NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
3
the large number of drugs to be worked through in a limited period this was
impossible.
All the tracings shown are portions of continuous records and the time
tracing, where shown, indicates seconds.
Table showing source and date of original tablets and of tablets or
drugs used as controls.
Drug.
ORIGINAL.
CONTROL.
Source.
Date.
Source.
Date.
Aloin Compound .
. . .
. B. W. & Co. .
1906
B. W. & Co. .
1910
Ammon. Carbonas
.
. .
. P. D. & Co. .
1907
Ditto .
.
1910
Colchicini Salicylas
. .
.
. Ditto .
.
1907
Ditto .
.
1910
Extr Euonymin Siccum
.
.
. Ditto .
.
1907
Ditto .
.
1910
Hydrarg. Subchlor. .
.
.
. Ditto .
.
1907
B. & T.
.
1910
Phenacetinum .
.
.
. . Ditto .
.
1907
B. W. & Co. .
1910
Phenacetinum cum Caffeinâ . .
. Ditto .
.
1907
Ditto .
.
1910
Pil. Plumbi cum Opio . .
.
. Ditto .
.
1907
B. M. S.
.
1910
Pil. Hydrarg. Subchlor. Co. .
.
. Ditto .
. Unknown
. Ditto .
.
1910
Soda Mint .
.
. .
.
. Ditto .
.
1907
B. W. & Co. .
1910
Sod. Chlorid.
.
.
.
.
. Ditto .
.
1907
B. & T.
.
1910
Tinct. Camph. Co.
.
.
. . Ditto .
. Unknown . S. S. & Co. .
1910
Tinct. Digitalis .
.
. .
. Ditto .
.
1907
B. & Co.
.
1910
Tinct. Opii
.
.
.
.
. Ditto .
.
1907
Ditto .
.
1910
Zinc. Sulphas
. .
. .
. B. W. & Co. .
1906
B. & T.
.
1910
Hypodermic Tablets.
Apomorphin. Hydrochlorid. .
.
. B. W. & Co. .
1903
P. D. & Co. .
1910
Atropin and Morphin. Sulph.
.
. Ditto .
.
1903
Ditto .
.
1910
Digitalin .
.
.
.
.
. Ditto .
.
1903
B. W. & Co. .
1910
Morphin. Tartras
.
. .
. Ditto .
.
1903
P. D. & Co. .
1910
Physostigminæ Salicylas
. .
. Ditto .
.
1903
Ditto .
.
1910
Strophanthin .
.
.
.
. Ditto .
.
1903
Ditto .
.
1910
Abbreviations used in the foregoing table.
B. W. & Co.—Messrs. Burroughs Wellcome and Co.
P. D. & Co.—Messrs. Parke Davis and Co.
B . M . S . — M e d i c a l S t o r e - k e e p e r t o G o v e r n m e n t , B e n g a l .
S. S. & Co.—Messrs. Smith Stanistreet and Co., Calcutta.
B. and T.—Messrs. Baird and Tatlock, London.
B. and Co.—Messrs. Bathgate and Co., Calcutta.
B 2
4
All the control drugs which were used were in tablet form, with the
exception of those obtained from Messrs. Baird and Tatlock which were
fresh salts guaranteed chemically pure, and those obtained from Messrs.
Bathgate and Co., and Messrs. Smith Stanistreet and Co., which were fresh
tinctures prepared according to, and complying with the tests laid down by,
the British Pharmacopœia.
Report by the Chemical Examiner to the Government of Bengal on the
Drug Tablets submitted—
Pills of Lead Acetate and Opium—
Break up with difficulty even on boiling.
Chemical change has taken place.
Lead is present in correct amount, but some has become insoluble in
water.
Opium seems, to have decomposed.
Morphia present.
Opinion—Bad.
Tinct. Camph. Co.—
Opium barely detectable.
Opinion—Bad.
Tinct. of
Opii—
Estimating Morphia these contain approximately B. P. strength
of opium.
Opinion—Good.
Pill Calomel Co.—
Break up with great difficulty even on boiling.
Calomel correct and no Mercuric Salt ( i.e., Soluble Salt) present.
Rhubarb and Colocynth cannot be estimated.
Tinct. of Digitalis—
No chemical means of estimating.
Hypoderms of Digitaline
—
Do not follow the chemical characters as laid down in books and the
glucosides cannot be precipitated from solution.
Frog's heart would shew whether Digitaline is still active.
The chemical tests for Digitaline are, I believe, quite untrustworthy.
Tabloid Ammonium Carbonate—
These have lost weight through decomposition.
5
Phenacetin and Caffein—
Chemical reactions of both drugs are given but complete separation
cannot be effected. I consider the Tabloids to be good.
Phenacetin —
Perfectly good.
Hydrargyri Subchloridum—
Pure and correct in weight.
Aloin Compound—
Reactions of Aloin correct. I consider these Tabloids good.
Colchicine Salicylas—
Chemical reactions of Colchicine and Salicylic Acid correct; weight
approximately correct. I consider the. Tabloids good.
Ext. Euonymi Siccum—
I cannot find chemical reactions for Euonymin.
All the Hypoderms, Physostigmine Salicylas, Atropine and Morphine,
Apomorph. Hydrochlor. and Morphine Tarta rate are chemically
active and pure.
The Strophanthin cannot be satisfactorily judged chemically.
Tabloids of Sodium and Zinc Chloride are pure and in good condition.
Tabloids of Soda mint contain the Sodium Bicarbonate in a pure state, but the
peppermint though present cannot be.estimated.
Tablet Aloin Compound.
These tablets have a complex composition and contain Aloin (gr.
1/5),
Strychnine Sulphate (gr. 1/60), Extra ct of Belladonna (gr. ⅛ ), and Puly. Ipecac.
(gr.1/16).
As I had no means of separating out the several ingredients, all I was
able to do was to compare the old with the fresh tablets as regards the general
action of the combined drugs.
The actions which were especially made the object of observation were,
i n t h e c a s e o f A l o i n , s t i m u l a t i v e o n t h e l a r g e i n t e s t i n e , p u r g a t i v e , a n d c h o l a g o g u e ,
and in the case of Strychnine Sulphate, increase of cord reflexes, and in the
frog, spasms.
( 1 ) PURGATIVE AND CHOLAGOGUE ACTION ON DOG.
To one dog of 16
. 5 kilos, 1.092 grams of fresh tablet (0.065 gram per kilo)
triturated in 10 c.c. of water was given by the mouth.
6
To another dog of 19 .2 kilos, 1.264 grams of old tablet was given in the
same way.
In neither case was there any apparent effect, the dogs being kept under
observation for 48 hours and eating, sleeping, and defæcating normally. There
was no sign of cholagogue or cathartic action.
(2) PURGATIVE AND CHOLAGOGUE ACTION ON MAN.
Two laboratory attendants of nearly equal weight volunteered for the
experiment, and two fresh tablets were given to one, the other receiving two
old tablets.
The man who had received the fresh tablets had three motions within ten
hours, the first motion being passed three hours after administration of the
drug and being semi-solid, the second and third being fluid in consistence.
There was a considerable amount of griping which began five hours after the
dose had been taken and lasted five hours.
The man who had received the old tablets had no griping and passed one
soft solid motion ten hours after taking the drug.
(3) EFFECT WHEN INJECTED IN SOLUTION INTO PERITONEAL
CAVITY OF FROG.
Two solutions of equal strength were made, solution A containing five old
tablets in five c.c. of water, and solution B five fresh tablets in the same amount
of water. The old tablets dissolved more easily than the fresh ones, the solution
in both cases being turbid and that of the old tablets being darker in colour
than that of the new.
The solutions were filtered and one c.c. of A injected into frog X, frog Y
receiving one c.c. of B. Frog X, five minutes after receiving the injection,
showed strong muscular contracture, all the muscles being firmly contracted.
On the application of any external stimulus to the skin, the contractions in-
creased in severity, spasms typical of strychnine poisoning being produced.
This condition lasted for 25 minutes when respiration stopped, death occurred
and the frog ceased to react to any stimulus. Frog Y, which had received the
fresh solution, remained for five minutes without showing any sign of being
affected by the drug. At the end of that period a condition of rigid muscular
contracture set in, the contractions becoming spasmodic on the application of
external stimuli, but the spasms being more severe and lasting longer than in
7
the case of frog X. This condition only lasted for five minutes, when death
took place and the muscles relaxed.
In both cases death was verified by opening the animal and exposing the
heart.
The results of these experiments would appear to indicate that the old
tablets, while still retaining a very considerable degree of activity, have deterio-
rated to an appreciable extent when compared with the fresh tablets.
Ammonium Carbonate Tablets.
These showed much efflorescence, and some had crumbled to powder. On
opening the bottle a strong ammoniacal odour was given off.
Some of the Pharmacopœial chemical tests were carried out in addition to
the animal experiments.
(1) Loss OF WEIGHT.
Three sets of five tablets each, taken at random from among the old and
the new tablets, were weighed and the loss of weight compared. One 5 grain
tablet should weigh 0 . 324 gram and five tablets, should thus weigh 1.620
grams.
Fresh Tablets.
Weight in grams.
Loss of weight.
Loss per tablet.
1st set . . . . .
1.353
0.267
0.0534
2nd set . . . . .
1.332
0.288
0 . 0 5 7 6
3rd set .
.
.
.
.
1.338
0.282
0.0564
Old Tablets.
1st set .
.
.
.
.
1.554
0.066
0.0134
2nd set .
.
.
.
.
1.536
0 . 0 8 4
0.0168
3rd set .
.
.
.
.
1.549
0.071
0.0142
The smaller loss of weight in the case of the old tablets is probably due to
water absorbed during the commencing process of deliquescence. In appearance
the new tablets were much better preserved than the old.
8
(2) Two SOLUTIONS WERE THEN MADE.
A containing 5 per cent. of the fresh tablets and B containing 5 per cent.
of the old tablets, i. e., five grams of each made up to 100 c.c. with distilled
water. Solution A was clear and solution B was turbid. When treated (a)
with Silver Nitrate solution and subsequent supersaturation with Nitric Acid,
(b) with Barium Nitrate solution, and (c) with Barium Chloride solution, no
difference was found between the reactions given by A and B.
(3) VOLUMETRIC ESTIMATION.
Two grams of the old tablet were dissolved in a mixture of 50 c.c. each of
water and Normal Volumetric Solution Sulphuric Acid, boiled for ten minutes
to expel the liberated CO2 and cooled. The solution was then titrated against
Normal Volumetric Solution Potassium Hydroxide, Litmus test solution being
used as an indicator. The amount of Normal KOH required for exact neutrali-
sation was 22.5 c.c. as compared with 12.7 c.c. which ought to be sufficient when
perfectly fresh translucent salt is used.
The test was repeated using two grams of the fresh tablets, and the amount
of Normal KOH required for neutralisation was 23.9 c.c.
Comparing the two tablet drugs with fresh salt in perfect condition con-
taining 100 per cent. of Ammonia, the old tablets contained 56 per cent. and
the fresh tablets 53 per cent. of Ammonia.
(4) PHYSIOLOGICAL ACTION OF THE TABLETS. (See Plate I.)
Ammonium Carbonate in therapeutic doses shows activity mainly as a
cardiac, gastric and respiratory stimulant and an expectorant. The action on
the isolated heart of the frog was chosen as an index of comparison between the
old and the new tablets.
A 1 per cent. solution of each was made up, A containing 1 per cent. of
old tablets and B containing 1 per cent. of fresh tablets. A frog was pithed
and the heart isolated and arranged for recording contractions. Normal
contractions were recorded for five minutes (Plate 1, Chart 1, No. 1), 0.5 c.c. of
solution B was then allowed to flow slowly over the heart, and an immediate
slight diminution in the amplitude of the contractions was observed lasting 13
seconds (No. 2). Thereafter the contractions continued normal in character
and regularity but slightly less in amplitude for 70 seconds, when irregu-
larity became apparent (Nos. 3 and 4), which continued to the end of the
experiment half an hour after the application of the drug.
9
The experiment was repeated with a fresh frog, 0.5 c.c. of solution A being
applied in the same way. A normal tracing was first recorded (Plate 2, Chart
2, No. 1). The drug was then applied and the contractions became gradually
smaller for four minutes, when they reached their minimum (Nos. 2, 3, and
5). The contractions then began to increase in strength (No. 6) and, at 8
minutes after the application of drug, the tracing was again very nearly
normal (No. 7) and remained so to the end of the experiment.
The inference to be drawn from the foregoing experiments is that both
sets of tablets have deteriorated very markedly when compared with the fresh
salt, but that between the old (1907) tablet and the new (1910) tablet there is
very little difference in degree of deterioration, the old tablet in fact showing
greater activity than the new.
Colchicine Salicylate Tablets.
These tablets showed no visible signs of deterioration and were indistin-
guishable in appearance from fresh tablets against which they were tested.
Frogs were used for the experiments as being the most convenient
and easily obtainable animals and as giving reliable and comparable results.
Colchicine Salicylate being a compound salt, one had to take into account
the action both of Colchicine and of Salicylic Acid. Pure Colchicine is
said to have very little action on the frog, but the impure preparation produces
toxic effects.
Salicylic Acid and Salicylates when injected into the frog in large
doses may produce paralysis, whereas applied locally they are toxic to frog's
muscle. On the heart, small doses have no effect, but large doses cause cardiac
paralysis, dilatation of peripheral vessels, and fall of blood pressure.
Two solutions were made, A being a 0.1 per cent. solution of the
old tablets and B being a 0.1 per cent. solution of the fresh tablets to be
used as a control. A was slightly turbid before filtering, B was perfectly
clear.
(1) ACTION ON ISOLATED HEART OF PITIED FROG. (See Plate II).
Heart isolated and arranged for recording contractions on a drum moving
slowly at a constant rate.
Contractions were recorded for five minutes before the application of
the drug (Plate II, Chart 1, No. 1). 0.5 c.c. of solution A was then allowed
to flow over the heart and the contractions were recorded for five minutes.
Me result was a gradual diminution in the amplitude of the contraction
10
(Nos. 2 and 3). At the end of five minutes a second dose was applied.
without any further diminution in the contractions being produced (No. 4).
The same experiment was repeated in another frog, using solution B (fresh
drug).
The contractions were recorded for five minutes before the application
of the drug (No. 1).
0.5 c.c. of solution B was then applied, and an immediate diminution.
in the amplitude and slight slowing of the rate of contraction were seen
(Plate II, Chart 2, No. 2). The contractions remained small and fairly regular
during the next five minutes (No. 3), when (5 minutes after the first applica-
tion) a second dose of 0.5 c.c. was applied. This caused a still further reduc-
tion in the amplitude of the contractions (No. 4). On the drug being
washed off with normal saline solution, the heart rapidly resumed its normal
action both as regards amplitude and rate of contraction (No. 5).
(2) EFFECT ON PERIPHERAL VESSELS, AS SHOWN BY PERFUSING
VESSELS OF PITHED FROG WITH DRUG.
Pithed frog and apparatus arranged as stated on page 2. The frog
was perfused with normal saline solution until bloodless, and then the saline
solution traversing the peripheral circulation was measured during successive
five minute periods. When the flow had become constant and uniform,
normal saline solution containing 2 per cent. of solution A was perfused,
and the amount traversing the peripheral circulation in successive five minute
periods was similarly measured. The results obtained are noted below :—
Amount passed in successive 5 minute periods in c.c.
Normal Saline
Solution.
Saline containing
Solution A.
36
39
33
37.5
3 6
36.5
37
31
37
30
37
11
The experiment was then repeated with a fresh frog, using first normal
saline solution and then saline solution containing 2 per cent. of solution
B, the figures obtained being as follows :—
Amount passed in successive 5 minute periods in c.c.
Normal Saline
Solution.
Saline containing
Solution B.
32
34
36
33
33.5
31
33.5
29
34
28
34
34
34
34
34
This experiment was verified by repeating it several times with fresh
frogs and the results obtained were in each instance approximately the same.
The results would indicate that the old tablets have a slight transient
dilating effect followed by a constricting action. In the case of the fresh
drug there is a slight transient constricting action only.
(3) ACTION ON MUSCLE AS SHOWN ON A MUSCLE NERVE PREPARATION.
(See Plate III.)
A muscle nerve preparation (i.e. Gastrocnemius muscle with Sciatic
nerve attached) was dissected out of a pithed frog and arranged in the ordinary
way for recording single contractions on a rapidly moving drum, a revolving
contact-maker being attached to the shaft of the drum in such a manner
that successive stimuli were applied at the same point in each revolution
of the drum.
A muscle curve was then recorded under normal conditions (uppermost
curve, Chart 1, Plate III). 0.25 c.c. of solution A was then allowed to flow
over the muscle and a second curve recorded two minutes after the appli-
cation of the drug (middle curve, Chart 1).
A third curve was recorded five minutes after the application of the drug.
c2
12
The experiment was then repeated with a fresh nerve muscle prepara-
tion, using solution B, the same curves being recorded after the same intervals,
(Chart 2, Plate III).
In the case of solution A (old tablets), the first drug curve, two minutes.
after the application of the drug, shows only a slight deviation from the
normal, the contraction being a shade less and the relaxation period shorter.
In the second drug curve, five minutes after the application of the drug, the
contraction is only half the normal, the latent period is considerably prolonged,
and the relaxation period shortened.
In the case of solution B (fresh tablets), the first curve, at two minutes,
shows less amplitude and considerable lengthening both of the latent and
of the relaxation periods. The second curve, at five minutes, shows a pro-
longed latent and a shortened relaxation period, with greatly diminished
amplitude.
The results of these experiments would indicate that very little, if any,
deterioration has occurred in the 1907 tablets, which yield results varying
very slightly from those obtained with the 1910 tablets.
Euonymin Siccum Tablets.
This drug acts almost entirely as a drastic purgative and a cholagogue. Its
effect on man and on dogs was studied when given by the mouth, crushed and
suspended in water. Equal quantities of freshly prepared crushed tablet were
similarly administered as controls.
(1) EFFECT ON MAN.
Two laboratory attendants of nearly equal weight were selected and to one
(A) two grains of old tablet, and to the other (B) two grains of fresh tablet
were administered at 3 P.M.
" A " had one motion on getting up at 6 A.M. next morning, solid but soft
in consistence and greenish yellow in colour.
" B " had two motions on getting up at the same time next morning, the
first being soft but solid, and the second being fluid. The colour of both was
greenish yellow.
(2) EFFECT ON DOGS.
Two dogs of approximately equal weight were taken and to A a dose of
two grains of fresh tablet was given at 11 A.M., B at the same time receiv
ing two grains of old tablet. No effect was produced in either dog,
13
A week later the same dogs were taken and " A " received six grains of
fresh and " B " received six grains of old tablet, the drugs being administered
at 12-30 P.M.
" A " at 6 P.M. passed a motion and in the early morning passed another,
both motions being copious, greenish yellow in colour and solid in consistence.
" B " at 5 P.M. passed one motion and passed another in the night, the
total quantity being somewhat less than that passed by " A ". Both motions
were solid and greenish yellow in colour.
From these results it would appear that the old tablets retain a very con-
siderable degree of activity, but show some slight deterioration and loss of
power when compared with the fresh tablets.
Hydrargyri Subchloridum Tablets.
The chief non-specific action of Calomel is that of a mild purgative. These
tablets were tested for this on man and on dogs, control experiments being car-
ried out with equal quantities of fresh Calomel, not made up in tablet form.
(1) ACTION ON MAN.
Two laboratory attendants of nearly equal weight, A and B, were taken
for this experiment, and at 2 P.M. " A " was given by the mouth three one-
grain tablets, " B " getting three grains of the fresh salt at 2-30 P.M.
" A " defæcated three times within the next eighteen hours, one ordinary
stool at 6 P.M., one watery stool at 11 with much griping, and one loose
motion at 6 A.M. next morning.
" B " defæcated twice within the same period, one ordinary stool at 8 P.M.,
and one watery motion the following morning at 5 A.M. He had no griping
or pain.
(2) ACTION ON DOGS.
Two grains of fresh salt was given to a dog of eighteen kilos and two one-
grain tablets to another dog of nineteen kilos without any apparent effect.
This experiment was repeated using a larger dose. The same dogs were
used, a week having been allowed to elapse in order to ensure their being
quite normal after the previous experiment. Five grains of the fresh salt was
given to one dog and five one-grain tablets to the other.
The dog which received the fresh salt hiccoughed for five minutes after
getting it. Thereafter it showed no abnormal signs for eight hours when it
vomited a large quantity of undigested food. It did not defæcate during the
eighteen hours following the administration of the drug.
14
The dog which received the tablets passed urine ten minutes later and at
fifteen minutes passed a large black hard mass of fæces. At 54 minutes it
vomited about two ounces of yellowish matter mixed with froth and mucus.
At 8½ hours it vomited a large quantity of undigested food, but it did not again
defecate during the 24 hours it was kept under observation.
This experiment was repeated later with the same doses, a negative result
again being obtained.
No information was afforded by the experiments on dogs as to the relative
activity of the tablets and the fresh drug, but the human experiments show
that the tablets have retained their full activity and give results equal to those
of the fresh drug.
Phenacetinum Tablets.
Phenacetin being practically insoluble in water (1 in 1,700), the tablets
had to be crushed and administered suspended in water, by the mouth.
Tablets manufactured in 1905 were tested against an equal weight of 1910
tablets.
(1) ANTIPYRETIC ACTION ON RABBITS.
Two rabbits of equal weight were given an abnormally high temperature
by injecting hypodermically into each of them 0.5 c.c. of purulent matter from
a septic wound.
Rabbit A.
Temperature before injection of septic material
.
.
.
101 .4
Temperature 48 hours late
.
.
.
.
.
.
103
With the temperature at 103, 0.5 gram of crushed 1910 tablets were administer-
ed in water by the mouth at 1-45 P.M., and the temperature recorded every
half hour till 4-30.
Temperature at
1-45
103
,,
, ,
2-15
102.5
,,
, ,
2-45
102
,,
, ,
3
101.6
,,
,,
3-30
102.6
,,
, ,
4
103
,,
, ,
4-30
103
Rabbit B.
Temperature before injection of septic material .
.
. 101
Temperature 48 hours later . .
. .
. .
. .
..
. .
103.3