It seems the grapefruit might just be .. replacing .. the drugs and therefore
leading to toxicity .. ?
Am J Cardiovasc Drugs. 2004;4(5):281-97. Related Articles, Links
Interactions between grapefruit juice and cardiovascular drugs.
Bailey DG, Dresser GK.
Department of Medicine and Lawson Health Research Institute, London Health
Sciences Centre, London, Ontario, CanadaDepartment of Physiology &
Pharmacology, University of Western Ontario, London, Ontario, Canada.
Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms.
Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced
by commercial grapefruit juice given as a single normal amount (e.g. 200-300mL)
or by whole fresh fruit segments. As a result, presystemic metabolism is
reduced and oral drug bioavailability increased. Enhanced oral drug
bioavailability can occur 24 hours after juice consumption. Inhibition of
P-glycoprotein (P-gp) is a possible mechanism that increases oral drug
bioavailability by reducing intestinal and/or hepatic efflux transport.
Recently, inhibition of organic anion transporting polypeptides by grapefruit
juice was observed in vitro; intestinal uptake transport appeared decreased as
oral drug bioavailability was reduced.Numerous medications used in the
prevention or treatment of coronary artery disease and its complications have
been observed or are predicted to interact with grapefruit juice. Such
interactions may increase the risk of rhabdomyolysis when dyslipidemia is
treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or
simvastatin. Potential alternative agents are pravastatin, fluvastatin, or
rosuvastatin. Such interactions might also cause excessive vasodilatation when
hypertension is managed with the dihydropyridines felodipine, nicardipine,
nifedipine, nisoldipine, or nitrendipine. An alternative agent could be
amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1
receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit
juice interacting with the antidiabetic agent repaglinide may cause
hypoglycemia, and interaction with the appetite suppressant sibutramine may
cause elevated BP and HR. In angina pectoris, administration of grapefruit
juice could result in atrioventricular conduction disorders with verapamil or
attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance
drug toxicity for antiarrhythmic agents such as amiodarone, quinidine,
disopyramide, or propafenone, and for the congestive heart failure drug,
carvediol.Some drugs for the treatment of peripheral or central vascular
disease also have the potential to interact with grapefruit juice. Interaction
with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause
serious systemic vasodilatation especially when combined with a nitrate.
Interaction between ergotamine for migraine and grapefruit juice may cause
gangrene or stroke. In stroke, interaction with nimodipine may cause systemic
hypotension.If a drug has low inherent oral bioavailability from presystemic
metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce
serious overdose toxicity, avoidance of grapefruit juice entirely during
pharmacotherapy appears mandatory. Although altered drug response is variable
among individuals, the outcome is difficult to predict and avoiding the
combination will guarantee toxicity is prevented. The elderly are at particular
risk, as they are often prescribed medications and frequently consume
grapefruit juice.
PMID: 15449971 [PubMed - in process]
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J Agric Food Chem. 2004 Jul 14;52(14):4414-8. Related Articles, Links
Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the
flavonol quercetin, in human platelets.
Sheu JR, Hsiao G, Chou PH, Shen MY, Chou DS.
Graduate Institutes of Medical Sciences and Pharmacology, Taipei Medical
University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan. [email hidden]
The aim of this study was to systematically examine the inhibitory mechanisms
of rutin, a well-known flavonoid in platelet aggregation. In this study, rutin
concentration-dependently (250 and 290 microM) inhibited platelet aggregation
in human platelets stimulated by agonists (i.e., collagen). Rutin (250 and 290
microM) did not significantly interfere with the binding of FITC-triflavin to
the glycoprotein IIb/IIIa complex in human platelets. Rutin (250 and 290
microM) markedly inhibited intracellular Ca(2+) mobilization and thromboxane
A(2) formation in human platelets stimulated by collagen. Rapid phosphorylation
of a platelet protein of M(r) 47000 (P47), a marker of protein kinase C
activation, was triggered by collagen (1 microg/mL). This phosphorylation was
markedly inhibited by rutin (250 and 290 microM). On the other hand, rutin (250
and 290 microM) did not significantly increase the formations of cyclic AMP and
nitric oxide/cyclic GMP in platelets. In conclusion, these results indicate
that the antiplatelet activity of rutin may involve the following pathways:
rutin inhibited the activation of phospholipase C, followed by inhibition of
protein kinase C activity and thromboxane A(2) formation, thereby leading to
inhibition of the phosphorylation of P47 and intracellular Ca(2+) mobilization,
finally resulting in inhibition of platelet aggregation.
PMID: 15237945 [PubMed - indexed for MEDLINE]
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