Medicamentos de alto impacto sanitario y económico: el necesario equilibrio entre innovación y sostenibilidad / Medicines of high health and economic impact: The required balance between innovation and sustainability

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Relevancia clínica de la selectividad de los inhibidores del cotransportador sodio-glucosa tipo 2 / Clinical relevance of the selectivity of sodium-glucose cotransporter-2 inhibitors

La selectividad es la propiedad de un farmaco para unirse de forma preferente a una estructura biologica.La mayor parte de los farmacos pueden unirse y estimular o inhibir mas de un sistema. Por ello es interesante que sean selectivos para la estructura sobre la que se pretende actuar y que con las dosis empleadas no ejerzan efectos sobre otras que pueden producir reacciones adversas. La selectividad se valora mediante experimentos in vitro sobre organos o celulas aislados. Si se pretende comparar farmacos, el experimento debe realizarse sobre el mismo tejido y con el mismo diseno. Aun asi, los datos obtenidos no se pueden extrapolar directamente a la clinica, por la influencia de las propiedades farmacocineticas, que son las que permiten que el farmaco llegue en concentracion adecuada al lugar de accion. En el caso de los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) se valora su capacidad para inhibir el SGLT2 renal sin modificar el SGLT1 intestinal, cuya inhibicion podria producir reacciones adversas digestivas. Se calcula la concentracion necesaria para inhibir cada uno de los transportadores y el cociente entre la que inhibe SGLT1 y la necesaria para inhibir SGLT2. Cuanto mayor sea el cociente, mayor sera la selectividad y menor el riesgo de reacciones adversas digestivas. Los 3 iSGLT2 recientemente introducidos en terapeutica son suficientemente selectivos sobre SGLT2 como para que no sean esperables efectos sobre SGLT1 intestinal. Para diferenciar a los componentes de este grupo puede ser mas interesante analizar sus propiedades farmacocinéticas que sus caracteristicas farmacodinamicas, como la selectividad (AU)

Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design. Even so, the results cannot be directly extrapolated to clinical practice due to the influence of pharmacokinetic properties, which allow an adequate dose of the drug to reach the target site. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are able to inhibit renal SGLT2 without modifying intestinal SGLT1, whose inhibition could produce gastrointestinal adverse reactions. The concentration needed to inhibit each of the transporters is calculated, as well as the ratio between the concentration that inhibits SGLT1 and the concentration needed to inhibit SGLT2. The higher the ratio, the greater the selectivity and the lower the risk of gastrointestinal adverse reactions. The three SGLT2i recently introduced in the therapeutic arsenal are sufficiently selective for SGLT2 to make effects on intestinal SGLT1 unlikely. To differentiate the components of this therapeutic class, its pharmacokinetic properties should be analysed rather than its pharmacodynamic characteristics, such as selectivity (AU)

Clinical relevance of the selectivity of sodium-glucose cotransporter-2 inhibitors. / Relevancia clínica de la selectividad de los inhibidores del cotransportador sodio-glucosa tipo 2.

Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design. Even so, the results cannot be directly extrapolated to clinical practice due to the influence of pharmacokinetic properties, which allow an adequate dose of the drug to reach the target site. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are able to inhibit renal SGLT2 without modifying intestinal SGLT1, whose inhibition could produce gastrointestinal adverse reactions. The concentration needed to inhibit each of the transporters is calculated, as well as the ratio between the concentration that inhibits SGLT1 and the concentration needed to inhibit SGLT2. The higher the ratio, the greater the selectivity and the lower the risk of gastrointestinal adverse reactions. The three SGLT2i recently introduced in the therapeutic arsenal are sufficiently selective for SGLT2 to make effects on intestinal SGLT1 unlikely. To differentiate the components of this therapeutic class, its pharmacokinetic properties should be analysed rather than its pharmacodynamic characteristics, such as selectivity.

Olmesartán: evidencia y práctica clínica / Olmesartan: evidence and clinical practice

Olmesartán medoxomilo es un antagonista no peptídico del receptor AT1 de la angiotensina con afinidad superior a la de otros fármacos del grupo. Ha demostrado en numerosos ensayos clínicos su eficacia antihipertensiva y su buena tolerabilidad. Se ha comparado en ensayos clínicos con otros fármacos del grupo (azilsartán, candesartán, irbesartán, losartán y valsartán). En general, el efecto de olmesartán administrado por vía oral, una sola vez al día a dosis de entre 20 y 40 mg, ha sido superior en cuanto a la reducción de cifras tensionales, se ha iniciado antes y ha persistido durante 24 h. Varios metaanálisis han confirmado estas ventajas de olmesartán. Hay algunos estudios que demuestran propiedades organoprotectoras, en especial de restauración de la función endotelial. El patrón y la frecuencia de las reacciones adversas son comparables a los del placebo. Como consecuencia de sus propiedades farmacodinámicas y farmacocinéticas, olmesartán puede presentar ventajas sobre otros fármacos antagonistas del receptor de la angiotensina en el tratamiento de la hipertensión arterial (AU)

Olmesartan medoxomil is a nonpeptide angiotensin II-type I receptor (AT1) antagonist with greater affi nity for this receptor than other drugs in this class. Several clinical trials have demonstrated its effi cacy in lowering blood pressure and its good tolerability. This drug has been compared in clinical trials with other drugs in the same class (azilsartan, candesartan, irbesartan, losartan and valsartan). In general, olmesartan administered orally at a dose of between 20 and 40 mg has provided superior effi cacy in lowering blood pressure; this effect is initiated earlier than with other drugs and persists for 24 hours. The advantages of olmesartan have been confi rmed by several meta-analyses. Some studies show organ protective properties, especially in restoring endothelial function. The pattern and frequency of adverse reactions are similar to those of placebo. As a result of its pharmacodynamic and pharmacokinetic properties, olmesartan could offer advantages over other angiotensin receptor antagonists in the treatment of hypertension (AU)

La actividad de la renina plasmática. Papel de la inhibición directa de la renina / Plasma renin activity. Role of the direct renin inhibition

La renina es la enzima encargada de transformar el angiotensinógeno en angiotensina I, primer paso en la activación del sistema renina-angiotensina (SRA). La actividad de la renina plasmática (ARP) mide la capacidad de la renina para producir angiotensina I a partir de angiotensinógeno, se expresa como concentración de angiotensina I generada por unidad de tiempo (ng/ml/h) y se utiliza para valorar el grado de activación del SRA. Hay relación entre valores de ARP y enfermedad cardiovascular. Se ha descrito que valores de ARP alta se asocian con mayor incidencia de infarto agudo de miocardio, pérdida de función renal, peor pronóstico de la insuficiencia cardiaca y aumento de la mortalidad por causa cardiovascular. La inhibición del SRA con fármacos inhibidores de la enzima de conversión de la angiotensina o con antagonistas del receptor de la angiotensina incrementa la secreción de renina, y por lo tanto la ARP, como consecuencia de la interrupción del mecanismo de retroalimentación negativa que regula la secreción de renina a partir de las concentraciones de angiotensina II. Sin embargo, los inhibidores directos de la renina, como el aliskiren, aunque también interrumpen el mecanismo de retroalimentación y aumentan la secreción de renina, disminuyen la ARP porque bloquean su actividad catalítica. Esta característica diferencial de los inhibidores directos de la renina puede conferirles ventajas en cuanto a la reducción del riesgo cardiovascular (AU)

Renin is the enzyme responsible for the conversion of angiotensinogen into angiotensin I, the first step in the activation of the renin-angiotensin system (RAS). Plasma renin activity (PRA) provides a measure of the capacity of renin to produce angiotensin I from angiotensinogen and is expressed as the rate of increase in the angiotensin-I concentration (i.e. ng/mL per hour). The PRA level is used to evaluate the degree of activation of the RAS. There is a relationship between the PRA level and cardiovascular disease. It has been reported that a high PRA level is associated with an increased incidence of myocardial infarction, with the loss of kidney function, with a poor prognosis in patients with heart failure, and with increased mortality due to cardiovascular causes. Inhibition of the RAS by angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists increases renin secretion and, thereby, increases the PRA level. This is due to interruption of negative feedback mechanism that regulates renin secretion in accordance with the angiotensin-II concentration. However, direct renin inhibitors such as aliskiren, although they also interrupt the feedback mechanism and increase renin secretion, reduce PRA by blocking renin’s catalytic activity. This distinctive property of direct renin inhibitors could be advantageous in helping to reduce cardiovascular risk (AU)

Solifenacin pharmacology.

Antimuscarinics are the drugs of choice for the treatment of overactive bladder syndrome, and their benefit/risk ratio depends largely on selectivity for the different subtypes of muscarinic receptors. Solifenacin is the antimuscarinic that presents greatest selectivity for M3 bladder receptors, which may translate into a lower incidence of undesirable effects related to other receptor subtypes. Metabolic pathways of the antimuscarinics may impact efficacy and appearance of interactions. Solifenacin is metabolized only by the CYP3A4, giving three inactive metabolites and one with a similar activity to the original compound. However, other drugs in the group are also a substrate for the CYP 2D6 which presents polymorphisms, whereby their pharmacokinetics may be modified in slow metabolizers. The risk of interactions of solifenacin is low, and it is lower than that of the antimuscarinics which are also metabolized by the CYP 2D6. The unaltered fraction of solifenacin which is eliminated in urine, together with the active metabolite, can contribute to the therapeutic effect by acting on the urothelium receptors. It is not necessary to adjust doses of solifenacin in elderly patients or those with moderate liver or kidney impairment.

Farmacología de la solifenacina / Solifenacin pharmacology

Los antimuscarínicos son los fármacos de primera elección para el tratamiento del síndrome de vejiga hiperactiva y su relación beneficio/riesgo depende en gran medida de la selectividad por los distintos subtipos de receptores muscarínicos. Solifenacina es el antimuscarínico que muestra mayor selectividad por los receptores M3 vesicales, lo que puede traducirse en una menor incidencia de reacciones adversas relacionadas con otros subtipos de receptor. Las vías metabólicas de los antimuscarínicos pueden influir en la eficacia y en la aparición de interacciones. Solifenacina es metabolizada sólo por el CYP3A4 originando tres metabolitos inactivos y uno con actividad similar a la del compuesto original. Sin embargo, otros fármacos del grupo son también sustrato para el CYP 2D6 que presenta polimorfismos, por lo que su cinética se puede modificar en los pacientes metabolizadores lentos. El riesgo de interacciones de solifenacina es bajo, e inferior al de los antimuscarínicos que se metabolizan también por el CYP 2D6. La fracción inalterada de solifenacina que se elimina por orina junto con el metabolito activo pueden contribuir al efecto terapéutico actuando sobre los receptores del urotelio. No es necesario ajustar las dosis de solifenacina en pacientes de edad avanzada o con insuficiencia hepática o renal moderadas(AU)

Antimuscarinics are the drugs of choice for the treatment of overactive bladder syndrome, and their benefit/risk ratio depends largely on selectivity for the different subtypes of muscarinic receptors. Solifenacin is the antimuscarinic that presents greatest selectivity for M3 bladder receptors, which may translate into a lower incidence of undesirable effects related to other receptor subtypes. Metabolic pathways of the antimuscarinics may impact efficacy and appearance of interactions. Solifenacin is metabolized only by the CYP3A4, giving three inactive metabolites and one with a similar activity to the original compound. However, other drugs in the group are also a substrate for the CYP 2D6 which presents polymorphisms, whereby their pharmacokinetics may be modified in slow metabolizers. The risk of interactions of solifenacin is low, and it is lower than that of the antimuscarinics which are also metabolized by the CYP 2D6. The unaltered fraction of solifenacin which is eliminated in urine, together with the active metabolite, can contribute to the therapeutic effect by acting on the urothelium receptors. It is not necessary to adjust doses of solifenacin in elderly patients or those with moderate liver or kidney impairment(AU)

Drug utilization and off-label drug use among Spanish emergency room paediatric patients.

OBJECTIVE: To describe the use of medicines and to determine the frequency of off-label use in emergency room paediatric patients. PATIENTS AND METHODS: A prospective, observational and descriptive study was carried out in the setting of the paediatric emergency room of a Spanish general hospital. Medicines used by children <14 years prior to their emergency room visit were analysed based on information collected from parents/guardians and relatives for each drug prescription. Off-label use was defined as the utilization of a drug at an indication, dosage, frequency or route of administration that differed from the specifications in the Summary of Product Characteristics or by children outside the authorized age group. RESULTS: The patient cohort comprised 462 children, among whom 336 children had been prescribed 667 prescriptions. Of the medicines prescribed, 90% fell into only five 5 Anatomical Therapeutic Chemical Classification System groups. The most frequent active principles were ibuprofen and paracetamol. Of a total of 152 different formulations recorded, no paediatric information was provided for 40 formulations, and one formulation was contraindicated in children. Based on the established criteria, 338 prescriptions were off-label: no paediatric information or contraindication in children were available (82 prescriptions); the drug was used for an indication different from the authorized one (111 prescriptions); drug use was inconsistent with age recommendations (16 prescriptions); drug use was inconsistent with dose/frequency (129 prescriptions). Of the 152 formulations, 107 were occasionally used in an off-label manner. CONCLUSIONS: Although the mean number of drugs used in children is small, off-label use is frequent. Research efforts should target paediatric studies that allow a rational drug use in children.

Aliskiren: el primer inhibidor directo de la renina introducido en terapéutica / Aliskiren: first direct renin inhibitor approved for clinical use

El sistema renina-angiotensina está implicado en el control de la función cardiovascular y el equilibrio electrolítico e integrado por un conjunto de péptidos y enzimas que conducen a la síntesis de la angiotensina II que actúa en receptores específicos. La activación del sistema se inicia con la liberación de la renina. Recientemente se ha introducido en terapéutica el grupo de los inhibidores directos de la renina cuyo primer representante es el aliskiren, aprobado recientemente para el tratamiento de la hipertensión arterial. Disponer de un inhibidor directo de la renina que pueda administrarse por vía oral es importante porque la inhibición de la renina se plantea como la forma más eficaz de bloquear el sistema renina-angiotensina al actuar en su punto inicial, la transformación de angiotensinógeno en angiotensina I, paso limitante del sistema, sin afectar al metabolismo de las cininas ni producir fenómeno de escape, además de reducir la actividad de renina plasmática (AU)

The renin-angiotensin system is involved in the control of cardiovascular function and electrolytic balance and incorporates a set of peptides and enzymes that lead to the synthesis of angiotensin II, which acts on specific receptors. Activation of this system begins when renin is released. Direct renin inhibitors have recently been introduced into the therapeutic arsenal. The first representative is aliskiren, which was recently approved for the treatment of hypertension. This drug can be administered through the oral route. The availability of an orally administered renin inhibitor is important because renin inhibition is considered to be the most effective way to block the renin-angiotensin system as it acts at its starting point, at a rate-limiting step in the system: the conversion of angiotensinogen to angiotensin I. In addition, the drug does not affect kinin metabolism, avoids the escape phenomenon and reduces plasma renin activity (AU)

Cold medication containing oral phenylephrine as a cause of hypertension in children.

A 5-year-old girl presented hypertension [24-h blood pressure (BP) average 135/80 mmHg, above the 99th BP percentile], as confirmed by ambulatory BP monitoring, following the use of a cold preparation (2.5 ml every 8 h for 4 days) containing phenyephrine (1 mg/ml). There was a clear relationship between the administration of the medication and hypertension, and between normalized BP values (24-h BP average 109/66 mmHg, 90th percentile) and the withdrawal of the medication. Alternative causes of hypertension could not be found. This is the first reported case of children's hypertension related with oral administration of phenylephrine. The potential risk of medicines containing sympathomimetic drugs should not be underestimated, and cold preparations should be included in the differential diagnosis of the etiology of hypertension in children.

Nuevos lenguajes informáticos en la difusión de información sobre medicamentos / New computerized languages for information on drugs

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[Drug-drug interactions. An update]. / Interacciones medicamentosas. Nuevos aspectos.

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. The simultaneous administration of several medicines to the same patient can facilitates their appearance. It is difficult to determine their incidence, but it is related to the number of drugs administered simultaneously. Although it is impossible to remember all the clinical relevant interactions, to bare in mind their existence and the possible mechanisms of production can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein and other drug transporters. Interactions between drugs and grapefruit juice or St John's wort are frequent and it is important to bear in mind in clinical practice.

Interacciones medicamentosas. Nuevos aspectos / Drug-drug interactions. An update

Se denomina interacción farmacológica a la modificación cuantitativa o cualitativa del efecto de un fármaco causada por la administración simultánea o sucesiva de otro. La polimedicación facilita la aparición de interacciones cuyo resultado puede ser una reacción adversa o la pérdida de efecto terapéutico. La incidencia es difícil de determinar, pero se relaciona fundamentalmente con el número de fármacos administrados conjuntamente al mismo paciente. Aunque es imposible recordar todas las interacciones de interés clínico, conocer su existencia y mecanismos de producción ayuda a identificarlas y prevenirlas. Las que con mayor frecuencia causan problemas son las de tipo farmacocinético, sobre todo las relacionadas con el metabolismo a través del sistema del citocromo P450 o el aclaramiento presistémico por la glucoproteína P u otros transportadores. Las interacciones entre fármacos y zumo de pomelo o hierba de San Juan son cada vez mejor conocidas y deben tenerse en cuenta en la práctica diaria

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. The simultaneous administration of several medicines to the same patient can facilitates their appearance. It is difficult to determine their incidence, but it is related to the number of drugs administered simultaneously. Although it is impossible to remember all the clinical relevant interactions, to bare in mind their existence and the possible mechanisms of production can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein and other drug transporters. Interactions between drugs and grapefruit juice or St John's wort are frequents and it is important to bare in mind in clinical practice

Effects of dopamine in isolated rat colon strips.

The aim of the present work is to investigate the effects of dopamine on isolated rat colon strips, and whether dopamine receptors are involved in these effects. Experiments on spontaneous motility and under potassium contraction were performed with dopamine and isoprenaline, both in the absence and presence of antagonists (distal colon strips, isotonic recording, Tyrode solution, 31 degrees C, 1 g of resting tension). At higher concentration (10(-4) mol/L), dopamine abolished spontaneous motility of the rat colon and this effect was not modified by antagonists. In isolated rat colon strips that were depolarized with potassium, dopamine produced concentration-dependent relaxation, without significant differences in reserpinized rats. Preincubation with sulpiride or Sch 23390, dopamine antagonists, did not modify the effects of dopamine. Propranolol shifted the concentration-response curve to the right, though in a noncompetitive manner. Prazosin and yohimbine (alpha-antagonists) did not modify the response to dopamine. Isoprenaline produced a concentration-dependent relaxant response to the KCl-induced contraction antagonized by propranolol, but not by prazosin, in a noncompetitive manner. In conclusion, dopamine exhibits a relaxant effect on the isolated rat colon, which is not mediated by specific dopamine receptors or alpha-adrenoceptors but it may be mediated by atypical beta-adrenoceptors.

[Antihypertensive drug-drug interactions]. / Interacciones farmacológicas de los fármacos antihipertensivos.

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admissions are treated with potentially dangerous drug associations and up to a 6% of fatal events are due to this circumstance. Among antihypertensive drugs, diuretics and angiotensin converting enzyme inhibitors are less affected by drug-interactions. Lipophilic beta-blockers agents may present some clinical relevant interactions, whereas calcium channel blockers, especially the non-dihydropiridinic ones, are implied in clinically relevant pharmacokinetic interactions. Among the angiotensin receptor blockers there are differences that would have to be considered when they are used in patients who receive other drugs. Although it is impossible for the doctor to remember all the clinical relevant interactions, it is important to bear in mind their existence and the possible mechanisms of production which can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein. Enzymes of the cytochrome P450 system may present polymorphisms that can explain the individual differences in the response to drugs or the appearance of drug-interactions.

Interacciones farmacológicas de los fármacos antihipertensivos / Antihypertensive drug-drug interactions

Se denomina interacción farmacológica a la modificación cuantitativa ocualitativa del efecto de un fármaco por la administración simultánea o sucesiva de otro. Los pacientes con hipertensión arterial, sobre todo los ancianos, presentan con frecuencia enfermedades concomitantes que requieren la administración conjunta de varios medicamentos, lo que facilita la aparición de interacciones. La falta de eficacia del tratamiento antihipertensivoes un hecho relativamente frecuente que, en ocasiones, se debe a interacciones de los fármacos antihipertensivos con otros tratamientos concomitantes. La incidencia de las interacciones es difícil de determinar, pero se relaciona con el número de fármacos administrados conjuntamente. Entre el 37 y el 60% de los pacientes que ingresan en un hospital están tratados con asociaciones de medicamentos potencialmente peligrosas y hasta un6% de acontecimientos mortales son debidos a esta circunstancia. Entre los fármacos antihipertensivos, los diuréticos y los inhibidores de la enzima conversiva de la angiotensina (IECA) son los menos afectados por las interacciones. Los bloqueadores beta adrenérgicos liposolubles pueden presentar algunas con interés clínico, mientras que el grupo de los antagonistas del calcio, en especial los no dihidropiridínicos, es el más implicado en interacciones farmacocinéticas que pueden tener importancia clínica. Los antagonistas del receptor de la angiotensina II (ARA II) presentan diferencias entre ellos que deberían ser tenidas en cuenta al administrarlos apacientes que reciben otros medicamentos. Aunque para el médico práctico es imposible recordar todas las interacciones de interés clínico, tenerlas presentes y considerar los posibles mecanismos de producción puede ayudar a identificarlas y contribuir a su prevención. Las interacciones que con mayor frecuencia causan problemas son las de tipo farmacocinético, sobre todo las relacionadas con el metabolismo a través del sistema del citocromo P450 o el aclaramiento presistémico por medio de la P-glucoproteína. El hecho de que algunas isoformas del citocromo puedan presentar polimorfismos explican las diferencias interindividuales en la respuesta a algunos fármacos o en la presentación de interacciones

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a differentone. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37and 60% of hospital-admissions are treated with potentially dangerous drug associations and up to a 6% of fatal events are due to this circumstance. Among antihypertensive drugs, diuretics and angiotensin converting enzymein hibitors are less affected by drug-interactions. Lipophilic beta-blockers agents may present some clinical relevant interactions, whereas calcium channel blockers, especially the non-dihydropiridinic ones, are implied in clinically relevant pharmacokinetic interactions. Among the angiotensin receptor blockers there are differences that would have to be considered when they are used in patients who receive other drugs. Although it is impossible for the doctor to remember all the clinical relevant interactions, it is important to bear in mind their existence and the possible mechanisms of production which can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein. Enzymes of the cytochrome P450 system may present polymorphisms that can explain the individual differences in the response to drugs or the appearance of drug-interactions