be observed in a healthcare facility.
    3) ADMISSION CRITERIA: Patients who remain symptomatic despite adequate treatment should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected midodrine overdose, the possibility of multidrug involvement should be considered. Symptoms of overdose are similar to reported side effects of the medication.
    J) PHARMACOKINETICS
    1) Tmax: Midodrine (prodrug), oral: about 30 min; desglymidodrine (active drug): 1 to 2 hr. Midodrine is rapidly absorbed with maximum plasma levels obtained 30 min postingestion. Desglymidodrine (active drug), Bioavailability: 93%. Neither midodrine nor desglymidodrine are bound to plasma proteins to any significant extent. Volume of distribution for midodrine is 4 to 4.6 L/kgExcretion: Midodrine (prodrug), Renal: insignificant. The renal clearance of desglymidodrine is of the order of 385 mL/minute, mostly, about 80% via active secretion. Elimination half-life: Midodrine (prodrug): 25 min. Desglymidodrine (active drug): 3 to 4 hr.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause hypertension (eg, MAO Inhibitors, methamphetamine).

Range Of Toxicity

    A) TOXICITY: The acute toxic/lethal dose of midodrine has not been reported. Two adults developed hypertension, bradycardia, and CNS depression following the ingestion of 205 and 250 milligrams, respectively. They both fully recovered without sequelae.
    B) THERAPEUTIC DOSE: ADULTS: 10 mg 3 times daily. Single doses as high as 20 mg have been given to patients; however, severe and persistent systolic supine hypertension was observed at a high rate (45%). CHILDREN: The safety and effectiveness of midodrine in the pediatric population has not been established. Midodrine 0.06 mg/kg orally was effective in increasing blood pressure in children (6 months to 12 years of age) with infection-related hypotension in 1 single-blind study. In this study, midodrine produced significant increases in blood pressure regardless of the type of infection (pneumonia, enteritis, meningitis).

Clinical Effects

Summary Of Exposure

    A) USES: Midodrine is used to treat symptomatic orthostatic hypotension of various etiologies.
    B) PHARMACOLOGY: Midodrine forms desglymidodrine, an alpha(1)-agonist, and exerts its action by activating the alpha-adrenergic receptors of the arteriolar and venous vasculature, thus resulting in an increase in vascular tone and elevation of the blood pressure. It has no effect on beta-adrenergic receptors.
    C) TOXICOLOGY: Excessive alpha stimulation can produce hypertension and reflex bradycardia.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Supine and sitting hypertension, paresthesia (including hyperesthesia and scalp paresthesia), pruritus, piloerection, chills, urinary urge, retention, and frequency. OTHER: Reflex bradycardia, associated with dizziness, and syncope; rash; abdominal pain.
    F) WITH POISONING/EXPOSURE
    1) Information on human overdose is limited. Reported effects have included hypertension, bradycardia, and lethargy.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Chills may occur.
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) CHILLS: In a 3-week placebo-controlled trial, chills developed in 4.9% of patients (n=82) taking midodrine compared with none of the patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Midodrine elevates blood pressure via an effect on alpha-adrenergic receptors (Fouad-Tarazi et al, 1995).
    b) Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10 mg dose (Prod Info midodrine hcl oral tablets, 2006; Fouad-Tarazi et al, 1995).
    c) Systolic blood pressure of 200 mmHg was reported in approximately 13.4% of patients after receiving 10 mg of midodrine, and appeared primarily to occur in patients with elevated pretreatment systolic blood pressures (mean 170 mmHg) (Prod Info midodrine hcl oral tablets, 2006).
    d) In a 3-week placebo-controlled trial, supine hypertension developed in 7.3% of patients (n=82) taking midodrine compared with none of the patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).
    2) WITH POISONING/EXPOSURE
    a) Hypertension may occur with overdose (Prod Info midodrine hcl oral tablets, 2006).
    b) CASE REPORT: An adult developed hypertension (systolic BP greater than 200 mmHg) after ingesting 250 mg midodrine (Prod Info midodrine hcl oral tablets, 2006).
    B) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) A slight reduction in the heart rate may occur after administration of midodrine (Prod Info midodrine hcl oral tablets, 2006; Fouad-Tarazi et al, 1995).
    b) MECHANISM: Possibly due to vagal reflex (Prod Info midodrine hcl oral tablets, 2006).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: An adult developed hypertension and bradycardia after ingesting 205 mg midodrine (Prod Info midodrine hcl oral tablets, 2006).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) LETHARGY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: An adult developed hypertension, bradycardia, and lethargy (unresponsive to voice but responsive to painful stimuli, unable to talk) after ingesting 205 mg midodrine (Prod Info midodrine hcl oral tablets, 2006).
    B) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, paresthesia (including hyperesthesia and scalp paresthesia) developed in 18.3% of patients (n=82) taking midodrine compared with 4.5% patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, pain (including abdominal pain) developed in 4.9% of patients (n=82) taking midodrine compared with none of the patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) RETENTION OF URINE
    1) WITH THERAPEUTIC USE
    a) Urinary retention and urgency have been reported at therapeutic doses (Prod Info midodrine hcl oral tablets, 2006; Fouad-Tarazi et al, 1995).
    b) MECHANISM: Desglymidodrine acts on alpha-adrenergic receptors of the bladder neck (Prod Info midodrine hcl oral tablets, 2006; Fouad-Tarazi et al, 1995).
    c) In a 3-week placebo-controlled trial, urinary retention developed in 5 patients (n=82) taking midodrine (Prod Info midodrine hcl oral tablets, 2006).
    2) WITH POISONING/EXPOSURE
    a) Urinary retention may occur with overdose (Prod Info midodrine hcl oral tablets, 2006).
    B) DYSURIA
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, dysuria (dysuria [1], increased urinary frequency [2], impaired urination [1], urinary retention [5], and urinary urgency [2]) developed in 13.4% of patients (n=82) taking midodrine compared with none of the patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, pruritus (including scalp pruritus) developed in 12.2% of patients (n=82) taking midodrine compared with 2.3% patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).
    B) CUTIS ANSERINA
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, piloerection developed in 13.4% of patients (n=82) taking midodrine compared with none of the patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).
    2) WITH POISONING/EXPOSURE
    a) A sensation of coldness and piloerection may occur with overdose (Prod Info midodrine hcl oral tablets, 2006).
    C) ERUPTION
    1) WITH THERAPEUTIC USE
    a) In a 3-week placebo-controlled trial, rash developed in 2.4% of patients (n=82) taking midodrine compared with 1.1% patients (n=88) on placebo (Prod Info midodrine hcl oral tablets, 2006).

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) RATS/MICE - Long-term studies using 3 to 4 times the maximum recommended daily human dose (on a milligram/square meter basis) did not demonstrate any carcinogenic effects (Prod Info ProAmatine(R), midodrine, 1998).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs (especially blood pressure and pulse) and obtain an ECG.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who remain symptomatic despite adequate treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An adult with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be observed in a healthcare facility.

Monitoring

    A) Monitor vital signs (especially blood pressure and pulse) and obtain an ECG.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs (especially blood pressure and pulse) and ECG.
    2) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    B) HYPERTENSIVE EPISODE
    1) Monitor vital signs regularly. For mild/moderate hypertension without evidence of end organ damage, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning.
    2) For hypertensive emergencies (severe hypertension with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure 20% to 25% within one hour), sodium nitroprusside is preferred. Nitroglycerin and phentolamine are possible alternatives.
    3) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    4) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    5) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    6) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    7) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    8) PHENTOLAMINE/INDICATIONS
    a) Useful for severe hypertension, particularly if caused by agents with alpha adrenergic agonist effects usually induced by catecholamine excess (Rhoney & Peacock, 2009).
    9) PHENTOLAMINE/ADULT DOSE
    a) BOLUS DOSE: 5 to 15 mg IV bolus repeated as needed (U.S. Departement of Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, 2004). Onset of action is 1 to 2 minutes with a duration of 10 to 30 minutes (Rhoney & Peacock, 2009).
    b) CONTINUOUS INFUSION: 1 mg/hr, adjusted hourly to stabilize blood pressure. Prepared by adding 60 mg of phentolamine mesylate to 100 mL of 0.9% sodium chloride injection; continuous infusion ranging from 12 to 52 mg/hr over 4 days has been used in case reports (McMillian et al, 2011).
    10) PHENTOLAMINE/PEDIATRIC DOSE
    a) 0.05 to 0.1 mg/kg/dose (maximum of 5 mg per dose) intravenously every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Singh et al, 2012; Koch-Weser, 1974).
    11) PHENTOLAMINE/ADVERSE EFFECTS
    a) Adverse events can include orthostatic or prolonged hypotension, tachycardia, dysrhythmias, angina, flushing, headache, nasal congestion, nausea, vomiting, abdominal pain and diarrhea (Rhoney & Peacock, 2009; Prod Info Phentolamine Mesylate IM, IV injection Sandoz Standard, 2005).
    12) CAUTION
    a) Phentolamine should be used with caution in patients with coronary artery disease because it may induce angina or myocardial infarction (Rhoney & Peacock, 2009).
    13) NITROGLYCERIN/INDICATIONS
    a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).
    14) NITROGLYCERIN/ADULT DOSE
    a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).
    15) NITROGLYCERIN/PEDIATRIC DOSE
    a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).
    C) PSYCHOMOTOR AGITATION
    1) Although no CNS effects have been reported for midodrine at therapeutic doses, toxic doses may have some adverse CNS effects.
    a) INDICATION
    1) If patient is severely agitated, sedate with IV benzodiazepines.
    b) DIAZEPAM DOSE
    1) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    2) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) LORAZEPAM DOSE
    1) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
    2) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    d) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.

Enhanced Elimination

    A) HEMODIALYSIS
    1) The active metabolite, desglymidodrine is dialyzable. Midodrine has a large volume of distribution and significant amounts would not be removed by hemodialysis or hemoperfusion(Prod Info midodrine hcl oral tablets, 2006).

Range Of Toxicity

Summary

    A) TOXICITY: The acute toxic/lethal dose of midodrine has not been reported. Two adults developed hypertension, bradycardia, and CNS depression following the ingestion of 205 and 250 milligrams, respectively. They both fully recovered without sequelae.
    B) THERAPEUTIC DOSE: ADULTS: 10 mg 3 times daily. Single doses as high as 20 mg have been given to patients; however, severe and persistent systolic supine hypertension was observed at a high rate (45%). CHILDREN: The safety and effectiveness of midodrine in the pediatric population has not been established. Midodrine 0.06 mg/kg orally was effective in increasing blood pressure in children (6 months to 12 years of age) with infection-related hypotension in 1 single-blind study. In this study, midodrine produced significant increases in blood pressure regardless of the type of infection (pneumonia, enteritis, meningitis).

Therapeutic Dose

    7.2.1) ADULT
    A) 10 mg orally 3 times daily at 3- to 4-hour intervals (during daytime hours) (Prod Info midodrine HCl oral tablets, 2013)
    B) Single doses as high as 20 mg have been given to patients; however, severe and persistent systolic supine hypertension was observed at a high rate (45%) (Prod Info midodrine HCl oral tablets, 2013).
    7.2.2) PEDIATRIC
    A) The safety and effectiveness of midodrine in the pediatric population has not been established (Prod Info midodrine HCl oral tablets, 2013).
    B) Midodrine 0.06 mg/kg orally was effective in increasing blood pressure in children (6 months to 12 years of age) with infection-related hypotension in 1 single-blind study. In this study, midodrine produced significant increases in blood pressure regardless of the type of infection (pneumonia, enteritis, meningitis) (McTavish & Goa, 1989).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The single dose that would be life threatening is unknown.

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) One patient who ingested ProAmatine(R) drops, 250 mg, and developed a systolic blood pressure of greater than 200 mmHg, was treated with phentolamine, and was discharged the same night without complaints (Prod Info midodrine hcl oral tablets, 2006).
    2) One patient ingested 205 milligrams of ProAmatine (R) (41 5-milligram tablets), was found lethargic and unable to talk, unresponsive to voice but responsive to painful stimuli, hypertensive, and bradycardic. The patient fully recovered the next day without sequelae (Prod Info midodrine hcl oral tablets, 2006).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)MOUSE:
    a) 246 mg/kg (RTECS, 2002)
    2) LD50- (ORAL)RAT:
    a) 68800 mcg/kg (RTECS, 2002)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Midodrine forms desglymidodrine, an alpha(1)-agonist, and exerts its action by activating the alpha-adrenergic receptors of the arteriolar and venous vasculature, thus resulting to an increase in vascular tone and elevation of the blood pressure. It has no effect on beta-adrenergic receptors (Prod Info midodrine hcl oral tablets, 2006).

References

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) American Heart Association: 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2005; 112(24 Suppl):IV 1-203. Available from URL: http://circ.ahajournals.org/content/vol112/24_suppl/. As accessed 12/14/2005.
    3) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    4) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    5) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    6) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
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