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Nicotinic acid: Its action on the peripheral vascular system
KIWTINIC
ACID:
ITS
ACTION
VASCULAR
ON
THE
PERIPHERAL
SYSTEM
Ros J. POPKIS, Los ANGELES,
RID. CALIF.
N
IWTINIC acid and its compounds have been used successfully in the treatment of canine black tongue,l pellagra,2-5 and hightone deafness.” Observers have been unanimous concerning the OCcurrence of a sensation of heat and flushing following the use of this drug. In each case, the reaction was of short duration, occurred within a few minutes after the ingestion of as little as 30 mg., and disappeared within thirty minutes. Spies, Bean, and Stone” found, in the majority of their cases, that this reaction coincides with an actual increase in the surface temperature of the face and neck, and a decrease in the temperature of the hands and feet. In view of this apparent action on the peripheral blood vessels, the possibility that the drug might he uwd in the treatment of peripheral vascular diseases was investigated. Fifteen adults were given 30 to 120 mg. of nicotinic acid by mouth. The effect on surface temperatures, oscillometer readings, pulse and respiratory rates, oral temperatures, and blood pressure was observed before, and from ten to thirty minutes after, the ingestion of the drug. The observations were made under standard conditions, after the subjects had rested for fortyfive to sixty minutes in the recumbent position in a room kept at a constant temperature (70” F.). The body weights were all within normal limits. None of the subjects was acutely ill. There were nine women and six men in the series. Of these, four were normal; three had thromboangiitis obliterans; three, arteriosclerosis obliterans; one, essential hypertension; one, menopausal syndrome; and three, vasospastic disorders.
There were no prolonged untoward effects in any of the cases. Flushing and a sensation of heat, when they occurred, appeared in from seven to ten minutes, and disappeared within thirty minutes ; they were more severe and lasting with the larger doses of t.he drug. Transitory tingling of the face and ears, itching, a sensation of heat over the arms and back, and slight dizziness were noted occasionally. There was no appreciable effect on blood pressure except in two cases, in which it was markedly lowered. In no instance was it raised. Respiratory and pulse rates and oral temperatures varied slightly. li’rom the tabulation it can be seen that, regardless of the amount of the drug and the condition of t,he patient, surface temperatures were very inconstant. Reddening and flushing of the skin may occur with of
From the Department Lebanon Hospital. Los Received for publication
of Peripheral Vascular Angeles, Calif. June 17, 1939.
697
Diseases,
Outpatient
Clinic,
Cedars
---
60 M
16 F’
35 F
I
8
4
lj
30 M
3
‘10 F
60 mg.
40 F
5
30 mg.
35 F
2
100 mg.
80 mg.
80 mg.
80 mg.
ti0 mg.
30 mg.
F
50
1
DOSE
PVI.SE
AGEAND BEX
A&D
CASE
RESPIRATORY
.~.
disorder
Ar-
--
Vasoapastic disorder of hands (Raynaud ‘s syndrome).
Vasospastic of feet.
Hypertension. teriosclerosis obliterans.
Normal.
Thromboangiitis obliterans.
-
__-
_~--
TEMPERATURE,
DIAGNOSIS
ORAL
Vasospastic disorder of hands (Raynaud ‘s Syndrome).
Normal
Normal
RATES,
un-
Face decreased 0.9 to 1.6” C. Fingers increased 0 to 2.0” C. Toes decreased (0 to 1.5” c I. Face increased 0.5 to 1.5” C. Fingers decreased 0.8 to 3.0” C. Toes decreased 0.2 to 1.1” .~____... Cent.
Face increased 1.4 to 1.8” Cent. Fingers showed slight increases and decreases. Toes decreased 0.1 to 2.0” c. Face decreased 0.3 to 0.5” C. Fingers decreased 0.5 t,o 2.0” C. Toes decreased 0.1 to 1.0” Cent. Face and fingers no change. Toes decreased 0.3 to 1.G” c. _____ b’ace increased L 0.6 to 0.7’ ( Fingers decreased 0 ti 1.2” C. Toes decreased 0 to 0.6” c/. ~ -Not done.
toes
TEMPERATURES
Face, fingers, changed.
STRFAC'E
READINGS
OR CHAXCED
ONLY
No
All
decreased Both calves (Fig. 1.)
-
3.x un-
change except slight decreases.
for
-.. very
decreased 0.2 to 1.9 div. points. (Fig. 2.)
-. Right arm div. pts. chauged.
Left calf, ankle no change. Right calf and ankle decreased 0.5 to L-1 division points. No change except left ankle decreased 1.3 division noints. I -. All decrcaacd from 0.1 to 1.5 division points (Fig. 1).
Slight decrease in both calves and ankles, 0.1 to 0.8 division points. (Jalves unchanged. Ankles decreased 0.4 to 0..7 dir. points.
OSCILLOMETER
NOT CJIAKGE, STATED
OBSERVATIONS
I
AXD BLOOD PRESSURE DID MINIMAL UNLESS OTHERWISE
EXPERIMENTAL
TABLE
sensnt iG
OR
Flushing of fact ing and tingling.
-
- ~. \vith
.-
itch.
Flushing ofm:hT gling. Oral temp. reduced from 98.2”F. to .974°F. . Entire right half of body to the knee, flushed, warm with itching. I,eft side, neck WRS warm. Hlight itclring and flushing of face. Blood pressure dropped from 225/11:: to 160/95. ~, ~None except for flu&i= forehead with sensation of cold.
None.
Gth
~I_
UNCIIANCTE~)
REACTIOXS
Face flushed of heat.
None.
~LIGlITLy,
s
$ F
E c: 2 c;
7 %
5 g
3 2i
K
AGE AND SEX
63 M
61 M
45 M
50 F
45 F
32 F
49 M
CASE
9
10
11
12
1.3
14
15
120 mg.
syn-
hyperten-
Thromboangiitis obliterans. (Lumbar sympathectomy 8 years previously.)
Normal.
Menopausal drome.
100 mg.
120 my.
Essential eion.
Thromboangiitis obliterans.
100 mg.
mg.
Arteriosclerosis obliterane.
100 mg.
1uo
Arteriosclerosis obliterans.
DIAGNOSIS
mg.
DOSE
100
TElIPERATCKES
I--COiYT
'D
done.
done.
Face increased 0.5 to 0.6O C. Fingers increased 1.1 to 2.6” C. Toes increased 0.1 to 1.6’ Cent.
Face decreased 0.6 to 1.5” C. Fingers-thumbs decreased 0.2 to 3.4” C. and little fingers increased 0.3 to 1.6” C. Toes decreased 0.5 to 1.7” Cent.
Not
Not
Face increased 0 to 0 7” C Fingers decreased 0.8 td 3.0° C. Toes increased 0.1 to 1.3” Cent. Face decreased 0.4 to 1.2’ C. Fingers increased 1.3 to 1.8” c. Toes unchanged. Face decreased 0.4 to 0.6” C. Fingers and toes very slight changes.
STRFACE
TABLE
done.
READIXGS
911 decreased points (Fig.
0.2 to 2.0 div. 4).
Left arm unchanged. Left calf increased 1.0 div. pt. Right calf decreased 1.5 div. point. All decreased 1.2 to 2.5 div. points (Fig. 3).
Left ankle and right calf unchanged. Right ankle and left calf decreased 1.0 div. points. Right calf increased 0.2 div. pt. Left calf increased 0.5 div. pt. (Fig. 2.) Not done.
Not
OSC‘ILT.03IETER
with
with
itch-
itcll-
Nausea within 6 Face, arms, legs flushed resembling burn with marked Chills. Oral temp. from 98.6” F. to Malaise present. Face flushed.
minutes. became a sunitching. dropped 98’ F.
Blood press. dropped from 190/100 to 1111/80 within 20 minutes. Pulse remaining 64, weak and thready. Near collapse. None
None.
Flushing of face ing and tingling.
Flushing of face ing and tingling.
REACTION8
W
z
2 ii=1 3 0 G
zi z 2 ” z ; $
700
THE,
AMERICAS
HEART
JOURSAI,
either an increase or decrease in surface temperature, with or without the sensation of warmth. In Cases 7 and 14 the face became red and flushed, but the surface temperature decreased, and the sensation was one of cold. The amplitude of the oscillometric tracings diminished in the majority of the cases, particularly when large doses of the
Fig. l.-Graphs I. Upper chart: left calf and ankle at rest. minutes after 80 Mg. nicotinic acid. Marked reduction of amplitude Arst reading in calf. Subject was a normal woman, 20 years old. Graphs II. Upper chart: right arm at rest. Lower chart: 10 Mg. nicotinic acid. Blood pressure dropped from 225/113 to 160/95, tracing. Subject was a UO-year-old man, suffering from hypertension sclerosis obliterans.
Lower chart: 15 of tracing from minutes after 80 as shown in the and arterio-
drug were used. The diminution varied from slight to marked in eleven of the thirteen cases in which tracings were recorded. These changes were not absolutely consistent.. In two cases there was a definite increase in amplitude. Untoward reactions, while alarming in one subject (Case 12), were of short duration. One subject (Case 14) was rendered extremely uncomfortable by chills and a fall of body
POPKIN
:
NICOTINIC!
ACID
‘701
In all of the subjects the effects of the drug had disaptemperature. peared completely within thirty to forty minutes. In many instances the peak of the reaction was very short, lasting less than ten minutes.
Fig. Z.-Graphs III. Upper chart: right calf and ankle at rest. Lower chart: 15 minutes after 80 Mg. nicotinic acid. Generalized reduction in amplitude. Patient was a girl, 16 years old, suffering from severe Raynaud’s disease of the lower extremities. Graphs IV. Upper chart: left calf at rest. Lower chart: 15 minutes after 100 Mg. nicotinic acid. This was one case in which increased pulsation occurred. Patient was a man. 45 years old, suffering from thr,omboangiitis obliterans.
The discordant results are difficult to explain. Other observer$, * have noted surface-temperature changes, cardiovascular and gastrointestinal symptoms, substernal oppression, and pruritus or other skin manifestations. They have attributed some of their findings to a histamine or a parasympathetic action of the nicotinic acid. The discordant results of this study may have been due to individual differences in susceptibility, to variations in the rate of absorption of the
702
THE
AMERICAN
HEART
JOURNAI,
drug from the gastrointestinal tract, and to the fact that the observations, especially the surface temperature measurements, were made at certain arbitrarily selected times. Although it is difticult to reconcile the decreased oscillometric readings and the occasional marked fall in blood pressure with a parasympathetic effect, a histamine’ action does apparently account for most of the phenomena observed. Many unrelated substances
S.-Graphs V. Upper chart: right 120 Mg. nicotinic acid. Graphs VI. Upper chart: left ankle at nicotinic acid. All pulsations were reduced in amplitude. subject, a normal woman, 32 years of age. after
Fig.
calf
at
rest. These
rest. Lower: recordings
Lower 15
chart:
minutes were
15 after from
minutes 120 the
Mg. same
give this reaction. They include tissue extracts, secretin, peptones and other product,s of protein cleavage, blood serum, and bacterial products. It also occurs in traumatic shock. Histamine causes a contraction of smooth muscle regardless of its innervation, and an increased permeability and dilatation of the capillary bed. This action
POPKIN
:
NICOTINIC
703
ACID
is clearly apparent in the majority of the cases observed, and occurs even after sympatheetomy (Case 15). Substernal oppression may be the result of coronary artery constriction, although electrocardiographic tracings have been reported to show nothing abnormaL3 The lowered surface temperature observed when the skin is flushed and red may be due to stasis of blood in the engorged capillary bed. ,4 further pharmacologic action of histamine is an initial stimulation
Fig. 4.-Graphs Mg. nicotinic Graphs VIII. same individual. 49 years old, sympathectomy 120
VII. Upper chart: left acid. Tracings from right calf, All pulsations are reduced suffering from thromboangiitis eight years previously.
calf
at
rest.
Lower:
before and after nicotinic in amplitude. Patient obliterans. He had
15
minutes
had
acid, was
after in
a
a
the man, lumbar
of the gastrointestinal tract, followed by a relaxation. This may explain the nausea, vomiting, belchin g, and other gastrointestinal symptoms reported by most observers. Spies, et al.,” injected nicotinic acid intracutaneously in normal subjects, thereby obtaining wheals and pruritus which were similar to those produced by histamine.
704
THE
AMERICAN
HEART
JOURNAL
1. Nicotinic acid, administered orally, in single doses, in the majority of cases causes transitory flushing of the skin, tingling, itching, and sensations of heat, regardless of the condition of the subject or the size of the dose. 2. The changes in the surface temperature of the face, fingers, and toes are variable and unpredictable. 3. The amplitude of the oscillometric tracings is diminished in the majority of cases, and the degree of diminution varies direct,ly with the quantity administered. 4. It is suggested t,hat the effects of nicotinic acid are similar to those prodaced by hist,amine. 2. Kicotinic acid is of little value in the treatment of peripheral vascular disease because it produces uncomfortable symptoms and arterial constriction, and because whatever favorable effects it may have are of very short duration. REFERENCES
1. Elvehjem, C. A., Madden, R. J., Woolley, D. W., and Strong, F. M.: Relation of Nicotinic Acid and Nicotinic Acid Amide to Canine Black Tongue, J. am. Chem. Sot. 59: 1767, 1937. Pellagra Successfully Treated 2. Smith, D. T., Ruffin, J. M., and Smith, Susan G.: With Nicotinic Ac.id, J. il. M. A. 109: 2054, 1937. Treatment of Subclinical Classic 3. Spies, T. D., Bean, W. B., and Stone, R. E.: Pellagra. The Fse of Nicotinic Acid, Nicotinic Acid Amide and Sodium Nicotinate With Special Reference to the Vasodilator Action and the Effect on Mental Symptoms, J. A. M. A. 111: 584, 1938. 1. Sebrell, W. H., and Butler, R. E.: A Reaction to the Oral Administration of Nicotinic Acid, J. A. M. A. 111: 2286, 1938. Treatment of Pellagra With Nicot,inic 5. Rachmilewitz, M., and Glueck, Helen: Acid, Brit. MY. J. 2: 346, 1938. Nicotinic Acid and the Eighth Serve: Preliminary Report, 6. Selfridge, G.: Ann. Otol. R,hin. and Laryng. 48: 39, 1939. 7. Sollmann, T.: Manual of Pharmacology, Philadelphia, 1937, W. B. Saunders.
ACID:
ITS
ACTION
VASCULAR
ON
THE
PERIPHERAL
SYSTEM
Ros J. POPKIS, Los ANGELES,
RID. CALIF.
N
IWTINIC acid and its compounds have been used successfully in the treatment of canine black tongue,l pellagra,2-5 and hightone deafness.” Observers have been unanimous concerning the OCcurrence of a sensation of heat and flushing following the use of this drug. In each case, the reaction was of short duration, occurred within a few minutes after the ingestion of as little as 30 mg., and disappeared within thirty minutes. Spies, Bean, and Stone” found, in the majority of their cases, that this reaction coincides with an actual increase in the surface temperature of the face and neck, and a decrease in the temperature of the hands and feet. In view of this apparent action on the peripheral blood vessels, the possibility that the drug might he uwd in the treatment of peripheral vascular diseases was investigated. Fifteen adults were given 30 to 120 mg. of nicotinic acid by mouth. The effect on surface temperatures, oscillometer readings, pulse and respiratory rates, oral temperatures, and blood pressure was observed before, and from ten to thirty minutes after, the ingestion of the drug. The observations were made under standard conditions, after the subjects had rested for fortyfive to sixty minutes in the recumbent position in a room kept at a constant temperature (70” F.). The body weights were all within normal limits. None of the subjects was acutely ill. There were nine women and six men in the series. Of these, four were normal; three had thromboangiitis obliterans; three, arteriosclerosis obliterans; one, essential hypertension; one, menopausal syndrome; and three, vasospastic disorders.
There were no prolonged untoward effects in any of the cases. Flushing and a sensation of heat, when they occurred, appeared in from seven to ten minutes, and disappeared within thirty minutes ; they were more severe and lasting with the larger doses of t.he drug. Transitory tingling of the face and ears, itching, a sensation of heat over the arms and back, and slight dizziness were noted occasionally. There was no appreciable effect on blood pressure except in two cases, in which it was markedly lowered. In no instance was it raised. Respiratory and pulse rates and oral temperatures varied slightly. li’rom the tabulation it can be seen that, regardless of the amount of the drug and the condition of t,he patient, surface temperatures were very inconstant. Reddening and flushing of the skin may occur with of
From the Department Lebanon Hospital. Los Received for publication
of Peripheral Vascular Angeles, Calif. June 17, 1939.
697
Diseases,
Outpatient
Clinic,
Cedars
---
60 M
16 F’
35 F
I
8
4
lj
30 M
3
‘10 F
60 mg.
40 F
5
30 mg.
35 F
2
100 mg.
80 mg.
80 mg.
80 mg.
ti0 mg.
30 mg.
F
50
1
DOSE
PVI.SE
AGEAND BEX
A&D
CASE
RESPIRATORY
.~.
disorder
Ar-
--
Vasoapastic disorder of hands (Raynaud ‘s syndrome).
Vasospastic of feet.
Hypertension. teriosclerosis obliterans.
Normal.
Thromboangiitis obliterans.
-
__-
_~--
TEMPERATURE,
DIAGNOSIS
ORAL
Vasospastic disorder of hands (Raynaud ‘s Syndrome).
Normal
Normal
RATES,
un-
Face decreased 0.9 to 1.6” C. Fingers increased 0 to 2.0” C. Toes decreased (0 to 1.5” c I. Face increased 0.5 to 1.5” C. Fingers decreased 0.8 to 3.0” C. Toes decreased 0.2 to 1.1” .~____... Cent.
Face increased 1.4 to 1.8” Cent. Fingers showed slight increases and decreases. Toes decreased 0.1 to 2.0” c. Face decreased 0.3 to 0.5” C. Fingers decreased 0.5 t,o 2.0” C. Toes decreased 0.1 to 1.0” Cent. Face and fingers no change. Toes decreased 0.3 to 1.G” c. _____ b’ace increased L 0.6 to 0.7’ ( Fingers decreased 0 ti 1.2” C. Toes decreased 0 to 0.6” c/. ~ -Not done.
toes
TEMPERATURES
Face, fingers, changed.
STRFAC'E
READINGS
OR CHAXCED
ONLY
No
All
decreased Both calves (Fig. 1.)
-
3.x un-
change except slight decreases.
for
-.. very
decreased 0.2 to 1.9 div. points. (Fig. 2.)
-. Right arm div. pts. chauged.
Left calf, ankle no change. Right calf and ankle decreased 0.5 to L-1 division points. No change except left ankle decreased 1.3 division noints. I -. All decrcaacd from 0.1 to 1.5 division points (Fig. 1).
Slight decrease in both calves and ankles, 0.1 to 0.8 division points. (Jalves unchanged. Ankles decreased 0.4 to 0..7 dir. points.
OSCILLOMETER
NOT CJIAKGE, STATED
OBSERVATIONS
I
AXD BLOOD PRESSURE DID MINIMAL UNLESS OTHERWISE
EXPERIMENTAL
TABLE
sensnt iG
OR
Flushing of fact ing and tingling.
-
- ~. \vith
.-
itch.
Flushing ofm:hT gling. Oral temp. reduced from 98.2”F. to .974°F. . Entire right half of body to the knee, flushed, warm with itching. I,eft side, neck WRS warm. Hlight itclring and flushing of face. Blood pressure dropped from 225/11:: to 160/95. ~, ~None except for flu&i= forehead with sensation of cold.
None.
Gth
~I_
UNCIIANCTE~)
REACTIOXS
Face flushed of heat.
None.
~LIGlITLy,
s
$ F
E c: 2 c;
7 %
5 g
3 2i
K
AGE AND SEX
63 M
61 M
45 M
50 F
45 F
32 F
49 M
CASE
9
10
11
12
1.3
14
15
120 mg.
syn-
hyperten-
Thromboangiitis obliterans. (Lumbar sympathectomy 8 years previously.)
Normal.
Menopausal drome.
100 mg.
120 my.
Essential eion.
Thromboangiitis obliterans.
100 mg.
mg.
Arteriosclerosis obliterane.
100 mg.
1uo
Arteriosclerosis obliterans.
DIAGNOSIS
mg.
DOSE
100
TElIPERATCKES
I--COiYT
'D
done.
done.
Face increased 0.5 to 0.6O C. Fingers increased 1.1 to 2.6” C. Toes increased 0.1 to 1.6’ Cent.
Face decreased 0.6 to 1.5” C. Fingers-thumbs decreased 0.2 to 3.4” C. and little fingers increased 0.3 to 1.6” C. Toes decreased 0.5 to 1.7” Cent.
Not
Not
Face increased 0 to 0 7” C Fingers decreased 0.8 td 3.0° C. Toes increased 0.1 to 1.3” Cent. Face decreased 0.4 to 1.2’ C. Fingers increased 1.3 to 1.8” c. Toes unchanged. Face decreased 0.4 to 0.6” C. Fingers and toes very slight changes.
STRFACE
TABLE
done.
READIXGS
911 decreased points (Fig.
0.2 to 2.0 div. 4).
Left arm unchanged. Left calf increased 1.0 div. pt. Right calf decreased 1.5 div. point. All decreased 1.2 to 2.5 div. points (Fig. 3).
Left ankle and right calf unchanged. Right ankle and left calf decreased 1.0 div. points. Right calf increased 0.2 div. pt. Left calf increased 0.5 div. pt. (Fig. 2.) Not done.
Not
OSC‘ILT.03IETER
with
with
itch-
itcll-
Nausea within 6 Face, arms, legs flushed resembling burn with marked Chills. Oral temp. from 98.6” F. to Malaise present. Face flushed.
minutes. became a sunitching. dropped 98’ F.
Blood press. dropped from 190/100 to 1111/80 within 20 minutes. Pulse remaining 64, weak and thready. Near collapse. None
None.
Flushing of face ing and tingling.
Flushing of face ing and tingling.
REACTION8
W
z
2 ii=1 3 0 G
zi z 2 ” z ; $
700
THE,
AMERICAS
HEART
JOURSAI,
either an increase or decrease in surface temperature, with or without the sensation of warmth. In Cases 7 and 14 the face became red and flushed, but the surface temperature decreased, and the sensation was one of cold. The amplitude of the oscillometric tracings diminished in the majority of the cases, particularly when large doses of the
Fig. l.-Graphs I. Upper chart: left calf and ankle at rest. minutes after 80 Mg. nicotinic acid. Marked reduction of amplitude Arst reading in calf. Subject was a normal woman, 20 years old. Graphs II. Upper chart: right arm at rest. Lower chart: 10 Mg. nicotinic acid. Blood pressure dropped from 225/113 to 160/95, tracing. Subject was a UO-year-old man, suffering from hypertension sclerosis obliterans.
Lower chart: 15 of tracing from minutes after 80 as shown in the and arterio-
drug were used. The diminution varied from slight to marked in eleven of the thirteen cases in which tracings were recorded. These changes were not absolutely consistent.. In two cases there was a definite increase in amplitude. Untoward reactions, while alarming in one subject (Case 12), were of short duration. One subject (Case 14) was rendered extremely uncomfortable by chills and a fall of body
POPKIN
:
NICOTINIC!
ACID
‘701
In all of the subjects the effects of the drug had disaptemperature. peared completely within thirty to forty minutes. In many instances the peak of the reaction was very short, lasting less than ten minutes.
Fig. Z.-Graphs III. Upper chart: right calf and ankle at rest. Lower chart: 15 minutes after 80 Mg. nicotinic acid. Generalized reduction in amplitude. Patient was a girl, 16 years old, suffering from severe Raynaud’s disease of the lower extremities. Graphs IV. Upper chart: left calf at rest. Lower chart: 15 minutes after 100 Mg. nicotinic acid. This was one case in which increased pulsation occurred. Patient was a man. 45 years old, suffering from thr,omboangiitis obliterans.
The discordant results are difficult to explain. Other observer$, * have noted surface-temperature changes, cardiovascular and gastrointestinal symptoms, substernal oppression, and pruritus or other skin manifestations. They have attributed some of their findings to a histamine or a parasympathetic action of the nicotinic acid. The discordant results of this study may have been due to individual differences in susceptibility, to variations in the rate of absorption of the
702
THE
AMERICAN
HEART
JOURNAI,
drug from the gastrointestinal tract, and to the fact that the observations, especially the surface temperature measurements, were made at certain arbitrarily selected times. Although it is difticult to reconcile the decreased oscillometric readings and the occasional marked fall in blood pressure with a parasympathetic effect, a histamine’ action does apparently account for most of the phenomena observed. Many unrelated substances
S.-Graphs V. Upper chart: right 120 Mg. nicotinic acid. Graphs VI. Upper chart: left ankle at nicotinic acid. All pulsations were reduced in amplitude. subject, a normal woman, 32 years of age. after
Fig.
calf
at
rest. These
rest. Lower: recordings
Lower 15
chart:
minutes were
15 after from
minutes 120 the
Mg. same
give this reaction. They include tissue extracts, secretin, peptones and other product,s of protein cleavage, blood serum, and bacterial products. It also occurs in traumatic shock. Histamine causes a contraction of smooth muscle regardless of its innervation, and an increased permeability and dilatation of the capillary bed. This action
POPKIN
:
NICOTINIC
703
ACID
is clearly apparent in the majority of the cases observed, and occurs even after sympatheetomy (Case 15). Substernal oppression may be the result of coronary artery constriction, although electrocardiographic tracings have been reported to show nothing abnormaL3 The lowered surface temperature observed when the skin is flushed and red may be due to stasis of blood in the engorged capillary bed. ,4 further pharmacologic action of histamine is an initial stimulation
Fig. 4.-Graphs Mg. nicotinic Graphs VIII. same individual. 49 years old, sympathectomy 120
VII. Upper chart: left acid. Tracings from right calf, All pulsations are reduced suffering from thromboangiitis eight years previously.
calf
at
rest.
Lower:
before and after nicotinic in amplitude. Patient obliterans. He had
15
minutes
had
acid, was
after in
a
a
the man, lumbar
of the gastrointestinal tract, followed by a relaxation. This may explain the nausea, vomiting, belchin g, and other gastrointestinal symptoms reported by most observers. Spies, et al.,” injected nicotinic acid intracutaneously in normal subjects, thereby obtaining wheals and pruritus which were similar to those produced by histamine.
704
THE
AMERICAN
HEART
JOURNAL
1. Nicotinic acid, administered orally, in single doses, in the majority of cases causes transitory flushing of the skin, tingling, itching, and sensations of heat, regardless of the condition of the subject or the size of the dose. 2. The changes in the surface temperature of the face, fingers, and toes are variable and unpredictable. 3. The amplitude of the oscillometric tracings is diminished in the majority of cases, and the degree of diminution varies direct,ly with the quantity administered. 4. It is suggested t,hat the effects of nicotinic acid are similar to those prodaced by hist,amine. 2. Kicotinic acid is of little value in the treatment of peripheral vascular disease because it produces uncomfortable symptoms and arterial constriction, and because whatever favorable effects it may have are of very short duration. REFERENCES
1. Elvehjem, C. A., Madden, R. J., Woolley, D. W., and Strong, F. M.: Relation of Nicotinic Acid and Nicotinic Acid Amide to Canine Black Tongue, J. am. Chem. Sot. 59: 1767, 1937. Pellagra Successfully Treated 2. Smith, D. T., Ruffin, J. M., and Smith, Susan G.: With Nicotinic Ac.id, J. il. M. A. 109: 2054, 1937. Treatment of Subclinical Classic 3. Spies, T. D., Bean, W. B., and Stone, R. E.: Pellagra. The Fse of Nicotinic Acid, Nicotinic Acid Amide and Sodium Nicotinate With Special Reference to the Vasodilator Action and the Effect on Mental Symptoms, J. A. M. A. 111: 584, 1938. 1. Sebrell, W. H., and Butler, R. E.: A Reaction to the Oral Administration of Nicotinic Acid, J. A. M. A. 111: 2286, 1938. Treatment of Pellagra With Nicot,inic 5. Rachmilewitz, M., and Glueck, Helen: Acid, Brit. MY. J. 2: 346, 1938. Nicotinic Acid and the Eighth Serve: Preliminary Report, 6. Selfridge, G.: Ann. Otol. R,hin. and Laryng. 48: 39, 1939. 7. Sollmann, T.: Manual of Pharmacology, Philadelphia, 1937, W. B. Saunders.