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SUBSTANCES ACTING ON THE URINARY SYSTEM.



6 7



from Brunton's work, shows the various ways in which they
probably act, many in more ways than one :








f Digitalis,






Caffeine,
Increased car- 1 Alcohol ;






diac action [Strophanthus,




Generally . . . .


[ Sparteine,






General vas-


Erythrophloeum,]
Digitalis,






cular contrac-


Squill,


P Q1CA




tion


Convallaria,


ivaise




Strychnine,


arterial .




Cold to skin.


pressure




- Act on vaso- f , same ag aboye>






motor centres I






- Contract


f Broom,






efferent


.


Caffeine (large






vessels


Locally on


doses),
Buchu,
Uva ursi,




Locally
in kidney




kidney.


Juniper,
Turpentine,
Copaiba,




t Cantharides.




Dilate, chiefly f




, ' ,, , Caffeine,
locally, renal j Ufea


-


vessels [




f Urea,




| Caffeine,




Increase water excreted . i


[Theobromine So-






dio-salicylate,






Calomel,


Act on secreting




Colchicum,]


nerves or renal cells




Liquor Potassae,




Increase water and solids


Potassium Acetate,
Potassium Citrate,




excreted


Potassium Nitrate,






Sodium Citrate and




.


other salines.



Therapeutics. Diuretics are used in cardiac 'and pulmon-
ary diseases when, owing to the general vascular disturbance, the
quantity of urine falls below the normal standard. Also, in dis-
eases in which there is excess of fluid in certain parts of the body ;
for example, pleuritic effusion and ascites, with the object of get-
ting rid of as much fluid as possible by the kidneys. Also, they
may be used to dilute the urine, e.g. , when it is prone to deposit



68



PHARMACOLOGY AND THERAPEUTICS.



its solids. Lastly, in certain forms of kidney disease, although
in these maladies it is always a question how far it is desirable to
stimulate diseased organs. It is of great importance to remem-
ber that diuretics may act in many different ways ; that there are
many causes for diminution in the quantity of urine secreted,
and that it is difficult to say in any particular case what is the
cause of the decrease in the quantity secreted. Therefore, it is
usual to give diuretics in combination, in the hope that if one
of them does not have the desired result another will.

2. Drugs diminishing the quantity of urine secreted. These
are such as produce acute inflammation of the kidney when given
in large doses ; e.g., turpentine, cantharides, phosphorus. [Ex-
algin is reputed to diminish the quantity of urine.] They are
never given for this purpose in medicine.

3. Drugs rendering the urine acid. There is one drug that
can do this, and that is benzoic acid, for in its passage through
the kidney it is converted into hippuric acid. Benzoic acid is,
therefore, given when from any cause the urine undergoes alka-
line decomposition anywhere within the urinary passages. Sali-
cylic acid will, to a slight extent, increase the acidity of the
urine, as will very large doses of citric acid, tartaric acid [borax,
and possibly saccharin. The free use of carbonated water also
increases the urinary acidity (Ultzmann). Urotropin is the
most reliable remedy to render an alkaline urine acid].

4. Dntgs which render the urine alkaline. [Some] salts of
the metals, potassium, sodium, lithium, calcium, will do
this [e.g., the carbonates, berates and hydroxides]; even the
tartrates, citrates, [malates, lactates,] and acetates, for they es-
cape by the kidney as carbonates. Nitric acid is said to increase
the amount of ammonia in the urine, and thus to render it
slightly alkaline. Ammonium salts given internally do not
render the urine alkaline, because they are decomposed in the
body, urea being probably formed ; [they may even increase the
acidity from the larger amount of nitric acid excreted.]

Lithontriptics are drugs which prevent the decomposition,
in the urinary passages, of the solids of the urine. If this fluid
be acid, uric acid often crystallizes out, forming gravel or uric



SUBSTANCES ACTING ON THE URINARY SYSTEM. 69

acid calculus ; less often lime oxalate crystallizes, giving rise to
lime oxalate calculus. When there is any likelihood of the for-
mation of either of these calculi, alkalies should be given. If
the urine is undergoing alkaline decomposition phosphates are
liable to crystallize out. In this case the object will be to render
the urine acid and aseptic. This will be attained by giving
benzoic acid or benzoates, salicylic acid or the salicylates, [uro-
tropin, or the other] urinary antiseptics.

Therapeutics. The chief use of alkalies is to diminish the
acidity of the urine, so as to render the precipitation of uric acid
unlikely ; or to render it alkaline, so as to attempt to dissolve a
uric acid calculus. We know of no drug which will dissolve a
lime oxalate calculus. Alkalies are also given to gouty subjects,
partly to alkalize the blood, but also partly to alkalize the urine,
for such persons are very prone to deposit uric acid in the urine.
Potassium urate is much more soluble than sodium urate, and
lithium urate is perhaps even more soluble ; citrates and acetates
are not likely to upset the digestion, consequently the drugs
most used are the potassium and lithium citrates. Copious
draughts of water, by diluting the urine, aid in preventing the
deposition of uric acid or lime oxalate calculi. Natural alkaline
waters are largely used [especially those containing lithium] .

5. Drugs preventing the urine from decomposing. If the urine
is retained in the bladder by stricture or from any other cause, it
will undergo alkaline decomposition, and the same result may be
brought about by the admixture of pus with the urine. This is
generally due to inflammation of the pelvis of the kidney or the
bladder. This decomposition of the urine may be prevented by
giving drugs which in their excretion by the urine render it asep-
tic. Such are



(1) Urotropin.

(2) Benzoic acid.

(3) Salicylic acid.

(4) Uva Ursi.

(5) Copaiba.



(6) Cubeb.

(7) Oil of Sandal Wood.

(8) [Saccharin.]

(9) Many volatile oils.
(10) Boric acid.



6. Drugs altering the composition of the urine. Almost any
drug will do this, either because it is excreted in the urine, or



7<D PHARMACOLOGY AND THERAPEUTICS.

because it sets up some changes in the body, the products of
which are excreted in the urine ; but here we shall only refer to
certain striking ones.

Turpentine, cantharides and salicylic acid in large doses will cause blood
to appear in the urine, because they set up inflammation of the kidney.

Potassium chlorate, all nitrites, acetanilid, pyrogallic acid, poisoning by
the mushroom, (Helvella esculenta) and transfusion of animal's blood, break
up red blood -corpuscles, and the products are excreted by the urine rendering
it dark. Large doses of mineral acids, arsenic, naphtol [and naphtalin] are
said occasionally to produce the same result.

Phosphorus in large doses causes leucin and tyrosin to appear in the urine,
and the urea is greatly increased.

The saline diuretics increase the solids of the urine.

The chrysophanic acid in rhubarb and senna makes the urine, if it is acid,
a brownish color ; if it is alkaline, a purplish red. Logwood renders alkaline
urine reddish or violet Santonin colors acid urine yellow or greenish-yellow,
and alkaline urine, reddish. Carbolic acid, naphtalin, creosote and other
preparations of tar, as well as the arbutin in uva ursi, [chimaphila and gaul-
theria] make it dark greenish- brown. Picric acid makes it a bright yellow,
and methyl violet a dark blue. The urine of persons poisoned with carbonic
oxide remains sweet for months.

Poisoning by carbonic oxide, [curare,] amyl nitrite and turpentine, and
sometimes [chloroform, camphor,] mercury, morphine, chloral, [hydrocyanic]
acid, sulphuric acid, alcohol, lead compounds, and salicylic acid lead to the
appearance in the urine of a body which like sugar reduces Fehling' s copper
solution. Some authorities state that the urine, after the administration of
these drugs, does not contain glucose, but glycuronic acid ; for although it re-
duces blue copper solutions, it does not undergo alcoholic fermentation on the
addition of yeast [or give the phenyl-hydrazin test]. The administration
of phloridzin, [a glucoside from the bark of stem and root of the apple, pear,
plum and cherry, which, when continuously heated with dilute mineral acids,
is resolved into glucose and phloretin], leads to the production of genuine
glucose in the urine.

Other drugs cause a peculiar odor in the urine ; for example, the smell of
violets is produced by turpentine. The aromatic odor of cubeb and copaiba
can be detected in the urine after the administration of these bodies.

Lead, if taken for long periods, produces chronic interstitial inflammation
of the kidney. It is stated that rarely mercury will do the same.

7. Drugs acting on the bladder and urethra. The only ones
of any practical value are sedatives to the urinary tract.

If the urine is decomposing, drugs preventing its decomposition come



DRUGS ACTING ON THE BODILY HEAT. /I

under this head. Other sedatives are opium, belladonna, hyoscyamus,
pareira, buchu and uva ursi, which are direct sedatives to the vesical and
urethral mucous membrane. If the urine is excessively acid, alkalies are
urinary sedatives.

Urinary sedatives are used very largely in cases of cystitis and urethritis,
whatever the cause may be. Local astringent and antiseptic injections are
also employed.

DIVISION VII. DRUGS ACTING ON THE BODILY HEAT.

A. Antipyretics, or Drugs which decrease the Bodily
Temperature. There are few if any drugs which can lower
the temperature in health. Some, it is true, will cause the tem-
perature to fall below normal, if given to a healthy man in large
enough doses to induce severe collapse. The word antipyretic is
limited to those drugs which bring down the temperature when
it is raised owing to disease. We know that the greatest amount
of heat is produced in the muscles, and that there is a special
part of the corpus striatum presiding over this production ; that
heat is lost mostly by radiation from the vessels of the skin and
by the evaporation of sweat, and that these vessels and the sudo-
riparous glands are under the control of the central nervous
system. Heat is also lost through the lungs. As the produc-
tion and loss are in health so accurately adjusted, many observers
believe that there is a part of the cerebrum whose function is to
maintain the balance between the production and the loss. Also,
all parts of this complex mechanism are supplied with blood-
vessels, alterations in the calibre of which must affect the activity
of the parts they supply.

There is every reason for believing that the part of the central
nervous system which presides over the loss of heat (thermo-
lysis), that which presides over the production of heat (ther-
mogenesis), and that which possibly presides over the balance
between the production and the loss (thermotaxis), can, each
of them be influenced by afferent impulses reaching them from
various parts of the body, and thus we see each of these three
functions can probably be reflexly affected (see diagram on next
page).

Antipyretics which increase the loss of heat. All sudorifics and



72 PHARMACOLOGY AND THERAPEUTICS.

all dilators of the cutaneous vessels act as antipyretics. Cold,
such as a cold bath, increases the loss of heat by direct abstraction.



Balance
' between produffym\

and loss

\Thermotaxis

Cortical'?'



froducfit




Drugs which probably diminish the production of heat. Our
knowledge about these is at present uncertain, but it is very
probable that phenacetin, antipyrin, and acetanilid dimin-



DRUGS ACTING ON THE BODILY HEAT. 73

ish the production by their action on the corpus striatum ; and
that quinine, salicylic acid, and salicin, also diminish the
production ; but we do not know upon what part of the thermo-
genetic apparatus they act. A cold bath not only abstracts heat,
but, after it has been in operation some little time, diminishes
the production.

Antimony, aconite, and digitalis are probably antipyretic through their
effect on the circulation, but precisely how they act is not known. Sometimes
the removal of some irritation which is acting reflexly may lower the tempera-
ture. In this way purgatives are occasionally antipyretics.

Therapeutics. The sole use of antipyretics is to lower the
temperature in fever.

Drugs which increase the loss of heat were formerly popular
as antipyretics, especially alcohol, spirit of nitrous ether, anti-
mony, ipecacuanha, and opium, but now they are not much used.
Cold is more often employed, either by cold sponging, ice, or a
cold bath. Sponging with hot water will, by the vascular dila-
tation and subsequent sweating it induces, reduce a febrile tem-
perature.

Of the drugs which probably alter the production, acetanilid
and [antipyrin] are dangerous because of the collapse they may
produce ; quinine and salicylic acid are rather uncertain, except
in ague and rheumatic fever respectively. [Antipyrin] and
phenacetin are most in demand ; they are certain antipyretics.
Phenacetin is very safe, but is less powerful. They are quickly
absorbed, and so act promptly ; they are far more powerful anti-
pyretics than any drugs which act by increasing the loss of heat,
and these are very uncertain in their action, often not lowering
the temperature at all. Another reason for preferring drugs
which diminish thermogenesis is that it is much more rational
to lower the temperature by decreasing the production of heat
than by increasing the loss, for then the production will, if any-
thing, go on faster than before, in consequence of the attempt
to compensate for the increased loss. Antipyretics should be
rarely given, for probably fever is often beneficial.

B. Drugs which cause a rise of Temperature. Bella-



74 PHARMACOLOGY AND THERAPEUTICS.

donna, picrotoxin, and cocaine in poisonous doses may do this.
How they act is not known.

Tuberculin, various albumoses and certain animal poisons, such as that of
shell-fish, will cause a rise of temperature. Their mode of action is unknown.

We know of no drugs acting on thermotaxis.

DIVISION VIII. DRUGS ACTING ON RESPIRATION.

Respiration can be modified by such very various influences
that it is difficult to decide upon the exact mode of action of any
drug which affects it. For example, alterations in the blood and
in the air will modify it ; the respiratory centre itself may be
influenced, either directly or reflexly, from almost any organ in
the body ; or, again, the movements of the respiratory muscles
themselves may be interfered with ; and, lastly, respiration is
much under the influence of the circulatory apparatus. Further-
more, the chief object in medicine is to remove the cause of the
respiratory ^difficulty rather than to act upon respiration itself.

We have already spoken of those drugs which produce changes
in the blood and the circulation, and the consideration of those
modifications of the temperature, moisture, and pressure of the
air which are of value in medicine, belongs to a book on general
therapeutics. We will, therefore, now consider the respiratory
drugs under the following heads :

A. Drugs altering the Composition of the Air in-
haled. [This division is devoted to drugs which, inhaled, have
some direct effect on the respiratory mucous membrane, on bron-
chial and pulmonary contents, and have certain remote effects.]
It is found convenient to administer some drugs, although they
are not given for their influence on respiration, by making the
patient inhale them ; such are anaesthetics and amyl nitrite.

Some drugs when inhaled are particularly irritating to the
bronchial mucous membrane, causing dilatation of the vessels,
increased secretion, and reflexly, cough from the stimulation of
the sensory nerves of the bronchial mucous membrane.

Such are cold dry air, iodine, bromine, chlorine, senega, ipecacuanha,



DRUGS ACTING ON RESPIRATION. 75

sulphurous anhydride, nitric acid fumes, ammonia, and tobacco. These are
rarely used therapeutically as inhalations, and their inhalation is to be particu-
larly avoided in irritable conditions of the bronchi.

The drugs which, when inhaled, are soothing to the bron-
chial mucous membrane, [but] are rarely employed, are

Hydrocyanic acid. | Conium.

Inhalations which are used to stimulate the bronchi, that
is to say, to increase their vascularity, secretion, and muscular
power, are



(l) Carbolic acid
(2)Oilofcaju P ut} TTlxx -; E 1 - 20 ^-]
(3) Oleum pini sylvestris, TH.XXX. ;
[2.00 c.c.]



(4) Tinctura ben- ->
zoini composita,

(5) Creosote, U^ss.; [I 5 c.cj

(6) Oil of cubeb. J



The amounts given after each are the quantities that should be added to a
pint [500 c.c.] of water at 140 F. ; [60 C. ]

Inhalations which are used to disinfect foul secretions
from the bronchial mucous membrane are those of



(1) Creosote.

(2) lodoform.

(3) Mild solutions of benzoin.

(4) Carbolic acid.



(5) Sulphurous anhydride.

(6) Oil of juniper.

(7) Oil of cubeb.

(8) [Oil of eucalyptus.]



Inhalations for relieving spasm of the bronchial tubes are
those of



(1) Coniura. -

(2) Stramonium. -

(3) Chloroform.






(4) Ether.

(5) Amyl nitrite.



B. Drugs acting on the Respiratory Centre. If the

drug, when injected into the carotid artery, very quickly produces
its effect on respiration, it is concluded that it acts on the res-
piratory centre. Another experiment often used to determine
whether the drug acts on the centre, or on the vagal terminations
in the lung, is to cut the vagi and to observe whether it acts sim-
ilarly before and after the section.



PHARMACOLOGY AND THERAPEUTICS.
Drugs which directly stimulate the respiratory centre are



(1) Strychnine.

(2) Ammonia (very powerful).

(3) Apomorphine.



(4) Belladonna.

(5) Stramonium.

(6) Hyoscyamus.



Drugs which depress the respiratory centre are



(1) Physostigmine (very pow-

erful).

(2) Chloral [hydrate.]

(3) Chloroform.

(4) Ether.

(5) Alcohol.

(6) Opium.

(7) Hydrocyanic acid.

(8) Codeine.



(9) Aconite.
(10) Veratrine.
(n) Conium.

(12) Caffeine.

(13) Quinine.

(14) Ipecacuanha.

(15) Antimony salts (very

weak).



Alcohol, ether, chloroform, caffeine, and quinine slightly excite, before
they depress [the respiratory centre].

Therapeutics. The drugs which excite the respiratory cen-
tre may be used when there is any difficulty in respiration, espe-
cially with the view of increasing the force of the respiratory act
whilst other means are employed to get rid of the cause of the
difficulty. They are, of course, most frequently required in dis-
eases of the lungs, especially bronchitis. Ammonia and apomor-
phine are often employed, as they are also powerful expectorants ;
and belladonna is useful when there is too much secretion from
the bronchial tubes.

Substances which depress the respiratory centre are very little
needed for this action ; but the centre for the reflex act of cough-
ing is in the close neighborhood of the respiratory centre, and
opium, hydrocyanic acid, codeine, conium, and ipecac-
uanha are often very valuable in allaying the continual hacking
cough whch so frequently accompanies disease of the heart and
lungs.

The drugs which relieve cough are very numerous, for it may
be reflexly set up by irritation of so many peripheral parts, viz.,
nose, throat, pharynx, ear, teeth, larynx, trachea, bronchi, lungs,
pleura, stomach, and liver ; and consequently its removal may



DRUGS ACTING ON RESPIRATION. 77

depend upon the removal of peripheral irritation in any of those

organs.

C. Drugs affecting the Bronchial Secretion.

(a) Those increasing it :



(1) [Apomorphine.]

(2) All alkalies, especially am-

monium carbonate and
other salts.

(3) [Cocillana.]

(4) Ipecacuanha.

(5) Senega

(6) Squill.-

(7) Turpentine.

(8) [Terebene.]



(9) Camphor.

(10) Benzoin.

(11) Balsam of Peru.

(12) " " Tolu.

(13) Antimony salts.

(14) Sulphur.

(15) Iodine.

(16) Tobacco.

(17) Pilocarpus.

(18) Many volatile oils.



[It is probable that volatile oils and substances containing them decrease
the amount of bronchial secretion as a later effect].

(6) Those decreasing it :



(1) Acids.

(2) Belladonna.



(3) Stramonium.

(4) Hyoscyamus.



Many authorities think that under some circumstances alkalies decrease the
secretion.

(c) Those disinfecting it: Drugs which, when inhaled, act in this way
have already been mentioned. Copaiba, cubeb, [eucalyptus,] and many vola-
tile oils are excreted partly by the bronchial mucous membrane, and thus will
disinfect the secretion.

Therapeutics. In bronchitis, remedies which increase the
secretion are used when it is so viscid that it sticks to the tubes
and cannot be coughed up ; and those which decrease it are
employed when it is too watery to be easily expectorated. The
use of the disinfectants is obvious.

D. Drugs relaxing spasm of the Muscular Coat of
the Bronchial Tubes, or Antispasmodics. It is believed
that [the symptom] asthma is due to a spasmodic contraction of
the bronchial tubes, and as



(1) Stramonium.

(2) Belladonna.



(4) Grindelia.

(5) [Aspidosperma.]



(3) Hyoscyamus.
relieve [this symptom], it is concluded that these drugs relax



78 PHARMACOLOGY AND THERAPEUTICS.

spasm of the muscular coat of the bronchial tubes. Stramonium
is the most powerful. It is very likely, judging by their anal-
ogous action in other parts of the body, that the following drugs
act in the same way :

Chloroform, ether, opium, chloral [hydrate], cannabis indica, amyl nitrite,
and conium.

Therapeutics. Stramonium is of great use [for relief of the
symptom] asthma, and this and the other drugs may be employed
for cases of bronchitis in which it is probable that the irritation
caused by the inflammation of the tubes sets up spasm of them.
Many of these muscular depressants in all probability depress the
nerves at the same time.

E. Drugs acting on the Vessels of the Bronchi.
These are the same as have been already described (p. 56) as
acting on the vascular system generally,

F. Expectorants. The modes of action of drugs acting
on the respiratory system are so complex that it is usual to regard
most of them clinically, simply as drugs which hinder or aid the
expectoration of the contents of the bronchial tubes. Those
which aid it are divided into two groups, named after their
action, not on the lungs, but on the circulation.

I. Stimulating expectorants. These are stimulants to the circulation gen-
erally. They are



(1) Acids.

(2) Ammonium salts.

(3) [Cocillana.]

(4) Senega.

(5) Squill.

(6) Benzoin.

(7) Benzoic acid.

(8) Balsam of Tolu.



(9) Balsam of Peru.

(10) Turpentine preparations.

(11) Terebene.

(12) Oleum Pini Sylvestris.

(13) Nux Vomica.

(14) Sulphur.

(15) Quillaja.



2. Depressing expectorants. These depress the general circulation.
They are



(1) Alkalies.

(2) Antimony salts.

(3) Ipecacuanha.

(4) Lobelia.



(5) Pilocarpus.

(6) Apomorphine.

(7) Potassium Iodide.



DRUGS ACTING ON THE DIGESTIVE APPARATUS. 79

Therapeutics. It is almost impossible to lay down any gen-
eral directions. The prescriber must consider in any case before
him whether he wishes to stimulate or to depress the circulation,
to increase or to diminish or to disinfect the expectoration, to
stimulate the respiratory centre, to overcome spasm of the bron-
chial tubes, or to allay a hacking cough ; and he must combine
his remedies according to the answer he makes to these ques-
tions. Warmth to the chest and warm drinks are sedative, and
increase the amount of secretion. Cold and cold drinks have an
opposite effect.

G. Drugs which in Man sometimes produce Cheyne-
Stokes Breathing. These are morphine, potassium bromide,
and chloral hydrate. In animals the following in addition may
do it : picrotoxin, muscarine, digitalin, strychnine and ammo-
nium carbonate.

DIVISION IX. DRUGS ACTING ON THE DIGESTIVE APPARATUS.

A. Drugs acting on the Teeth. Soaps and powders are
used for cleaning the teeth. The basis of most tooth powders
is chalk, which acts mechanically ; charcoal is sometimes used in
the same way. As the food is very liable to collect and decom-
pose between the teeth, antiseptics, as quinine, borax and car-
bolic acid, are often mixed with tooth powders. Astringents
such as [krameria] are employed if the gums are too vascular.



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