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YOHIMBINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Yohimbine is an alkaloid from Corynanthe yohimbe which has long been touted for its use as an aphrodisiac and more recently as a central alpha-2-receptor antagonist. It is an indole derivative, similar to reserpine. Its actions are opposite those of clonidine.

Specific Substances

    1) Aphrodine
    2) Pausinystalia yohimbe
    3) Corynine
    4) Quebrachine
    5) Corynanthe yohimbe (same plant as Pausinystalia yohimbe)
    6) Rauwolfia serpentina (roots only)
    7) Yo Yo
    8) Methyl 17alpha-hydroxy-yohimban-16alpha-carboxylate hydrochloride
    9) CAS 146-48-5
    10) Molecular Formula: C21-H26-N2-O3.HCl

Available Forms Sources

    A) FORMS
    1) Yohimbine is an odorless, crystalline substance which was available as a powder, tablet and intravenous solution (Shannon & Neuman, 2000). Several generic preparations are available in health food or nutritional stores in the United States.
    2) The following products are only available outside the United States:
    1) Vikonon (Savoy Labs - UK): 5 mg yohimbine, caffeine 65 mg, and various vitamins
    2) Potensan (Medo-Chemicals-UK): 5 mg yohimbine, 500 mcg strychnine, amylobarbitone
    3) Afrodex (ICN): 5 mg yohimbine, methyltestosterone, nux vomica (discontinued, 1973)
    4) Yobinol (Napp): 3 mg yohimbine
    B) USES
    1) In the Rubiaceae family, indigenous to Congo, Cameroon, Gabon, yohimbine is used as an aphrodisiac and mild hallucinogen, and has been on the USFDA unsafe herb list as of March, 1977. Yohimbine has been used in veterinary medicine as a reversal agent for xylazine (Tyler, 1987).
    2) Yohimbine has been used as an antidote for clonidine overdose, although it is not FDA approved for this indication (Roberge et al, 1996).

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: Yohimbine, an indole alkaloid derivative, is available as a prescription medication, dietary supplement and sold illegally. It has been used as a hallucinogen, aphrodisiac, and has been prescribed for the treatment of male erectile dysfunction and reduced libido in women. Herbal products containing various amounts of yohimbine have been sold in various forms (eg, pill, bark, liquid).
    B) PHARMACOLOGY: Yohimbine is an indole alkaloid derivative isolated from the bark of the tree (Pausinystalia yohimbe). It acts as a selective antagonist at alpha-2-receptors. As a centrally acting alpha-2 adrenergic blocking agent, yohimbine can increase sympathetic outflow and potentiate the release of norepinephrine producing an increase in peripheral sympathetic activity. Yohimbine readily penetrates the CNS.
    C) TOXICOLOGY: It antagonizes the effects of xylazine causing an increase in heart rate and blood pressure, CNS stimulation, antidiuresis, and hyperinsulinemic effects.
    D) EPIDEMIOLOGY: Exposure has occurred. There have been rare reports of fatalities following acute intoxication.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Common adverse events include nausea, vomiting, abdominal pain, tachycardia, anxiety/agitation, hypertension, flushing, diaphoresis, tremor, chest pain, chills, tachypnea, mydriasis and altered menta behavior.
    2) SEVERE EFFECTS: Serious events reported infrequently with yohimbine products have included myocardial infarction, atrial fibrillation, QTc interval prolongation, seizure, acute renal failure, and priapism.
    3) ABUSE: Yohimbine may be smoked or used in a tea or as a mild hallucinogen. It is commonly reported to cause anxiety.
    F) WITH POISONING/EXPOSURE
    1) OVERDOSE: Overdose effects are anticipated to be an extension of pharmacologic effects. Drowsiness, anxiety, disorientation, tremors, irritability may occur following overdose. Massive overdoses have resulted in seizures and coma as well as cardiovascular effects (ie, hypertension, tachycardia).

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Routine laboratory studies are not needed unless otherwise clinically indicated.
    C) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    D) Monitor renal function as necessary following a significant exposure.
    E) Toxic serum concentrations have not yet been established.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor vital signs and mental status. Initially treat anxiety/agitation with benzodiazepines as indicated. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary. Sedation with benzodiazepines may be helpful in agitated patients with hypertension and tachycardia.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. For severe hypertension sodium nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. Initially treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    C) DECONTAMINATION
    1) PREHOSPITAL: Activated charcoal should be considered following a recent toxic ingestion if the patient is alert, not vomiting and able to protect their airway.
    2) HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is alert and able to maintain their airway.
    D) ANTIDOTE
    1) There is no known antidote.
    E) AIRWAY MANAGEMENT
    1) Airway management is unlikely to be necessary following a mild to moderate exposure. Airway support including intubation and ventilation may be needed in patients that require large doses of benzodiazepines secondary to severe agitation or in patients that develop seizures and/or coma.
    F) SEIZURES
    1) Seizure activity has been reported infrequently following yohimbine intoxication. Administer IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    G) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis would be of value following an exposure; it may be indicated in patients that develop acute renal failure.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic child or a child with only mild gastrointestinal or drowsiness following a minor exposure (eg, a single tablet or dietary supplement) can be managed at home with adult supervision. Adults with an inadvertent overdose and minor symptoms can be managed at home.
    2) OBSERVATION CRITERIA: Patients with persistent clinical effects (eg, alterations in CNS function, hypertension) or more than mild toxicity should be referred to a healthcare facility. They may require supportive measures including monitoring and treatment.
    3) ADMISSION CRITERIA: Patients should be admitted, if symptoms persist or fail to respond to therapy (ie, ongoing CNS effects). Patients with evidence of significant neurologic toxicity (i.e. seizures, persistent agitation) or cardiac toxicity 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 yohimbine overdose, an acute on chronic exposure may occur. The possibility of multidrug involvement should also be considered.

Range Of Toxicity

    A) TOXICITY: MILD TOXICITY: Doses of 18 mg daily were well tolerated except for a few cases of mild nausea and dizziness. Fifteen to 20 mg orally induced hypertension. SEVERE TOXICITY: A patient developed severe hypertension (BP 259/157 mmHg) and seizures/coma following a massive ingestion of 5 g of yohimbine. The patient recovered without sequelae following aggressive supportive care. A 25-year-old man ingested 3 g of yohimbine and developed hypotension, confusion, seizures, tachycardia and prolonged QRS interval and recovered uneventfully. FATALITY/CHRONIC USE: A young man developed a witnessed seizure and elevated vital signs and died a short time later following chronic use of yohimbine; his death was attributable to yohimbine toxicity alone.

Clinical Effects

Summary Of Exposure

    A) USES: Yohimbine, an indole alkaloid derivative, is available as a prescription medication, dietary supplement and sold illegally. It has been used as a hallucinogen, aphrodisiac, and has been prescribed for the treatment of male erectile dysfunction and reduced libido in women. Herbal products containing various amounts of yohimbine have been sold in various forms (eg, pill, bark, liquid).
    B) PHARMACOLOGY: Yohimbine is an indole alkaloid derivative isolated from the bark of the tree (Pausinystalia yohimbe). It acts as a selective antagonist at alpha-2-receptors. As a centrally acting alpha-2 adrenergic blocking agent, yohimbine can increase sympathetic outflow and potentiate the release of norepinephrine producing an increase in peripheral sympathetic activity. Yohimbine readily penetrates the CNS.
    C) TOXICOLOGY: It antagonizes the effects of xylazine causing an increase in heart rate and blood pressure, CNS stimulation, antidiuresis, and hyperinsulinemic effects.
    D) EPIDEMIOLOGY: Exposure has occurred. There have been rare reports of fatalities following acute intoxication.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Common adverse events include nausea, vomiting, abdominal pain, tachycardia, anxiety/agitation, hypertension, flushing, diaphoresis, tremor, chest pain, chills, tachypnea, mydriasis and altered menta behavior.
    2) SEVERE EFFECTS: Serious events reported infrequently with yohimbine products have included myocardial infarction, atrial fibrillation, QTc interval prolongation, seizure, acute renal failure, and priapism.
    3) ABUSE: Yohimbine may be smoked or used in a tea or as a mild hallucinogen. It is commonly reported to cause anxiety.
    F) WITH POISONING/EXPOSURE
    1) OVERDOSE: Overdose effects are anticipated to be an extension of pharmacologic effects. Drowsiness, anxiety, disorientation, tremors, irritability may occur following overdose. Massive overdoses have resulted in seizures and coma as well as cardiovascular effects (ie, hypertension, tachycardia).

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Hypothermia may result following a yohimbine overdose due to peripheral alpha 1 blockade (Varkey, 1992).
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) Hypertension has been reported frequently with yohimbine use (Kearney et al, 2010).
    3.3.5) PULSE
    A) WITH THERAPEUTIC USE
    1) Tachycardia has been reported frequently with yohimbine use (Kearney et al, 2010).

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Mydriasis has been reported with yohimbine use (Kearney et al, 2010)
    3.4.6) THROAT
    A) WITH THERAPEUTIC USE
    1) SALIVATION: Increased salivary secretions 60 to 180 minutes after healthy volunteers were given 14 mg of yohimbine (Chatelut et al, 1989).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypertension is a common adverse event reported with yohimbine use (Kearney et al, 2010).
    b) Early literature is unclear on whether to expect hyper- or hypotension. Subsequent studies have shown that while pithed or amobarbitol sedated animals will show a decrease in blood pressure, normal animals and humans will show hypertension (Goldberg & Robertson, 1983; Charney et al, 1983). Hypertensive crisis has been reported with chronic use (Ruck et al, 1999; Shih et al, 1995).
    c) CASE SERIES: Henauer et al (1984) measured the systolic blood pressure increases in 10 patients who served in each of 3 groups; central, 30 mg doses and 60 mg doses. The increase after the 60 mg dose was 4 times higher than that after placebo and twice as high as with the 30 mg group. All differences were statistically significant. Actual increases were 36+/-14 mmHg for the 60 mg dose groups and 20+/-11 mmHg for the 30 mg dose. The differences for diastolic pressure were not significant.
    d) Patients with essential hypertension have a greater rise in blood pressure with yohimbine than controls (Goldstein et al, 1989).
    e) CASE REPORT: Hypertensive crisis occurred following ingestion of 1 tablet of a yohimbine herbal product for a month in a 63-year-old man. Vital signs included a blood pressure of 240/140 mmHg and heart rate 120 beats/minute and were associated with severe headache and weakness. Treatment was begun with nitroprusside which was changed to clonidine after one day. The patient recovered and was discharged with no sequelae and with no continued antihypertensive therapy (Ruck et al, 1999).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A case of transient hypertension (168/88 torr, while standing) occurred in a 62-year-old man following the ingestion of 200 mg of yohimbine (Friesen et al, 1993).
    b) CASE REPORT: A patient developed severe hypertension following a massive ingestion of 5 g of yohimbine. Vital signs included blood pressure of 259/107 mmHg and heart rate of 140 beats/min. Treatment included furosemide, labetalol, clonidine, and urapidil with clinical improvement. The patient recovered and was discharged with no sequelae (Giampreti et al, 2009).
    B) TACHYARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Tachycardia is a common adverse event reported with yohimbine use (Kearney et al, 2010).
    b) Palpitations can also develop (Henauer et al, 1984; Ruck et al, 1999).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: Tachycardia (106 beats/minute) was noted in a 62-year-old man approximately 2 hours following the ingestion of 200 mg yohimbine. ECG was normal. Treatment consisted of decontamination and observation. His heart rate returned to 80 beats/minute within 19 hours of the ingestion (Friesen et al, 1993a).
    C) ATRIAL FIBRILLATION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Atrial fibrillation and retrosternal chest pain occurred in a 38-year-old man following a 350 mg overdose of yohimbine. It was ascertained that no other medication was taken. An ECG showed atrial fibrillation with a ventricular rate of 150 beats/minute. Normal sinus rhythm was recorded the following day (Varkey, 1992). The causal relationship to yohimbine is not clear.
    D) ORTHOSTATIC HYPOTENSION
    1) WITH THERAPEUTIC USE
    a) Patients with orthostatic hypotension seem to be very sensitive to yohimbine. A 5 mg dose may increase blood pressure, while greater than 20 mg is needed in a healthy volunteer (to raise the blood pressure 40 mmHg systolic) (Brodde et al, 1983). Lecrubier et al (1981) showed that yohimbine diminishes the orthostatic hypotension seen with the use of tricyclic antidepressants (clomipramine).
    E) CHEST PAIN
    1) WITH THERAPEUTIC USE
    a) Chest pain has been reported with yohimbine use (Kearney et al, 2010).
    F) VASODILATATION
    1) WITH THERAPEUTIC USE
    a) Yohimbine can dilate the blood vessels of the skin, as well as mucous membranes. It may cause lower blood pressure (Tyler, 1987).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) TACHYPNEA
    1) WITH THERAPEUTIC USE
    a) Tachypnea has been reported following yohimbine use (Kearney et al, 2010).
    B) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Increased mucus secretion and bronchoconstriction occurred in a 60-year-old man who had been taking 5.4 mg orally, 3 times per day (Landis & Shore, 1989).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness has been reported with therapeutic use (Goldberg & Robertson, 1983).
    2) WITH POISONING/EXPOSURE
    a) Dizziness/lightheadness has been reported following acute exposure (Friesen et al, 1993a). Incoordination was seen after ingestion of 250 mg of yohimbine "street powder" (Linden et al, 1985).
    B) ANXIETY
    1) WITH THERAPEUTIC USE
    a) Anxiety and/or agitation are common adverse event reported with yohimbine use (Kearney et al, 2010)
    b) In some normal individuals yohimbine produces mild anxiety. In patients with pre-existing anxiety disorders, yohimbine causes more of an increase in anxiety than it does in depressed or normal patients (Charney et al, 1982; Homberg & Gershon, 1961; Price et al, 1984).
    c) CASE SERIES: Henauer et al (1984) tested 10 normal subjects with doses of 30 and 60 mg of yohimbine. Only 5 of 10 patients (mostly 60 mg dose) became more anxious than controls.
    2) WITH POISONING/EXPOSURE
    a) Irritability and/or anxiety have been reported following overdose (Friesen et al, 1993a). Incoordination was seen after ingestion of 250 mg of yohimbine "street powder" (Linden et al, 1985).
    C) ALTERED MENTAL STATUS
    1) WITH THERAPEUTIC USE
    a) Altered mental status/behavior has occurred with yohimbine use (Kearney et al, 2010).
    D) INSOMNIA
    1) WITH THERAPEUTIC USE
    a) Insomnia has been reported (Goldberg & Robertson, 1983).
    E) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Severe "squeezing" headache has been reported (Goldberg & Robertson, 1983; Linden et al, 1985).
    F) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) Short term, reversible paresthesias of the legs and feet have been reported in diabetics treated for impotency (Morales et al, 1982).
    2) WITH POISONING/EXPOSURE
    a) Short term, reversible paresthesias of the legs and feet have been reported following overdose (Linden et al, 1985; Friesen et al, 1993a).
    G) AMNESIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Varkey (1992) reports a case of lethargy, confusion and retrograde amnesia in a 38-year-old man following an overdose of 350 mg of yohimbine. Retrograde amnesia persisted for four days.
    H) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A patient developed severe hypertension and seizures/coma following a massive ingestion of 5 g of yohimbine. Vital signs included a blood pressure of 259/157 mm Hg and heart rate of 140 beats/min. Treatment included furosemide, labetalol, clonidine, and urapidil with response. The patient recovered and was discharged with no sequelae (Giampreti et al, 2009).
    b) CASE REPORT/CHRONIC USE: A 23-year-old male body-builder, with a history of creating his own energy and protein drinks that contained yohimbine and caffeine along with steroid use, collapsed outside of a fitness center. Prior to collapsing, he had called a friend and stated that he 'thought he was dying'. Upon admission to the ER, he had developed seizures and his vital signs became elevated. He died several hours later. Upon autopsy he was noted to have cardiomegaly, pulmonary edema and congestion. Despite the presence of caffeine, diphenhydramine and yohimbine, it was determined that yohimbine toxicity alone was the cause of death (Anderson et al, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting are common adverse event reported with yohimbine use (Kearney et al, 2010).
    b) Nausea, which was easily reversed by decreasing the dose, was reported in patients being treated with 18 mg a day (Morales et al, 1982).
    c) Spontaneous vomiting and gastric distress have been reported (Goldberg & Robertson, 1983) .
    2) WITH POISONING/EXPOSURE
    a) Nausea has been observed following overdose (Linden et al, 1985).
    b) Spontaneous vomiting and gastric distress have been reported following overdose (Friesen et al, 1993).
    B) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) Abdominal pain was a common adverse event reported with yohimbine use (Kearney et al, 2010).
    C) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea has been reported (Goldberg & Robertson, 1983).
    D) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) Anorexia has been reported (Goldberg & Robertson, 1983).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) Acute renal failure has been reported infrequently following yohimbine use (Kearney et al, 2010).
    b) CASE REPORT: A 42-year-old man developed acute renal failure following the ingestion of 16.2 mg of yohimbine. The patient concurrently developed a lupus-like syndrome with a generalized cutaneous skin eruption. Although there is a temporal relationship, it excludes the possibility that the patient developed lupus as a primary process. The following plasma laboratory values were abnormal: BUN 103 mg/dL, creatinine 8.9 mg/dL, potassium 6.3 mEq/L, chloride 108 mEq/L, and bicarbonate 16.5 mEq/L. Urinalysis was positive for albuminuria. Erythrocyte sedimentation rate was 87 mm/h and ANA was positive. Following 2 weeks of hydration therapy the patient improved and was discharged. At a 4 month follow-up, an ultrasound revealed small kidneys consistent with chronic renal failure (Sandler & Aronson, 1993)
    B) DYSURIA
    1) WITH THERAPEUTIC USE
    a) Dysuria, and back and genital pain are infrequent complaints (Goldberg & Robertson, 1983). Studies have shown yohimbine to be 3 to 4.3 times as effective as placebo in relieving male impotency (Sobotka, 1969).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH THERAPEUTIC USE
    a) Flushing is a common adverse event reported with yohimbine use (Kearney et al, 2010; Goldberg & Robertson, 1983).
    B) EXCESSIVE SWEATING
    1) WITH THERAPEUTIC USE
    a) Diaphoresis has been reported with yohimbine use (Kearney et al, 2010).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) DRUG-INDUCED LUPUS ERYTHEMATOSUS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A dose of 16.2 mg of yohimbine was associated with a cutaneous drug eruption, progressive renal failure, and a lupus-like syndrome (Sandler & Aronson, 1993).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Routine laboratory studies are not needed unless otherwise clinically indicated.
    C) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    D) Monitor renal function as necessary following a significant exposure.
    E) Toxic serum concentrations have not yet been established.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Toxic serum concentrations have not yet been established.

Methods

    A) CHROMATOGRAPHY
    1) A technique for analysis of yohimbine by use of high pressure liquid chromatograph and spectrofluorometer has been described (Owen et al, 1987).

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 should be admitted, if symptoms persist or fail to respond to therapy (ie, ongoing CNS effects). Patients with evidence of significant neurologic toxicity (i.e. seizures, persistent agitation) or cardiac toxicity should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic child or a child with only mild gastrointestinal or drowsiness following a minor exposure (eg, a single tablet or dietary supplement) can be managed at home with adult supervision. Adults with an inadvertent overdose and minor symptoms 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) Patients with persistent clinical effects (eg, alterations in CNS function, hypertension) or more than mild toxicity should be referred to a healthcare facility. They may require supportive measures including monitoring and treatment.

Monitoring

    A) Monitor vital signs and mental status.
    B) Routine laboratory studies are not needed unless otherwise clinically indicated.
    C) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    D) Monitor renal function as necessary following a significant exposure.
    E) Toxic serum concentrations have not yet been established.

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) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Monitor vital signs and mental status. Initially treat anxiety/agitation with benzodiazepines as indicated. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary. Sedation with benzodiazepines may be helpful in agitated patients with hypertension and tachycardia.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. For severe hypertension sodium nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. Initially treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    B) MONITORING OF PATIENT
    1) Monitor vital signs and mental status.
    2) Routine laboratory studies are not needed unless otherwise clinically indicated.
    3) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    4) Monitor renal function as necessary following a significant exposure.
    5) Toxic serum concentrations have not yet been established
    C) 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.
    D) HYPERTENSIVE EMERGENCY
    1) 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.
    2) 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).
    3) 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).
    4) 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).
    5) 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).
    6) 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).
    7) 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).
    8) 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).
    9) 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).
    10) 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).
    11) 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).
    12) 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).
    13) 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).
    E) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 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) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 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, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    F) FEELING AGITATED
    1) Diazepam has been shown to be effective in reducing yohimbine induced anxiety (Dose: Adult: 5 to 10 mg; Children: 0.1 to 0.3 mg/kg). This may be given orally, or if necessary, IV slowly (Charney et al, 1983). Intramuscular lorazepam can also be administered.
    G) EXPERIMENTAL THERAPY
    1) CLONIDINE: In a study using normal volunteers who ingested 30 mg of yohimbine (Charney et al, 1983), clonidine 5 mcg/kg was found to eliminate not only yohimbine-induced anxiety but also the increases in blood pressure, plasma 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG), and other autonomic symptoms. Before clonidine could be recommended as a routine antidote for yohimbine, more clinical testing needs to be done. It has been reported that the use of a imidazoline such as clonidine can cause paradoxical hypertension (some action at alpha-1-receptors).
    2) Ingram (1962) pretreated patients with atropine, chlorpromazine, reserpine and amobarbital, then administered 0.1 mg/kg yohimbine. He found that amobarbital and reserpine reduced both the pressor and anxiety effects, atropine reduced the pressor, and chlorpromazine potentiated both anxiety and autonomic response. The value of the use of these drugs AFTER ingestion or injection is unknown. One of the prime benefits of this study may be in predicting pharmacologic interactions for patients already taking one of these drugs, who subsequently is exposed to yohimbine (Ingram, 1962).

Enhanced Elimination

    A) SUMMARY
    1) It is unknown if hemodialysis would be of value following an exposure; it may be indicated in patients that develop acute renal failure.

Abstracts

Case Reports

    A) ADULT
    1) A 16-year-old gir took an estimated 250 mg of a white powder alleged to be yohimbine. Within 20 minutes she was weak, had generalized paresthesias, loss of coordination, and was dissociative. She had a severe headache, was dizzy, and had tremors. A severe pressure-like substernal chest pain was noted 4 hours postingestion, and remained for 2 hours before subsiding spontaneously. The next day the patient remained nauseous, weak, dizzy, and sweating, with the severe headache and intermittent palpitations. A physician's examination more than 30 hours after ingestion revealed a BP of 150/80, pulse 116 and respirations of 24. She was anxious and had a fine tremor of the extremities, a blotchy erythematous rash on her back, and submucosal hemorrhage in the right tympanic membrane. Symptoms resolved spontaneously, but lasted almost 36 hours (Linden et al, 1985).

Range Of Toxicity

Summary

    A) TOXICITY: MILD TOXICITY: Doses of 18 mg daily were well tolerated except for a few cases of mild nausea and dizziness. Fifteen to 20 mg orally induced hypertension. SEVERE TOXICITY: A patient developed severe hypertension (BP 259/157 mmHg) and seizures/coma following a massive ingestion of 5 g of yohimbine. The patient recovered without sequelae following aggressive supportive care. A 25-year-old man ingested 3 g of yohimbine and developed hypotension, confusion, seizures, tachycardia and prolonged QRS interval and recovered uneventfully. FATALITY/CHRONIC USE: A young man developed a witnessed seizure and elevated vital signs and died a short time later following chronic use of yohimbine; his death was attributable to yohimbine toxicity alone.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Dose of 0.1 mg/kg may produce stimulant effects in man (Ingram, 1962).
    2) When given for impotence, doses of 6 mg 3 times a day were well tolerated except for a few cases of mild nausea and dizziness which decreased when the dose was reduced (Morales et al, 1982).
    3) Yohimbe bark contains 6% alkaloids, primarily yohimbine (Tyler, 1983).

Minimum Lethal Exposure

    A) CASE REPORT
    1) CHRONIC USE: A 23-year-old male body-builder, with a history of creating his own energy and protein drinks that contained yohimbine and caffeine along with steroid use, collapsed outside of a fitness center. Prior to collapsing, he had called a friend and stated that he 'thought he was dying'. Upon admission to the ER, he developed seizures and his vital signs became elevated. He died several hours later. Upon autopsy he was noted to have cardiomegaly, pulmonary edema and congestion. Despite the presence of caffeine, diphenhydramine and yohimbine, it was determined that yohimbine alone was the cause of death (Anderson et al, 2013).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Doses of 15 to 20 mg orally induced modest elevations of systolic blood pressure as well as autonomic symptoms of piloerection and rhinorrhea (Charney et al, 1982), but no behavioral changes.
    2) Nausea, which was easily reversed by decreasing the dose, was reported in patients being treated with 18 mg a day (Morales et al, 1982).
    B) CASE REPORT
    1) CASE REPORT: A patient developed severe hypertension and seizures/coma following a massive ingestion of 5 g of yohimbine. Vital signs included blood pressure of 259/157 mm Hg and heart rate of 140 beats/min. Treatment included furosemide, labetalol, clonidine, and urapidil with response. The patient recovered and was discharged with no sequelae (Giampreti et al, 2009).
    2) CASE REPORT: A case of tachycardia (106 bpm) and transient hypertension (168/88 torr, while standing) occurred in a 62-year-old man following the ingestion of 200 mg of yohimbine (Friesen et al, 1993).
    3) CASE REPORT: A 25-year-old male bodybuilder ingested a massive amount of yohimbine (3 g) and developed hypotension, confusion, seizures, tachycardia and prolonged QRS interval and recovered uneventfully (Cimolai & Cimolai, 2011).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CHRONIC USE: A 23-year-old male body-builder, with a history of chronic yohimbine, caffeine and steroid use, collapsed outside of a fitness center. Upon admission to the ER, he developed seizures and his vital signs became elevated. He died several hours later. A postmortem yohimbine level (iliac blood) was 7,400 ng/mL. Toxicology testing was positive for caffeine, diphenhydramine and yohimbine; however, caffeine and diphenhydramine were not elevated. Yohimbine alone was determined to be the cause of death (Anderson et al, 2013).
    a) A second patient was a 37-year-old man that was found unresponsive with a reported recent history of taking a dietary supplement to lose weight. His postmortem blood (heart) level was 5400 ng/mL. Yohimbine was the only drug detected. (Anderson et al, 2013).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 16 mg/kg ((RTECS, 2000))
    2) LD50- (ORAL)MOUSE:
    a) 43 mg/kg ((RTECS, 2000))
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 37 mg/kg ((RTECS, 2000))

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Yohimbine enhances blood pressure and heart rate responses to a variety of stimuli which reflexively increases sympathetic outflow through multiple pathways (Goldberg & Robertson, 1983). Yohimbine is a competitive antagonist selective for alpha-2-receptor antagonist. It may also interact with alpha-1 adrenoceptors and in high concentrations, serotonin and dopamine receptors. As a centrally acting alpha-2 adrenergic blocking agent, yohimbine can increase sympathetic outflow and potentiate the release of norepinephrine. This will increase peripheral sympathetic activity. Yohimbine readily penetrates the CNS (Shannon & Neuman, 2000).
    B) Non alpha-2 receptor actions of yohimbine include alpha-1 antagonism (concentrations greater than 10(-5) M), local anesthetic action (concentrations greater than 10(-3) M), anticholinesterase activity (concentrations greater than 10(-3) M), monoamine oxidase inhibitor (concentrations greater than 10(-3) M), dopamine antagonist, serotonin antagonist (in vitro in concentrations greater than 10(-5) M), serotonin agonist (doses of 20 mg/kg).

Toxicologic Mechanism

    A) Yohimbine is an alpha-2 adrenergic antagonist that antagonize the effects of xylazine, increase the heart rate and blood pressure, cause CNS stimulation and antidiuresis, and cause hyperinsulinemic effects (Plumb, 1991).

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Yohimbine is FDA approved to reverse the effects of xylazine in dogs. While side effects of its use are uncommon, they may include hypersensitivity or anaphylaxis to its use, return of ability to feel painful stimuli, transient apprehension, CNS excitement, salivation, muscle tremors, and increased respiratory rates (Plumb, 1991).
    11.1.13) OTHER
    A) OTHER
    1) Yohimbine intravenously reduced recovery times of fallow deer immobilized with xylazine/ketamine (Stewart & English, 1990).

Range Of Toxicity

    11.3.1) THERAPEUTIC DOSE
    A) CATTLE
    1) For xylazine reversal in cattle and other bovines: 0.125 milligram/kilogram intravenously (Plumb, 1991)
    B) DOG
    1) For xylazine reversal in dogs and other canines: 0.11 milligram/kilogram slowly intravenously (Plumb, 1991)
    C) HORSE
    1) For xylazine reversal in horses and other equines: 0.075 milligram/kilogram intravenously (Plumb, 1991)
    D) CAT
    1) For xylazine reversal in cats and other felines: 0.5 milligram/kilogram intravenously (Plumb, 1991)
    11.3.2) MINIMAL TOXIC DOSE
    A) LACK OF INFORMATION
    1) No specific information on a minimal toxic dose was available at the time of this review.

Kinetics

    11.5.1) ABSORPTION
    A) LACK OF INFORMATION
    1) There was no specific information on absorption at the time of this review.
    11.5.2) DISTRIBUTION
    A) CATTLE
    1) Volume of distribution in steers is approximately 5 liters/kilogram (Plumb, 1991).
    B) DOG
    1) Volume of distribution in dogs is 4.5 liters/kilogram (Plumb, 1991).
    C) HORSE
    1) Volume of distibution in horses is 2 to 5 liters/kilogram (Plumb, 1991).
    11.5.4) ELIMINATION
    A) CATTLE
    1) Half-life is 0.5 to 1 hour (Plumb, 1991).
    B) DOG
    1) Half-life is 1.5 to 2 hours (Plumb, 1991).
    C) HORSE
    1) Half-life is 0.5 to 1.5 hours (Plumb, 1991).

Pharmacology Toxicology

    A) SPECIFIC TOXIN
    1) Yohimbine is an alpha-2 adrenergic antagonist that antagonizes the effects of xylazine, increases the heart rate and blood pressure, causes CNS stimulation and antidiuresis, and causes hyperinsulinemic effects (Plumb, 1991).

Sources

    A) SPECIFIC TOXIN
    1) Yobine(R): Yohimbine hydrochloride sterile solution for injection 2 milligrams/milliliter in 20 milliliter vials (manufactured by Lloyd and FDA approved for use in dogs).

Other

    A) OTHER
    1) SPECIFIC TOXIN
    a) Yohimbine HCl is commonly used to reverse the effects of xylazine in dogs, cats, horses, and many other species.
    b) Oral doses of yohimbine failed to increase serum prolactin levels in rats, suggesting that yohimbine is not useful as an antagonist for fescue toxicosis in cattle (Jernigan et al, 1986).

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