Yohimbine
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 1.7 Presentation, Formulation |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Properties of the substance |
| 3.3.1.1 Colour |
| 3.3.1.2 State/Form |
| 3.3.1.3 Description |
| 3.3.2 Properties of the locally available formulation |
| 3.4 Other characteristics |
| 3.4.1 Shelf-life of the substance |
| 3.4.2 Shelf-life of the locally available formulation(s) |
| 3.4.3 Storage conditions |
| 3.4.4 Bioavailability |
| 3.4.5 Specific properties and composition |
| 4. USES |
| 4.1 Indications |
| 4.1.1 Indications |
| 4.1.2 Description |
| 4.2 Therapeutic dosage |
| 4.2.1 Adults |
| 4.2.2 Children |
| 4.3 Contraindications |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. PHARMACOLOGY AND TOXICOLOGY |
| 7.1 Mode of action |
| 7.1.1 Toxicodynamics |
| 7.1.2 Pharmacodynamics |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 7.7 Main adverse effects |
| 8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological analyses and their interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple qualitative test(s) |
| 8.2.1.2 Advanced qualitative confirmation test(s) |
| 8.2.1.3 Simple quantitative method(s) |
| 8.2.1.4 Advanced quantitative method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple qualitative test(s) |
| 8.2.2.2 Advanced qualitative confirmation test(s) |
| 8.2.2.3 Simple quantitative method(s) |
| 8.2.2.4 Advanced quantitative method(s) |
| 8.2.2.5 Other dedicated method(s) |
| 8.2.3 Interpretation of toxicological |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central nervous system (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Others |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Relevant laboratory analyses |
| 10.2.1 Sample collection |
| 10.2.2 Biomedical analysis |
| 10.2.3 Toxicological analysis |
| 10.3 Life supportive procedures and symptomatic/specific treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussions |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
1. NAME
1.1 Substance
Yohimbine
1.2 Group
ATC classification index
All other therapeutic products (V03)/Other therapeutic
products (V03AX).
(WHO, 1992)
1.3 Synonyms
Aphrodine Hydrochloride
Chlorhydrate de Québrachine
Corynine Hydrochloride
Yo Yo
(Reynolds, 1993)
1.4 Identification numbers
1.4.1 CAS number
Yohimbine 146-48-5
Yohimbine Hydrochloride 65-19-0
1.4.2 Other numbers
RTECS
Yohimbine ZG1000000
1.5 Brand names, Trade names
Monocomponent products
Actibine, Aphrodyne, Dayto Himbin, Revervyl, Reverzine,
Yobine, Yocon, Yohimex, Yohydrol
Combination products
Afrodex, Ictho-Himbin, Pasuma, Pluriviron, Potensan, Potensan
Forte, Prowess, Vikonon
(To be completed by each Centre using local data)
1.6 Manufacturers, Importers
To be completed by each Centre using local data
1.7 Presentation, Formulation
Tablets, either as single ingredient or in combination with
other ingredients, for human use.
Sterile injectable solution for veterinary use.
Street drug (as a powder)
(To be completed by each Centre using local data)
2. SUMMARY
2.1 Main risks and target organs
Yohimbine is a centrally acting alpha-2-adrenoceptor blocking
agent. It may also interact with alpha-1-adrenoceptors and,
in high concentrations, serotonin and dopamine receptors.
Yohimbine is a monoamine oxidase inhibitor, and has the
potential to interact with tyramine-containing foods and
stimulants such as phenylephrine and phenylpropanolamine.
Yohimbine affects the gastrointestinal, genito-urinary,
respiratory, cardiovascular and central nervous systems.
2.2 Summary of clinical effects
Yohimbine produces cardiovascular effects, including
increases in heart rate and blood pressure.
Bronchospasm and increased mucous secretion has been
reported.
CNS effects include anxiety, hallucinations and manic
reactions.
Gastrointestinal effects include nausea, anorexia and
diarrhoea.
Dysuria, and back and genital pain have occurred.
Yohimbine has been used for its alleged aphrodisiac
properties but evidence of such an effect is lacking.
2.3 Diagnosis
There are no significant signs or symptoms which are a key to
clinical diagnosis.
Qualitative tests are available, and include Thin Layer
Chromatography and Gas Chromatography.
Although yohimbine may be quantified in the plasma by HPLC,
toxic levels have not yet been established.
2.4 First aid measures and management principles
Support respiratory and cardiovascular function. Emesis may
be indicated for substantial ingestions, especially if
initiated within 30 minutes of ingestion. Activated charcoal
may also be administered. Diazepam may be useful in reducing
anxiety.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Yohimbine is the principal indole alkaloid derived from the
bark of the Yohimbe Tree (Pausinystalia yohimbe = Corynanthe
yohimbi) (Rubiaceae). It is also found in the Rauwolfia root
and the dried bark of Aspidosperma quebracho.
(Reynolds, 1993)
3.2 Chemical structure
Structural formula
Molecular formula
Yohimbine C21H26N2O3
Yohimbine C21H26N2O3,HCl
Hydrochloride
Molecular weight
Yohimbine 354.4
Yohimbine 390.9
Hydrochloride
Structural Chemical names
Methyl 17alpha-hydroxy-yohimban-16alpha-carboxylate
hydrochloride.
(16alpha, 17alpha)-17-Hydroxyyohimban-16-carboxylic acid
methyl ester.
(Reynolds, 1993; Budavari, 1989)
3.3 Physical properties
3.3.1 Properties of the substance
3.3.1.1 Colour
No data available
3.3.1.2 State/Form
Yohimbine Hydrochloride
Orthorhombic plates
Prisms from alcohol
Yohimbine
Orthorhombic needles
3.3.1.3 Description
Yohimbine Hydrochloride
Decomposes at 302 °C
Soluble 1 in 120 of water and 1 in 400 of
alcohol
Aqueous solution pH approximately neutral
Yohimbine
Melting point 234 °C
Very slightly soluble in water
Soluble in ethanol and chloroform
Sparingly soluble in ether
3.3.2 Properties of the locally available formulation
To be completed by each Centre using local data.
3.4 Other characteristics
Store in a cool place. Do not freeze. Protect from light.
3.4.1 Shelf-life of the substance
No data available.
3.4.2 Shelf-life of the locally available formulation(s)
To be completed by each Centre using local data.
3.4.3 Storage conditions
Store in a cool place. Do not freeze. Protect from
light.
3.4.4 Bioavailability
To be completed by each Centre using local data.
3.4.5 Specific properties and composition
To be completed by each Centre using local data.
4. USES
4.1 Indications
4.1.1 Indications
In humans, yohimbine has been used for the treatment of
impotence.
In street use, Yohimbine has been misused as a mild
hallucinogen, and as an aphrodisiac.
As a veterinary preparation, yohimbine is used to
reverse xylazine-induced anaesthesia in animals
including deer, steers, dogs, cats and horses.
4.1.2 Description
Not relevant
4.2 Therapeutic dosage
4.2.1 Adults
Oral
0.1 mg/kg may produce stimulant effects.
6 mg three times daily has been used to treat
impotence.
Yohimbine has been given in doses up to 30 mg daily
(Moffat, 1986) and the German Pharmacopoeia states a
human dose of up to 100 mg/day (Dukes, 1988).
4.2.2 Children
No data available.
4.3 Contraindications
Yohimbine should not be used in cardiac, hepatic and renal
disease. It is a monoamine oxidase inhibitor, therefore
tyramine-containing foods and stimulants such as
phenylephrine and phenylpropanolamine should be avoided.
5. ROUTES OF ENTRY
5.1 Oral
Most common in humans.
5.2 Inhalation
The powdered street drug may be smoked.
5.3 Dermal
No data available.
5.4 Eye
No data available.
5.5 Parenteral
Yohimbine has been administered intravenously in clinical
research.
Accidental injection may occur, especially inveterinary
practice.
5.6 Other
No data available.
6. KINETICS
6.1 Absorption by route of exposure
The kinetic disposition of yohimbine was examined in 8 young
male subjects following a single oral dose of 10 mg yohimbine
hydrochloride. Oral absorption was rapid, with an oral
absorption half-life of 0.17 +/- 0.11 hours (approximately 11
minutes)(Owen et al, 1987). In a similar study the absorption
half-life was approximately 7 minutes (Guthrie et al., 1990).
Absorption is complete and peak plasma levels occur at 45 to
60 minutes after 10 mg orally (Owen et al, 1987; Guthrie et
al., 1990). The bioavailability showed a great variability,
ranging from 7 to 87% (Guthrie et al., 1990).
6.2 Distribution by route of exposure
Oral
Studies on the volume of distribution showed a very wide
range (mean 2.4 +/- 1.25 L/kg (Owen et al., 1987).
Parenteral
Rapid distribution phase after intravenous injection of 10
mg, alpha half-life approximately 6 minutes. Volume of
distribution was small (mean 0.26 L/kg) (Guthrie et al.,
1990).
6.3 Biological half-life by route of exposure
Yohimbine was rapidly eliminated from the plasma in 8 young
male patients receiving a single 10 mg dose of yohimbine
(half-life was 0.60 +/- 0.26 hours) (Owen et al., 1987).
After 10 mg yohimbine intravenously, half-life (beta) was
0.68 +/- 0.2 hours (Guthrie et al., 1990).
6.4 Metabolism
Since yohimbine is stable in blood, the rapid clearance of
yohimbine from human plasma suggests metabolism of the drug
by an organ with high blood flow, such as liver or kidney,
and a high extraction efficiency (Owen et al., 1987).
Ho et al. (1971) suggest that in mice the rapid metabolism of
yohimbine is primarily due to the hydrolysis of the 16-alpha
carboxylic acid methyl ester bond to yield yohimbinic acid.
However, the hydrolysis of yohimbine to yohimbinic acid is
unlikely to be a major metabolic route in humans. This is
based on data obtained from pharmacokinetic studies on
reserpine and raubasine, two indole alkaloids structurally
related to yohimbine.
Although both reserpine and raubasine contain a 16-alpha
carboxylic acid methyl ester moiety, de-esterification of
this group does not appear to be a significant metabolic
route for reserpine, and is not a rapid route for elimination
for raubasine in humans (Owen et al., 1987).
6.5 Elimination by route of exposure
Oral
Clearance after 10 mg yohimbine
Range 2.81 to 200 mL/min/kg
Mean 55.9 mL/min/kg
Less than 1% of unchanged drug was recovered in the urine in
24 hours.
(Owen et al., 1987).
Parenteral
Clearance after 10 mg yohimbine intravenously
Range 2.44 to 15.8 mL/min/kg
Mean 9.77 mL/min/kg
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
Yohimbine is a competitive antagonist selective for alpha
2-andrenoceptors, which are thought to be located on nerve
terminals and receptors and to mediate inhibition of
transmitter release. The presynaptic release of noradrenaline
is increased by an alpha-2-antagonist resulting in increased
sympathetic outflow. Yohimbine may also interact with alpha-
1-adrenoceptors and, in high concentrations, serotonin and
dopamine receptors (Dukes, 1988). Yohimbine has monoamine
oxidase inhibitory effects (Bhattacharya et al., 1991).
7.1.1 Toxicodynamics
It has been suggested that a central beta-origin
toxicity exists, since only beta blockers which cross
the blood-brain barrier are capable of antagonizing
this activity (Bourin et al., 1988).
7.1.2 Pharmacodynamics
Yohimbine is an alpha-2-adrenergic antagonist. It
increases the heart rate and blood pressure and causes
CNS stimulation and anti-diuresis (Reynolds et al.,
1989).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
An ingested dose of 1.8 g (100 times the
average daily dose) resulted in unconsciousness
for some hours, with priapism. The patient
recovered fully within a few days (Roth et al.,
1984; as cited in Dukes, 1988).
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
LD50 Oral (mouse) 43 mg/kg
LDLO Intravenous (mouse) 16 mg/kg
LDLO Intravenous (rabbit) 11 mg/kg
LD50 Subcutaneous (mouse) 20 mg/kg
LDLO Subcutaneous (rabbit) 50 mg/kg
(RTECS,1987)
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
No data available.
7.6 Interactions
Yohimbine has monoamine oxidase inhibitory effects, and
thus has the potential to interact with tyramine-containing
foods and stimulants such as phenylephrine and
phenylpropanolamine (Bhattacharya et al., 1991).
7.7 Main adverse effects
Principal adverse effects to be expected in humans with the
use of moderate doses are emotional arousal and a rise in
blood pressure and heart rate. An oral dose of 6 mg three
times per day resulted in only minimal adverse effects such
as dizziness and nervousness (Dukes, 1988).
8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological analyses and their interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple qualitative test(s)
Colour tests: Liebermann's Test - blue
Mandelin's Test - blue > green
8.2.1.2 Advanced qualitative confirmation test(s)
Thin-Layer Chromatography: system TA-Rf 63;
system TB-Rf 05; system TC-Rf 38 (Dragendorff
spray, positive; acidified iodoplatinate
solution, positive; Marquis Reagent, grey).
Gas Chromatography: system GA-RI 3296.
8.2.1.3 Simple quantitative method(s)
8.2.1.4 Advanced quantitative method(s)
High Pressure Liquid Chromatography. In plasma:
sensitivity 10 ng/mL, electrochemical
detection.
8.2.2 Tests for biological specimens
8.2.2.1 Simple qualitative test(s)
8.2.2.2 Advanced qualitative confirmation test(s)
8.2.2.3 Simple quantitative method(s)
8.2.2.4 Advanced quantitative method(s)
8.2.2.5 Other dedicated method(s)
8.2.3 Interpretation of toxicological
8.3 Biomedical investigations and their interpretation
No specific laboratory test are necessary unless clinically
indicated.
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.3.1.2 Urine
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
8.6 References
Goldberg MR et al. (1984) J Liq Chromat, 7: 1003-1004.
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Fatalities resulting from acute overdosage of yohimbine
have not been reported. Signs of overdosage include CNS
depression, ranging from drowsiness to coma.
Respiratory depression, hypothermia, diarrhoea,
vomiting, mental depression, flushing of the skin,
hypertension, cardiac arrhythmias, tachycardia and
short-term reversible paraesthesias of the legs and
feet may occur.
9.1.2 Inhalation
Mild hallucinations, including a disassociative state,
can occur when yohimbine is smoked (Linden et al.,
Siegel, 1976).
9.1.3 Skin exposure
Not relevant.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
Symptoms would be as for those listed in Section 9.1.1
(Ingestion).
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No data available.
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
Fatalities resulting from acute overdosage of yohimbine have
not been reported. Large overdoses may impair cardiac
function and cause CNS depression, including coma.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Tachycardia, atrial fibrillation and hypertension are
features of yohimbine toxicity. Systolic blood pressure
increased significantly in subjects given oral doses of
yohimbine. The differences for diastolic pressure were
not significant (Henauer et al., 1984).
Patients with orthostatic hypotension appear to be very
sensitive to the effects of 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)(Brosse et al., 1983).
9.4.2 Respiratory
Bronchospasm and increased mucous secretion have been
reported (Landis & Shore, 1989).
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
Dizziness, insomnia, headache and irritability
have been reported (Goldberg & Robertson,
1983).
Yohimbine produced manic reactions in bipolar
psychiatric patients. Symptoms included
tremulousness, restlessness, giddiness, rapid
speech, laughing, increased energy and euphoria
(Price et al., 1984).
Mild hallucinations, including a disassociative
state, can occur when yohimbine is smoked or
used in a tea (Linden et al, 1985; Siegel,
1976).
Inco-ordination was observed following abuse of
yohimbine (Linden et al., 1985). It is commonly
reported to cause anxiety (Charney et al.,
1983).
9.4.3.2 Peripheral nervous system
Short-term reversible paraesthesias of the legs
and feet were reported in diabetics being
treated for impotency and in overdoses (Morales
et al., 1982; Linden et al., 1985).
9.4.3.3 Autonomic nervous system
Not relevant
9.4.3.4 Skeletal and smooth muscle
Not relevant
9.4.4 Gastrointestinal
Nausea, vomiting, diarrhoea and anorexia have been
reported (Goldberg & Robertson, 1983).
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
Dysuria has been reported (Goldberg &
Robertson, 1983).
9.4.6.2 Others
Genital pain has been reported (Goldberg &
Robertson, 1983).
9.4.7 Endocrine and reproductive systems
Studies have shown yohimbine to be 3 to 3.4 times as
effective as placebo in relieving male impotency
(Sobotka, 1969).
9.4.8 Dermatological
Not relevant
9.4.9 Eye, ears, nose, throat: local effects
No data available.
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
Yohimbine is a monoamine oxidase inhibitor,
and thus has the potential for reacting with
tyramine-containing foods.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
No data available.
9.5 Other
No data available.
9.6 Summary
Not relevant
10. MANAGEMENT
10.1 General principles
Treatment is symptomatic and supportive, including
maintaining respiratory and cardiovascular function.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
Not relevant
10.2.2 Biomedical analysis
No specific analyses unless clinically indicated.
10.2.3 Toxicological analysis
Qualitative tests are available, and include Thin
Layer Chromatography and Gas Chromatography.
Although yohimbine may be quantified in the plasma
by HPLC, toxic levels have not yet been established.
10.3 Life supportive procedures and symptomatic/specific
treatment
Support respiratory and cardiovascular function.
Diazepam has been shown to be useful in treating yohimbine-
induced anxiety. Dose is given either orally or by slow
intravenous injection:
Adult 5 to 10 mg
Child 0.1 - 0.3 mg/kg bodyweight
If priapism is prolonged (more than 4 hours) then specific
treatment may be required, e.g. aspiration of the corpus
may be required.
10.4 Decontamination
Emesis should be considered following recent ingestion of
amounts exceeding the maximum therapeutic dose or if there
is evidence of any overdose, if the patient is not
comatose, is not convulsing, and has not lost the gag
reflex.
Where emesis is contraindicated, gastric lavage should be
considered.
Administer activated charcoal orally (adults 50 g; children
1 g/kg).
10.5 Elimination
No data available.
10.6 Antidote treatment
10.6.1 Adults
Clonidine has been used experimentally as an
antidote in normal volunteers to eliminate
yohimbine-induced anxiety (see Section 10.7).
10.6.2 Children
No data available
10.7 Management discussions
Clonidine 5 micrograms/kg bodyweight was found to eliminate
not only yohimbine-induced anxiety but also the increases
in blood pressure, plasma MHPG, and other autonomic
symptoms in a study using normal volunteers who ingested
30 mg yohimbine. However, before clonidine can be
recommended as a routine antidote for yohimbine toxicity,
further clinical evaluation is required (Charney et al.,
1983).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case 1
An ingested dose of 1.8 g yohimbine (100 times the average
daily rate) resulted in unconsciousness for some hours with
priapism. The patient recovered fully within a few days
(Roth et al., 1984; as cited in Dukes, 1988).
Case 2
A 38-year-old man with insulin dependent diabetes was
admitted two hours after taking 350 mg yohimbine. The drug
had been prescribed by a consultant psychiatrist for
erectile impotence complicated by depression.
On admission to hospital he was alert and oriented. His
blood pressure was 130/80 mmHg and his pulse was regular at
88 beats/minute. Six hours after admission he discharged
himself, but was readmitted 17 hours later in a drowsy and
confused state. He was having rigors and complained of
retrosternal pain. He did not appear to have taken any
other drug. His rectal temperature as 35.5°C and his blood
pressure was 135/85 mmHg. His hands and feet were warm and
well-perfused. Blood urea was 12.8 mmol/L, serum creatine
175 umol/L, and blood glucose 16.7 mmol/L. An electro-
cardiogram showed atrial fibrillation with a ventricular
rate of 150 beats/minute. The day after admission an
electrocardiogram showed sinus rhythm, and retrograde
amnesia for the preceding 24 hours persisted for four days.
Case 3
A 16-year-old female took an estimated 250 mg of a white
powder alleged to be yohimbine. Within 20 minutes she was
weak, had generalized paraesthesia, loss of coordination,
and was disassociative. She had a severe headache, was
dizzy, and had no tremors. A severe pressure-like
substernal chest pain was noted 4 hours post-ingestion, and
remained for 2 hours before subsiding spontaneously. The
next day, the patient remained weak and dizzy, with nausea,
sweating, severe headache and intermittent palpitations. On
examination more than 30 hours after ingestion, she had a
blood pressure of 150/80, pulse of 116 and respiration rate
of 24. She was anxious, with a blotchy erythematous rash on
her back and submucosal haemorrhage in the right tympanic
membrane. Symptoms resolved spontaneously but had lasted 36
hours (Linden et al., 1985).
11.2 Internally extracted data on cases
No data available.
11.3 Internal cases
To be completed by each Centre using local data.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
No specific antidote is available (see Section 10.7).
12.2 Specific preventive measures
Store in a cool place out of direct sunlight. Keep out of
reach of children.
12.3 Other
Not relevant.
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Authors Dr Wayne A. Temple
National Toxicology Group
University of Otago Medical School
Dr Nerida A. Smith
Pharmacy School
University of Otago
PO Box 913
Dunedin
New Zealand
Tel: 64-3-4797244
Fax: 64-3-4770509
Date July 1992
Reviewer Poisons Unit
New Cross Hospital
Avonley Road
London SE14 5ER
United Kingdom
Tel: 44-71-9555095
Fax: 44-71-6392101
Date July 1992
Peer Review Drs Deng, Ferner, Landoni, Maramba, Shintani,
Wickstrom. London, July, 1992.