Warfarin Pharmacology

Last Updated on September 9, 2022 by amin


What causes INR to rise?

A high INR level can happen when you take warfarin (Coumadin). Warfarin helps prevent blood clots. To do this, it slows the amount of time it takes for your blood to clot. This raises your INR level.

What is heparin protocol?

It is standard practice to give heparin, commencing with either an IV bolus of 10 000 U with repeated smaller bolus injections as required or as a weight-adjusted-dose regimen of 100 to 175 U/kg followed by 10 to 15 U/kg per hour.

Can you take Augmentin with warfarin?

Interactions between your drugs Using warfarin together with amoxicillin may increase the risk of bleeding, especially if you are elderly or have kidney or liver impairment. You may need more frequent monitoring of your prothrombin time or INR by your doctor to safely use both medications.

Does warfarin increase PT?

Warfarin typically prolongs the PT alone, but at high levels warfarin can prolong both tests. Heparin typically prolongs the aPTT alone (because PT reagents contain heparin-binding agents that block heparin effect), but at high levels heparin can prolong both tests.

Is warfarin an agonist or antagonist?

Vitamin K antagonists (VKAs) such as warfarin inhibit the enzyme vitamin K epoxide reductase and consequently the recycling of inactive vitamin K epoxide back to its active, reduced form [1].

What is difference between PT and PTT?

Recap. The prothrombin time (PT) test measures how quickly blood clots. The partial thromboplastin time (PTT) is mainly used to monitor a person’s response to anticoagulant therapies.

How does warfarin affect PT and aPTT?

Results Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive.

What drugs affect INR?

  • Colestipol. Estrogens. Sucralfate. Dicloxacillin, Naficillin.
  • Primidone. Rifampin. Ginseng. Griseofulvin.
  • Vitamin C (>500mg/day) CoEnzyme Q10. Green tea. Vitamin K.

Do antibiotics affect warfarin?

Antibiotics may interact with warfarin, increasing the risk for significant bleeding events.

Is warfarin an active drug?

Only unbound warfarin is biologically active. Warfarin accumulates in the liver, where the two isomers are metabolized via distinct pathways. Oxidative metabolism of the more active S isomer is effected by CYP2C9. Two relatively common variants, CYP2C9*2 and CYP2C9*3, have reduced activity.

How is warfarin synthesis?

The anticoagulant racemic warfarin is synthesized by the Michael addition of 4-hydroxycoumarin with benzalacetone in the present of equimolar amounts of imidazolium based ionic liquids [bmim] BF4 and [bmim] Br and other reaction solvents such as H2O, pyridine and ammonia in five different tests.

What is the chemical name for warfarin?

Warfarin sodium

PubChem CID 16204922
Structure Find Similar Structures
Chemical Safety Laboratory Chemical Safety Summary (LCSS) Datasheet
Molecular Formula C19H15NaO4
Synonyms Warfarin sodium 129-06-6 Sodium warfarin Jantoven Marevan More…

What affects PT and PTT?

PT and PTT are elevated with severe disease. In mild liver disease, only the PT will be elevated. With more severe disease, both the PT and PTT will be elevated due to decreased synthesis of vitamin K-dependent clotting factors which include factor II, factor VII, factor IX, and factor X.

What happens if your warfarin is too high?

If the INR is too high, you are at increased risk of bleeding. But the INR will usually come back down into the right range when you skip a couple doses of your medication. If you develop bleeding while your INR is too high, it can be life-threatening.

How does warfarin act as an anticoagulant?

Warfarin blocks the liver from using vitamin K to make clotting factors. This thins your blood, so it takes longer to clot.

Is warfarin oral or IV?

Warfarin for injection should be administered as a slow bolus over 12 minutes into a peripheral vein. 6 It is not to be given intramuscularly and is not approved for direct intravenous push.

What is the most common side effect of warfarin?

The main side effect of warfarin is bleeding. If you’re taking warfarin, you may have trouble stopping the bleeding from a cut on the hand or a nosebleed. More-serious bleeding may be inside the body (internal).

Is warfarin an enzyme inducer or inhibitor?

Examples of Common Drug-Drug Interactions Involving the Cytochrome P450 Enzyme System

Drug(s)/product Enzyme inhibitor or inducer Drug(s)
Amiodarone (Cordarone) CYP2C9 and CYP3A4 inhibitor Warfarin (Coumadin)
Carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin) CYP3A4 inducer Ethinyl estradiol-containing contraceptives

Aug 1, 2007

What are the indications for warfarin?

The three most common indications for warfarin therapy are; atrial fibrillation (AF) venous thromboemolism (VTE), and prosthetic heart valves. Atrial fibrillation is probably the most common indication for warfarin therapy in our community.

What antibiotics are safe with warfarin?

THE BOTTOM LINE When prescribing antibiotics for patients taking warfarin, try to choose agents with a lower likelihood of affecting INR such as penicillin G, clindamycin, and 1st- and 4th-generation cephalosporins.

Why is PT employed in monitoring a patient on a warfarin therapy?

A prothrombin time (PT) is a test used to help detect and diagnose a bleeding disorder or excessive clotting disorder; the international normalized ratio (INR) is calculated from a PT result and is used to monitor how well the blood-thinning medication (anticoagulant) warfarin (Coumadin) is working to prevent blood

What is the antidote for heparin?

Expert opinion: Despite of the low therapeutic index, protamine is the only registered antidote of heparins. The toxicology of protamine depends on a complex interaction of the high molecular weight, a cationic peptide with the surfaces of the vasculature and blood cells.

What causes INR to decrease?

Conditions known to decrease Coumadin effect and decrease INR include: Hypothyroidism. High vitamin K intake. Nephrotic syndrome.

Which antibiotics do not affect warfarin?

Cephalexin and clindamycin, which have minimal interactions with warfarin, are considered low-risk antibiotics, said the researchers.

What drugs increase INR with warfarin?

Warfarin drug interactions

Drug/Drug Class Effect on INR Proposed Mechanism
cimetidine increased Inhibition of Warfarin Metabolism
ciprofloxacin increased Inhibition of Warfarin Metabolism
clarithromycin increased Inhibition of Warfarin Metabolism
clofibrate increased Unexplained Mechanisms

Which drug increases action of warfarin?

Many of the drugs identified as potentiating warfarin’s effect are known inhibitors of CYP 2C9, including amiodarone, fluconazole, fluvastatin, fluvoxamine, isoniazid, lovastatin, phenylbutazone, and sertraline. Rifampin and secobarbital are both known inducers of CYP 2C9.

Why is heparin given before warfarin?

Heparin works faster than warfarin, so it is usually given in situations where an immediate effect is desired. For example, this medication is often given in hospitals to prevent growth of a previously detected blood clot.

What are the symptoms of warfarin overdose?

Symptoms of overdose may include the following:

  • bloody or red, or tarry bowel movements.
  • spitting or coughing up blood.
  • heavy bleeding with your menstrual period.
  • pink, red, or dark brown urine.
  • coughing up or vomiting material that looks like coffee grounds.
  • small, flat, round red spots under the skin.

What is the pharmacologic action of warfarin?

Warfarin is an oral anticoagulant, a drug that inhibits the clotting of blood. It prevents the formation of blood clots by reducing the production of factors by the liver that promote clotting, factors II, VII, IX, and X, and the anticoagulant proteins C and S.

What is INR affected by?

Vitamin K changes how your blood clots and affects your INR. Vitamin K is found in green leafy vegetables, broccoli, grapes, and other foods. Ask your healthcare provider for more information about what to eat when you have an elevated INR. Limit alcohol.

What are the signs of warfarin toxicity?

What are the signs and symptoms of warfarin toxicity?

  • Red spots on your skin that look like a rash.
  • Severe headache or dizziness.
  • Heavy bleeding after an injury.
  • Heavy bleeding during monthly period in women.
  • You have severe stomach pain or you vomit blood.
  • Pink, red, or dark brown urine.
  • Black or bloody bowel movements.

What type of chemical is warfarin?

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration.

What are the contraindications of warfarin?

Who should not take WARFARIN SODIUM?

  • operation on the spine.
  • cancer or malignancy.
  • polycythemia vera.
  • eye surgery.
  • caloric undernutrition.
  • low vitamin K levels.
  • anemia.
  • increased risk of bleeding due to clotting disorder.

What is the protein binding for warfarin?

Abstract. The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding.

What’s the difference between antiplatelet and anticoagulant?

Anticoagulants slow down clotting, thereby reducing fibrin formation and preventing clots from forming and growing. Antiplatelet agents prevent platelets from clumping and also prevent clots from forming and growing.

Why is INR used instead of PT?

INR levels are often used because they make it easier to compare results from different labs and different test methods. If you are not taking warfarin, your results may be in the form of INR levels or the number of seconds it takes for your blood sample to clot (prothrombin time).

What is the antidote for heparin and warfarin?

Individuals anticoagulated with warfarin or heparin are typically treated with specific antidotes such as vitamin K or protamine, respectively, if they bleed or require surgery.

What decreases the effect of warfarin?

Warfarin’s anticoagulant effect was inhibited by 3 antibiotics (griseofulvin, rifampin, and nafcillin); 3 drugs active on the central nervous system (barbiturates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfate; foods high in vitamin K; and large amounts of avocado.

How do drugs and chemicals interact with warfarin?

Warfarin’s hepatic metabolism and protein binding are the most common mechanisms for the occurrence of drug-drug interactions. Warfarin is metabolized via the cytochrome P450 system by CYP 2C9, 1A2, and 3A4. It is a racemic mixture with the S-enantiomer being 2.7 to 3.8 times more potent than the R-enantiomer.

What is warfarin pharmacokinetics?

Pharmacokinetics. The half-life of racemic warfarin ranges from 20 to 60 hours. The mean plasma half-life is approximately 40 hours, and the duration of effect is two to five days. 10 Thus, the maximum effect of a dose occurs up to 48 hours after administration, and the effect lingers for the next five days.

What is the antidote of warfarin?

A dose of vitamin K is used to reverse the action of warfarin (Coumadin), a blood thinner used routinely for more than half a century and, until recently, the only such option for most people.

What is the antidote for vitamin K?

Fresh frozen plasma (FFP) has been the mainstay for urgent anticoagulation reversal in patients taking vitamin K antagonists (eg, warfarin). FFP requires blood group typing and thawing before use.

Can Coumadin be given IV?

Intravenous Route Of Administration The intravenous dose of COUMADIN is the same as the oral dose. After reconstitution, administer COUMADIN for injection as a slow bolus injection into a peripheral vein over 1 to 2 minutes. COUMADIN for injection is not recommended for intramuscular administration.

What is a normal INR number?

In healthy people an INR of 1.1 or below is considered normal. An INR range of 2.0 to 3.0 is generally an effective therapeutic range for people taking warfarin for disorders such as atrial fibrillation or a blood clot in the leg or lung.

Can you give warfarin and heparin together?

Heparin is usually given short-term, and warfarin is added in combination with heparin, before heparin is stopped. It can take 5-7 days (or longer) for the warfarin to reach an adequate level for it to be given alone.

Warfarin Pharmacology

Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), an essential enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and thereby reduce the synthesis of active clotting factors.Jan 19, 2022

What is the purpose of INR?

An INR test measures the time for the blood to clot. It is also known as prothrombin time, or PT. It is used to monitor blood-thinning medicines, which are also known as anticoagulants. The INR, or international normalised ratio, can also be used to check if you have a blood clotting problem.

Why is PT high?

When the PT is high, it takes longer for the blood to clot (17 seconds, for example). This usually happens because the liver is not making the right amount of blood clotting proteins, so the clotting process takes longer. A high PT usually means that there is serious liver damage or cirrhosis.

What is the structure of warfarin?