Antihypertensives drug therapy Department of cardiology medicinel一、Goals of antihypertensive drug treatmentl二、Principles of antihypertensive drug treatmentl三、Antihypertensive drugsl（一）Diureticsl Thiazide, Loop diuretics, Potassium-sparing diuretics. l（二）Beta-adrenergic receptor blockersl（三）Calcium Channel Blockersl（四）Renin-Angiotensin converting enzyme Inhibitors（ACEI）l（五）Angiotensin Receptor Blocking （ARB）Agentsl（六） Alpha-adrenergic receptor antagonists l（七）Vasodilators、 Other drugsl四、Effective drug combinationsl一、Goals of antihypertensive drug treatment（抗高血压治疗目标） l The treatment of hypertension is aimed not at the simple reduction of blood pressure but at the prevention and to achieve the maximum reduction in the total risk of the cardiovascular morbidity and mortality.l As the relationship between cardiovascular risk and blood pressure is continuous, without a lower threshold低限, the goal of antihypertensive therapy should be to restore blood pressure to levels defined as “normal” or “optimal”. l It would seem desirable to achieve optimal or normal blood pressure in young, middle-aged or diabetic subjects (below 130/85mmHg) and at least high normal blood pressure in elderly patients(below 140/90mmHg millimeter mercury).l二、Principles of antihypertensive drug treatment（抗高血压药物治疗原则） l there is general agreement on the principles governing the use of antihypertensive drug to lower blood pressure, independent of the choice of particular drugs. These principles include:l1、 The use of low doses of drugs to initiate therapy（初始治疗使用低剂量） l Beginning with the lowest available dose of the particular agent, in an effort to reduce adverse effects. If there is a good response to a low dose of a single drug but the pressure is still short of adequate control, it is reasonable to increase the dose of the same drug, provided that it has been well tolerated好的接受.l2、The use of appropriate drug combinations to maximize hypotensive efficacy while minimizing side effects. （适当的药物联合应用使副作用减到最小而达到最大的降压效应）l It is often preferable to add a small dose of a second drug rather than increasing the dose of the original drug. This allows both the first and second drugs to be used in the low dose range that is more likely to be free of side effects避免副作用. In this context , the use of the fixed low-dose combinations that are increasingly available in the United States and Europe may be advantageous.3、Changing to a different drug class （可以更换完全不同类的药物 ）l Changing to a different drug class if there is very little response or poor tolerability可忍性很小 to the first drug used, before increasing the dose of the first drug or adding a second drug.4、The use of long-acting drugs providing 24h efficacy on a once-daily basis. （使用长效、一天24小时有效的药物）The advantages优势of such drugs include improvement in adherence顺应性to therapy and minimization最小of blood pressure variability血压波动, as a consequence of smoother平稳, more consistent协调blood pressure control.l5、Individualized therapy （个体化治疗） l Perhaps the most crucial factor关键因素in the selection process the presence of one or more concomitant conditions合并症, some that could be worsened变坏 by the drug chosen,others that could be improved改善. The choice of therapy should be individualized. l三、Antihypertensive drugs（抗高血压药物） l There are now eight to ten different classes of antihypertensive drugs of(depeding on how they are defined) which five(diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor antagonists) are suitable for initial or single drug therapy. i.e. first-line drugs.抗高血压治疗的发展Direct vasodilators-blockersSABsOthers Peripheral sympatholyticsGanglion blockersVeratrum alkaloidsCentral 2 agonistsCalcium antagonists- non DHPs-blockersThiazides diureticsCalcium antagonists- DHPsARBs1940s195019571960s1970s1980s1990s2001ACE inhibitors治疗效果耐受性l（一）Diureticsl Diuretics useful in the treatment ofl hypertension may be divided into four lmajor groups by their primary site of lAction within the tubule, starting in thel proximal portion and moving to the lcollecting duct：lagents acting on the proximal tubule, lsuch as carbonic anhydride inhibitors, lwhich have limited antihypertensive efficacy降压作用较小. lLoop diuretics;lthiazides and related sulfonamide compounds;lpotassium-sparing agens.l A thiazide is the usual choice, often in combination with a potassium sparing agent. Loop diuretics should be reserved for those patients with renal insufficiency or resistant hypertension.顽固lMechanism of actionl All diuretics initially lower the blood pressure by increasing urinary sodium excretion and by reducing plasma volume, extracellular fluid volume,and cardiac output.l within 6 to 8 weeks the lowered plasma, extracellular fluid volume，and cardiac output return toward normal. At this point and beyond,从这以后 the lower blood pressure is related to a fall in peripheral resistance, thereby i