Category: NUR1125

Which fruit to avoid with fexofenadine?

It is advised to avoid taking fexofenadine with fruit juices. But does this apply to all fruit juices or only grapefruit juice? And what about tomato juice – are tomatoes not also fruit?  And why the warning only about the juice – what happens if you eat the fruit instead of drinking the juice? 

Grapefruit and Drug Metabolism – A Closer Look at CYP Interactions: Many of us might have come across warnings about the potential interaction between grapefruit juice and certain medications. Let’s delve deeper into the science behind this. Grapefruits, along with other specific citrus fruits like pomelos and Seville oranges (often termed as bitter oranges or sour oranges), are rich in polyphenols, notably furanocoumarins. These compounds play a crucial role in inhibiting various cytochrome P450 enzymes, including CYP3A4, CYP1A2, CYP2C9, and CYP2D6.

Why does this matter? The inhibition of the CYP3A4 enzyme, in particular, impedes its ability to effectively metabolize certain drugs. As a result, there can be an unintended increase in the drug levels within the bloodstream, amplifying the risk of side effects or even toxicities. It’s noteworthy that CYP3A4 is pivotal for the metabolism of a wide range of medications. Consequently, grapefruit’s interaction can potentially affect the efficacy and safety of medications such as statins (targeting high cholesterol), calcium channel blockers (for managing hypertension), calcineurin inhibitors (used in immunosuppression), and benzodiazepines (prescribed for anxiety and insomnia).

Fruit and Fexofenadine – Reduced Absorption:  Contrary to the increased plasma concentration of drugs seen following inhibition of CYP enzymes, fruit juices decrease intestinal absorption of the second-generation H1 antihistamine, fexofenadine. The mechanism behind this interaction involves intestinal transporters, specifically organic anion-transporting polypeptides (OATPs).

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Hashimoto’s thyroiditis versus Hashimoto’s encephalopathy

Is Hashimoto’s encephalopathy related to Hashimoto’s thyroiditis?

• Hashimoto’s thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed, resulting in chronic hypothyroidism.
• Hashimoto’s encephalopathy is a rare neurological condition characterized by encephalopathy and thyroid autoimmunity. It shows a good clinical response to corticosteroids.

Hashimoto’s thyroiditis, so named because it was first described in a medical publication by Hakaru Hashimoto (1881-1934) in 1912, is an autoimmune disease. Typically the autoantibodies include antibodies against thyroid peroxidase (TPO). TPO is an enzyme expressed in the thyroid gland that is essential for the production of thyroid hormones. In Hashimoto’s thyroiditis, the thyroid gland is gradually destroyed, resulting in chronic hypothyroidism unless treated with thyroid hormone replacement. It is the most common form of hypothyroidism, affecting about 5% of people.

Hashimoto’s encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is an extremely rare (2.1 in 100,000) neurological condition characterized by encephalopathy and thyroid autoimmunity, which shows a good clinical response to corticosteroids.  First described by Brain, Jellinek and Ball in 1966, the condition was named for its association with Hashimoto’s thyroiditis, but the pathogenic autoantibodies are thought to be against alpha-enolase, a ubiquitous enzyme invovled in glycolysis. Glycolysis is the metabolic pathway that converts glucose to pyruvic acid releasing energy in the form of adenosine triphosphate (ATP).

Levothyroxine and cancer?

Is there an association between levothryoxine and breast cancer?

The short answer is that there is not sufficient evidence to draw any conclusion at this time. Patients who require levothyroxine should continue to take their medication as prescribed by their doctor. The risk of ultimately fatal myxedema due to severe untreated hypothyroidism is proven and real. The risk of cancer is speculative and not definitively proven.

When this question came up at the end of the lecture, my initial thought was that an association between levothryoxine and cancer is highly improbable. Oral levothyroxine essentially replaces your own endogenous thyroxine (T4). Treatment normalises T4 levels but should not cause supraphysiological levels of T4.  Even the route of absorption is largely physiological as endogenous T4 is recycled through enterohepatic circulation and is absorbed in the small intestine after being excreted in the bile. The only potentially “unnatural” exposure is as the levothryoxine tablet passes from the mouth to the stomach. In theory, there is no reason why taking levothyroxine should expose anyone to greater risk than having physiologically normal thyroid function would.
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