Hugh McGuigan.

An introduction to chemical pharmacology: pharmacodynamics in relation to ... online

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diagnostic aid in syphilis, tuberculosis,^ etc. Copper has been
advocated in the. treatment of carcinoma, etc. Platiniun, in
the form of platiniun black, has been used to a considerable ex-
tent by laboiatory workers. The chief suspensoid colloids are:


colloidal metals — Cu. Au.


kaohn, antimony sulphide, arsenious sulphide.



The emulsoid colloids make up the greater part of living ma-
terial. They are solutions of a Uquid in a Uquid; in other words,
the disperse phase as well as the solution is Uquid: This ac-


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counts for their having a greater viscosity than suspensoids.
Solutions of Uquids in Uquids have no sharp boundary lines as
might be expected between soUds and Uquids, and they have
Uttle, if any, electrical properties. When free from electrolytes,
they do not traveKwith the electric current, and are not as sus-
ceptible to electrolytes as suspensoids, which are precipitated by
traces of electrolytes. Emulsoids are precipitated only after
the addition of considerable quantities of electrolytes. Traces
of electrolytes seem to aid fluid solution, presumably by adding
their charge to the colloid.

Emulsoids are precipitated by suspensoids.. Colloidal iron
has been used for this purpose to remove the blood proteins in
blood sugar analysis. The excess of the suspensoid is removed
at the same time by the addition of an electrolyte like MgS04
or Na2S04. However, where there are large amounts of emul-
soid present, it forms a coating on the suspensoid particles and
prevents their complete precipitation by the electrolytes. This
is the chief objection to this method for blood-sugar work. *

The difference between emulsoid and suspensoid colloids is
probably due to a difference in the affinity of the two substances
for the solvent. Suspensoids have practically no aflBnity for
the solvent, and readily fall out of solution when their electric
charges are removed. Emulsoid colloids which are hydrophylic
require an excess of the neutrahzing salt to overcome the union
of the colloid and the water. Such colloids are called hydro-
phyl because they have an affinity for water. This is strikingly
illustrated in the change of viscosity in water caused by a. small
amount of colloid. A 1 per cent gelatine increases the viscosity
of water 29 per cent.


In an ordinary solution of an emulsoid colloid, the solvent or
water is the continuous phase. It is possible to think of a small
body going through the solution, passing around the isolated or
dispersed particles as a ship would sail around small islands.
When these colloids gel, a molecular arrangement of the disperse
phase takes place, and a network is formed. The water now
appears to be the disperse phase, as it is enmeshed in a cellular
network of colloid. One could think of a body being able to
pass along the network from any portion of it to any other over

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a continuous route. This netlike structure can be substantiated
by the use of the microscope.

When gelling occurs, the colloid acts more like a solid than a
liquid. Gelatin and agar-agar form gels readily, but on heating
they will liquefy, and again, on cooling, set or gel. Such sub-
stances are called reversible gels. Protoplasm, on heating, forms
an irreversible gel. If a gelatin or agar gel is allowed to stand
for some time, it contracts and some water is liberated. This proc-
ess of contraction with the Hberation of liquid is called syneresis.
Blood, on clotting, may show the same phenomenon, which is
well known in the preparation of bacterial media also. This
phenomenon may be of great importance in pharmacology. The
water holding capacity of protoplasm is changed in a similar
way, and the diuresis following jthe administration of alkalies
and salts has been explained on such a basis. It is well known
that the water holding capacity of gelatin and fibrin is modified
enormously by the presence of salts. ''


Colloids, according to the affinity of the disperse phase for the
dispersing medium may be classified as lyophile, where there is
a marked affinity of the disperse phase and the medium and
lyophobe, where no such affinity is shown. When water is the
dispersing medium, the terms hydrophile and hydrophobe are
also used.

In the lyophobe series, which is synonymous with sitepensoid,
the physical properties of the sol are very little. different from
those of tlie dispersing medium, while the physical properties
of the lyophile markedly change those of the medium. Much
greater concentrations of electrolytes are necessary to precipi-
tate the lyophile series of colloids. According to Pauli, both
ions of an elec.trolyte play a r61e in the precipitation of colloids.
While one ion precipitates, the other may have a solvent effect.
Cations as a rule act as precipitants, while anions are solvents,
the total action being the algebraic sum of these actions. From a
series of experiments, the relative efficiency of the ions in causing
precipitation, etc., has been arranged from the least to the most
effective. This series is known as the lyotropic series. The
following table shows the relative action of the various ions.


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Kations - Mg NH4 K Na Li


Fluoride... + + +

Sulphate ...+ + + + +

Phosphate + + +

Citrate + + +

Tartrate + + +

Acetate. — — + +

Chloride - - + + +

Nitrate — — — + +

The action of the ions in this series is so neariy the same se-
quence in many other reactions in which they can react only
indirectly that their action in most cases is thought to be on the
solvent or dispersing medium rather than on the colloid. The
sequence does not follow any chemical order as valence, atomic
weight, or the like; for example,

1. In the hydrolyses of esters by acids,
anions S04< (H20)< Cl< Br
kations H20< Li < Na< K < Rb <Cs

In this case, SO4 retards action, in all others the ions accelerate.

2. In the hydrolyses of esters by bases,
anions I > NO3 > Br > Cl> H20<S04
kations Cs> Rb > K > Li H2O

It is seen here that the ions that accelerated the acid hydrolysis
retard basic hydrolysis.

3. .The surface tension of aqueous solutions,
H2O < I < N03<C1 < SO4 <C03

All these ions increase surface tension. A similar influence is
exerted on viscosity.


As we have seen, there are various reasons for believing that
colloids are electrically charged: (1) they migrate in an electric
current; (2) oppositely charged colloids precipitate each other.

The proteins are amphoteric, but are more acid than basic.
The isoelectric point, i.e., the reaction in which they will not
migrate in the electric current, is:

Digitized by




Serum albumin 4.7

senun globulin , . . . 5.4

casein 4.7

oxyhemoglobin 6.74

It may be that all colloids to some degree at least are amphoteric.

The presence of colloids in a solution greatly lessens the action
of electrolytes. Suspensoid colloids are also protected by the
presence of emulsoid colloids of the same sign; suspensoids mixed
with emulsoids can be evaporated to dryness and the residue
redissolved in water. Without the emulsoid, the colloidal nature
of the suspensoid would be destroyed. Colloidal merciuy and
silver can be made more stable by admixture with emulsoid
colloids. This protective power is used in medicine to disguise or
lessen the taste of acid and bitter medicines. Solutions of gly-
cyrrhizse, acacia, etc., are used as vehicles because of this pro-
tective action on the nerves of taste.


Just as there is no sharp line between crystalloids and colloids
so there is no sharp Une between pharmaceutical emulsions and
emulsoid colloids. The emulsions of the pharmacist are, perhaps^
electrically charged to some extent, and this helps to hold them
in solution. The emulsifying agents used are usually gum
acacia or tragacanth which produce very viscous solutions which
settle very slowly. The magma of magnesia which is mainly
magnesiiun hydroxide resembles colloidal iron or iron hydrate.
Under a variety of conditions, all emulsions or emiilsoid colloids
"crack'' or precipitate. The cause of these changes may be:
(1) spontaneous; (2) heat or cold; (3) changes in the volume or
composition of the solvent; (4) the action of enzymes; (5) other
colloids; (6) electrolytes.

1. Spontaneous change. Just as any electrically charged
body may lose its charge and become neutral, so a colloidal solu-
tion after a time may crystalUze, precipitate, or otherwise lose its
colloidal character.


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2. Cold is especially liable to destroy pharmaceutical emul-
sions. 'Emulsoid colloids are also less stable on freezing. Heat
above the coagulative point of an emulsoid coagulates it. Heat
will also demagnetize iron.

3. The effect of changes in the volmne of a solvent is well
illustrated when a dilute solution of gelatin or agar is evaporated
to a small volume. It gels. If the solution is changed by
adding alcohol, the gelatin or agar is precipitated, in the first
instance there is no intramolecular change other than the abstrac-
tion of water and when this is again added, the emulsoid character
is jestored. In such a case, the change is reversible. In the
second there is an intramolecular change aside from the changes
in the solvent and this change is irreversible.

4. The action of enzymes. The clotting of blood and the
curdling of milk are types of irreversible gel formation. The
mechanisms of these actions are not well understood, but are due
to an electrical neutraUzation of the colloids, in all probability.

5. Suspensoid colloids are especially susceptible to the action
of electrolytes. The action here is due to the neutralization of
the charges on the suspensoid by the electrolyte. Emulsoids are
but little influenced by small amounts of electrolytes, due to their
characteristics being less well defined, but are precipitated by
larger amounts of the salts. That the electrical charge of the
emulsoid plays some part in the precipitation is seen in the series
of effectiveness of the anions in the salting out of non-electrolytes.


A substance in a gaseous state tends to increase its volume,
while substances in the liquid state tend to contract into the
smallest volume, or volume with the least surface area. The
surface in this condition, in all liquids behaves as if stretched.
This stretch or pull on the surface film is the result of unbalanced
molecular forces. In any Uquid the molecules have a definite
attraction for each other. This attraction has been estimated at
10,000 to 25,000 atmospheres. A molecule in the center is sub-
ject to the same force from all sides, and consequently there is
no movement one way or the other. Below the surface layer,
the molecules exert an attraction for those above them in the
surface layer, while those on the top are^ not attracted by the


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atmospheric gases, and bend or curve in the direction of the pull
from within, hence tend to assume the spherical form. The
thickness of this film, or the range of the molecular attraction
has been estimated at about 6 X 10~^ milUmetres.

This stretch or pull on the surface layer interferes with the
movements of the molecules, and for this reason confers on the
liquid some of the properties of a soUd, since in the soUd state,
freedom of movement in the molecules is Umited. Various meth-
ods have been devised to measure surface tension, the most
practical being the following. The average weight of a drop of
the fluid falling from a standardized pipette or stalagmometer is
taken. The surface tension of water is considered as unity, and
that of any other fluid, Uke blood or serum, is calculated by di-
viding the weight of the Uquid by the number of drops, and com-
paring this with water under the same conditiops.

Surface tension of Uquid = sp. gravity of solution multiplied

by number of drops of water

number of drops of solution

There are other methods, more accurate and correspondingly
more compUcated than this one. The above formula gives the
surface tension in relation to water. Since water has a tension
of 73 ergs, per square centimeter, the formula, to read in ergs.,
should be:

no. of drops of water X density of hquid
number of drops of liquid

The surface tension of Uquids in dynes per centimeter is

water 73

alcohol.-. 22

ether 16

Surface tension undoubtedly plays an important r61e in many
biological reactions. In phagocytosis or the taking up of bac-
teria by cells, substances (toxins?) which change the surface
tension modify the phagocytic power. The clumping of bacteria
and opsonic index, shows a change in the surface tension of bac-
teria; similarly anesthesia may in the last analysis be due to
changes in siuf ace tension.


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The following experiment by Rhumbler (Arch. Entwichlungs-
mech, 1898 (VII), 249) is interesting in this regard:

If one tries to pierce a drop of chloroform under water with a
fine glass rod, it is very diflScult or impossible. If now the rod
be coated with shellac it is sucked into the chloroform. The
shellac in this case changes the surface tension in a manner
similar to the changes that may occur in bacteria by toxins
or between nervous and muscular tissue by an anesthetic.


The distinctive character of solids is that the relative position
of the molecules is fixed and can not be changed except by the
expenditure of a relatively great force. The characteristic of a
liquid is its tendency to flow. The molecules can be moved with
relative ease; in gases, the fluidity is much greater than in liquids.
In liquids, although the particles move relatively easily, the
fluidity is not perfect. The particles adhere to each other so
that when a thread of the liquid moves, it drags some of the other
particles with it, and is in turn held back by them. There is
thus a movement of the different layers past each other in the
direction of the flow. This shearing, or internal friction, or
property of the particles to adhere to «ach other, is viscosity.
It is exerted only during movement. Ether, water, oils, balsams
and waxes are examples of fluids possessing progressively greater

The suspensoid colloids, which are soUd particles suspended
in a Uquid, have little intimate relation with the liquid in which
they are suspended, and hence have little viscosity, while the
emulsoid colloids, which are liquids in Uquids, have the properties
of liquids, and thus a greater viscosity than the suspensoids.

Surface tension is a surface phenomenon only. It is due to
the attraction or pull of the molecules on each other; it is exerted
at all times, but is only manifest at the boundary surfaces of
Uquids, because here the balance of force is upset. The force
of attraction of the molecules of a fluid for each other is exerted
at a very short range only — about 6 X 10""* milUmetre. All
molecules in a Uquid this distance below the surface wiU be
attracted with an equal force in all directions but the layers of
molecules in the surface fluid will be attracted only by those





below, without a balanced pull from above. Hence they will
tend to pack together and assume the spherical form, since
potential energy always tends to become a minimum. The sur-
face, therefore, contracts as much as the conditions will allow.
The strength of the pull of the molecules on each other will de-
pend entirely on the kind or chemistry of the molecule. In the
case of viscosity, this depends more on the physical state of the

The tendency of liquids to assume this spherical form can be

1. In Hammerschlag's method of determining the specific
gravity of the blood; mix benzene and chloroform until it is of the
same specific gravity as the blood. Then place a drop of blood
in the mixture and the blood will assume a spherical form.

2. Alcohol and water is made to the same density as olive oil.
Drops of olive oil in this will neither rise nor sink, but will
assume a globular form.

3. If conditions are imposed so that the liquid can not assume
the spherical form, it will assume the smallest surface area that
conditions will permit, as Van der Mensbrugge's experiment
shows : " A loop of fine silk is taken and tied to a wire ring. If the
whole be dipped into soap solution, so as to produce a film, the
loop floats in the film; the silk thread forming its boundary is
quite loose, and can be readily moved into any shape by means of

Fig. 2. — Mensbrugge's Experiment.

a fine needle wetted with the soap solution. (A) The film inside
the loop is now broken by touching it with a bit of filter paper cut

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to a fine point. The loop is immediately drawn to a circular
form by the tension of the film surrounding it, and can be felt to
resist attempts to change its shape by the needle. (B) The
soap solution should be prepared by the method of Boys (1912,
p. 170), from pure sodium oleate, with the addition of about 25
per cent, of glycerol."

Substances that lower the surface tension always collect on the
surface. They are never uniformly distributed through the
Uquid; float two small pieces of wood parallel to each other and a
few millimetres apart. Now let a drop of alcohol fall between
them. They will suddenly fly apart. "The reason for this is that
the surface tension of alcohol is less, than that of water, and the
drop of alcohol weakens the surf ace tension film between the
small pieces of wood so that it breaks, and they fly apart. In
the same way, a film of water on a glass sUde breaks when a drop
of alcohol or ether is added. Camphor placed 6n water darts
about over the surface, because it lowers the surface tension
unequally at different points and the rupture of the surface film
causes it to move.

Superficial Viscosity. — This is different from, and independ-
ent of surface tension, which, as we have said, is a constant stress
at the boundary of Uquids. Surfaxje viscosity is a sort of surface
friction which is manifest only when there is something to disturb
or rupture the film. If a Uquid assumes a globular form, it is due
to surface tension, independent of viscosity. Pure water has a
large surface tension, but no viscosity. It will not foam on
shaking. A solution of saponin has a marked superficial vis-
cosity, but no marked surface tension above that of water. A
magnetic needle placed on the surface of the saponin solution,
because of the viscosity is not changed in position by the earth's
magnetic directive force, while it will be changed in a water
solution. A saponin solution foams on shaking superficial
viscosity holding the bubble together while the surface tension is
tending to break it. Oil has a small surface tension but a large
surface viscosity.


The surface tension of a Uquid decreases with the rise of tem-
perature; hence comparisons should only be made of Uquids at


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the same temperature. As might be expected, the surface tension
varies enormously with composition, but no definite rule can be
made, nor from chemical composition can predictions of surface
tension be made with certainty. In a homologous series Uke the
paraffin series, increase in CH2 does not appreciably change sur-
face tension. Water has a surface tension of 73 dynes, alcohol
= 22, and ether = 16. Here it would seem that the introduction
of C2H6 decreases surface tension. Isomeric compounds have the
same surface tension only when they have similar constitutions.

Salts increase the surface tension of water, as do gum arable,
starch and plum gum. On the other hand, gelatin glue, egg
albumen, dextrin, cherry gum, and traces of fatty acids, soaps,
bile acids, tannic acid an(f resins lower it.

Since the same chemical fcubstance may be a suspensoid in one
dispel sion medium and an emulsoid in another, we find that the
same substance may lower surface tension in water and raise it in
alcohol, and vice versa. Thus the dye. Night Blue, lowers the
surface tension of water and raises it for alcohol.


As a rule, viscosity or internal friction increases with molecular
weight. An iso compound always has a larger coefficient of *
viscosity than the normal compound. In many cases, the mole-
cular viscosity can be calculated from known viscosity constants.
Thus the viscosity constant of


= 44.5


= 31.0


= 166.0


= 198.0

CI in monochlorides

= 256.0

I in monoiodides

= 374.0

Double linkage

= 48.0

Ring grouping

= 244.0

There is a relation between chemical constitution and viscosity,
although water and alcohol present exceptions to any relation yet
discovered. In suspensoids the viscosity is Uttle different from the
water-dispersing medium. There is also Uttle chemical union
here, it being merely a physical suspension. Colloids, however,


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show a marked viscosity, which depends upon the amount of the
colloid. One per cent, gelatine increases the viscosity of water
29 per cent.


Adsorption is the term applied to surface absorption. This
process has long been used by chemists to clarify Uquids, especi-
ally for polariscopic work. If a solution contains color, or is
otherwise opaque, it has been the custom to add powdered char-
coal, shake, and filter the solution. The coloring material in
most cases adheres to the surface of the particles of charcoal.

Filter paper also adsorbs certain colloids. If a piece of filter
paper is dipped into a solution of Congo red, it soon accumulates
enough of the dye on the surface so that the solution becomes-
visibly lighter in color. Fuller's earth and kaolin also absorb
coloring matter and alkaloids in the same way. Bunsen recom-
mended freshly precipitated ferric hydroxide as an antidote in
arsenic poisoning. He thought that a compound of basic ferric
arsenite was formed; 4Fe203, AS2O3, 5H2O. . Recent work shows
that this is an adsorption compound.

Charcoal condenses and absorbs gases, and for this reason has
been used in treatment of gas accumulation in the stomach and
intestines. The gas is adsorbed. Similarly, palladium and
platinum adsorbs hydrogen. In the gas chain method of deter-
mining hydrogen ion concentration, spongy platinum holds so
much hydrogen that it acts as an hydrogen electrode.

Selective Adsorption. — Colloidal materials in many cases, for
unknown reasons, exert a selective adsorption. Sea weeds, for
example, select iodine from the sea water out of all proportion to
the amount present. In the same way, plants take up potassium
as compared with sodium. Adsorption in all these cases may be
preliminary to chemical combination or chemical action; similar
to the adsorption of pepsin by fibrin. If a thread of fibrin is
introduced into a solution of pepsin, most of the ferment is soon
adsorbed by the fibrin.

Influence of Salts on Absorption. — Salts seem to have a marked
influence in some cases. Bone black does not absorb diptheria
toxin in water, but it is readily absorbed from saline or Ringer's
solution. Bone black adsorbs sugar in neutral solution, but not
when acidified with acetic acid.


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The explanation of adsorption is not easy. It is a surface
phenomenon, and is increased by increase of surface. In colloidal
solutions, the surface is enormous. It has been calculated that
in a red colloidal solution of gold containing 0.5 grams of gold in
a liter, the surface amounts to 8 square meters. Although col-
loidal solutions of the same sign may adsorb each other as in the
case of Congo red and filter paper, the kind of electric charge on
the solid does influence adsorption. When colloids of the same
sign are adsorbed, it may be that they are amphoteric.

Acid dyes are in general adsorbed by electro positive colloids
like clay and colloidal iron,_ while basic dyes are adsorbed by

Online LibraryHugh McGuiganAn introduction to chemical pharmacology: pharmacodynamics in relation to ... → online text (page 24 of 30)