Warfarin and Dabigatran, Similarities and Differences

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Warfarin and Dabigatran, Similarities and Differences

April 4, 2016 by danutdaagmailcom

Warfarin and Dabigatran, Similarities and Differences

Author and Curator: Danut Dragoi, PhD

What anticoagulants do?

An anticoagulant helps your body control how fast your blood clots; therefore, it prevents clots from forming inside your arteries, veins or heart during certain medical conditions.

If you have a blood clot, an anticoagulant may prevent the clot from getting larger. It also may prevent a piece of the clot from breaking off and traveling to your lungs, brain or heart. The anticoagulant medication does not dissolve the blood clot. With time, however, this clot may dissolve on its own.

Blood tests you will need

The blood tests for clotting time are called prothrombin time (Protime, PT) and international normalized ratio (INR). These tests help determine if your medication is working. The tests are performed at a laboratory, usually once a week to once a month, as directed by your doctor. Your doctor will help you decide which laboratory you will go to for these tests.

The test results help the doctor decide the dose of warfarin (Coumadin) that you should take to keep a balance between clotting and bleeding.

Important things to keep in mind regarding blood tests include:

Have your INR checked when scheduled.
Go to the same laboratory each time. (There can be a difference in results between laboratories).
If you are planning a trip, talk with your doctor about using another laboratory while traveling.

Dosage

The dose of medication usually ranges from 1 mg to 10 mg once daily. The doctor will prescribe one strength and change the dose as needed (your dose may be adjusted with each INR).

The tablet is scored and breaks in half easily. For example: if your doctor prescribes a 5 mg tablet and then changes the dose to 2.5 mg (2½ mg), which is half the strength, you should break one of the 5 mg tablets in half and take the half-tablet. If you have any questions about your dose, talk with your doctor or pharmacist.

What warfarin (Coumadin) tablets look like

Warfarin is made by several different drug manufacturers and is available in many different shapes. Each color represents a different strength, measured in milligrams (mg). Each tablet has the strength imprinted on one side, and is scored so you can break it in half easily to adjust your dose as your doctor instructed.

https://my.clevelandclinic.org/health/drugs_devices_supplements/hic_Understanding_Coumadin

Today, on the basis of 4 clinical trials involving over 9,000 patients, PRADAXA is approved to treat blood clots in the veins of your legs(deep vein thrombosis, or DVT) or lungs (pulmonary embolism, or PE)in patients who have been treated with blood thinner injections, and to reduce the risk of them occurring again.

In these trials, PRADAXA was compared to warfarin or to placebo (sugar pills) for the treatment of DVT and PE patients.

https://www.pradaxa.com/pradaxa-vs-warfarin?gclid=CMaRq7al9ssCFUxZhgodZuoC5w

Warfarin (NB-which goes by the brand name Coumadin, see link in here) reduces the risk of stroke in patients with atrial fibrillation (NB- atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. Some people refer to AF as a quivering heart, see link here) but increases the risk of hemorrhage and is difficult to use.

Dabigatran is a new oral direct thrombin inhibitor (NB-direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin). Some are in clinical use, while others are undergoing clinical development), see link in here.

Some international large clinical trials, see link in here, show results for patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.

Picture below shows a deep vein thrombosis which is a blood clot that forms inside a vein, usually deep within the leg. About half a million Americans every year get one, and up to 100,000 die because of it. The danger is that part of the clot can break off and travel through your bloodstream. It could get stuck in your lungs and block blood flow, causing organ damage or death, see link in here.

Image SOURCE: http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

The behaviour of blood thinning drugs is dependent on their physico-chemical properties and since a significant proportion of drugs contain ionisable centers a knowledge of their pKa (NB-pKa was introduced as an index to express the acidity of weak acids, where pKa is defined as follows. For example, the Ka constant for acetic acid (CH3C00H) is 0.0000158 (= 10-4.8), but the pKa constant is 4.8, which is a simpler expression. In addition, the smaller the pKa value, the stronger the acid, see link in here ) is essential, see link in here. The pKa is defined as the negative log of the dissociation constant, see link in here:

pk_a=-log₁₀(K_a) (1)

where the dissociation constant is defined thus:

K_a=[A][H⁺]/[AH]

Most drugs have pKa in the range 0-12, and whilst it is possible to calculate pKa it is desirable to experimentally measure the value for representative examples. There are a number of instruments that are capable of measuring pKa utilising Sirius T3 instrument, see link in here .

Table 1 below shows the pka values for warfarin, see link in here and dabigatran, see link in here.

Table 1

==========================

Anticoagulant pka

warfarin 4.99

dabigatran 4.24 11.51*

==========================

* dabigatran possess both acidic and basic functionality.

Both groups are at ionized at blood pH and exist as zwitterionic

structures, see link in here.

Adding physico-chemical features of anticoagulants utilized in “dissolving” blood clots is important for better understanding the de-blocking process within the veins utilizing anticoagulants.

SOURCE

http://theochem.chem.rug.nl/publications/PDF/ft683.pdf

http://www.rsc.org/chemical-sciences-repository/articles/article/dr000000003197?doi=10.1039/c5ra04680g

http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra11623f#!divAbstract

http://www.cambridgemedchemconsulting.com/resources/physiochem/pka.html

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

https://www.google.com/#q=define+atrial+fibrillation

https://www.researchgate.net/profile/Lars_Wallentin/publication/26777612_Dabigatran_versus_Warfarin_in_Patients_with_Atrial_Fibrillation/links/02bfe50c8c2fa639c0000000.pdf

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners