This document summarizes a study on the chronic toxicity of chloroquine, an antimalarial drug. In the study:
1) Two groups of 20 subjects each were given different dosage schedules of chloroquine for one year to study long-term toxicity - one group received 0.3 grams daily for 77 days then 0.5 grams weekly, the other received 0.5 grams weekly the whole time.
2) Toxic effects observed included visual difficulties, hair bleaching in blondes, mild skin eruptions in two subjects, slight weight loss, and temporary electrocardiogram changes in the daily dosage group.
3) Plasma chloroquine concentrations were measured,
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
The Effects of Rauwolfia Vomitoria Extract on the Liver Enzymes of Carbon Tet...IOSR Journals
Rauwolfia vomitoria is a natural medicinal plant which has been used over the years for the treatment of various ailments. The effects of extract of rauwolfia vomitoria on liver enzymes of carbon tetrachloride induced hepatotoxicity were observed in adult wistar rats weighing between 120g and 190g. They were divided into four groups A,B, C and D of six rats each. Group A served as the control and received 0.41ml of distilled water. The experimental groups B, C and D received different doses of drugs as follows : group B received 0.50ml of rauwolfia vomitoria extract, group C received 0.5ml of carbon tetrachloride and group D received 0.41ml of carbon tetrachloride + 0.4ml of rauwolfia vomitoria extract. The drugs were administered once in a day using intubation method for a period of twenty one days. Twenty four hours after the last administration, the animals were anaesthetized under chloroform vapour and dissected . liver tissues were removed and weighed. Blood samples were collected by cardiac puncture and Serum samples were separated from clot by centrifugation using bench top centrifuge. Activities of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were determined using randox kit method. The relative liver weight for carbon tetrachloride treated group were significantly higher (p<0.001)><0.001) than the control. The extract exhibited a liver protective effect against carbon tetrachloride induced hepatotoxicity
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
The Effects of Rauwolfia Vomitoria Extract on the Liver Enzymes of Carbon Tet...IOSR Journals
Rauwolfia vomitoria is a natural medicinal plant which has been used over the years for the treatment of various ailments. The effects of extract of rauwolfia vomitoria on liver enzymes of carbon tetrachloride induced hepatotoxicity were observed in adult wistar rats weighing between 120g and 190g. They were divided into four groups A,B, C and D of six rats each. Group A served as the control and received 0.41ml of distilled water. The experimental groups B, C and D received different doses of drugs as follows : group B received 0.50ml of rauwolfia vomitoria extract, group C received 0.5ml of carbon tetrachloride and group D received 0.41ml of carbon tetrachloride + 0.4ml of rauwolfia vomitoria extract. The drugs were administered once in a day using intubation method for a period of twenty one days. Twenty four hours after the last administration, the animals were anaesthetized under chloroform vapour and dissected . liver tissues were removed and weighed. Blood samples were collected by cardiac puncture and Serum samples were separated from clot by centrifugation using bench top centrifuge. Activities of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were determined using randox kit method. The relative liver weight for carbon tetrachloride treated group were significantly higher (p<0.001)><0.001) than the control. The extract exhibited a liver protective effect against carbon tetrachloride induced hepatotoxicity
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Multiple epidemics of chronic kidney disease of an unknown etiology (CKDu), primarily in young healthy agricultural workers, have emerged in agricultural communities around the world. It is proposed that heat stress, dehydration and/or toxicant exposures may be a cause of this emerging disease. We have hypothesized that the harvest and burning of sugarcane leading to inhalation of sugarcane ash may contribute to development of CKDu. Sugarcane stalks consist of ~80% amorphous silica and we have demonstrated that following burning of sugarcane, nano-sized silica particles (~200 nm) are generated.
Cycloartanes from Tabernaemontana coronaria (Jacq) Willd flowers with their c...Akhil Gupta
The n-hexane fraction of Tabernamontana coronaria (Jacq) Willd flowers afforded two cycloartane type triterpenes, cycloart-25-en-3β, 24 diol and cycloart-23-en-3β, 22α, 25triol for the first time from this plant, in addition to lupeol acetate, α-amyrin, cycloeucalenol, stigmasterol.
Intercontinental journal of pharmaceutical Investigations and ResearchSriramNagarajan19
Anti-inflammatory activity of the ethanolic extract of Portulaca quadrifida Linn. was studied in wister rats using the carrageenan induced left hind paw edema, carrageenan induced pleurisy and cotton pellet induced granuloma model. The ethanolic extract (200 mg/kg, p.o.,) produced the inhibition of carrageenan induced rat paw edema. It also showed an inhibitory effect on leukocyte migration and a reduction on the pleural exudates as well as reduction on the granuloma weight in the cotton pellet granuloma method. The results indicated that the ethanolic extract produced significant (P<0.001) anti-inflammatory activity when compared with the standard and untreated control.
Intake of Black Vinegar on Anthropometric Measures, Cardiometabolic Profiles,...mahendrareddychirra
Obesity and type 2 diabetes mellitus are the most important chronic diseases around the world. They are associated with huge medical expenditure and with increasing morbidity and mortality among related cardio-metabolic diseases in developing and developed countries [1,2].
Vinegar was first reported to have anti-glycemic effects since 1988 in animal and human studies [3]. Vinegar may be associated with improved insulin sensitivity and delayed gastric emptying that accompanied improved glycemic control and reduced body weight [4,5].
Sugarcane Ash and Sugarcane Ash-Derived Silica Nanoparticles Alter Cellular M...Arthur Stem
Multiple epidemics of chronic kidney disease of an unknown etiology (CKDu), primarily in young healthy agricultural workers, have emerged in agricultural communities around the world. It is proposed that heat stress, dehydration and/or toxicant exposures may be a cause of this emerging disease. We have hypothesized that the harvest and burning of sugarcane leading to inhalation of sugarcane ash may contribute to development of CKDu. Sugarcane stalks consist of ~80% amorphous silica and we have demonstrated that following burning of sugarcane, nano-sized silica particles (~200 nm) are generated.
Clinical Toxicology by dr.tayyaba rphpptBIANOOR123
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La reprise sera décarbonée ou ne sera pas
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Les deux temps forts de cet évènement
- Les journées entreprises de la Banque africaine de développement avec au programme deux jours de conférences, des ateliers sectoriels et la possibilité de présenter votre entreprise lors d'un "Brown bag seminar" ou d'obtenir des rendez-vous.
- Des rencontres avec les autres banques et agences de développement pour un focus sur la Côte d'Ivoire : réserve de projets, pistes novatrices de cofinancements, l'action des institutions régionales, et l'accompagnement du secteur privé par les banques locales.
eCommerce appetite and adoption is at an all-time high.
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Mercatus has released the results from a survey conducted in the first quarter of 2016 in a brand new report entitled “Insights into Grocery eCommerce 2016”.
Among the key findings in the report:
Your customers, regardless of age, are online, consider themselves to be technologically savvy, and are making more digital purchases than ever before.
Consumers are willing to order groceries from locations other than their favorite store for the convenience of click-and-collect shopping.
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
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mortality, and public health costs than all illicit drugs combined. The
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(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
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drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
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the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
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Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
STUDIES ON THE CHRONIC TOXICITY OF CHLOROQUINE 1948
1. STUDIES ON THE CHRONIC TOXICITY OF
CHLOROQUINE (SN-7618)
Alf S. Alving, … , C. Merrill Whorton, Theodore N. Pullman
J Clin Invest. 1948;27(3):60-65. https://doi.org/10.1172/JCI101974.
Research Article
Find the latest version:
http://jci.me/101974/pdf
Pdf
2. STUDIES ON THE CHRONIC TOXICITY OF CHLOROQUINE
(SN-7618) 1
BY ALF S. ALVING, LILLIAN EICHELBERGER, BRANCH CRAIGE, JR.,2 RALPH
JONES, JR.,2 C. MERRILL WHORTON,2 AND THEODORE N. PULLMAN 2
(From the Malarial Research Unit, Department of Medicine, University of Chicago)
(Received for publication March 12, 1947)
Ch loroquine, 7-chloro-4- (4-diethylamino-l-
methylbutylamino) quinoline, is an antimalarial
drug of the 4-amino quinoline series. It has been
shown to have antimalarial activity similar to and
superior to that of quinacrine in avian malaria, and
in trophozoite- and sporozoite-induced vivax and
falciparum malaria in man (1, 2, 3, 4).
The present study was undertaken for the pur-
pose of establishing whether chloroquine can be
administered for prolonged periods as a suppres-
sive drug without causing serious toxicity. To
accentuate toxic manifestations and establish the
margin of safety, larger dosages than those neces-
sary for suppressive treatment were administered.
Normal inmate volunteers at the Illinois State
Penitentiary at Stateville served as subjects for
these investigations.
PROCEDURES AND METHODS
The subjects under study were selected on the
basis of history and physical examination to ex-
clude any volunteer with physical disability or
neurosis. The following observations and tests
were made prior to initiating treatment and were
repeated at frequent intervals during the early
1 This investigation was carried out under a contract,
recommended by the Committee on Medical Research,
between the Office of Scientific Research and Develop-
ment and the University of Chicago. The work was
planned in cooperation with the Panel on Clinical Test-
ing of Antimalarials of the Board for Coordination of
Malarial Studies. This work was further aided by the
participation of Army Medical Officers assigned to the
project by the Surgeon General, U. S. Army.
The authors express their thanks to the Malaria Study
Section of the National Institute of Health for editorial
assistance and for arrangements in regard to the publi-
cation of this paper. They are also grateful to the
Abbott Laboratories, E. I. du Pont de Nemours and
Company, Inc., E. R. Squibb and Sons, Eli Lilly and
Company, Sharp and Dohme, Inc., and Wyeth,' Inc., for
contributing toward the publication costs.
2 Captain, M.C., A.U.S.
course of medication and later at gradually increas-
ing intervals:
General
Subjective symptoms
Oral temperature
Weight
Physical appearance
Cardiovascular System
Pulse rate
Blood pressure
Electrocardiogram
Blood
Erythrocyte count
Leucocyte count, total
and differential
Hemoglobin
Liver
Urine urobilinogen
Serum bilirubin
Cephalin-tholesterol floc-
culation
Kidneys
Urinalysis
Blood non-protein nitro-
gen
Phenolsulfonphthalein
excretion
Nervous System
Visual acuity
Diplopia
Visual accommodation
(monocular)
Nystagmus
Extraocular movements
Tremor
Coordination and gait
Handwriting
Romberg test
Deep reflexes
Toxicity studies were begun simultaneously on
two groups of 20 subjects each. The first group
was placed on a weekly-dosage schedule of 0.5
gram of chloroquine base, administered orally once
a week. The second group was given a total daily
dosage of 0.3 of the base in two doses (0.1 and
0.2 gram) for 77 days. At the end of this period
the volunteers in the latter group joined those on
the weekly-dosage regime at 0.5 gram (base) once
a week, and both groups continued on this sched-
ule for a total time of one year. Placebos were
given for one week before and for two months
after the year of chloroquine administration.
During the periods of placebo administration no
change was made in the routine of observation.
Because of parole, discharge, or for administra-
tive reasons, 10 men failed to complete the full
year.
Chemical method. The drug was determined in plasma
by the method of Brodie et al. (5) with the following
modifications: 30 ml. of heptane and 2 ml. of ethyl alcohol
(charcoal treated and redistilled until non-fluorescent)
were placed in a 60-ml. glass stoppered bottle. Ten ml.
60
3. CHRONIC TOXICITY OF CHLOROQUINE
"LOW" LEVELS...PLASMAS COLLECTED
PRIOR TO SUCCEEDING DOSE OF DRUG.
i: RANGE & MEAN VALUE FOR GROUP.
I I4 t I I I II I II I
0.GCMOA8IIL
0ak
OM C14 VI
0,5|||| GM CHLOROQUI NE ONCE A WEEK | P|||LAcESo
4o 20 2 17 14 14 14
_ 10 5 0 0 0
HE 0 44
w_ C0 0 0
io 0 712 7 74A
770 75.7 74.7 74 74 740 7S,.6 7
400
-300
-200
100
60
20
-1 0 4 12 2 24 30 32 36 40 46 52 56
lIME IN WEEKS
60
FIG. 1. ToXICITY OF CHLOROQUINE
Daily-dosage study. Plasma concentrations represent range and mean of the "low" levels; plasmas were
drawn prior to the succeeding dose of the drug. The body weights are the average of only 12 cases, those
lacking complete records being excluded. Drug dosages are expressed in terms of the base.
of plasma and 5 ml. of 02 N NaOH were added and-the
mixture shaken for 15 minutes. After the two phases
separated, the water phase was aspirated and the heptane
layer was poured into a 125-ml. glass-stoppered bottle
containing 50 ml. of 0.1 N NaOH and shaken for 10
minutes. After the phases separated, the water phase
was aspirated. Washing with 0.1 N NaOH was re-
peated three times. Prior to the third washing, 1 ml.
of the non-fluorescent ethyl alcohol was added. After
the separation of layers, and the aspiration of the water
phase, 20 ml. of the heptane phase were transferred by
means of a pipette, just previously rinsed with the non-
fluorescent alcohol, to a 40-ml. glass,-stoppered pointed
centrifuge tube containing 6 ml. of 0.05 N HCL. The
mixture was then shaken for 10 minutes. The heptane
layer was removed by aspiration and 5 ml. of the acid
phase were transferred to a tall fluorometer tube con-
taining 0.25 ml. of a 5 per cent cysteine solution. Two
and one-half ml. of buffer solution (buffer: 6 volumes of
0.6 N sodium hydroxide and 5 volumes of 0.6 M boric
acid in 0.6 N potassium chloride) were then added.
All tubes (blanks, standards and unknowns) were
placed in an irradiator for two hours' treatment with
ultra-violet light emitted by an HA mercury arc lamp.
Since the distance from the light to all tubes was not
uniform, the tubes, after one hour of irradiation, were
moved to the opposite side of the irradiator for the second
hour of treatment.
The intensity of fluorescence of the samples was deter-
mined in a Coleman Photofluorometer, Model 12 A, using
B-1-S and PC-1 filters.
RESULTS
Concentration of drug in the plasma. In the
group of volunteers receiving 0.3 gram of chloro-
quine daily the drug plasma concentrations, prior
to the morning dose, increased for the first four
weeks and remained on a plateau thereafter (Fig-
ure 1). There was a wide individual range. The
level usually varied inversely with the body weight
of the subject. When the dosage was reduced
(after 77 days), 11 weeks elapsed before the
plasma concentrations in this group fell to the lev-
els of the group in which subjects had received
0.5 gram weekly from the start of the experiment.
In the weekly-dosage studies the individual
"low" values, collected just prior to the next dose,
0
I
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Ox= 00
tL 20w
-c
SAC0
VISUAL
2
HEADACw0
R
IL BLEACHI4
2 T WAVE
>' DEPRESS
AV WT
KG
Il
61
4. ALVING, EICHELBERGER, CRAIGE, JR., JONES, JR., WHORTON, AND PULLMAN
z I
WO PE
7ZP LIT
O.~t, 24
°CYIS
CJ oi
TOTAL NO
CASES
VISUAL
HEADACHE
O HAIR
- BLEACHJING
>, ERUPTION
AV WT
KG.
I
ER
rER
,0
DO
ifLOW" LEVELS-PLASMAS COLLECTED
PRIOR TO SUCCEEDING DOSE OF DRUG.
I _ RANGE & MEAN VALUE FOR GROUP.
,,ff tltIAIdIfI f I I I I I IIIf I I I f I I ,
LACE11111
0.GM CHLOROQUINE ONCE A WEEK LPLACEBO--X
1~~~~~~[IIIIIIIIII11 I1111 I 1-1-11 III II1 n0aia£18 1 18 17 16 t1
lo 2 2 0 0
o 3 7 3 4 2
o _ 1 0 0 0
o __I o I 0 2 0
73iA 73,3 70 7iq 7i.3 77 7
,.I I . .
-1 0 4 12 le 20 24 38 32 36 40 4 00
TIME IN WEEKS
FIG. 2. ToXICITY OF CHLOROQUINE
Weekly-dosage study. Plasma concentrations represent range and mean of the "low" levels; plasmas were
drawn prior to the succeeding dose of the drug. Body weights represent the average of those 14 individuals
who completed the experiment. Drug dosages are expressed in terms of the base.
rarely fell below 20 gamma per liter and the means
of these weekly values were usually between 25
and 40 gamma per liter (Figure 2).
During the first seven weeks of drug adminis-
tration in the weekly-dosage group a record of the
highest plasma concentrations was made by col-
z
0
PER
LITER
z
W. 30011T r 300
z
Id
z
0
0
-J
I
0
(I)
2004T
100 -
60
20-
I
I
J 0 1 2 3 4 5 6 7
0. DAYS AFTER WEEKLY ORAL DOSE (0.5GM)
FIG. 3. PLASMA CHLOROQUINE CONCENTRATION
Means and ranges of plasma concentrations during
seven days following termination of oral administration
of 0.5 gram of chloroquine base to each of 18 individuals.
lecting samples five hours after the weekly dose of
0.5 gram. The peak concentrations ranged from
44 to 346 gamma per liter. The mean peak con-
centrations for the group rose week by week, as
follows: 89, 135, 176, 154, 197, 252, and 215
gamma per liter.
The rate of decline of the plasma concentration
after one of the weekly doses is shown in Figure
3. In 48 hours the mean concentration (94 gamma
per liter) was less than half of the six-hour level
(215 gamma per liter). At seven days the mean
had fallen to 29 gamma per liter.
Toxicity. The toxic phenomena encountered
in the daily-dosage study were visual difficulties,
bleaching of the hair, and electrocardiographic
changes. Skin eruptions occurred in the weekly-
dosage study. Some individuals in both groups
lost weight and had headaches (Figures 1 and 2).
Visual symptoms were noted by half the sub-
jects in the daily-dosage study but by only an oc-
casional subject in the weekly-dosage group.
These symptoms consisted of a difficulty in chang-
ing focus quickly from a near to a far object. The
tests for visual acuity, power of monocular ac-
commodation, and diplopia failed to demonstrate
objective abnormality. However, no tests for
speed of accommodation were performed. The
visual symptoms in the daily-dosage group disap-
100
*60
*20
62
'rs
5. CHRONIC TOXICITY OF CHLOROQUINE
ow
CONTROL 11 WEEKS
FIG. 4. TOXICITY OF CHLOROQUINE
53WEEKS
Electrocardiograms taken after 11 weeks of chloroquine at 0.3 gram of base daily. Normal curves
returned in spite of continued dosage at 0.5 gram of base weekly.
peared when the dosage was lowered to 0.5 gram
weekly.
Shortly after the conclusion of the daily-dosage
study, it was noticed that the hair of one of the
blond subjects was lighter near the roots. Ex-
amination of others showed that bleaching had
occurred in all blond subjects in the daily-dosage
experiment and possibly in one of the two blond
subjects in the weekly-dosage test. The hair
gradually regained its normal color after reduc-
tion of the dosage in the former group.
Electrocardiographic changes were noted in 12
of the 20 men in the daily-dosage study. The
changes consisted of a concordant diminution of
the height of the T-waves in some or all of the
leads. No other evidence of cardiovascular ab-
normality was observed, and the T-waves regained
their original amplitudes after the dosage was re-
duced (Figure 4).
In two individuals in the weekly-dosage group,
mild skin eruptions developed during the last few
months of drug administration. The eruptions oc-
curred over the flexor surfaces of the extremities
and on the trunk. In one subject the lesions con-
sisted of reddish violaceous papules and annular
macules with a ring of papules about a paler center.
The appearance resembled lichen planus, but no
single lesion was typical of that disease. Histo-
logical studies showed only chronic inflammation.
In the other subject there were reddish macules
of similar distribution which on histological sec-
tion were suggestive of lichen planus. The case
histories of the two individuals with skin eruptions
are presented elsewhere (6).
Both groups lost weight. The weight loss was
slight but probably significant. At 38 weeks, the
average weight had fallen 2.6 kg., most of which
was regained in the placebo period. Of 26 indi-
2
3
CF2!
63
6. ALVING, EICHELBERGER, CRAIGE, JR., JONES, JR., WHORTON, AND PULLMAN
viduals with complete weight records, 23 lost
weight. Most of the weight loss in the daily-dos-
age group occurred during the 77 days when dos-
age was high and was not regained until the
placebo period.
The appraisal of headaches was difficult. In the
daily-dosage studies, headaches, different from
those previously experienced, were noted by six of
the 20 subjects. During the course of the weekly-
dosage experiments, headaches were occasionally
reported. Sometimes they recurred for several
weeks in the same individual 6 to 12 hours after
the drug was administered. Occurring in the oc-
cipital or frontal areas, or both, the headaches were
usually mild, but lasted several hours and were
occasionally still present the following morning.
Only those headaches which seemed to be attribut-
able to the drug by temporal relationships and his-
tory were included in Figures 1 and 2. Two sub-
jects, however (Figure 2), continued to have,
headaches during the second placebo period.
The other tests and observations failed to re-
veal abnormalities.
DISCUSSION
The amount of chloroquine base recommended
for the treatment of an attack of vivax or falci-
parum malaria is 1.5 grams in three days, and for
suppression, 0.3 gram a week (1). The daily-
dosage group received 23.1 grams in 77 days and
the weekly-dosage schedule was 0.5 gram a week.
In both studies, therefore, the dosage used was
considerably in excess of that required for anti-
malarial therapy or suppression. This difference -
is further emphasized by a comparison of the
plasma chloroquine concentrations attained in
these studies with the concentrations required for
antimalarial suppression. In the daily dosage
studies mean "low" plasma concentrations in ex-
cess of 200 gamma per liter were maintained for
10 weeks while a plasma chloroquine concentra-
tion of 10 gamma per liter is adequate for anti-
malarial suppression (7). Individual "low" val-
ues in excess of 500 gamma per liter occurred with-
out unusual symptoms.
The toxic manifestations in the group on the
daily-dosage schedule were in fact reversible and
caused no incapacity. There were unequivocal
visual disturbances similar to those described by
other observers (7, 8, 9, 10). The T-wave de-
pression in the electrocardiograms was similar to
that reported as a result of drugs unrelated to
chloroquine (11, 12, 13, 14, 15, 16). It was prob-
ably. non-specific and without clinical significance.
The bleaching of the hair gradually disappeared
after the dosage was reduced, as it did in cases
described by Butler (9).
The toxic symptoms which occurred in the sub-
jects on the weekly-dosage regime were milder.
It should be emphasized that the difficulty in ac-
commodation was a common complaint in sub-
jects who received 0.3 gram daily but it was very
rare in those who received 0.5 gram once a week.
The skin eruption which developed in two indi-
viduals was mild but similar to that reported dur-
ing suppressive therapy with quinacrine. More
extensive experience with chioroquine will be
necessary to determine its incidence and serious-
ness. In both cases the rash faded rapidly after
the year of treatment was completed.
The temporal relationship of headaches to medi-
cation suggested an etiological relationship, but
their unpredictability in incidence, location, and
severity made it impossible accurately to appraise
this symptom even after a year of close observa-
tion. The loss of body weight was small and dis-
appeared with discontinuance of medication.
The special tests performed gave no clue to the
mechanism of the toxic effect of chloroquine.
SUMMARY AND CONCLUSION
1. Two groups of inmate volunteers of 20 each
were given chloroquine (SN-7618) orally for
one year in greater dosages than those required
for antimalarial therapy or suppression, in order
to detect and evaluate any toxic reactions.
2. The first group took 0.3 gram (base) daily
for 77 days and 0.5 gram (base) once weekly
thereafter. On the higher dosage, visual disturb-
ances, headache, bleaching of the hair, electro-
cardiographic changes, and slight weight loss were
observed. These changes caused no incapacity and
diminished or disappeared when the dosage was
decreased.
3. The second group, which received 0.5 gram
(base) weekly from the beginning of investiga-
tions, had occasional headaches, slight weight loss,
and, in two cases, a skin eruption resembling lichen
planus.
64
7. CHRONIC TOXICITY OF CHLOROQUINE
4. Under the conditions of this investigation, it
can be concluded that chloroquine is a safe anti-
malarial compound when given in the recom-
mended dosage.8
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65