Reserpine
1. NAME
1.1 Substance
Reserpine
1.2 Group
Antihypertensive
1.3 Synonyms
Reserpinium
1.4 Identification numbers
1.4.1 CAS number
50-55-5
1.4.2 Other numbers
1.5 Brand names, Trade names
Serpalan
Serpasil
Novoreserpine
Reserfia
1.6 Manufacturers, Importers
To be completed by local centre
2. SUMMARY
2.1 Main risks and target organs
The main risks associated with reserpine poisoning are
central nervous system depression , the development of
psychiatric depression, cardiovascular toxicity, and
gastrointestinal irritation.
The main target organs are the central nervous system,
cardiovascular system, and gastrointestinal tract.
2.2 Summary of clinical effects
The clinical effects include sedation and lethargy,
which can rarely progress to coma, and gastrointestinal
irritation which includes nausea, vomiting, and abdominal
cramping. Gastrointestinal irritation can be severe and
result in ulceration, perforation, and hemorrhage.
Psychiatric depression can be severe and lead to suicidal
thoughts and there can be nightmares, and vertigo.
Cardiovascular effects include hypotension and bradycardia.
Nasal congestion and flushing are also frequent. Hypothermia
has also been described. These effects are generally more
common with poisonings, oral daily reserpine doses greater
than 0.5 mg.
The most commonly reported effects were facial flushing,
lethargy which rarely progressed to coma, hypotension and
bradycardia. Death has been described from hypotension in 2
patients.
2.3 Diagnosis
The diagnosis of reserpine toxicity is primarily based
on a history of reserpine ingestion. The potential for
reserpine toxicity should be considered in cases where there
is no specific history of ingestion but there is potential
access to reserpine, the presence of hypertension treated
with unknown medications, or the use of unidentified herbal
medications.
2.4 First aid measures and management principles
The management of reserpine toxicity should be based
primarily on supportive care of the patient's respiratory and
cardiovascular function. The airway should be protected and
oxygenation adequate. Blood pressure should be adequate for
tissue perfusion. Gastrointestinal decontamination with
activated charcoal should be undertaken and the patient
monitored until symptoms of toxicity resolve. If hypotension
occurs and does not respond to the administration of
intravenous fluid, the administration of a direct acting
vasoconstrictor such as phenylephrine, norepinephrine, or
metaraminol is recommended, based on the catecholamine
depleting action of reserpine.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
An alkaloid from the roots of certain species of
Rauwolfia, family Apocynacea, usually Rauwolfia serpintina or
R. Vomitoria. Reserpine can also be synthesized.
(USPC, 1989)
3.2 Chemical structure
Methyl 11, 17 alpha-dimethoxy-18 beta (3,4,5-trimethoxy
benzolyl) reserpate
3.3 Physical properties
3.3.1 Properties of the substance
3.3.1.1 Colour
White or pale buff to slightly
yellow coloured. Darkens slowly on exposure
to light when powder, more rapidly when in
solution.
(USPC, 1989)
3.3.1.2 State/Form
Small crystals or crystalline
powder
(USPC, 1989)
3.3.1.3 Description
The pure alkaloid obtained from
Rauwolfia serpentina. A odorless, light
coloured crystalline powder which is
insoluble in water, freely soluble in
chloroform and acetic acid, and very slightly
soluble in alcohol and ether. The pKa is
6.6. In solution it unstable in the presence
of alkali.
(USPC, 1989)
3.3.2 Properties of the locally available formulation
To be added by local centres
3.4 Other characteristics
3.4.1 Shelf-life of the substance
To be added by local centres
3.4.2 Shelf-life of the locally available formulation
To be added by local centres
3.4.3 Storage conditions
Store in airtight containers, protect from
light.
(USPC, 1989)
3.4.4 Bioavailability
The reported bioavailability after oral
ingestion is approximately 50%.
(Reynolds, 1993)
3.4.5 Specific properties and composition
No information available
4. USES
4.1 Indications
4.1.1 Indications
4.1.2 Description
Hypertension
Raynaud's phenomenon
Possibly for prevention of attacks of familial
Mediterranean fever
Possibly for treatment of thyroid storm not responsive
to standard therapy
Historically reserpine has also been used for the
treatment of schizophrenia and tardive dyskinesia,
however, these uses are not used in current clinical
practice.
(USPC, 1989; Reynolds, 1993)
4.2 Therapeutic dosage
4.2.1 Adults
Hypertension: oral doses of 0.1 mg or 0.25 mg
daily, usually in conjunction with an oral
diuretic.
Raynaud's phenomenon: oral doses of 0.1 mg to 0.25 mg
daily.
Note: doses of 0.5 mg daily or greater are associated
with an increased frequency of depression and
psychiatric adverse effect.
(USPC, 1989; Reynolds, 1993)
4.2.2 Children
Hypertension: 0.005 mg/kg to 0.020 mg/kg body
weight daily, in 1 or 2 divided doses.
(USPC, 1989)
4.3 Contraindications
1) Absolute
Pregnancy
Psychiatric depression
Active peptic ulcer disease
Ulcerative colitis
Parkinson's disease
Phaeochromocytoma
Hypersensitivity to any rauwolfia alkaloid
2) Relative contraindications where the use of reserpine
should be undertaken with caution and started with lower
doses
Elderly patients
Cardiac arrhythmias
Myocardial infarction
Renal insufficiency
Asthma
(USPC, 1989; Reynolds, 1993)
5. ROUTES OF ENTRY
5.1 Oral
The most common route of administration and
poisoning
(McKown, et al, 1963; Pfeifer, et al, 1976)
5.2 Inhalation
No data available
5.3 Dermal
No data available
5.4 Eye
No data available
5.5 Parenteral
Intramuscular injection has been used for the urgent
treatment of hypertension. Intra-arterial injection has been
described in Raynaud's syndrome, but appears to be
ineffective. (Surwit, et al, 1983; Reynolds, 1993)
5.6 Other
No data available
6. KINETICS
6.1 Absorption by route of exposure
The reported bioavailability is approximately 50% to 70%
after oral ingestion. Absorption is relatively rapid, with
peak concentrations achieved approximately 1 to 2 hours after
administration of an oral solution. Slower absorption, with
peak concentrations at 2 to 4 hours has also been reported.
(Maass, et al, 1969; Reynolds, 1993)
6.2 Distribution by route of exposure
The volume of distribution has not been reported. It is
widely distributed into the brain, liver, spleen, kidney, and
adipose tissue. Reserpine binds to red blood cells and in
the peripheral neuron at its site of action. It is reported
not to bind to plasma protein. (Maass, et al, 1969; USPC,
1989) Reserpine crosses the placental barrier, and is found
in breast milk. (Briggs, et al, 1986; Ellenhorn & Barceloux,
1988; USPC, 1989; Reynolds, 1993) An initial half-life of
distribution of approximately 4 to 5 hours is observed after
oral administration. (Maass, et al, 1969)
6.3 Biological half-life by route of exposure
Reserpine can be described using a two compartmental
pharmacokinetic model. The elimination half-life ranges from
45 to 168 hours in plasma. Because of binding to red blood
cells, the terminal elimination half-life is longer when
whole blood levels is measured, and has been reported to be
386 hours. (Maass, et al, 1969) The half-life is longer in
patients with renal insufficiency. Zsoter and associates
(1973) observed that the elimination half-life was
significantly prolonged in patients with creatinine clearance
values of less than 10 mL/min.
6.4 Metabolism
Hepatic metabolism accounts for less than 50% of the
elimination of reserpine, with the remainder being eliminated
in the faeces, and some unmetabolized reserpine and
metabolites being eliminated in the urine. (USPC, 1989) In
man, metabolites are methylreserpate and trimethoxybenzoic
acid. (Maass et al, 1969) Metabolism may be more important
with intramuscular administration.(Zsoter, et al, 1973)
6.5 Elimination by route of exposure
The elimination of reserpine and its metabolites in the
faeces ranges from 30% after intramuscular administration to
approximately 60% after oral administration, primarily as
unmetabolized reserpine, over a 4 day period after the
administration of 0.25 mg to 0.50 mg doses. (Maass et al,
1969; Zsoter et al, 1973) Over the same time period
approximately 8% of the administered dose was recovered in
the urine, primarily as the trimethoxybenzoic acid
metabolite.
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
The mechanism of reserpine's toxic effects is
similar to the mechanism of it's pharmacologic
effects. Reserpine inhibits normal sympathetic
activity in both the CNS and peripheral nervous system
by binding to catecholamine storage vesicles. This
prevents the normal storage of catecholamines and
serotonin in the nerve cell, with the result being
catecholamine depletion. Reserpine has also been
described as inhibiting catecholamine synthesis by
blocking the uptake of dopamine into the storage
vesicle. (Ellenhorn & Barceloux , 1989; Gilman et al,
1990)
7.1.2 Pharmacodynamics
Reserpine inhibits normal sympathetic activity
by decreasing the storage of catecholamines at the
pre-synaptic, CNS, and peripheral neuron. Reserpine
binds to the storage vesicles, causing catecholamines
to leak into the synapse so that they are not
available for release when the pre-synaptic neuron is
stimulated. The process appears to affect serotonin
storage in a similar manner.
These actions result in a reduction in both cardiac
output and peripheral vascular resistance with long
term therapy, which takes approximately 3 weeks to
develop after the initiation of therapy. Heart rate
and renin concentrations decrease, and there is sodium
and water retention. (Gilman, et al, 1990)
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
There are few reported cases of
reserpine poisoning in adult patients. In a
series of 151 cases reported from the United
States from 1959 to 1960 only 4% were adults.
Nausea, vomiting, hypotension, sedation, and
coma were described in these patients.
(McKown et al, 1963) It would be expected
that poisoned adults would have bradycardia,
facial flushing, and the other symptoms
associated with reserpine poisoning in
children.
Psychiatric depression is historically the
most important adverse effect associated with
the chronic administration of reserpine for
the treatment of hypertension. The
depression is most common with daily doses of
0.5 mg or greater, and the frequency is
significantly decreased when the dose is 0.25
mg or lower. The depression is often severe,
can occur in patients without a prior history
of depressive illness, and may last for
months after reserpine is discontinued.
(Anon, 1976)
7.2.1.2 Children
Most of the reported cases of
reserpine poisoning have been in children.
In the series of cases reported by McKown and
associates (1963), 142 of the 151 cases of
rauwolfia poisoning were in children less
than 13 years of age. Approximately 40% of
the cases had some symptoms, Mild CNS
depression such as lethargy or sedation was
the most common symptom, and facial flushing
the next most common. Hospitalization for
toxicity was needed in 24 of the 142
pediatric cases. Nausea, vomiting,
hypotension and vertigo were also described.
Loggie and associates (1967) reported that
during the period of 1962 to 1965 there were
no cases of serious toxicity in 225 reports
of accidental ingestion.
Individual cases of toxicity include
information about potential doses of
reserpine ingested and the time course of
toxicity. A 20 month-old-male who ingested
260 mg reserpine had symptoms of lethargy,
flushing, rapid pulse rate and slowed
respiration. Within 21 hours the symptoms had
primarily resolved without any specific
therapy other than a cathartic. A mild
leucocytosis resolved within 2 weeks.
(Hubbard, 1955) Three cases of reserpine
ingestion in children between 30 months and 4
years of age, who ingested doses of reserpine
as large as 25 mg (2 cases), and an unknown
dose (1 case), demonstrated a wide range of
toxicity. All cases had some lethargy and
CNS depression which progressed to coma.
Bradycardia and hypothermia was also
documented in all cases, while the youngest
child also had an episode of hypertension and
tachycardia starting about 10 hours after
ingestion. (Loggie, et al, 1968)
7.2.2 Relevant animal data
No data available
7.2.3 Relevant in vitro data
No data available
7.3 Carcinogenicity
There does not appear to be an association between
reserpine administration and cancer. Three studies in the mid
1970's reported an increased risk of breast cancer in female
patients who had taken reserpine for the treatment of
hypertension. After these studies, an additional 9 studies
concluded that there was no increase in the risk of breast
cancer associated with reserpine therapy. It appears that a
flaw in the initial study designs resulted in an exclusion
bias which may have falsely suggested a positive relationship
between reserpine use and breast cancer. (Horwitz &
Feinstein, 1985)
Studies in rats and mice using doses at least 100 fold
greater than the usual human dose have demonstrated an
increased incidence of mammary fibroadenomas, malignant
tumors of the seminal vesicles, and malignant adrenal
medullary tumors, (USPC, 1989)
7.4 Teratogenicity
Reserpine administered in large doses has been
demonstrated to be teratogenic in rats and guinea pigs.
(USPC, 1989) There are no controlled studies in humans. In
48 cases of mothers who had taken reserpine during their
first trimester of pregnancy, the incidence of birth defects
was 8%, higher than expected, although no major types of
malformations were seen. There was no increased risk of
birth defects in women who ingested reserpine at any time
during their pregnancy. (Briggs, et al, 1986)
7.5 Mutagenicity
Recent studies have suggested a lack of mutagenic,
genotoxic, and recombinogenic effects. (von Poser, et al,
1990)
7.6 Interactions
The following drugs have been reported to interact with
reserpine:
Alcohol and CNS depressant drugs - increased sedation
Nonsteroidal antiinflammatory drugs - increased risk of
gastric irritation
Drugs with antimuscarinic actions - increased gastric acid
secretion
Beta-adrenergic blocking agents - additive beta adrenergic
blockade
Bromocriptine - increased serum prolactin and decreased
bromocriptine activity
Digitalis glycosides - possible increase in bradycardia and
arrhythmias
Quinidine - possilbe increase in arrhythmias
Estrogens - decrease antihypertensive effects of
reserpine
Drugs causing extrapyramidal adverse effects - potentiate
extrapyramidal activity
Antihypertensive agents- hypotension
Levodopa - decreased efficacy of levodopa
Monoamine oxidase inhibitors - increased CNS depression or
increased blood pressure and CNS stimulation
Sympathomimetics - decreased effects of reserpine
(Ellenhorn & Barceloux, 1988; USPC, 1989; Reynolds,
1993)
7.7 Main adverse effects
The main adverse effects described with the therapeutic
administration of reserpine include lethargy and sedation,
psychiatric depression, hypotension, nausea, vomiting,
abdominal cramping, gastric ulceration, nightmares or vivid
dreams, bradycardia, and bronchospasm (in asthmatics) Much
less common are symptoms of skin rash or itching,
Parkinsonian effects, and thrombocytopenia. Adverse effects
are more common with daily doses of reserpine of 0.5 mg or
greater. The lethargy and sedation is more common when other
CNS depressant drugs are being used concurrently.
Adverse reactions were reported in 26 of 231 hospitalized
patients who received reserpine (Pfeifer et al, 1976) Three
reactions after intramuscular reserpine doses of 0.5 mg or
greater were considered life-threatening (hypotension in 2
patients, cerebral edema in 1 patient), but no deaths were
attributed to reserpine. Bronchospasm has been described
when reserpine is administered to asthmatics, and may be
relatively common (Segal, 1970) A case of withdrawal
psychosis has been described (Samuels & Taylor, 1989).
(Pfeifer, et al, 1976; USPC, 1989; Reynolds, 1993)
8. TOXICOLOGICAL ANALYSES ETC.
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 analyses
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
8.3.4 Interpretation of biomedical investigations
8.4 Other biomed. investigations etc.
8.5 Overall Interpretation etc.
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Poisoning with reserpine most commonly results
in lethargy, sedation, and infrequently results in
coma. Other effects include psychiatric depression,
hypothermia, facial flushing, nausea, vomiting,
abdominal cramping, and cardiovascular toxicity
including hypotension and bradycardia. (McKown, et al,
1963; Loggie, et al, 1967)
9.1.2 Inhalation
No data available
9.1.3 Skin exposure
No data available
9.1.4 Eye contact
No data available
9.1.5 Parenteral exposure
After intramuscular injection of therapeutic
doses of reserpine, hypotension, bronchospasm,
lethargy and sedation have occurred. These effects are
most commonly secondary to larger doses (0.5 mg or
greater), and are not expected to be any different
than the adverse effects associated with oral
reserpine administration.
(Pfeifer, et al, 1976; Segal, 1969)
9.1.6 Other
No data available
9.2 Chronic poisoning
9.2.1 Ingestion
The development of psychiatric depression,
which can be severe, and gastric ulceration and
hemorrhage are the most severe adverse effects of
chronic reserpine therapy. Nasal congestion, dry
mouth, diarrhoea, abdominal pain, lethargy,
Parkinsonian features, breast enlargement,
galactorrhoea, impotence, sodium retention, peripheral
oedema, and weight gain have been reported much less
commonly. (Anon, 1976; USPC, 1989; Reynolds,
1993)
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
The administration of intramuscular reserpine
results in adverse effects similar to those seen with
oral administration. They are more commonly reported
following intramuscular injection because of the
larger doses administered and the increased
bioavailability associated with this route (Pfeifer,
1976).
9.2.6 Other
No data available
9.3 Course, prognosis, cause of death
Symptoms of toxicity develop over the first 4 hours
after ingestion. Symptoms generally resolve over 18 to 24
hours. Approximately 15% of the children described by McKown
et al (1963) required admission to the hospital for
observation. The prognosis is generally very good, and
patients recover without sequelae (Hubbard, 1955; Loggie et
al, 1967).
The psychiatric depression can take months to resolve (Anon,
1976).
Two deaths following reserpine poisoning have been reported
in the Russian literature. Both cases were adults who died
of cardiovascular collapse and multi-organ system failure in
the first few days after ingestion. One patient was known to
have ingested 5.0 mg of reserpine. (Landyshev, et al, 1969;
Rogal, et al, 1989)
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Cardiovascular effects associated with
reserpine poisoning are relatively uncommon, with only
2 cases of hypotension reported in a total of 151
patients. (McKown, et al, 1963) Bradycardia is also
described, and there is one case of tachycardia and
hypertension which developed approximately 10 hours
after ingestion. (Loggie et al, 1967) Angina-like
symptoms, and dysrrhythmias are possible when
reserpine is administered to patients taking a
digitalis glycoside, quinidine, or procainamide.
(Ellenhorn & Barceloux, 1988).
9.4.2 Respiratory
Upper respiratory bronchospasm and nasal
congestion may occur.
9.4.3 Neurological
9.4.3.1 CNS
The most common symptoms with
poisoning are lethargy and sedation, which
occurred in 44% of 151 rauwolfia poisonings.
(McKown, et al, 1963). Coma is much less
common. A decrease in body temperature may
develop. With poisonings, psychiatric
depression may occur, however, it is more
commonly described with chronic reserpine
use. Additional CNS effects include
nightmares and vivid dreams, vertigo,
headache, dizziness, nervousness, anxiety,
and rarely deafness. (Ellenhorn & Barceloux,
1988). The development of extrapyramidal
symptoms including dystonia and Parkinson's
symptoms is reported, though it is not clear
whether these develop after poisonings, or
only with chronic therapy. (Haddad &
Winchester, 1983) Tardive dyskinesia has
also been suggested, though cases are not
identified in the literature. (Bacher &
Lewis, 1984). There is a case of reserpine
withdrawal psychosis which developed over 1
week after a 66 year old female ceased the
daily ingestion of 3 mg of reserpine.
(Samuels & Taylor, 1989) Reserpine lowers
the seizure threshold, however, clonic
seizures have been described in only one case
(Loggie et al, 1967)
9.4.3.2 Peripheral nervous system
The effects of reserpine on the
peripheral nervous system catecholamine
stores would be expected to diminish the
responsiveness of the reserpine poisoned
patients to indirect acting vasoconstrictors
such as dopamine. Direct acting agents such
as phenylephrine, metaraminol, and
norepinephrine are suggested as
vasoconstrictors for the treatment of
hypotension which is unresponsive to
intravenous fluids. (Reynolds,
1993)
9.4.3.3 Autonomic nervous system
No direct effects are described.
The development of gastrointestinal
ulceration is described as being due to
increased gastric acid secretion which could
be due to changes in autonomic nervous system
function. (Reynolds, 1993)
9.4.3.4 Skeletal and smooth muscle
Gastric cramping is described.
Muscle weakness can also occur. (USPC,
1989)
9.4.4 Gastrointestinal
Abdominal cramping, nausea, vomiting. Gastric
ulceration and hemorrhage are less common. (USPC,
1989; Reynolds, 1993)
9.4.5 Hepatic
No data available
9.4.6 Urinary
9.4.6.1 Renal
No data available
9.4.6.2 Other
Painful or difficult urination is
described as a rare adverse effect of chronic
therapy. (USPC, 1989)
9.4.7 Endocrine and reproductive systems
Chronic therapy is associated with breast
engorgement and galactorrhoea. Gynaecomastia,
increased prolactin concentrations, decreased libido
and impotence are also potential adverse effects of
chronic therapy. It is not known whether these
effects occur with acute poisonings. (Reynolds,
1993)
9.4.8 Dermatological
Facial flushing, rashes, and pruritis.
(Reynolds, 1993)
9.4.9 Eye, ear, nose, throat: local effects
Nasal congestion, sialorrhoea, slight decrease
in color vision, conjunctival injection, lachrymation,
and miosis. (USPC, 1989; Reynolds, 1993)
9.4.10 Haematological
Thrombocytopenic purpura (Reynolds, 1993)
9.4.11 Immunological
Angioimmunoblastic lymphadenopathy (Ellenhorn
& Barceloux, 1988)
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available
9.4.12.2 Fluid and electrolyte disturbances
Sodium and water retention with the
development of edema. (Reynolds, 1993)
9.4.12.3 Others
No data available
9.4.13 Allergic reactions
There is cross sensitivity with reserpine
among the different rauwolfia substances. Reports of
allergic reactions were not identified. (USPC, 1989)
9.4.14 Other clinical effects
Not identified
9.4.15 Special risks
The administration of reserpine at the end of
pregnancy can cause nasal congestion, respiratory
distress, cyanosis, poor feeding, and lethargy in the
newborn infant.
Reserpine is accepted therapy during breastfeeding
based on the recommendations of the American Academy
of Pediatrics. (Briggs et al, 1986.)
9.5 Other
Most reserpine poisonings were reported in the 1960's,
and there are few recently described cases. Toxicity is
generally not severe and results most commonly in lethargy
and sedation, and gastrointestinal irritation. Hypotension,
usually mild and not requiring treatment, mild hypothermia,
and bradycardia are less frequently seen. Psychiatric
depression is more likely to occur with chronic therapy with
doses of 0.5 mg or greater daily, as are the majority of the
other reported adverse and toxic effects of reserpine.
Facial flushing also occurs in poisonings.
9.6 Summary
10. MANAGEMENT
10.1 General principles
The patient should be assessed to determine that the
airway is clear, oxygenation is adequate, and the blood
pressure and heart rate are compatible with adequate tissue
perfusion. Patients with a recent ingestion may benefit from
activated charcoal. The patient should be observed until
symptoms resolve. Treatment of symptoms such as bradycardia
and hypotension should follow the general principles of
supportive care. The use of atropine and H2-histamine
receptor antagonists may be considered for treatment of
gastric hyperacidity.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
Laboratory analysis for the presence of
reserpine in urine or blood has not been demonstrated
to be useful in the management of the poisoned
patient.
10.2.2 Biomedical analysis
There are no specific laboratory analyses
which would be required as part of the assessment and
management of reserpine toxicity.
10.2.3 Toxicological analysis
Reserpine assays are not generally performed,
and it is unlikely that they would be of benefit in
the management of reserpine toxicity.
10.2.4 Other investigations
A history of the ingestion of reserpine or
other rauwolfia alkaloids, the presence of
hypertension which may be treated by reserpine, or
access to reserpine is the most useful information
when assessing the likelihood of reserpine poisoning
as a diagnosis.
10.3 Life supportive procedures etc.
The patient should be evaluated to determine that the
airway is clear, breathing and circulation are adequate, and
observed until clinical signs of toxicity have resolved,
Symptomatic bradycardia can be treated with atropine.
Hypotension is treated initially with intravenous fluids. If
vasopressor drug therapy is necessary, norepinephrine,
phenylephrine, or metaraminol would be more likely to be
effective, based on the mechanism of reserpine's toxicity
(Reynolds, 1993)
10.4 Decontamination
If the patient has symptoms of reserpine toxicity upon
presentation for treatment, or a history of the ingestion of
reserpine as a poisoning or overdose, gastrointestinal
decontamination may be considered. Activated charcoal
administration would likely be of benefit in the first few
hours after ingestion, however, there is no data available to
indicate that reserpine is adsorbed to activated charcoal, or
is beneficial in the treatment of reserpine ingestions. It
is probably less likely that ipecac syrup or gastric lavage
would be useful in treatment.
10.5 Elimination
There is no evidence that forced diuresis, changing
urinary pH, and other measures such as hemodialysis or
hemoperfusion are effective in increasing reserpine
elimination from the body. These treatments are not
recommended for the treatment of reserpine poisonings.
10.6 Antidote treatment
10.6.1 Adults
None
10.6.2 Children
None
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case 1. A 20 month old boy ingested 260 mg of
reserpine, and was discovered to be lethargic, and flushed
with slowed respirations, a rapid pulse rate, and temperature
of 101.4 F four hours later. He was treated with two
teaspoonfuls of magnesia magma and observed. He was
lethargic, had facial flushing, nasal congestion, and was
otherwise normal the next day. (Hubbard 1956)
Case 2. A 3 year old female ingested an unknown dose of
reserpine which could have been as large as 25 mg. She was
drowsy and had a mild decrease in temperature to 95.5 o F
measured rectally. She had no other findings and her heart
rate, respiration, and blood pressure remained normal. She
recovered over the next 48 hours without specific therapy.
(Loggie et al, 1967)
Case 3. A 2 year old male, the brother of Case 2 above, also
presented after ingestion of an unknown dose of reserpine
which could have been as large as 25 mg. He was drowsy and
had constricted pupils upon presentation to the hospital,
with a normal temperature, pulse, respiratory rate, and blood
pressure. Over the next 7 hours he became more lethargic and
was comatose 9 hours after presentation. He had a rectal
temperature of 96.4 o F, and his blood pressure decreased to
95/60 mmHg. An hour later his blood pressure had increased
to 170/110 mmHg and remained elevated for approximately a day
and one half. He had tremor and episodic clonic movements of
his arms and legs during this time. The boy's mental status
started to improve about 18 hours after ingestion, and had
returned to normal 10 hours later. Gastric lavage and a
saline enema were administered when the boy was admitted to
the hospital, and maintenance doses of intravenous fluids
administered over the first 36 hours. (Loggie et al,
1967)
11.2 Internally extracted data on cases
To be entered by each centre
11.3 Internal cases
To be entered by each centre
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
None
12.2 Specific preventive measures
None
12.3 Other
None
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14. AUTHOR(S), ETC.
Dr. S. Lall, New Delhi
Reviewer, Dr. Wm A. Watson, Kansas City
Reviewed at INTOX-9, Cardiff, Wales, Sept, 1996