Drug Information Report

Drug Information Report

As it is stated in the executive summary above, the purpose of this report is to provide information to the relevant parties regarding the Coumadin drug. In particular, this report will focus on the therapeutic effects, dosages and methods of administration, and also the adverse effects of the drug and the precautions.

Background Information

Coumadin is a drug known in a number of terms depending on the field it is studied;

• The pharmacists have a synonym for the counter trade name of Coumadin drug – Warfarin (Pinel, 2009)
• For anticoagulant poisons, they are referred to as coumarins
• They are also known in the defense-chemical in plants world as Coumarin

Coumadin in this report will be treated as a drug in the pharmaceutical context.

Description of the Drug

Coumadin is the trade name of this drug in the pharmacological world. It is described as one of the essential drugs that are in use and wide circulation in the world today.

Coumadin is an anticoagulant and is widely used to prevent thrombosis. Thrombosis is a medical condition leading to the formation of blood clots inside blood vessels like veins and aortas which lead to the obstruction of the flow of blood. The flow of blood in the circulatory system is vital for the survival of human beings. Coumadin also prevents thromboembolism. Thromboembolism is a more complicated condition of thrombosis as it combines both thrombosis and embolism. Embolism is a situation where an intravascular tissue gets dislodged and is migrated to other parts of the circulatory system leading to a blockage of these blood vessels. This blockage of circulatory system leads to accumulation of lactic acid and if the condition is not put to check, it eventually translates to death of body cells. The blockage of circulatory system could turn out to be fatal.

Brief History of the Drug

Coumadin was initially developed for use in the chemical world as a pesticide, being applied to kill mice and rats. However, later, when it was discovered that the drug could prevent coagulation, its uses changed and it is now among one of the most widely used anticoagulants in operating rooms and in hospitals all over the world (Horton & Bushwick, 1999). Blood clots can result into a stroke, heart attack, or other serious medical conditions if they get formed in the legs or lungs (Bristol-Meyers, 2011). Its use as a pesticide became redundant and other stronger drugs took its place (Scully, 2002).

Mechanism of Action of Coumadin

It should be noted that although Coumadin as a prescription medicine is used primarily as an anticoagulant, it contains no anticoagulant properties. This brings us to wonder how this drug operates and to understand this, we take a look at the mechanism of action of the drug and its therapeutic effects in the ensuing discussion.

When exposed to fungi, Coumadin transforms into a natural anticoagulant referred to as dicoumarol. Dicoumarol, a chemical substance of both plant and fungi that occurs naturally and is used extensively in laboratories as a reductase inhibitor acts as a mycotoxin anticoagulant. Dicoumarol was discovered in the animal world in the clover plant after research showed that animals that ate the clover plant developed bleeding conditions. Dicoumarol falls under the class of drugs put under 4-hydroxycoumarin derivative anticoagulant drugs. 4-hydroxycoumarin derivative anticoagulant drugs act as competitive inhibitors to vitamin K. Vitamin K is a group of fat-soluble vitamins that are required by the body for the formation of proteins that are responsible for blood coagulation. Coumadin acts as an inhibitor to this, preventing the formation of these proteins by vitamin K and consequently, prevents the coagulation of blood or thrombosis.

According to Light & Kulkarni (2006), Coumadin has a number of therapeutic uses and some of these uses are described below:

• Prophylaxis and management of venous thrombosis and its extension, thromboembolism or in other terms pulmonary embolism
• Prophylaxis and treatment of complications relating to atrial fibrillation and/or prosthetic valve replacement
• Reducing death risks, recurrent myocardial infarction and events such as embolic strokes or systemic embolization after myocardial infarction
• Prevention of dysfunction of arterial-venous dialysis access
• Reduce the occurrence of incidence of thrombosis in arteriovenous fistula or graft

Therapeutic Effects of Coumadin

Coumadin or warfarin, as it is known in other areas in the medical field, has a number of effects. Some of these therapeutic effects are as illustrated in the following sentences:

• Anticoagulation is the major use of the drug. It is used here to inhibit the formation of clots in areas and blood vessels where blood is flowing slowly as a result of low pressure. Some of these vessels include arteries and veins
• If thrombosis (blood clot formation) has already occurred, the drug is used to prevent the occurrence of thromboembolism, the migration of the clots to other areas inside the vessels blocking the blood supply to vital organs like the heart and the brains
• Treatment of venous thrombosis

Therapeutic Uses of Coumadin

There are a number of therapeutic uses of Coumadin, some of them are mentioned below:

• Correction of excess anticoagulation
• Management of anticoagulation in patients who have had intracranial bleeding

Pharmacokinetics of Coumadin

Pharmacokinetics is the pharmacologist’s breakdown of the composition and utility of a drug in regard to a number of factors including absorption, distribution, metabolism and excretion of the drug (Shikata et al., 2004). Coumadin has a mixture of both the R- and S-enantiomers of the anticoagulant warfarin. S-enantiomer displays up to 2-5 times more activity in form of anticoagulation than its counterpart, the R-enantiomer in humans, but generally has a more rapid clearance than the R-enantiomer (Bristol-Meyers, 2011).

Coumadin’s pharmacokinetics are broken down as follows;

Absorption of the Drug

The drug is administered orally. Absorption into the body is almost immediate. However, it takes up to four hours before the full effect of the drug can take place. This point where the full effect of the drug takes place after being absorbed into the body is referred to as the peak concentration point.

Distribution of the Drug

Once the drug is absorbed into the body, a small volume of about 0.14 liters per kilogram of the drug is used to act as the distribution mechanism of the drug. One complete cycle of distribution of the drug may take between 6 to 12 hours and this is noted after the patient had a drink. Almost all the drug (99%) is bound to the proteins present in plasma from where it starts working after reaching peak concentration point.

Metabolism of the Drug

The drug is eliminated from the body almost entirely by the process of metabolism. Generally, metabolism refers to the breakdown of food particles in the body and transformation of the same into energy. Warfarin (Coumadin) is selectively metabolized by microsomal enzymes hepatic cytochrome P-450 (CYP450) leading to the inactivation of the hydroxylated metabolites and by reductases to reduced metabolites with minimal anticoagulant activity. Recognized metabolites of Coumadin include dehydrowarfarin, two diastereoisomer alcohols, and 4′-, 6-, 7-, 8-, and 10-hydroxywarfarin.

The CYP450 isozymes that are active participants in the metabolism of coumadin include isozymes CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. A polymorphic enzyme, CYP2C9, is the principal form of human liver CYP450 that regulates the in vivo anticoagulant activity of warfarin (WAMSG, n.d). Patients having one or more variant of CYP2C9 alleles have decreased S-coumadin/Warfarin clearance.

Excretion of the Drug

From the research that has been carried out by other scholars, it has been observed that over 90% of Coumadin that is administered into the body orally is excreted from the body in urine. Urine is one of the most vital parts of the metabolic system.

After the first single dose is taken, the final half-life of the drug is approximated to be one week. Before this date is reached, the drug would have undergone an effective half-life ranging from 20 to 60 hours. From the initial discussion on pharmacokinetics of Coumadin  has been observed and showed that the S-enantiomer of warfarin clears twice as fast as the R- enantiomer. This implies that the half-life of the R-enantiomer is more prolonged than that of the S-enantiomer taking the factor of the volumes distributed by both enantiomers to be equal. The half-life of R-enantiomer ranges from 37 to 89 hours, whereas that of S-warfarin ranges from 21 to 43 hours. Once the half-life of this warfarin is over, the metabolism process takes control and flushes it out of the system in urine.

Adverse Effects of Coumadin

There are a number of adverse effects associated with taking Coumadin as a drug. Some of these effects are described below:

1. Bleeding – this is the major effect of using the drug. Bleeding as a result of taking this drug may be propagated by a number of reasons as shall be discussed at a later stage in this paper.
2. Skin necrosis or gangrene is the death of skin tissue. It occurs when blood clots are formed and they block the flow of blood to some parts of the body. Mostly, this occurs during the initial stages of using Coumadin (Bristol-Meyers, 2011).
3. The purple toes syndrome is when the colors of the toes turn either purple or dark in color and are painful to touch.
4. Induces Arterial calcification/osteoporosis is a disease associated with low bone mass and tissue loss leading to weak bones (Pierson, 2011).
5. Some of cardiovascular affiliations are Chest pains, Angina, Hypotension, Syncope, Vasculitis, oedema and haemorrhagic shock.
6. Central nervous system afflictions – such as Coma, fatigue of the brain, dizziness, constant headaches, stroke of the brain, fever and lethargic conditions.
7. Haematological related Afflictions – such as leukopenia, anaemia, hematoma, Agranulocytosis and retroperitoneal. Also some hidden and unknown sites such as colon cancer may also escape the treatment of anticoagulation of Coumadin.
8. Hepatic afflictions such as Cholestatic jaundice, hepatitis and hepatic injuries.
9. Respiratory afflictions such as tracheobronchial calcification and Dyspnoea.
10. Skeletal afflictions such as muscular pains, joint pains, osteoporosis (weakening of the bone), paralysis and paraesthesia.
11. Gastrointestinal afflictions such as abdominal pains, anorexia, diarrhea, flatulence, intestinal bleeding, ulcers, nausea, abdominal cramps and vomiting.
12. Dermatological afflictions such as rash, pruritus, urticarial, alopecia, dermatitis

Dosages of Coumadin

The dosage of the Coumadin varies depending onto who it is administered to. Adults have a different dosage from pediatrics. Dosage of Coumadin may also be individualized according to how each individual responds to the treatment of  the drug. The dosage prescribed by a doctor to be taken by a specific individual depends on the international normalized ratio (INR) of that person (Lind et al., 1997). The dosage to be taken is summarized in the table below:

(Light & Kulkarni, 2006).

If a patient misses a dose at a specific time of the day that he was supposed to take, he or she should make sure to take the dosage as quickly as possible on the same day. The patient should never attempt to take a double dose the next day as a way of compensating what he/she forgot to take the previous day.

Modes of Administration of the Drug

Administration of a drug is how a drug gets into the body so that it can conduct the intended use. Coumadin is administered into the body in two ways – tablet or injection forms.

Tablet Form

Coumadin tablets are single-faced, with one face printed with numerals as 1, 2, 2-1/2, 3, 4, 5, 6, 7-1/2, or 10 overlaid and inscribed with the word “COUMADIN” and the opposite face is left plain. They also come in different colors, each color denoting the potency of the drugs. The tablet may be taken only after the doctor had prescribed it. The medicine can be taken with or without food. The tablets should be stored at room temperature, away from heat.

Injection Form

Coumadin is also administered via an injection. The drug is contained in vials. These vials give 5 mg of Coumadin after reconstitution is done with sterile water (about 2.7 ml). In other words, the maximum yield is given as 2.5 ml of 2mg/ml solution (Bristol- Meyers, 2011). The net content of a Coumadin vial is 5.4mg lyophilized powder. This is injected directly into the body according to the prescription given by a medical doctor or through the intravenous drip.

Contraindications

• Pregnancy – use of coumadin during pregnancy is restrained because the drug may cause bleeding in the uterus and it may pass through the placenta wall. This might consequently lead to abortions, stillbirth, birth defects among other undesirable incidences.
• Hemorrhagic situations is when the patient has hemorrhagic tendencies, the drug should not be administered as it may lead to excessive bleeding and may result into hemoptysis, gum bleeding and other forms of bleeding leading to a considerable blood loss.
• Potential or recent surgery – major traumatic surgery that results in large, open surfaces. This could lead to high blood dyscrasias
• Noncompliant patient, alcoholic patient, unsupervised senile or psychotic patient
• Pericarditis or pericardial effusion, malignant hypertension and subacute bacterial endocarditis
• Patients with history of coumadin – induced necrosis
• Patients with high sensitivity nature to the drug or any other component present in the drug
• Alcoholic patients – administration of the drug to patients with a high level of alcoholic intoxication quotient in their bodies may lead to acute hypoprothrombinemic effects.

Warning and Precautions

• Acute tissue necrosis – continued use of coumadin may result in necrosis or occurrence of gangrene. In acute cases, this may even result into the amputation or debridement of some organs of the body that are affected. The precaution here is to stop the continued use of the drug with immediate effect and seek the counsel of a medical doctor as soon as possible.
• Occurrence of systematic atheroemboli and /or cholesterol microemboli – if in some of these cases the necrosis is so advanced that it becomes almost fatal, the precaution is to discontinue the use of the drug and seek the immediate assistance of a medical doctor (Bristol-Meyer, 2011).
• For pregnant women with mechanical heart valve, the usage of the drug may result into damage of the fetus. The precaution here is to seek medical help from a qualified medical doctor on how to use the drug without endangering or putting to harm the fetal (Hirsh, Cade & Gallus, 1970).
• Occurrence of heparin-induced thrombocytopenia. Usage of Coumadin in such a case may result into fatalities such as death or amputations. The precaution taken here would be to stop the usage of the drug and wait until the platelet count in the body has returned back to normal before re-initiating the administration of the drug. Administration of the drug when the platelets are below the normal level may result into cell deaths.

Food and Drug Interactions

There are quite a number of food interactions that are related to Coumadin. Some of them are discussed below:

• Coumadin and alcohol – hypoprothrombinemic responses have been documented from patients who have an acute level of alcohol intoxication (Majerus et al., 1996). The risk of bleeding increases with the increase of alcohol take.
• Coumadin and multivitamins – multivitamins which have vitamin Kin may prompt the hypoprothrombinemic effects of anticoagulants in some of the patients because vitamin K is one of the vital components for the formation of thrombosis. Resistance to anticoagulation has been associated with a high intake of foods containing vitamin K.

There are no particular types of food that one has to avoid during Coumadin therapy, but proper guidelines are to be provided to enhance the safety of Coumadin medication (Health Reference Center, 2001). If a patient on Coumadin therapy consumes greater amounts of vitamin K than he/she usually consumes, the effects of Coumadin will be less visible, and this would contribute to a rise in the blood clotting risk. On the other hand, if a patient consumes less amount of vitamin than he/she consumes, the effects of Coumadin drug will increase, and can also result in overdose.

Therefore, patients on Coumadin treatment are required to maintain consistency in the consumption of vitamin K. The differences in the levels of vitamin K can cause the IRN to change. The patient should not quit consumption of foods containing vitamin K, but he/she should be able to identify foods that contain high levels of vitamin K and try to maintain consistency every day when consuming them. Vitamin K is found in large quantities in foods such as green leafy vegetables (cabbage, spinach, collards, Swiss chard and coriander), liver, Brussels sprouts and broccoli. A patient taking Coumadin drug must avoid rapid changes in his/her daily consumption of these foods.

Moreover, there are foods whose interaction with Coumadin drug may not be associated with vitamin K. During the administration of Coumadin drug, people are advised to avoid consumption of cranberry juice and other products made from cranberry. However, there are some controversies surrounding the importance of interaction between Coumadin and cranberry. Consumption of alcohol affects the effectiveness of Coumadin drug in numerous ways. For most people, moderate consumption of alcohol is normal, but excessive consumption of alcohol can increase the risk of bleeding.

Drug Interactions

There is quite a substantial number of drugs that seem to interact with Coumadin both on an increasing and decreasing effect levels. Some of these drugs are indicated in the table below:

(Light & Kulkarni, 2006)

Additional Information on Coumadin

Special care is taken when administering Coumadin to the following:

• The elderly – the elderly may have weak systems and they may be more resistant to anticoagulant therapeutic treatment. There is a high chance of these class of people developing thrombosis or even thromboembolism.
• Children – safety measures to administer and monitor this drug in children have not yet been established and put to the test.
• Women at their ovulation – ovulating women are at a higher risk of developing ovarian hemorrhage during this time of ovulation.

Information Sheet on Coumadin

This sheet summarizes all the information on Coumadin in an understandable manner;