Monograph: |
ETHAMSYLATE
The purpose of this manual is to provide scientific infornnation on:
1) haemostatic process, 2) steps of haeinostasis and 3)
pharmacological profile of Sylate as a specialist haemostat.
Sylate, the internationally accepted anti haemorrhagic agent is
particularly effective in case of capillary bleeding because it has
unique mechanism of action which differs from other conventional
haemostats.
HAEMOSTASIS:There are two well defined stages which condition
normal haemostasis
1) Primary haemostasis: It is a physiological process, destined to
arrest biceding which depends on platelet number, platelet function
and vascular structure. The first step in the haemostatic process is the
adherence of platelets to the subendothelium of the injured vessel to
form an initial macroscopic platelet aggregate which through the
release of mediators, causes further platelets to aggregate, leading to
the formation of a haemostatic platelet plug.
2) Secondary haemostasis: Subsequently the activated coagulation
factors will lead to the formation of fibrin which will intermingle
with platelets to form a platelet fibrin thrombus.
In the normi~l conditions, the exposed blood to the contact phase i.e.
denuded subendothelial layer will induce a series of reactions
initiating with the activation of factor XII (HAGEMAN) followed by
factors XI, IX & VIII until the transformation of fibrinogen into fibrin.
Fibrin by its carbohydrate component will act like collagen, leading
further to the response of platelets & the formation of a platelet fibrin
thrombus.
Normally the platelet fibrin thrombus is destroyed by the activation
of the fibrinolytic system & is then washed away by the circulation as
the repair takes place.
DRUG PROFILE OF SYLATE
Molecule
- Ethamsylate.
Active principle - Diethylammoniurn 1.4 - dihydroxy 3-
benzenesulfonate.
Nature
- Synthetic antihaemorrhagic agent -
chemically unrelated to haemostatic of
hormonal origin, to vasoconstrictors or
to antifibrinolytic agents
Strength
- 250 mg. / 500 mg. Tab; 250mg/2ml amp.
Form
- Oral (Tablet), Injection
- Presentation
SYLATE 250 ( 250 mg. ethamsylate) strip of 10's
SYLATE 500 ( 500 mg. ethamsylate) strip of 6's
SYLATE Inj ( 250 mg. ethamsylate) 2 ml ampoule
1) ABSORPTION
The in situ gastrointestinal absorption of the
haemostatic ethamsylate was studied. It has been
carried out on male Wistar rats. Experiment showed
very poor gastric absorption, but considerable
intestinal absorption rate (absorption rate constant
k (a) = 0.39 +/-0-19 h-l), absorption half life
t[(half){k (a)}= 1.94 +/- 0.60h)]. The iron pair diffusion
across the intestinal wall seems to be the main reason
responsible for fast intestinal absorption.
2) METABOLISM:
The studies in rabbits with carbon 14 tagged
ethamsylate showed that with intravenous injection
of 30 mg/kg, the maximum level is reached within the
first minute. The blood clearance is relatively rapid:
β’After 5mins. 22 to 30 % of the injected substance is
found in the blood. oAfter I hour, only 6.5 to 13.5%
remains.
PHARMACOKINETIC :
Autoradiography shows that the product is
distributed in all the essential organs and this is in
relation to their degree ofvascularization.
3) Excretion:
It is immediate and rapid essentially by the urinary
tract and to some extent by the biliary and intestinal
routes. It is excreted practically intact.
SALIENT FEATURES
- Non-Hormonal Haemostatic Agent.
- Unrelated to Vasoconstrictor.
- Unrelated to Antifibrinolytics.
- Exerts inlpact on platelet
-vessel-wall interaction.
- Possesses antihyaluronidase action.
- Induces "Reversible " Platelet aggregation
- Normalises Haemostatic Process.
SYLATE modifies:
1) SYLATE increases the number of young
haemostaticaly active platelets. By electron
microscopic study of the megakaryocytes it has
been observed that under the influence of
Ethamsylate (SYLATE) the glycogen content of
the megakaryocytes is increased. This
improvement of the glycogen content of the
megakaryocytes is closely related to a
consequent increase in the number of glycogen
rich platelets released by them in the
circulating blood.
2) Even in case of platelet dysfunction, SYLATE
normalises platelet aggregation induced by
ADP and adrenaline.
3) Enhances platelet's ability to adhere to the
subendothelial layer.
4) SYLATE shortens the bleeding time.
5) SYLATE corrects PF3 i.e. phpholipids
availability.
6) SYLATE corrects PF4 (platelet factor) i.e.
antiheparin activity, release.
7) SYLATE improves clot retraction.
Other important features:
1) No effect on the Quick time (Prothrombin
time ) and coagulation time.
Benefit: SYLATE DOES NOT MODIFY THE
PLASMA CLOTTING FACTORS.
2) NO effect on the fibrinogen level.
Benefit: SYLATE DOES NOT INFLUENCE THE
COAGULATION FACTORS.
3) Does not affect the fibrinolytic system.
Benefit : SYLATE HAS NO ANTIFIBRINOLYTIC
ACTION.
- No known Contraindication
- SYLATE may be given in association
with any other drug.
- No Toxic or Teratogenic effects.
- No known Serological or allergic side effects.
~ Promotes formation of a haemostatic plug
without risk of thrombosis.
- Excellent tolerance profile
- SYLATE can be given safely even to the
elderly & children.
MENORRHAGIA,METRORRHAGIA,DUB
(PRIMARY & SECONDARY)
- Considered as the first line of therapy
in menorrhagia in women of all ages/
- Safe & Effective in the control of meno-metrorrhagia
as well as with myoma - associated menorrhagia.'
-IT Brings about a highly significant reduction in both
severity & duration of menorrhagia.3
~ In > 70Β°/o of the cases SYLATE completely stops
metrorrhagia of various etiologies ( where the
pregnancy continued to term, treatment with
SYLATE did not effect the infants.)'
Premedication with SYLATE is indispensable
for the prevention of diffuse bleeding.
SYLATE brings a substantial reduction
of operative haemorrhages in 96Β°/o cases.
Better cicatrization is obtained by a
reduction of the serous fluid oozing
from the wound5
In open -heart surgery, SYLATE helps to maintain
the INTEGRITY AND FUNCTION OF THE
PLATELETS IN THE EXTRA-CORPOREAL
CIRCULATION resulting in safeguarding the
patient against post-operative haemorrhages!
In Neurosurgery, SYLATE definitely controls
bleeding in the first five minutes in more
than 90Β»/o cases"
In Plastic and Reconstructive Surgery:
SYLATE is highly effective as an antihaemorrhagic
in patients undergoing DESLOUGHING
AFTER SEVERE BURNS, EXCISION OF SKIN
TUMORS, CORRECTION OF CONGENITAL
MALFORMATIONS, AESTHETIC
AND CORRECTIVE OPERATIONS,
REPARATIVE SURGERY
OF FACIAL MUTILATION.
IN UROLOGY
IT REDUCES SIGNIFICANTLY POSTOPERATIVE HEMATURIA BY HALF AND SIGNIFICANTLY SHORTENS ITS DURATION.
Properties:
Ethamsylate crosses the placental barrier. Maternal
and cord blood contains similar concentrations of
ethamsylate. Pharmacological effects appear within
one hour of oral administration and within one to five
minutes of parenteral administration SYLATE is
excreted unchanged via the urinary, biliary and
intestinal routes and after one hour only 6.5 -11.5%
remains in the blood. SYLATE was found to have no
teratogenic effects when studied in experimental
animals over three generations.
DOSAGE
SYLATE Inj: Adults
Pre-operative : I to 2 ampoules i.v. or i.m. I hour before
surgery
Peri-operative : I to 2 ampoules i.v. Repeat the dosage if
necessary
Post-operative : I to 2 ampoules i.v. or i.m. Repeat every
4-6 hours as long as the bleeding risk persists
Local Treatment : Soak a swab with the content of an
ampoule and apply to the haemorrhagic area, or in the
tooth socket after dental extraction. The application
may be repeated when necessary; it may be associated
with oral or parenteral administration.
Children : Half the adult dose.
Neo natology : 10 mg/ kg body weight (O.lml = 12.5mg)
injection i.m. within 2 hours after birth then every 6
hours for 4 days.
SYLATE Tablets (250mg/500 mg) : Adults
Post- operative : 500 mg to be repeated every 4-6 hours
as long as the risk of haemorrhage persists.
Gynaecology:
In menorrhagia and metrorrhagia: 250-500 mg three
times daily (according to severity of the Case).
In persistent menorrhagia the treatment recommended
is 500 mg three times daily for 10 consecutive days
starting 5 days before the expected date of
menstruation.
Internal Medicine : 500 mg to 1500 mg per day until all
risk of haemorrhages have completely subsided.
Children: Half the adult dose.
Limitations for use : As for most drug, SYLATE shouldn't
be administered during the first trimester of pregnancy.
Tolerance : SYLATE is generally well tolerated. However,
nausea, headache, skin rashes have occurred
infrequently.
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