considered of medicinal importance from the very early times and have attracted the attention of the practitioners of the indigenous system of medicine. It has been used as an anthelmintic, as an antidote against snake bite and bites of other poisonous insects, in diarrhoea, dysentery, cholera and also as an ecbolic. In recent years interest has been stimulated in this drug, because of its well marked hypnotic and sedative properties. It forms the chief if not the only constituent of the various ‘insanity cures’ which are so widely advertised in the lay press. Its use in the treatment of high blood pressure is of a very recent origin and is the outcome of the pharmacological investigations carried out on this drug. This use may be said to be, still in an experimental stage and hence any record of careful clinical observations, would be valuable in assessing the true value of this drug in the treatment of hyperpicsia.Chemically, the root contains a number of alkaloids. Sen and Bose (1931) found two alkaloids, with different melting points. Siddiqui and Siddiqui (1931) have reported five alkaloids to which they have given names of Ajmaline, Ajmalinine, Ajmalicine, Scrpentine, and Serpentinine. Von Italie and Steenhaur mention the presence of a least three alkaloids, the nature and identity of which is more or less the same, as found by Siddiqui and Siddiqui. An alkaloid isolated by the Chemistry Department of the Tropical School of Medicine, Calcutta, was experimentally studied by Chopra, Gupta and Mukherjee (1933).
As a result of their pharmacological studies
they found that this alkaloid has a toxic action on lower forms of life like
Paramoecia Caudatum in dilution of 1 in 20,000. Its toxicity on higher animals
was variable. Frogs were quite tolerant, whereas the white mice were very
susceptible. The toxicity also varied with the route of administration, the
drug being much more toxic, when given intravenously or intraperitoneally, than
when given subcutaneously.
On the circulatory system, the drug lowered
the blood pressure of cats under anaesthesia, effect lasting for a considerable
time. If spinal cats were used the effect produced was very slight, which
showed that probably the fall in blood pressure was due to vasodilatation,
resulting from the depression of the vasomotor centre in the medulla oblongata.
The fall in blood pressure was also noticed after the terminations of the vagi
were paralysed with atropine, showing that vagal inhibition does not play much
part in the fall produced. The fall in blood pressure was also partly due to
diminished cardic output, which they found on
myocardiographic
studies. On perfusing the drug through isolated vessels, Chopra and his
co-workers found, that it definitely decreased the number of drops of the
perfusate per minute, which meant that it produces ‘vasoconstriction’ though
they have erroneously called it vasodilatation.
Both on the intact, as well as the isolated
mammalian heart, the drug seemed to have a slight depressant action. The
alkaloid had a stimulant action on the plain muscles of the alimentary canal
and the uterus. However, its most interesting action was noticed on the central
nervous system, which it seems to depress in the reverse order of development.
That is, the highest centres, which are the last to be developed, are usually
the first to be affected. It produces drowsiness, diminution in motor activity,
diminution in the appreciation of sensory stimuli, depression of the medullary
centres.
In view of the fact, that the chemistry of
this drug is not finally settled (Siddiqui and Siddiqui having recently revised
their own findings) and because the pharmacological action of the other
alkaloids had not yet been worked out, I decided to use the crude drug for this
clinical investigation. The preparation which was used in most of the cases was
Serpina tablets, prepared by The Himalaya Drug House, Dehra-Dun. In some cases
liquid extract of Rauwolfia
serpentina prepared by Smith
Stanistreet, Calcutta, was also used.
For this investigation, cases of high blood
pressure, were divided into two groups, those without renal damage and those
with renal damage. The first group constituted what Sir Clifford Albutt had
described ‘hyperpiesia’ and some latter writers as ‘essential hypertension’.
The second group constituted cases of high blood pressure subsequent to chronic
glomerulotubular nephritis. In every case, before starting the drug, the
patient was put for a fortnight on ‘high blood pressure regime’, which
consisted of proper diet, proper amount of rest and exercise, proper attention
to personal hygiene and bowels. The regime invariably resulted in slight fall
in blood pressure and figure thus obtained, was taken, as the initial blood
pressure, in the cases described hereafter.
Group I –
Cases of Hyperpiesia:
Case 1 – A young man of 22, Hindu, vegetarian, highly nerve strung, first
came under observation in the Medical Ward in October, 1940, with symptoms of
throbbing palpitation and insomnia. Kidney function normal; vessel wall
palpable; B.P. 210/125; he was put on Serpina tablets ( 1 tablet daily at bed
time). B.P. after one week 182/100, after one month 160/90. Completely relieved
of symptoms. Used ½ tablet daily for another month and then gave it up; felt
very fit till November, 1941, when the symptoms again reappeared; B.P. in
November, 1941, was 200/110; a few days’ use of Serpina tablets again brought
it down to 170/95 with complete relief of symptoms.
Case 2– An old Christian lady of 65, non-vegetarian
with a life full of worries and anxieties had been suffering from headache,
throbbing sensation, insomnia, palpitation, flushes and tingling sensations in
extremities for about a year before she consulted me in November,
1940. Vessel wall very
much thickened and marked hypertrophy of the left ventricle. Kidneys showed no
apparent damage; initial B.P. 220/115. After one week’s use of Serpina tablets
(one tablet at bed time) it was 200/105. She had been using this drug almost
continuously for over a year and her blood pressure in November 1941 was
165/85, with complete relief of all symptoms except tingling sensations in her
extremities.
Case 3– A young boy of 17, Hindu, vegetarian,
highly emotional and nerve-strung, consulted me in December, 1940, for attacks
of fainting fits. Kidneys normal, vessel wall not palpable; no hypertrophy of
the heart. Initial B.P. 165/100, after one month’s use of Serpina tablets (one
tablet at bed time) 140/90; he used Serpina for about 3 months and then gave it
up. B.P. recorded six months after discontinuing the drug was 142/90. The drug
incidentally also proved useful for his fainting fits, which were in all
probability functional in origin.
Case 4 – A middle aged man of 50, Hindu, vegetarian,
very obese (weight 260 lbs) came under observation in December, 1940, for
symptoms of palpitation, giddiness, breathlessness, headache and severe
insomnia; kidney function normal, vessel wall thickened, size of the heart
could not be made out, congestion at the bases of lungs. Initial B.P. 220/140.
After one month’s use of Serpina tablets (one tablet at bed time) B.P. was
180/110. Since then he has been using the drug continuously with small breaks
of 10 days, after 4 weeks’ use. His B.P. on 1st December was 178/105 with
complete relief of his symptoms.
Case 5 – A middle aged man of 53, Hindu,
non-vegetarian, came under observation in July, 1940, with throbbing pain over
his heart, insomnia, breathlessness, history of haematemesis, vessel wall thickened;
hypertrophy of the left ventricle; kidneys normal; initial B.P. 235/110. After
a fortnight’s use of Extract Rauwolfia serpentina (10 drops at bed time) B.P. was 185/90, after one months’ use
165/90, with complete relief of symptoms. He gave up the drug after one month
and now uses it occasionally for three or four days, when any of the symptoms
appear. His B.P. now ranges about 180/100.
Case 6 – A middle aged man of 48, Hindu,
non-vegetarian, first came under observation in July, 1920, with attacks of
cardiac pain, anginal in type; obese (weight 190 lbs); vessel wall palpable,
slight enlargement of the heart; kidneys normal; B.P. 188/100. He was given
Extract Rauwolfia
serpentina (10 drops at bed time)
in November, 1940. B.P. after fortnight’s use came down to 168/86. He gave up
the drug then, was again seen in October, 1941. B.P. was 210/110; he was put on
Serpina tablets (one tablet at bed time); he used it for a fortnight and then
gave it up. B.P. 10 days after discontinuing the drug was 185/100. It had no
effect on his anginal pains, which were however, relieved with Deriphyllin.
Case 7 – An old man of 60, Hindu, non-vegetarian,
who had been under my observation for high blood pressure for about 10 years
and in whom with careful regime and occasional use of bromides and luminal, I
had succeeded in keeping his B.P. under control between 180 to 200 systolic and
110 to 120 diastolic. Vessel wall palpable, no hypertrophy of the heart. No
kidney damage. During this interval whenever there has been any cause of worry
or anxiety
his blood pressure has
tended to shoot up and on one occasion (marriage of his daughter) it shot up to
260/140; with the use of Serpina tablets (one at bed time) it came down in 3
days to 200/110. He uses the drug only occasionally, when he has any symptoms
and he tells me, that 2 or 3 days’ use of Serpina tablet, invariably relieves
him of his symptoms, which are usually heaviness in the head and giddiness. He
had a fair experience of bromide and luminal and used to get some relief from
their use but is definitely of the opinion that Serpina tablets are superior to
them.
Case 8 – A middle aged man of 55, Hindu,
non-vegetarian, came under my observation in August, 1941, with symptoms of
throbbing sensation, dyspnoea and pain in the legs; had suffered from diabetes
5 years ago, but the day he consulted me, his urine was sugar and albumin free;
vessel wall palpable, hypertrophied left ventricle; congestion at the bases of
lungs. B.P. was 190/120; after one month’s use of Serpina tablets (one tablet
at bed time) B.P. came down to 158/90, with relief of symptoms. The hypertrophy
of the left ventricle and the congestion at the bases of lungs had also
disappeared.
The above eight cases are illustrative of
some commonly met forms of hyperpiesia. Cases nos. 1, 2 and 3 were those
occurring in highly nerve-strung individuals, who worry over trifles and who
are exceedingly emotional. All three of them derived immense relief and no. 3,
who was an early case of hyperpiesia may be regarded as cured for the time
being.
Nos. 4 and 6 were examples of hyperpiesia
occurring in obese patients. In both of these also, blood pressure was lowered
with the use of Serpina tablets and symptoms attributed to high blood pressure
were relieved.
Nos. 4 and 8 were examples of hyperpiesia
with early hypertensive heart failure in both of which with the fall in blood
pressure produced by Serpina tablets, symptoms of high blood pressure and
consequent left ventricular failure were relieved.
The drug has been given altogether in 18
cases of this type with almost similar results as noted above. The above eight
are just illustrative cases of the type of action, which is produced by Rauwolfia
serpentina in this type of high
blood pressure.
Group II –
Cases with Renal Damage
Case 1 – A middle aged man of 52, Hindu, vegetarian
was admitted to the Medical Wards with symptoms of cardiac failure, marked
dyspnoea, enlargement of the liver and oedema; the urine contained albumin,
hyaline and granular casts, urea concentration was 0.8%, blood urea 106 mgm per
100 cc. Marked hypertrophy and dilatation of the left ventricle. B.P. 240/150.
After a month’s rest, proper diet and digoxin the symptoms of congestive heart
failure disappeared. Blood urea came down to 86 mgm per cent. B.P. came down to
220/140. He was then put on, one tablet of Serpina at bed time, rest and diet
restrictions were continued. After one month’s treatment with Serpina tablets
blood pressure came down to 182/110, with consequent improvement in the
hypertrophy and dilatation of the left ventricle.
The patient is
continuing to use ½ tablet of Serpina daily, is fairly comfortable and without
any signs of congestive failure.
Case 2 – A lady of 40, Hindu, vegetarian was
admitted with symptoms of impending uraemia, (drowsiness, twitchings, rapid
breathing, insomnia, severe tinnitus, severe headache), B.P. 225/135; left
ventricle hypertrophied but no evidence of congestive failure; urine contained
albumin, hyaline and granular casts, specific gravity 1006; blood urea was 146
mgm per 100 cc. In addition to bland diet consisting of fruit juices and
glucose and alkalis and calcium, she was put on Serpina tablets (one tablet at
bed time). After 3 days the B.P. was 208/118, after 10 days it was 178/105 and
the patient was completely relieved of her intense headache, tinnitus and
insomnia, the blood urea coming down to 120 mgm per 100 cc. The case is still
under treatment.
The above 2 cases, are cases of severe renal
damage, with high blood pressure and cardiovascular changes, in which Serpina
tablets are not only tolerated but did succeed in lowering the blood pressure
and thus producing relief of symptoms, which were caused by high blood
pressure. The lowering of blood pressure did not prove injurious to the
existing kidney damage.
DOSAGE
Except in the beginning, when I used the drug
twice daily, I have restricted to a single 5 grain tablet of Serpina, or to a
single dose of Extract Rauwolfia
serpentina 10-15 minims. When 2
doses were given one morning and one evening, some patients complained of
lethargy during the day, so in subsequent cases I have restricted to a single
dose given at bed time. After the blood pressure has been lowered to a
beneficial level, the effect is often maintained even by ½ tablet. In many cases
after a month’s course of treatment a gap of 10 days was given and it was
noticed, that the effect of the drug continued, during this gap. The drug is a
very efficient, mild hypnotic and as most of these patients with high blood
pressure had insomnia and their headache, throbbing pain etc., were worse
during night or early morning, the night time was thought to be the best for
the administration of this drug.
TOLERANCE
With the above dosage, no bad effects of this
drug were noticed, the drug was well tolerated, did not produce any
gastro-intestinal symptoms. One young man felt some sexual weakness and was
alarmed, but the condition completely disappeared, after the drug was
discontinued. One patient complained of vague pains in the body during its use
and I made it a point to inquire about this symptom from all subsequent
patients but none of them complained of it; one patient who was a subject of
bronchial asthma felt that Serpina aggravated his asthmatic condition, but I
understand that he is now tolerating the liquid extract all right. The fact
leads me to believe that there might have been something in the crude drug to
which he was susceptible. Patients nos. 2 and 4 have used it for over a year
now, without any untoward effects.
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