Prepared by/ Al-Baraa Akram De Montfort University-faculty of health and life sciences Leicester-United Kingdom I had the idea of this...
Prepared by/ Al-Baraa Akram
De Montfort University-faculty of
health and life sciences
Leicester-United Kingdom
I had the idea of this research in
one of the lectures which was about Cardiovascular Diseases at Assiut
University in Egypt in 2017 during my study of clinical pharmacy when the lecturer told us that the anticoagulant warfarin
is used in the form of warfarin sodium to facilitate its absorption, but
sodium, as you know, causes an increase in blood pressure, and for most hypertensive
patients, most of them are Elderly people who may suffer from a combination of
chronic diseases such as heart disease and diabetes, especially those with high
blood pressure.
Sodium causes increasing blood
pressure, which is an undesirable problem that may occur in a hypertensive
patient who suffers from blood clots, so the use of warfarin sodium may lead to
an increase in his blood pressure in what is known as the famous clinical term
Drug-Disease interaction.
So I thought: What if we replace
sodium with potassium to get warfarin potassium, and thus avoid sodium problems
for hypertensive patients?
One of you might say: Potassium
causes some heart problems, and here I would like to point out that the dose of
warfarin generally ranges between 1 mg to 5 mg per day, while the harmful dose
of potassium is 6.5 mg per day.
Before implementing the idea in
practice, I asked myself:
Which is better to replace the sodium
atom with a potassium atom within this organic compound?
Is the simple substitution reaction
preferred or the double substitution reaction?
1-If the simple substitution reaction
was better, how can you get elementary potassium?
2- If the double replacement reaction is
better, what is the concentration of potassium hydroxide required to complete
the reaction? And is it better for substitution reactions or any potassium salt
e.g., potassium iodide is better?
It was not easy, especially at that
time when potassium was scarce in the market, so the experiment was carried out
on a small scale in its infancy. I asked Dr. Noha Gamal Fekry, Assistant
Lecturer at the Department of Pharmaceutical Chemistry at Sphinx University, to
enlighten me on how to implement the project in practice, and then I sought the
help of my sister Razan Akram,a graphic designer to design some figures which
were found in introduction section for my research paper that explains the
mechanism of action of warfarin. I implemented the research project in a time
that took me 8 months with the help of Dr. Abdurrahman Abo El-ela, a demonstrator in the
department of microbiology in Merit University.
To carry out the experiment I needed to prepare an acid like hydrochloric acid to convert ONa group into OH, filter papers, beaker, conical flask, potassium base e.g., potassium hydroxide and mortar
1- In the mortar, grind 100 mg warfarin sodium tablets properly until you get the powder form to increase the surface area
2- Dissolve the powder of warfarin sodium in 100 ml water and add HCl to allow sodium to substitute hydrogen and convert the ONa group into OH in the warfarin molecule according to the chemical equation
C19H15NaO4 +HCl+H2O→NaCl+ H2O+ C19H16O4
3- Filter the solution in a filter paper to get rid of the liquid and leave the powder to dry
4- Add the powder of warfarin back to fresh water and add potassium base as shown in chemical equation below
C19H16O4+KOH → C19H15KO4+H2O
5- Filter the solution again using a
filter paper, and then leave the powder to dry to get warfarin potassium
N.B. After getting warfarin in the
3rd step, you can use organic solvent to extract warfarin only then alkalize it
using potassium base (potassium hydroxide); the OH group will be ionized into
OK