Drug Interactions

Jane's Unexpected Reaction

Meet Jane, a 65-year-old woman with high blood pressure and arthritis. She takes medication A, a calcium channel blocker, to manage her blood pressure, and medication B, a nonsteroidal anti-inflammatory drug (NSAID), for her arthritis pain.

One day, Jane develops a severe headache and decides to take an over-the-counter medication, medication C, for quick relief. Medication C contains a common ingredient called acetaminophen (paracetamol), which is often used to reduce pain and fever.

However, shortly after taking medication C, Jane experiences dizziness, lightheadedness, and a sudden drop in blood pressure. Concerned, she contacts her doctor who suspects a drug interaction.

Drug Interaction

Drug interaction refers to the phenomenon where the effects of one drug are altered when it is taken alongside another drug, or in the presence of certain foods, beverages, or other substances.

Drug interactions can affect the 

• Pharmacokinetics
• Pharmacodynamics

Pharmacokintetic Interactions

Absorption

Some drugs can interfere with the absorption of another drug from the gastrointestinal tract.

• Antacids can reduce the absorption of certain antibiotics.
• Cholesterol-lowering drugs, may have reduced absorption when taken with high-fat meals
• Consuming dairy products, such as milk, yogurt, or cheese, along with tetracycline antibiotics, can interfere with the absorption of the medication

Distribution

Drug interactions can occur when drugs compete for binding sites on plasma proteins, leading to altered distribution. This can affect the free concentration of the drugs in the body. 

• NSAIDs, such as ibuprofen or naproxen, can displace warfarin from its binding sites on plasma proteins, leading to an increase in the free concentration of warfarin in the blood. This can potentiate the anticoagulant effect of warfarin and increase the risk of bleeding.
• Cimetidine, a medication used to reduce stomach acid production, can inhibit the metabolism of diazepam in the liver. This can prolong the effects of diazepam and increase the risk of sedation and central nervous system depression
• Phenytoin, an antiepileptic drug, binds extensively to plasma proteins, primarily albumin. Concurrent administration of other drugs that also bind to albumin, such as certain antibiotics (e.g., sulfonamides), can displace phenytoin from albumin and increase the free concentration of phenytoin. This can lead to an increased risk of phenytoin toxicity.

Metabolism

Drugs can interact by inhibiting or inducing drug-metabolizing enzymes in the liver, altering the metabolism of co-administered drugs. 

• Consuming grapefruit juice while taking certain statin medications, such as atorvastatin or simvastatin, can interfere with the metabolism of the drug. Grapefruit juice contains compounds that inhibit an enzyme responsible for breaking down statins in the liver. As a result, the statin concentration in the blood can increase, leading to an increased risk of side effects.
• Acetaminophen is a common over-the-counter pain reliever and fever reducer. Drinking alcohol while taking acetaminophen can increase the risk of liver damage. Both alcohol and acetaminophen are metabolized in the liver, and the combination can overwhelm the liver's capacity to process these substances, causing liver toxicity.
• Fluoxetine and Monoamine Oxidase Inhibitors (MAOIs): Fluoxetine is an antidepressant, and MAOIs are another class of antidepressants. Combining these medications can result in a drug-drug interaction known as serotonin syndrome, characterized by symptoms such as agitation, confusion, rapid heartbeat, high blood pressure, and even seizures. This interaction occurs due to the accumulation of serotonin in the brain.

Excretion

Drug interactions can affect renal excretion, leading to changes in drug elimination. 

• Probenecid and Penicillin: Probenecid is a medication used to treat gout by increasing the excretion of uric acid. When taken with penicillin, probenecid can inhibit the renal excretion of penicillin, leading to increased blood levels of the antibiotic. This interaction can enhance the effectiveness of penicillin and prolong its action.
• Diuretics and Lithium: Diuretics are medications that promote increased urine production, while lithium is a mood stabilizer used to treat bipolar disorder. Diuretics can reduce the excretion of lithium by the kidneys, leading to increased levels of lithium in the blood. This interaction can potentially result in lithium toxicity, characterized by symptoms such as tremors, confusion, and irregular heartbeat.

Pharmacodynamic Interactions

• Monoamine Oxidase Inhibitors (MAOIs) and Tyramine-rich Foods: MAOIs are medications used to treat depression and other mental health conditions. These drugs inhibit the enzyme monoamine oxidase, which breaks down certain neurotransmitters in the brain. When MAOIs are taken with tyramine-rich foods such as aged cheeses, cured meats, and fermented foods, it can lead to a dangerous increase in blood pressure known as a hypertensive crisis. This occurs because MAOIs prevent the breakdown of tyramine, causing it to accumulate and exert potent vasoconstrictive effects.
• Warfarin and Vitamin K-rich Foods: Warfarin is an anticoagulant medication used to prevent blood clotting. Vitamin K is essential for blood clotting, and consuming large amounts of vitamin K-rich foods such as leafy green vegetables, broccoli, and Brussels sprouts can counteract the anticoagulant effect of warfarin. Consistently varying vitamin K intake can make it difficult to maintain stable anticoagulation levels, requiring careful monitoring and adjustment of warfarin dosage.
• Grapefruit Juice and Calcium Channel Blockers: Calcium channel blockers are medications used to treat high blood pressure and heart conditions. Grapefruit juice can inhibit the metabolism of certain calcium channel blockers, increasing their blood levels and intensifying their effects. This interaction can potentially lead to excessive lowering of blood pressure and an increased risk of adverse effects such as dizziness and fainting.
• Alcohol and Central Nervous System Depressants: Alcohol is a central nervous system depressant, and when consumed with other medications that have similar effects, such as benzodiazepines or opioids, it can enhance their sedative effects. This combination can lead to excessive drowsiness, impaired coordination, and increased risk of accidents or respiratory depression.

Explanation of Jane's Unexpected Reaction

A drug interaction occurred between medication C (acetaminophen) and medication A (calcium channel blocker). Both drugs can lower blood pressure, but when taken together, their effects were additive, resulting in a significant drop in Jane's blood pressure.

Medication A (calcium channel blocker) works by relaxing the blood vessels, allowing better blood flow and reducing blood pressure. On the other hand, medication C (acetaminophen) can also lower blood pressure as a side effect.

When Jane took both medications together, their combined effect on blood pressure was more potent than either drug alone. This unexpected interaction caused her symptoms of dizziness and lightheadedness.

Some case studies

Mrs. Johnson, a 70-year-old woman with a history of atrial fibrillation, is prescribed warfarin, an anticoagulant, to prevent blood clotting. During a routine check-up, her doctor discovers that her International Normalized Ratio (INR), a measure of blood clotting time, is consistently outside the target range. Upon further investigation, it is revealed that Mrs. Johnson has significantly increased her consumption of leafy green vegetables, such as spinach and kale. What could be the possible reason that her INR is outside target range?

Mr. Johnson, a 45-year-old man, is taking an antidepressant medication called Sertraline for his depressive symptoms. He recently developed severe back pain and was prescribed a muscle relaxant called Cyclobenzaprine by his primary care physician. However, Mr. Johnson also takes over-the-counter St. John's Wort supplement for his mood. What could be the potential drug interaction.

Ms. Smith, a 60-year-old woman, has been diagnosed with high blood pressure and is prescribed the medication Amlodipine to control her blood pressure. She is also a big fan of grapefruit and consumes it daily. What could be the possible drug interaction?