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Basic psychopharmacology
Published in Jonathan P Rogers, Cheryl CY Leung, Timothy RJ Nicholson, Pocket Prescriber Psychiatry, 2019
Jonathan P Rogers, Cheryl CY Leung, Timothy RJ Nicholson
These are commonly used and easily forgotten about when taking a drug history or explaining how to take a medication. St John's wort (Hypericum perforatum) induces CYP2C9, CYP2C19 and CYP3A4. This can cause the OCP to fail.Drinking alcohol as a one-off inhibits CYP2E1 and CYP3A4, but chronical alcohol use induces these enzymes. Patients who return from a one-off binge should have their medications reviewed before being administered (a) to avoid compounding respiratory depression and (b) to ensure there is no important pharmacokinetic interaction. In chronic alcoholism, dosing is complex because some cytochrome enzymes are induced, but active drug concentrations may be higher because of lower blood proteins.Tobacco induces CYP1A2, but NRT does not have this effect. Therefore, active smoking reduces clozapine levels, but smoking cessation causes an increase in clozapine levels.Grapefruit juice inhibits CYP1A2 and CYP3A4, so should generally be avoided by patients taking medications that are metabolised by these pathways.
Ciclosporin
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Murtaza Khan, John Berth-Jones
Several branded formulations are available in the UK in the following forms: Capsules: 25 mg and 100 mg ciclosporin (Neoral, Gengraf, modified), 25 mg, 50 mg and 100 mg ciclosporin (Sandimmune, non-modified).Oral solution: sugar-free solution containing ciclosporin 100 mg/mL. This may be mixed with orange or apple juice to improve the taste but not with grapefruit juice. Avoid milk due to the unpleasant tasteSandimmune is also available in a concentrate for i/v infusion containing ciclosporin 50 mg/mL.
Mammalian CYP2D Members A Comparison of Structure, Function, and Regulation
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Grapefruit juice significantly increases the plasma concentrations of drugs that are substrates for CYP3A4 such as felodipine, triazolam, midazolam, diazepam, terfenadine, cyclosporine, and nifedipine (Bailey and Dresser 2004; Bailey et al. 2000, 2003). The principal components of grapefruit juice have been identified as the furanocoumarin bergamottin and its metabolite 6′,7′-dihydroxybergamottin, as well as the flavonoids naringenin, naringin, quercetin, and kaempferol. Bergamottin is a potent inhibitor of human CYP3A4. In humans, grapefruit juice exposure decreases concentrations of intestinal CYP3A4 but does not affect CYP3A5, 1A1, 2D6 protein, or 3A4 mRNA (Lown et al. 1997). In contrast to the results described above, long-term grapefruit juice treatment in rats has been shown to increase nifedipine clearance (Mohri et al. 2000). In mice, a single dose of grapefruit juice inhibits hepatic oxidative enzyme activity, whereas multiple dosing increases activity (Dakovic-Svajcer et al. 1999). The results of these rodent studies imply that grapefruit juice is both an inhibitor and an inducer. However, this compound is both an inhibitor and an inducer of P450 enzymes in dogs. Bergamottin predosing increases the plasma levels of diazepam in beagle dogs (Sahi et al. 2002). In dog hepatic microsomes, bergamottin treatment for 10 days reduces the activity of CYP3A12 by 50% and 1A1/2 by 75%. Tolbutamide hydrox-ylase activity does not change, and CYP2B11 activity is moderately induced. In jejunal microsomes, CYP3A12 activity doubles with bergamottin treatment. CYP2B11 and 1A1/2 activity and tolbutamide hydroxylation are not detected.
Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats
Published in Drug and Chemical Toxicology, 2022
Alireza Malayeri, Reza Badparva, Mohammad Amin Mombeini, Layasadat Khorsandi, Mehdi Goudarzi
Naringenin, abbreviated as NAR (5, 7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one), is a citrus flavanone and the predominant flavanone in Citrus paradisi or grapefruit (up to 10% of dry weight) (Figure 1). It is responsible for the bitterness of grapefruit juice and is recognized as one of the most consumed flavonoids (Ortuno et al.1995, Lee et al.2004, Moon et al.2011, Khajevand-Khazaei et al.2018). NAR exhibits anti-carcinogenic (Frydoonfar et al.2003), anti-inflammatory (Bodet et al.2008), anti-estrogenic (Bovee et al.2008), and anti-tumor effects (Kanno et al.2005). Furthermore, it seems to possess free radical scavenging properties, which effectively quench oxygen-derived free radicals, given the presence of hydroxyl groups (−OH) in its structure (Zbarsky et al.2005).
Role of hesperidin and fresh orange juice in altering the bioavailability of beta-blocker, metoprolol tartrate. An in vivo model
Published in Xenobiotica, 2022
Rabiha Salam, Syeda Nayyab Batool Rizvi, Naqi Hussain, Shama Firdous, Muhammad Zaheer, Muhammad Naeem
In recent years drug bioavailability has become a matter of keen interest in the development of drugs. In the nutritional study, the co-administration of fruit juice with a drug has a considerable effect on its bioavailability. Grapefruit juice has significantly altered the bioavailability of a number of drugs including fexofenadine, felodipine, lovastatin, cyclosporin, triazolam, silenafil, talinolol, simvastatin, acebutolol, and buspiron (Bailey et al. 1991; Hukkinen et al. 1995; Yee et al. 1995; Kantola et al. 1998; Lilja, Kivistö, Backman, et al. 1998; Lilja, Kivistö, Neuvonen 1998; Jetter et al. 2002; Schwarz et al. 2005; Lilja et al. 2005a; Glaeser et al. 2007). Orange juice has also been reported to suppress the bioavailability of drugs including ciprofloxacin, fexofenadine, and beta-blockers (celiprolol and atenolol) (Dresser et al. 2002; Neuhofel et al. 2002; Lilja et al. 2004; 2005b). Orange juice consumption does not affect cytochromes P450 activity in vivo (Takanaga et al. 2000). The decreased bioavailability of drugs with orange juice might be due to an indirect effect on OATPs (Organic anion transporting proteins) from enhanced intestinal fluid volume by the non-specific osmotic effects of the solutes. OATPs are the membrane transporter proteins that facilitates the sodium-independent uptake of substrate compounds through the gastrointestinal wall acting in opposing fashion to efflux transporter in the intestines such as p-glycoproteins. However the exact aetiology by which orange juice reduces the bioavailability of drugs is not known.
The citrus flavanone naringenin prevents the development of morphine analgesic tolerance and conditioned place preference in male rats
Published in The American Journal of Drug and Alcohol Abuse, 2021
Atena Alifarsangi, Saeed Esmaeili-Mahani, Vahid Sheibani, Mehdi Abbasnejad
Surprisingly, it has been reported that citrus juices such as grapefruit juice interfere with the metabolism of the opiates and maximizes their effects (19). In addition, oral administration of grapefruit juice enhances morphine antinociception and prevents tolerance by increasing the intestinal absorption of this agent (20). Dietary consumption of grapefruit products increases the concentrations and effects of oxycodone in clinical use (21). However, citrus juices are known as dangerous opioid potentiators and traditionally, opioid addicted persons do not like to drink citrus fruit juices including orange, lime, lemon and grapefruit. Grapefruit juice and its main component naringenin inhibit the cytochrome P450 family, critical enzymes for metabolizing almost 50% of the drugs in liver and small intestinal epithelial cells (22). It has been shown that the CYP450 system plays a key role in the metabolism of various opioids and therefore, affects the metabolism, interactions and clinical significance of opioids (23,24).