11. INTERACTIONS:01. Interacción 29/11/12 14:38 Página 1866 Nutr Hosp. 2012;27(5):1866-1875 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Revisión Interactions between antihypertensive drugs and food B. Jáuregui-Garrido1 and I. Jáuregui-Lobera2 1Department of Cardiology. University Hospital Virgen del Rocío. Seville. Spain. 2Bromatology and Nutrition. Pablo de Olavide University. Seville. Spain. Abstract INTERACCIONES ENTRE FÁRMACOS ANTIHIPERTENSIVOS Y ALIMENTOS Objective: A drug interaction is defined as any alter- ation, pharmacokinetics and/or pharmacodynamics, Resumen produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. Objetivo: la interacción de medicamentos se define como These interactions can affect the antihypertensive drugs, cualquier alteración, farmacocinética y/o farmacodiná- altering their therapeutic efficacy and causing toxic mica, producida por diferentes sustancias, otros tratamien- effects. The aim of this study was to conduct a review of tos, factores dietéticos y hábitos como beber y fumar. Estas available data about interactions between antihyperten- interacciones pueden afectar a los fármacos antihipertensi- sive agents and food. vos, alterando su eficacia terapéutica y causando efectos Methods: The purpose of this review was to report an tóxicos. El objetivo de este estudio fue realizar una revisión update of main findings with respect to the interactions de los datos disponibles acerca de las interacciones entre los between food and antihypertensive drugs by way of a fármacos antihipertensivos y los alimentos. search conducted in PubMed, which yielded a total of 236 Métodos: El objetivo de esta revisión fue proporcionar articles initially. una puesta al día sobre los principales resultados con res- Results: After excluding different articles, which were pecto a las interacciones entre alimentos y fármacos antihi- not focusing on the specific objective, the main results pertensivos mediante una búsqueda realizada en PubMed, refer to interactions between antihypertensive drugs and que dio lugar inicialmente a un total de 236 artículos. food (in general) as well as between antihypertensive Resultados: Tras la exclusión de diferentes artículos agents and grapefruit juice. que no estaban centrados en el objetivo específico, los Discussion: Food may affect the bioavailability of anti- resultados principales se refieren a las interacciones entre hypertensive drugs and this should be carefully consid- los fármacos antiarrítmicos y alimentos en general y ered. Advising patients to remove the grapefruit juice entre dichos fármacos y el zumo de pomelo. from their diet when treatment with these drugs seems to Discusión: Los alimentos pueden afectar a la biodispo- be the best recommendation. Given these interactions nibilidad de los fármacos antihipertensivos y ello debe ser and the associated potential adverse effects the anamnesis considerado cuidadosamente. Advertir a los pacientes must include detailed information about the specific que supriman el zumo de pomelo en su dieta cuando están eating habits of the patients. en tratamiento con estos fármacos parece la mejor reco- (Nutr Hosp. 2012;27:1866-1875) mendación. Dadas estas interacciones y sus potenciales efectos adversos, la anamnesis debe incluir información DOI:10.3305/nh.2012.27.6.6127 detallada sobre los hábitos alimentarios de los pacientes. Key words: Antihypertensive drugs. Food-drugs interac- (Nutr Hosp. 2012;27:1866-1875) tions. Grapefruit juice. Diet. DOI:10.3305/nh.2012.27.6.6127 Palabras clave: Fármacos antihipertensivos. Interacciones entre alimentos y medicamentos. Zumo de pomelo. Dieta. Abbreviations AT1 receptor: Angiotensin 1 receptor. AUC: Area under the curve (Area under the plasma ACE: Angiotensin-converting enzyme. concentration time curve). ARBs: Angiotensin II receptor blockers. BA: Bioavailability. BP: Blood pressure. Correspondence: I. Jáuregui-Lobera. Cmax: Maximum plasma concentration. Bromatology and Nutrition. cGMP: cyclic guanosine monophosphate. Pablo de Olavide University. CYP: Cytochrome P450 gene family. Virgen del Monte, 31. 41011 Seville. Spain. DASH: Dietary Approach to Stop Hypertension. E-mail: [email protected] / [email protected] DBP: Diastolic blood pressure. Recibido: 21-VIII-2012. HT: Hypertension. Aceptado: 24-VIII-2012. IP3: Inositol triphosphate. 1866 11. INTERACTIONS:01. Interacción 29/11/12 14:38 Página 1867 NaCl: Sodium chloride, common salt. and inhibitors of the CYP system, so the association of OAT: Organic anion transporter. antihypertensive drugs with other drugs and/or food OCT: Organic cation transporter. which use the CYP for their metabolism may be toxic. P-gp: P-glycoprotein. Together with CYP, it should be noted, due to its meta- SBP: Systolic blood pressure. bolic importance, the P-glycoprotein (P-gp), a family of t1/2: Drug elimination half-life. membrane transporters located in the brush border of the tmax: Time after administration of a drug when the enterocytes’ membranes. In addition to mobilizing maximum plasma concentration is reached. endogenous substances, the P-gp mobilizes certain drugs including some antihypertensive drugs.9-11 Drug interactions are defined as any alteration, phar- Introduction macokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary Hypertension (HT), which is defined as a chronic factors and habits such as drinking and smoking.12 elevation of systolic and/or diastolic blood pressure These interactions may affect the antihypertensive (BP), is in all probability the most common chronic drugs, modifying their therapeutic efficacy and the disease today. The main clinical significance of HT, adverse effects. which is not a disease in the usual sense of the word, The aim of this study was to conduct a review of lies on the future risk of vascular disease. Apart from available data about interactions between antihyper- various causes of HT, the most frequent case is the tensive drugs and food. essential HT (up to 95%).1,2 In the regulation of BP, there are different involving factors (sympathetic nervous system, kidney, hormonal Method systems), one of them being the composition of the diet. Thus, sodium, potassium, magnesium, lipids and total The review was conducted through a PubMed search. energy intake influence the control of BP.3 In the largest The initial search term was “Interactions between antihy- international study on the relationship between sodium pertensive drugs and food,” which resulted in a total of and BP (INTERSALT),4 the analysis of more than 337 articles. Later, other specific searches were 10,000 participants showed that a variation of 100 mmol performed, by entering “ Interactions between loop sodium intake modified the systolic BP (SBP) 2.2 diuretics and food”, “ Interactions between calcium mmHg, being lower the effect on diastolic BP (DBP). As channel blockers and food”, “Interactions between ACE for diet, one of the most relevant studies (DASH: Dietary inhibitors and food”, “Interactions between ARBs and Approaches to Stop Hypertension)5 showed that BP food”, “Interactions between hydralazine and food” and levels decreased with a diet low in saturated fat, choles- “Interactions between grapefruit juice and antihyperten- terol and total fat and high in fruits, vegetables and sive agents”. Having excluded the repeated articles, a total skimmed or semi-skimmed milk, that is a diet rich in of 236 articles were considered. Then those that did not magnesium, calcium, potassium, protein and fibre. In a make specific reference to the object of the review were later study (DASH-sodium),6 it was observed that with rejected. Articles without an abstract were also excluded. any level of sodium, the greatest reduction in BP was With respect to case reports and letters, because of the achieved with the DASH diet and even better with a scarcity of articles focusing specifically on a subject, sodium intake of only 1,500 mg of sodium per day. some of them were considered. Apart from the articles Regarding the treatment of HT, it is correct when its included after the search, some other articles and/or chap- continued efficacy is proven and it has minimal side ters were considered due to its relevance. effects. The goal is to achieve and maintain a SBP below 140 mmHg and a DBP below 90 mmHg.7 Apart from general measures of treatment (stress manage- Results ment, moderate salt restriction, regular exercise and moderate reduction of other risk factors) 8 there is a full Interactions between food and diuretics arsenal of antihypertensive drugs: diuretics, alpha and beta-blockers, calcium channel blockers, angiotensin- The simultaneous intake of food and some loop converting enzyme (ACE) inhibitors, angiotensin II diuretics such as furosemide and bumetanide causes a receptor blockers (ARBs) and others such as sodium decrease of the BA of these drugs, which in the case of nitroprusside, monoxidine, hydralazine and minoxidil. furosemide seems to be very high (approximately With regard to the bioavailability (BA) of antihyper- 30%).13 In a review, Bard et al. corroborated the exis- tensive drugs, it is noted the importance of the tence of a decrease in the BA of loop diuretics when cytochrome P450, a family of enzymes (encoded by the administered orally with food, although, only one gene CYP) located in the liver and gastrointestinal tract, study found a decrease in urinary excretion of these which represents the major source of metabolic activity drugs after taken