What lab test will a client taking warfarin be required to complete to evaluate therapeutic effects of the medication quizlet?

Many factors can influence the therapeutic efficacy of a drug, including pharmacokinetics, which refers to the passage of drugs into the body, through it, and out of the body.

Think of pharmacokinetics as a drug’s journey through the body, during which it passes through four different phases: absorption, distribution, metabolism, and excretion (ADME). The four steps are:

• Absorption: Describes how the drug moves from the site of administration to the site of action.
• Distribution: Describes the journey of the drug through the bloodstream to various tissues of the body.
• Metabolism: Describes the process that breaks down the drug.
• Excretion: Describes the removal of the drug from the body.

Let’s look at these phases in more detail:

Absorption

Absorption is the movement of a drug from its site of administration to the bloodstream. The rate and extent of drug absorption depend on multiple factors, such as:

• Route of administration
• The formulation and chemical properties of a drug
• Drug-food interactions

The administration (e.g., oral, intravenous, inhalation) of a drug influences bioavailability, the fraction of the active form of a drug that enters the bloodstream and successfully reaches its target site.

When a drug is given intravenously, absorption is not required, and bioavailability is 100% because the active form of the medicine is delivered immediately to the systemic circulation. However, orally administered medications have incomplete absorption and result in less drug delivery to the site of action. For example, many orally administered drugs are metabolized within the gut wall or the liver before reaching the systemic circulation. This is referred to as first-pass metabolism, which reduces drug absorption.

Distribution

The process of drug distribution is important because it can affect how much drug ends up in the active sites, and thus drug efficacy and toxicity. A drug will move from the absorption site to tissues around the body, such as brain tissue, fat, and muscle. Many factors could influence this, such as blood flow, lipophilicity, molecular size, and how the drug interacts with the components of blood, like plasma proteins.

For example, a drug like warfarin is highly protein-bound, which means only a small percentage of the drug is free in the bloodstream to exert its therapeutic effects. If a highly protein-bound drug is given in combination with warfarin, it could displace warfarin from the protein-binding site and increase the amount that enters the bloodstream.

Additionally, there are anatomical barriers found in certain organs like the blood-brain barrier, preventing certain drugs from going into brain tissue. Drugs with certain characteristics, like high lipophilicity, small size, and molecular weight will be better able to cross the blood brain barrier.

Metabolism

Cytochrome P450 (CYP450) enzymes are responsible for the biotransformation or metabolism of about 70-80% of all drugs in clinical use.

What are some factors that affect drug metabolism?

• Genetics can impact whether someone metabolizes drugs more quickly or slowly.
• Age can impact liver function; the elderly have reduced liver function and may metabolize drugs more slowly, increasing risk of intolerability, and newborns or infants have immature liver function and may require special dosing considerations.
• Drug interactions can lead to decreased drug metabolism by enzyme inhibition or increased drug metabolism by enzyme induction.

Generally, when a drug is metabolized through CYP450 enzymes, it results in inactive metabolites, which have none of the original drug’s pharmacologic activity. However, certain medications, like codeine, are inactive and become converted in the body into a pharmacologically active drug. These are commonly referred to as prodrugs.

As you can imagine, having genetic variations in CYP2D6, the metabolic pathway for codeine, can have significant clinical consequences. Usually, CYP2D6 poor metabolizers (PMs) have higher serum levels of active drugs. In codeine, PMs have higher serum levels of the inactive drug, which could result in inefficacy. Conversely, ultra-rapid metabolizers (UMs) will transform codeine to morphine extremely quickly, resulting in toxic morphine levels.

The FDA added a black box warning to the codeine drug label, stating that respiratory depression and death have occurred in children who received codeine following a tonsillectomy and/or adenoidectomy and who have evidence of being a CYP2D6 UM.

Excretion

Elimination involves both the metabolism and the excretion of the drug through the kidneys, and to a much smaller degree, into the bile.

Excretion into the urine through the kidneys is one of the most important mechanisms of drug removal.

Many factors affect excretion, such as:

• Direct renal dysfunction, which could prolong the half-life of certain drugs and necessitate dose adjustments.
• Age, which can contribute to differing rates of excretion and impact dosing of medications.
• Pathologies that impact renal blood flow, such as congestive heart failure and liver disease can make drug excretion less efficient

Whether it’s a patient who just had gastric bypass surgery, a CYP2D6 poor metabolizer, or a patient with renal dysfunction, an individual’s characteristics affect these four processes, which can ultimately influence medication selection.

In conclusion

The world of pharmacokinetics is vast, but understanding the basic mechanisms that govern the pharmacokinetics of a drug is vital to designing individualized treatment regimens for patients.

The Genomind PGx test report covers 9 pharmacokinetic genes that affect drug exposure and may inform drug dosage. Ask about pharmacokinetic genes during your next consultation!

Deliver targeted and personalized care with Genomind.

Register with Genomind to use our precision tools and services and help your patients get better.

References

1. Sakai JB. Pharmacokinetics: The Absorption, Distribution, and Excretion of Drugs. In: Practical Pharmacology for the Pharmacy Technician. 2009:27-40.
2. Doogue MP. Polasek TM. The ABCD of clinical pharmacokinetics. Ther Adv Drug Saf. 2013;4(1):5-7.
3. Fender AC and Dobrev D. Bound to bleed: how altered albumin binding may dictate warfarin treatment outcome. Int J Cardiol Heart Vasc. 2019;22:214-215.
4. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 2009;9(Suppl 1):S3.
5. Zanger UM. Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103-41.
6. Ortiz deMontellano PR. Cytochrome P450-activated prodrugs. Future Med Chem. 2013;5(2):213-228.

Warfarin (brand names Coumadin and Jantoven) is a prescription medication used to prevent harmful blood clots from forming or growing larger. Beneficial blood clots prevent or stop bleeding, but harmful blood clots can cause a heart attack, stroke, deep vein thrombosis or pulmonary embolism. Because warfarin interferes with the formation of blood clots, it is called an anticoagulant (PDF). Many people refer to anticoagulants as *blood thinners; however, warfarin does not thin the blood but instead causes the blood to take longer to form a clot.

How Does Warfarin Work?

The formation of a clot in the body is a complex process that involves multiple substances called clotting factors. Warfarin decreases the body’s ability to form blood clots by blocking the formation of vitamin K–dependent clotting factors. Vitamin K is needed to make clotting factors and prevent bleeding. Therefore, by giving a medication that blocks the clotting factors, your body can stop harmful clots from forming and prevent clots from getting larger.

Monitoring and Dosing Tips

The goal of warfarin therapy is to decrease the clotting tendency of blood, not to prevent clotting completely. Therefore, the effect of warfarin must be monitored carefully with blood testing. On the basis of the results of the blood test, your daily dose of warfarin will be adjusted to keep your clotting time within a target range. The blood test used to measure the time it takes for blood to clot is referred to as a prothrombin time test, or protime (PT). The PT is reported as the International Normalized Ratio (INR).

The INR is a standardized way of expressing the PT value. The INR ensures that PT results obtained by different laboratories can be compared. It is important to monitor the INR (at least once a month and sometimes as often as twice weekly) to make sure that the level of warfarin remains in the effective range. If the INR is too low, blood clots will not be prevented, but if the INR is too high, there is an increased risk of bleeding. This is why those who take warfarin must have their blood tested so frequently.

Unlike most medications that are administered as a fixed dose, warfarin dosing is adjusted according to the INR blood test results; therefore, the dose usually changes over time. Coumadin/ warfarin pills come in different colors, and each color corresponds to a different dose (see graphic below).

Difference Between Brand-Name and Generic Medications

Generic drugs are supposed to have the same dosage, therapeutic effects, route of administration, side effects, and strength as the original drug. The U.S. Food and Drug Administration requires that all generic drugs be as safe and effective as brand-name drugs.

Generic drugs are often less expensive than their brand-name counterparts, because the generic manufacturers have not incurred the expenses of developing and marketing a new drug. In the United States, trademark laws do not allow generic drugs to look exactly like the brand-name drug; however, the generic drug must have the same active ingredients. In the case of Coumadin (a brand-name product) and warfarin (a generic product), the manufacturers attempted to keep the colors consistent with the strength of the pills. The goal is to allow the patient to identify the color-coded dose and prevent mix-ups or errors. Therefore, if the color or dose of the dispensed tablet appears different from the pill taken previously, the patient should immediately notify the dispensing pharmacist or healthcare provider.

In 2006, the Food and Drug Administration issued a public health advisory to healthcare professionals and consumers that U.S. prescriptions filled abroad may give patients the wrong active ingredient for treating their health condition. Some FDA–approved products have the same brand names as drug products marketed outside the United States but contain completely different active ingredients. Therefore, patients who fill U.S. prescriptions abroad, either when traveling or online, need to maintain caution and vigilance. We advise U.S. residents against purchasing drugs at foreign Internet pharmacies. Foreign drugs may use identical or potentially confusing brand names for products with active ingredients that differ from U.S. drugs. Warfarin has many foreign brand names (Table 1). Patients who do fill prescriptions abroad should ensure the accuracy and quality of the medication dispensed.

Warfarin must be taken exactly as prescribed.

Never increase or decrease your dose unless instructed to do so by your healthcare provider. If a dose is missed or forgotten, call your healthcare provider for advice.

Foreign Brand Names for Warfarin

Side Effects

The major complications associated with warfarin are clotting due to underdosing or bleeding due to excessive anticoagulation. The most serious bleeding is gastrointestinal or intracerebral. Excessive bleeding can occur in any area of the body, and patients taking warfarin should report any falls or accidents, as well as signs or symptoms of bleeding or unusual bruising, to their healthcare provider.

Signs of unusual bleeding include:

• bleeding from the gums,
• blood in the urine,
• bloody or dark stool,
• a nosebleed, or
• vomiting blood.

An unusual headache or a headache that is more severe than usual may signal intracerebral bleeding.

When to Call Your Healthcare Provider

If you experience the following signs of bleeding, you should call 911 or your healthcare provider immediately:

• Severe headache, confusion, weakness or numbness
• Coughing up large amounts of bright red blood
• Vomiting blood
• Bleeding that will not stop
• Bright red blood in stool
• Fall or injury to the head
• Headache that is severe or unusual

Some simple changes to decrease the risk of bleeding while taking warfarin include the following:

• Use a soft-bristle toothbrush
• Floss with waxed floss rather than unwaxed floss
• Shave with an electric razor rather than a blade
• Take care when using sharp objects, such as knives and scissors
• Avoid activities that have a risk of falling or injury (e.g., contact sports)

Warfarin and Lifestyle

Changes in daily living can affect the INR. It is important to know common do’s and don’ts for warfarin therapy.

Pregnancy

Warfarin is not recommended during pregnancy. A woman who becomes pregnant or plans to become pregnant while undergoing warfarin therapy should notify her healthcare provider immediately.

Surgery/Dental and Other Medical Procedures

It is important to tell all your healthcare providers that you are taking warfarin. If you are having surgery, dental work, or other medical procedures, you may need to stop taking warfarin.

Travel

Check with your healthcare provider if you expect to travel. While traveling, it is important to carry your medication with you at all times. Do not put medication into checked baggage.

Common Do's and Don'ts

Warfarin Interacts With Other Medications

Patients who take warfarin should consult with their healthcare provider before taking any new medication, including over-the-counter (nonprescription) drugs, herbal medicines, vitamins or any other products. Many medications can alter the effectiveness of warfarin, resulting in an INR that is either too high or too low. Some of the most common over-the-counter pain relievers, such as: ibuprofen (brand name Advil) and naproxen (brand name Aleve), enhance the anticoagulant effects of warfarin and increase the likelihood of harmful bleeding.

Warfarin Interacts With Alcohol and With Certain Foods

• Alcohol - Alcohol intake can affect how the body metabolizes warfarin. Patients undergoing warfarin therapy should avoid drinking alcohol on a daily basis. Alcohol should be limited to no more than 1 to 2 servings of alcohol occasionally. This means an average of one to two drinks per day for men and one drink per day for women. (A drink is one 12 oz. beer, 4 oz. of wine, 1.5 oz. of 80-proof spirits, or 1 oz. of 100-proof spirits). The antiplatelet effect of alcohol increases the risk of major bleeding, even if the INR remains within the target range.
• Foods - Some foods can interfere with the effectiveness of warfarin. The most important point to remember is to eat what you normally eat and not to make any major changes in your diet without contacting your healthcare provider.
• Vitamin K - Eating an increased amount of foods rich in vitamin K can lower the PT and INR, making warfarin less effective and potentially increasing the risk of blood clots. Patients who take warfarin should aim to eat a relatively similar amount of vitamin K each week. The highest amount of vitamin K is found in green and leafy vegetables such as broccoli, lettuce, and spinach. It is not necessary to avoid these foods; however, it is important to try to keep the amount of vitamin K you eat consistent. Download our quick reference guide to foods that are high and low in Vitamin K. (PDF)

Wear Medical Identification

Those who require long-term warfarin should wear a medical alert bracelet, necklace, or similar alert tag at all times. If an accident occurs and the person is too ill to communicate, a medical alert tag will help responders provide appropriate care. The alert should include a list of major medical conditions and the reason warfarin is needed, as well as the name and phone number of an emergency contact.

Where to Get More Information

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no 2 patients are exactly alike, and recommendations can vary from 1 person to another, it is important to seek guidance from a provider who is familiar with your individual condition.