NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
36
The experiment was repeated with a fresh muscle nerve preparation, using
solution B, when the maximum distance separating the coils and giving an
effective stimulus was found to be 24 c.m. before and 19 c.m. after the appli
-cation of the drug.
Taking the normal irritability of the muscle as 100, the old tablet solution
reduces it by 15 per cent. and the new tablet solution by 21 per cent.
(3) ACTION ON ISOLATED HEART OF PITHED FROG. (See Plates XI and XII.)
A frog was pithed and its heart exposed and arranged for recording con
-tractions. Normal contractions were recorded for five minutes (No. 1, Plate
XI). 0.5 c.c. of solution A was then allowed to flow slowly over the heart
(No. 2, Plate X). No immediate effect was perceptible, but in the course of one
minute the action became perceptibly slower, the rate of contraction falling to
75 per cent. of the normal as taken before the application of the drug (No. 3).
This diminution in rate increased up to three minutes after the application
of the drug and then the rate remained constant until the end of the experi
-ment (Nos. 4, 5, and 6).
The experiment was repeated with a fresh frog using solution B. A nor
-mal tracing was first taken (No. 1, Plate XII), and then the drug was applied,
(No. 2, Plate X). No immediate result was seen, but in the course of the next
forty seconds the rate of contraction had become noticeably slower (No. 3), and
at the end of one minute the rate of contraction had fallen to 77 per cent. of
the normal as taken before the application of the drug (No. 4). The rate
gradually got slower and slower until at the end of 7 minutes 30 seconds it
had fallen to 29 per cent. of the normal. The slowing was chiefly due to
prolongation of the diastole, the systole being only very slightly lengthened
(Nos. 5, 6, and 7). This condition of prolonged and irregular diastole per-
sisted up to the end of the experiment.
(4) EFFECT ON CONTRACTION OF STRIPED MUSCLE OF FROG. (See Plate X.)
A nerve muscle preparation was dissected out and arranged to record con
-tractions 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 (Plate X, Chart 1, No. 1). 0.25 c.c. of
solution A was then allowed to flow over the muscle and a second curve
was recorded, superimposed on the first, two minutes after the application of the
drug (Chart 1, No. 2).
37
The experiment was then repeated with a fresh muscle nerve preparation,
using solution B (Plate X, Chart 2, No. 1 normal, No. 2 drug).
In the case of solution A, the only noticeable feature in the drug affected
curve is a diminution in speed, both the contraction and the relaxation being
slower than normal.
In the case of solution B there is a marked lengthening of the latent
period, a slowing of the whole contraction, and a diminution in its amplitude.
The results of these experiments show that the rapidity of solution of the
old tablets is greatly diminished, and, although they retain considerable emetic
action, they have suffered a marked loss of activity when compared with fresh
tablets.
Physostigmine Salicylate.
(0.01 grain = 0.00065 gram.)
Solubility .—In 1 c.c. of water at room temperature, a new tablet dissolves
in 1 minute 10 seconds giving a clear solution; an old tablet takes 1 minute
30 seconds also giving a clear solution.
Two solutions Were made, each of ten tablets in 6.5 c.c. of distilled water,
being a solution of 1 mg. per c.c.
Solution A was made from old tablets and solution B from fresh tablets.
(1) MYOTIC ACTION ON RABBITS.
0.25 c.c. of solution A was instilled into the right eye of rabbit X and
0 . 2 5 c . c . o f s o l u t i o n B i n t o t h e r i g h t e y e o f r a b b i t Y . A t t h e e n d o f f i v e
minutes both rabbits showed contraction of the pupil, contraction being slightly
more marked in Y than in X. The duration of the effect was also slightly
greater in Y than it was in X, a small degree of contraction being present in
Y after the eye of X had regained its normal appearance. No signs of irrita
- t i o n w e r e p r e s e n t i n e i t h e r c a s e .
(2) MYOTIC ACTION IN MAN.
One laboratory attendant received 0.25 c.c. of solution A in his right eye
and another laboratory attendant received 0.25 c.c. of solution B. Partial con
- t r a c t i o n o c c u r r e d i n b o t h c a s e s , b u t n o d i f f e r e n c e i n t i m e o f c o m m e n c e m e n t , i n
degree, or in duration was perceptible.
Contraction never became extreme and began to pass off in one hour and
five minutes. There was no sign of irritation of the conjunctiva.
(3) INJECTION INTO LYMPH SAC OF FROG.
Frog X received 0.5 c.c. of solution A injected into dorsal lymph sac and
frog Y received 0.5 c.c. of solution B in a similar fashion.
38
No muscular twitchings, loss of reflexes, or muscular weakness were
detected. Both frogs remained apparently perfectly normal.
(4) ACTION WHEN APPLIED LOCALLY TO FROG'S MUSCLE. (See Plate XIII.)
A nerve muscle preparation was arranged for recording contractions on
a rapidly moving drum. The minimal stimulus was obtained with a distance
of 20 cm. between the coils. A normal contraction was recorded with the
secondary coil at a distance of 20 cm. from the primary, i.e., with the minimal
stimulus. 0.25 c.c. of solution A was then applied to the muscle and five
minutes later curves were taken with a distance between the coils of 20, 22,
and 24 cm. (Chart 1, Plate XIII).
The minimal stimulus was obtained at 24 cm., beyond which no contrac-
tion was elicited.
The experiment was repeated with a fresh muscle nerve preparation and
solution B and very similar results were obtained, the increased irritability of
the muscle after the application of the drug not, however, being so great. The
minimal stimulus was at 24 cm. here also (Plate XIII, Chart 2).
(5) VASO-CONSTRICTOR ACTION ON PERIPHERAL VESSELS OF PITHED
FROG.
The arrangements for perfusion of the drug were the same as in the case
of digitalis.
Each frog was first perfused with normal saline solution till bloodless, then
the saline solution traversing the circulation in periods of five minutes was
measured and when the flow was fairly constant, saline solution containing
0.2 per cent. of solution A or solution B was perfused and the amount flowing
through was measured.
Amount passed in successive 5-minute periods in c.c.
Normal Saline Solution.
Saline containing Solution A.
60
56
59
51
62
48
60
47
39
SECOND FROG.
Amount passed in successive 5-minute periods in c.c.
Normal Saline Solution.
Saline containing Solution B.
64
62
63
59
63
58
63
52
62
50
In both cases the vaso-constrictor action was well marked and approxi-
mately equal.
(6) ACTION ON ISOLATED HEART OF PITHED FROG. (See Plates XIV
and XV.)
Tracings were first taken using 0.5 c.c. of solution A and solution B which
were applied locally to the heart. In neither case was any deviation from the
normal perceptible.
The experiment was then repeated with fresh frogs, using stronger solu-
tions.
A normal tracing was first taken (Plate XIV, No. 1), and then 0.5 of an
old tablet dissolved in 0.5 c.c. of water was allowed to flow over the heart
(No. 2). No immediateeffect was seen, and during the following 90 seconds the
tracing was identical with that taken before the application of the drug (Nos.
3 and 4); 2 minutes 3 seconds after the application the only alteration in
the action was a slight increase in the auricular contraction (No. 5), which
gradually passed off (No. 6).
The experiment was repeated using a solution of fresh (1910) tablet of equal
strength on a fresh frog. Curves are shown (Plate XV, Nos. 1 to 6), corres-
ponding to those shown in the case of the old tablet. The drug has very little
effect.
The foregoing experiments indicate that there is no recordable deterioration
of the old tablets on comparison with fresh ones, the action of both being,
identical.
40
Strophanthin.
(0.002 grain=0.00013 gram.)
Rapidity of Solution. —One old tablet took 1 minute 55 seconds to dissolve
in one c.c. of distilled water at room temperature. One fresh (1910) tablet
dissolved in one c.c. of water in 55 seconds. The solution in both cases was clear.
Four solutions were made, A of ten tablets (old) in 13 c.c. of water (1.3
mgm. i n 13 c. c. , 0. 1 mgm. i n 1 c. c. 1 i n 10, 000), B of t he same st rengt h made
with fresh tablets, C consisting of five old tablets dissolved in five c.c. of water,
and D identical with C but made with fresh tablets.
(1) ACTION ON ISOLATED HEART OF PITHED FROG. (See Plates XVI,
XVII and XVIII.)
Heart isolated and arranged for recording contractions. A normal tracing
was first made (Plate XVI, No. 1). Then 0.5 c.c. of solution A was allowed to
flow slowly over the surface of the heart (No. 2). Then immediate effect was
a slight slowing of the heart to 90 per cent. of its former rate. This slowing
went on till the rate was only 75 per cent. of the normal (No. 3). At the end
of 2 minutes 20 seconds the heart began to show double contractions and some
irregularity, the contractions being 50 per cent. greater in amplitude than the
normal (No. 4). The irregularity became more marked, with occasional spas-
modic contractions followed by a prolonged diastole (No. 5). This irregular
type of contraction persisted until the end of the experiment (Nos. 6, 7, and 8).
The experiment was repeated with a fresh frog and solution B. The effect
was much less than was obtained with solution A. At the end of one minute
the rate was normal (Plate XVII, No. 3), but there was some irregularity with
incomplete relaxations. At 2 minutes the rate was a shade over the normal
(No. 4). No further alteration in the action took place (Nos. 5, 6, and 7). The
amplitude of the contraction was never increased and at times showed diminu-
tion.
Repetition of the experiment with a fresh frog and solution B gave a
similar result, there being, however, a very slight transient slowing (to 96 per
cent.) at 1 minute (Plate XVIII, No. 3 a). Otherwise the recordable effect of
the drug was nil.
The action of the drug being so little marked with the weak solutions
used, the experiment was repeated using the stronger solutions C and D.
41
(2) ACTION ON ISOLATED HEART (STRONGER SOLUTIONS). (See
Plates XIX and XX.)
Heart arranged as before and normal tracing taken (Plate XIX, No. 1).
0.5 c.c. of solution C applied at X (No. 2). No immediate effect was produced,
but at the end of 1 minute the rate had slowed down. to 93 per cent. of the
normal (No. 3), This slowing was transient, however, and at 2 minutes the
rate was normal (No. 4), and at 3 minutes 40 seconds the rate was some 5 per
cent. over normal (No. 5). The contractions got slightly weaker and at 7
minutes the first prolonged diastole was recorded (No. 6). prolonged diastole
kept recurring up to the end of the experiment, usually at intervals of seven
beats (Nos. 7 and 8).
The experiment was repeated with solution D and a fresh frog. The result
was identical, even to the recurrence of the prolonged diastole at intervals of
seven beats. (Plate XX.)
(3) EFFECT ON CONTRACTION OF STRIPED MUSCLE OF FROG.
(See Plate XXI.)
A nerve muscle preparation was arranged for recording single contractions
on a quickly moving drum with an automatic key. A normal curve was first
recorded. 0.5 c.c. of solution A was then applied to the muscle and three
minutes later a second contraction was recorded. The curve showed a consider-
able lengthening of the latent period, and a slight lengthening of the relaxation
period, as well as a smaller contraction (Plate XXI, Chart 1).
The experiment was repeated with a fresh muscle nerve preparation using
solution B.
The curves three and five minutes after the application of the drug show
the same features as in the case of solution A except that the curve recorded
after three minutes is slightly higher than the normal one (Chart 2).
The first experiment would show the old tablets to be considerably more
toxic than the fresh, but the other experiments (several others were done giving
results similar to those recorded)—do not bear this out, and I conclude from
them that there is very little difference in activity between the 1903 and the
1910 tablets.
Digitalin.
(0 01 grain.)
Solubility. —Very little difference was shown in rapidity of solution between
the old and the new tablets, the old taking only slightly longer. One old tablet G
42
dissolved in 1 c.c. water in 65 seconds and one new tablet dissolved in an equal
quantity in 55 seconds.
(1) ACTION ON ISOLATED HEART OF PITHED FROG WHEN INJECTED INT)
AURICLE. (See Plates XXII, XXIII, XXIV and XXV.)
Two solutions were made, A being one old tablet in 10 c.c. of normal saline
solution, and B being one fresh tablet in an equal amount of saline.
The heart was arranged in the usual way and a normal tracing was first
recorded (Plate XXII, No. 1). 0.5 c.c. of solution A was then injected into
the right auricle with a hypodermic syringe having a very fine needle. The
immediate effect was a well marked increase in the amplitude of the contrac-
tions, the rate however remaining the same (No. 2). This effect lasted for less
than a minute, the contractions dropping to smaller than the normal and also
quickening up to 7 per cent. above normal (Nos. 3 and 4). The amplitude
of the contraction continued to diminish up to the end of the experiment (30
minutes). The rate increased up to 18 per cent. over the normal (Nos. 5, 6, 7,
and 8).
The experiment was repeated with a fresh frog using 0.5 c.c. of solution B.
Plate XXIII, No. 1, is the normal tracing. The drug was injected at X (No. 2),
and the almost immediate effect was a slowing of the rate of contraction to
87 per cent. of the normal. There was no increase in the amplitude. The
slowness was maintained for the next 4 minutes and 40 seconds (Nos. 3 and 4),
when it gradually dropped to 82 per cent. and finally to 80 per cent., the
amplitude being greatly diminished and falling to about 65 per cent. of what
it was before the application of the drug (Nos. 5, 6, 7, and 8).
(2) EFFECT WHEN APPLIED TO EXTERNAL SURFACE OF ISOLATED HEART
OF PITHED FROG.
In this experiment stronger solutions were used, solution C consisting of
two old tablets dissolved in 2 c.c. of water and solution D being the same but
made with fresh tablets.
The heart was arranged as usual and a normal tracing taken, Plate XXIV
(No. 1). 0.5 c.c. of solution C was then allowed to flow slowly over the sur-
face of the heart (No. 2). The immediate effect was a slowing down to 90 per
cent. of the normal. At the end of 1 minute 40 seconds the rate was again
normal and the tracing was identical with the normal one (No. 3). From
43
this point onward till the end of the experiment, the contractions remained
the same, varying between a slight slowing down to 95 per cent. and normal
(Nos. 4, 5, 6, 7, and 8).
The experiment was repeated using 0.5 c.c. of solution D. (Plate XXV.)
The immediate effect was a quickening of the rate to 4 per cent. over nor-
mal (No. 2), but this was replaced 40 seconds after the application of the drug
by a slowing of the rate to 96 per cent. of the normal (No. 3). 2 minutes
30 seconds later the rate was again normal (No. 4), and it remained normal
to the end of the experiment (Nos. 5, 6, and 7). The amplitude throughout was
slightly greater than before the application of the drug and the action of the
heart was regular.
(3) VASO-CONSTRICTOR ACTION ON THE PERIPHERAL VESSELS OF PITHED FROG.
For this experiment a solution of five tablets in 25 c.c. of water was used,
A being the solution of the old tablets and B being that of the fresh.
The usual arrangements for perfusing the fluid through the peripheral
circulation of the frog were made, and after the frog was bloodless and the rate
of the saline solution flowing through was fairly constant, norma saline solu-
tion containing 2 per cent, of the drug solution was perfused and the effect
recorded. The results obtained are noted below:—
Amount passed in successive 5-minute periods in c.c.
Normal Saline Solution.
Saline containing Solution A.
34
40
35
40.5
35.5
40
36.5
37
36.5
35.5
36.5
35
30
28.5
29
28
G2
44
The experiment was repeated with a fresh frog using first normal saline
solution and then saline solution containing 2 per cent. of solution B. The
figures obtained were as follows :—
Amount passed in successive 5-minute periods in c.c.
Normal Saline Solution.
Saline containing Solution B.
30
31
30
34.5
30
43
30
48
51
51
49
5 8
59.5
53
49
43.5
39
34
27
24
22
In the case both of the old tablets and the new, the first effect is one of
vaso-dilatation, followed by one of constriction. In the case of the new tablets,
both these effects are considerably more pronounced than in the case of the
old.
This experiment was repeated several times, varying the strength of the
perfused drug, and the results obtained were closely similar to those detailed
above.
45
(4) ACTION WHEN APPLIED LOCALLY TO EXPOSED MESENTERIC
VESSELS OF PITHED FROG.
Two frogs were pithed and a loop of intestine of each with its attached
mesentery was placed under the low power of a microscope.
To the mesentery of frog X 0.25 c.c. of solution A was applied and to
the mesentery of frog Y, 0.25 of solution B.
In frog X circulation was sluggish and came to a stand—still 3 minutes
after applying the drug. No visible change in the calibre of the vessels took
place, but 40 minutes after the application there was an appearance of inflam-
mation with engorgement of the vessels.
In frog Y the immediate effect of the drug was to produce some vaso-
constriction, but the circulation got slower and slower and stopped at 4 minutes
30 seconds. At 20 minutes the larger vessels showed some engorgement and dila-
tation, the capillaries remaining the same. No further change was observed.
The net results of the tests done lead one to conclude that there is no de-
tectable or recordable difference in the action on the heart between the old and
the fresh tablets. The action on the blood-vessels, however, is more pronounced
in the case of the fresh tablets, and in regard to this vaso-constrictor action, the
old tablets appear to have undergone some deterioration.
Morphine Tartrate.
( 0.3 grain = 0.022 gram.)
Solubility. —One old tablet took 4 minutes 20 seconds to dissolve in
1 c.c. of water, the solution being clear.
One new tablet dissolved in 1 c.c. of water in 1 minute 42 seconds,
the solution being very slightly cloudy.
Two solutions were made, each of five tablets dissolved in 11 c.c. of distill-
ed water. Solution A was made from old tablets and solution B from fresh
tablets. 1 c.c. = 0.01 gram of Morphine Tartrate.
(1) ACTION ON FROG ON INTRA-PERITONEAL INJECTION.
Four frogs were taken and the solutions injected intra-peritoneally :
Frog W
received
1 c.c. of solution A
,,
X
, ,
3 ,,
, ,
A
,,
Y
, ,
1 ,,
, ,
B
,,
Z
,,
3 ,,
, ,
B
46
In all four cases the results observed were identical, namely, slight slowing
and diminution of reflexes on cutaneous stimulation. No loss of muscular
power, no spasms and no effect on respiration were perceptible.
(2) ACTION WHEN APPLIED LOCALLY TO EXPOSED MESENTERIC
VESSELS OF PITHED FROG.
Solution A and solution B produced the same result in equal times, namely,
dilatation of vessels, most marked in the arteries and arterioles. The dilatation
was of an approximately equal degree, and in both cases stasis occurred in the
sixth minute after the application of the drug.
(3) ACTION ON CATS, HYPODERMICALLY INJECTED.
Two cats of approximately equal weight were used. One cat received one
old tablet dissolved in 1 c.c. of water and hypodermically injected, the
other cat receiving one fresh tablet in similar fashion. The animals remained
under observation for five hours and failed to show symptoms of any kind,
apparently remaining in a perfectly normal state. No difference was detected
between the behaviour of the two animals.
(4) ACTION OF LARGER DOSE ON CAT HYPODERMICALLY INJECTED.
A cat weighing 1.6 kilos received two old tablets in solution hypoder-
mically. Ten minutes later there was salivation, frothy mucus running
from the mouth. The cat was drowsy and lay down and could not be made to
stand or move by stimuli such as pricking or pinching. It would not touch food
and one hour after the injection its pupils showed slight contraction. Two and
a half hours after the injection it took food and thereafter its behaviour
was normal. At no time was there any appearance of excitement.
Four days later, the same cat, having quite recovered from the effects
of the old tablets, was given two fresh tablets hypodermically.
Within five minutes of the injection mucus and froth began to run from
its mouth and at ten minutes the cat seemed drowsy and lay down, moving
its head. to and fro laterally for five minutes. It could not be made to stand.
One hour after the injection it again began to move its head laterally
from side to side and continued to do so for nearly half an hour. There
was slight contraction of the pupil. It took food 3¾ hours after the injection.
At no time were there any signs of excitement.
These results fail to show any difference in activity between the old
and the new tablets.
47
Atropine and Morphine Sulphate.
(Atropin. Sulph. 1/155 grain=0.000 43 gram.
Morphin. Sulph. ¼ grain=0.0162 gram.)
Action. —Atropine first stimulates and then depresses the central nervous
system. In the frog it dries up the skin by paralysing the skin glands.
It dilates the pupil and in moderate doses tends to arrest the movement of the
intestine. It also paralyses the terminations of the vagus in the heart.
Morphine in the frog paralyses the central nervous system and may
produce convulsions. In cats, large doses lead to restlessness and excitement.
It is a vaso-dilator especially affecting the cutaneous vessels, and gives rise to
low blood pressure. It contracts the pupil and stops the intestinal peristalsis
except in very large doses when it increases it.
Solubility—A solution (A) was made by dissolving five old tablets in 10
c.c. of water, giving a strength of 0.000215 gram of Atropin. Sulph. per c.c.
and 0.0081 gram of Morphin. Sulph. per c.c.
Solution B was made in the same way with new tablets. Rapidity
of solution was practically the same in both.
The fresh tablets gave a clear, almost colourless solution, the old tablet
solution having a brownish tinge.
(1) MYDRIATIC ACTION IN ANIMALS.
Two rabbits were used, one getting 0.25 c.c. of solution A instilled into
its right eye, the other rabbit getting an equal amount of solution B in a
similar fashion.
Both rabbits showed an equal degree of dilatation at identical periods.
Two guinea-pigs received 0.25 c.c. of solution A and solution B respec-
tively. In each case dilatation was perceptible at 15 minutes and was well
marked at 20 minutes.
(2) MYDRIATIC ACTION ON MAN.
At 1 P.M. one laboratory attendant had 0.25 c.c. of solution A instilled
into his eye, another attendant receiving 0.25 c.c. of solution B.
At 1-25 P.M. dilatation was perceptible in both cases. At 2 P.M. dilatation
in the case of solution A was complete and almost complete in the case of solu-
tion . B. At 4 P.M. dilatation from solution A was still complete and was still
present at 10 A.M. next morning, although much diminished. In the case
of solution B the dilatation had diminished slightly at 4 P.M. and at 10 A.M.
next day the eye was almost normal.