What enzyme metabolizes metoprolol?
What enzyme metabolizes metoprolol?
Metoprolol is primarily metabolized by the CYP2D6 enzyme. Approximately 8% of Caucasians and 2% of most other populations have absent CYP2D6 activity and are known as “CYP2D6 poor metabolizers.” In addition, a number of drugs inhibit CYP2D6 activity, such as quinidine, fluoxetine, paroxetine, and propafenone.
What is CYP2D6 enzyme?
The CYP2D6 enzyme catalyses the metabolism of a large number of clinically important drugs including antidepressants, neuroleptics, some antiarrhythmics, lipophilic β-adrenoceptor blockers and opioids.
What is CYP2D6 polymorphism?
CYP2D6 is perhaps the most extensively studied polymorphically expressed drug metabolising enzyme in humans; its polymorphism has a high clinical importance and was the first among the polymorphic P450s to be characterized at the molecular level.
What drugs inhibit CYP2D6?
|Strong inhibitors||Weak inhibitors|
|CYP2D6||bupropion, fluoxetine(g), paroxetine, quinidine(h), terbinafine||amiodarone, celecoxib, cimetidine, clobazam, cobicistat, escitalopram, fluvoxamine(a), labetalol, ritonavir(h,i,j), sertraline, vemurafenib|
How is metoprolol metabolized and excreted?
Metoprolol is primarily metabolized to α-hydroxymetoprolol and O-demethylmetoprolol by CYP2D6 (Fig. 1). Approximately 85% of metoprolol metabolites are excreted in the urine, as well as a small amount of unmetabolized drug, making urine an ideal biofluid for monitoring.
What does CYP1A2 metabolize?
CYP1A2 metabolizes endogenous compounds such as retinols, melatonin, steroids, uroporphyrinogen and arachidonic acids and plays a major role in procarcinogen activation and DDIs, due to induction and inhibition by several therapeutic drugs.
What are CYP3A4 substrates?
Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, with CYP3A4 responsible for about half of this metabolism; substrates include acetaminophen, codeine, ciclosporin (cyclosporin), diazepam, and erythromycin. The enzyme also metabolizes some steroids and carcinogens.
Why is CYP2D6 important?
CYP2D6 is responsible for the metabolism of the second highest number of drugs metabolized by P450 enzymes. Substrates for CYP2D6 can be found in Table 3.1. CYP2D6 is a particularly challenging enzyme to understand and study because of its genetic polymorphism.
What is the importance of CYP2D6?
Cytochrome P450 2D6 (CYP2D6) is a critical pharmacogene involved in the metabolism of ~20% of commonly used drugs across a broad spectrum of medical disciplines including psychiatry, pain management, oncology and cardiology.
What are the inducers of CYP2D6?
Dexamethasone and corticosterone were the most potent inducers of CYP2D6 followed by prednisolone and cortisol.
What happens if you inhibit CYP2D6?
CYP2D6 Inhibitors Drugs that inhibit CYP2D6 activity are likely to increase the plasma concentrations of certain medications, and, in some cases, adverse outcomes will occur (see Table 3 below right for a list of known inhibitors).
Is metoprolol metabolized by the kidneys?
The drug is extensively metabolised and only about 5% of an oral dose and 10% of an intravenous dose is excreted in unchanged form via the kidneys. Although 2 of the metabolites possess selective β1-adrenoceptor blocking activity, none of them contributes to the β-blocking effect of metoprolol.
What is the pathophysiology of metoprolol?
Metoprolol belongs to a class of drugs known as beta blockers. It works by blocking the action of certain natural chemicals in your body, such as epinephrine, on the heart and blood vessels. This effect lowers the heart rate, blood pressure, and strain on the heart.
What are CYP1A2 substrates?
Typical CYP1A2 substrates generally contain planar ring that can fit the narrow and planar active site of the enzyme, such as propranolol, clozapine, guanabenz, flutamide, imatinib, thalidomide, carbamazepine, lidocaine, theophylline, tacrine, tizanidine, zolpidem, riluzole, zileuton, and leflunomide.
What enzyme does CYP1A2 code for?
In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene….CYP1A2.
|PDB||List of PDB id codes 2HI4|
What are cytochrome P450 substrates?
Cytochrome P450s are heme-containing enzymes catalyzing the mixed-function oxidation of endogenous substrates, as well as xenobiotic molecules [1-4]. P450s are found in most living systems, from bacteria to humans, with more than 8500 P450 genes reported to date (drnelson.utmem.edu/CytochromeP450.html) [5, 6].
What are substrates inhibitors and inducers?
Some Common Substrates, Inhibitors and Inducers of CYP450 Isoenzymes
What are CYP2D6 and CYP2C19?
CYP2C19 and CYP2D6 are important drug-metabolizing enzymes that are involved in the metabolism of around 30% of all medications.
What induces CYP2D6?
What is cytochrome P450 3a4 and CYP2D6?
Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6.