in this lecture I'm going to talk about pharmacology of antihypertensive drugs 在这个讲座中，我将谈论抗高血压药物的药理学
so let's get right into it hypertension or high blood pressure is a 让我们直接进入高血压或高血压是一个
quite common disorder affecting many people who typically don't even notice 非常常见的疾病影响许多通常甚至没有注意到的人
any symptoms now in order to gain a better understanding of pharmacology of 现在任何症状，以便更好地了解药理学
antihypertensive agents first we need to review a basic physiology of blood 抗高血压药首先我们需要回顾一下血液的基本生理学
pressure regulation so when we talk about blood pressure we are generally 压力调节，所以当我们谈论血压时，我们一般
referring to the force or tension of blood pressing against the artery walls 指的是压迫动脉壁的血液的力或张力
now this pressure in the arteries is maintained by among other things 现在这种动脉压力是由其他因素维持的
contraction of the left ventricle systemic vascular resistance elasticity 左心室收缩全身血管阻力弹性
of the arterial walls as well blood volume in other words blood pressure is 动脉壁和血容量也就是血压
simply a product of cardiac output and systemic vascular resistance there are a 仅仅是心输出量和全身血管阻力的产物就有了
couple of major systems involved in blood pressure regulation first arterial 参与血压调节的几个主要系统首先是动脉
blood pressure is regulated by pressure sensitive neurons called baroreceptors 血压由称为压力感受器的压敏神经元调节
located in the aortic arch and carotid sinuses so for example if blood pressure 位于主动脉弓和颈动脉窦，例如血压
falls too low those baroreceptors can send signals to the adrenal medulla 那些压力感受器可以向肾上腺髓质发送信号
causing release of catecholamines and thus increase in sympathetic activity through 导致儿茶酚胺释放，从而增加交感神经活动
activation of alpha and beta receptors so activation of beta-1 receptors causes 激活α和β受体，从而激活β-1受体
increase in heart rate and stroke volume and thus increased cardiac output which 增加心率和每搏输出量，从而增加心输出量
leads to increase in blood pressure on the other hand activation of alpha-1 另一方面，α-1激活导致血压升高
receptors on smooth muscle causes vasoconstriction and thus increase in 平滑肌上的受体引起血管收缩，从而增加血管收缩
vascular resistance which again leads to increase in blood pressure now another 血管阻力再次导致血压升高
major system involved in blood pressure regulation is the 涉及血压调节的主要系统是
renin-angiotensin-aldosterone system so we also have baroreceptors in the 肾素 - 血管紧张素 - 醛固酮系统，所以我们也有压力感受器
kidneys that respond to fall in blood pressure or reduction of blood flow by 肾脏可以应对血压下降或血流减少
releasing enzyme called renin additionally renin secretion is also 释放称为肾素的酶另外肾素分泌也是
stimulated by sympathetic activation of beta-1 receptors 由β-1受体的交感神经激活刺激
in the kidneys now renin is necessary for the production of angiotensin II 在肾脏中，肾素对于血管紧张素II的产生是必需的
angiotensin II is a very potent vasoconstrictor which constricts systemic 血管紧张素II是一种非常有效的血管收缩剂，可以收缩全身
blood vessels thus increasing peripheral resistance angiotensin II also 血管因此也增加了外周血管阻力血管紧张素II
constricts renal blood vessels and stimulates aldosterone secretion which 收缩肾血管并刺激醛固酮分泌
leads to sodium and water retention thereby increased blood volume cardiac 导致钠和水潴留，从而增加心脏血容量
output and ultimately increased blood pressure now let's switch gears and 输出并最终增加血压现在让我们切换齿轮和
let's talk about antihypertensive agents so there are several major 让我们来谈谈抗高血压药，所以有几个主要的
classes of antihypertensive drugs which work by interrupting different parts of 通过打断不同部位起作用的一类抗高血压药物
this blood pressure regulating system first we have alpha-1 blockers such as 这个血压调节系统首先我们有α-1阻滞剂如
Doxazosin and Prazosin which block alpha-1 receptors on the smooth muscle 多沙唑嗪和哌唑嗪可阻断平滑肌上的α-1受体
thus causing decrease in systemic vascular resistance and ultimately 从而导致全身血管阻力降低并最终降低
decrease in blood pressure next we have selective beta blockers such as Atenolol 血压下降接下来我们有选择性β受体阻滞剂，如阿替洛尔
and Metoprolol which selectively block beta-1 receptors on the heart thus 和美托洛尔，它选择性地阻断心脏上的β-1受体
causing decrease in cardiac output and thereby decrease in blood pressure as 导致心输出量减少，从而降低血压
you may remember we also have non-selective beta blockers such as 你可能还记得我们也有非选择性β受体阻滞剂，如
Labetalol and Carvedilol that can additionally block alpha-1 receptors and 拉贝洛尔和卡维地洛可以另外阻断α-1受体和
thus simultaneously decrease vascular resistance furthermore beta blockers can 因此同时降低血管阻力，β受体阻滞剂也可以
inhibit beta-1 receptors present on the kidneys and thus suppress release of 抑制肾脏上存在的β-1受体，从而抑制肾脏的释放
renin formation of angiotensin II and secretion of aldosterone so these 肾素形成血管紧张素II和醛固酮分泌所以这些
effects result in decrease in systemic vascular resistance and again fall in 效果导致全身血管阻力降低，再次降低
blood pressure to learn more about alpha and beta blockers make sure you check 要了解更多有关α和β受体阻滞剂的血压，请务必检查
out my video about adrenergic antagonists now the next major class of 我的视频关于肾上腺素能拮抗剂现在是下一个主要类别
antihypertensive agents are centrally acting adrenergic drugs which work by 抗高血压药是中枢作用的肾上腺素能药物
blocking sympathetic activity within the brain example of drugs that belong to 阻止大脑中的交感神经活动属于的药物
this class are Clonidine and Methyldopa now Clonidine selectively stimulates 这一类是可乐定和甲基多巴，现在可乐定选择性地刺激
presynaptic alpha-2 receptors thus providing negative feedback to reduce 突触前α-2受体因此提供负反馈以减少
catecholamine production and release this leads to decrease 儿茶酚胺的产生和释放导致减少
in systemic vascular resistance and cardiac output and ultimately decreased 在全身血管阻力和心输出量方面最终下降
blood pressure Methyldopa on the other hand also lowers blood pressure through the 另一方面，甲基多巴的血压也会降低血压
same mechanism however unlike Clonidine it is not an 然而，与可乐定不同，它不是一种机制
agonist itself so first it must be converted to its active metabolite 激动剂本身首先必须转化为其活性代谢物
called methylnorepinephrine now let's move on to another major class of 现在让我们转向另一大类甲基去甲肾上腺素
antihypertensive agents that is calcium channel blockers so calcium channel 抗高血压药即钙通道阻滞剂，因此钙通道
blockers are divided into two main subclasses dihydropyridines and 阻断剂分为两个主要的亚类二氢吡啶和
nondihydropyridines now dihydropyridines selectively inhibit L-type calcium 非二氢吡啶现在二氢吡啶选择性地抑制L型钙
channels in the vascular smooth muscle under normal conditions when calcium 血管平滑肌中的通道在钙的正常条件下
enters the smooth muscle cell it causes it to contract which leads to increased 进入平滑肌细胞，使其收缩，导致增加
vascular resistance and thus increase in blood pressure so when dihydropyridine drug 血管阻力因此增加血压所以二氢吡啶类药物
blocks the entry of calcium into the vascular smooth muscle cell the 阻止钙进入血管平滑肌细胞
contraction is inhibited which leads to decreased resistance to blood flow and 收缩受到抑制，导致血流阻力降低
thus lowering of blood pressure example of drugs that belong to this group are 从而降低了血压这个属于该组的药物的例子
Amlodipine Felodipine Nicardipine and Nifedipine when it comes to side 氨氯地平非洛地平尼卡地平和硝苯地平
effects of dihydropyridines they're related to systemic vasodilation so you 二氢吡啶类药物的作用与全身血管舒张有关
can expect dizziness headache flushing and peripheral edema another side effect 可以预期头晕头痛潮红和外周水肿的另一个副作用
that may occur with this class is swelling of gums also known as gingival 这类可能会发生牙龈肿胀，也称为牙龈
hyperplasia now let's move on to nondihydropyridines which are non selective 增生现在让我们转向非二选择的非二氢吡啶
inhibitors of L-type calcium channels in other words they are not only capable of L型钙通道的抑制剂换句话说它们不仅能够
blocking calcium channels on vascular smooth muscle but also calcium channels 阻断血管平滑肌钙通道，也阻断钙通道
on cardiac cells such as those of SA node and AV node which leads to reduced 在诸如SA节点和AV节点的心脏细胞上导致减少
myocardial contractility slower heart rate and slower conduction that's why these 心肌收缩力心率减慢，传导速度慢，这就是为什么这些
agents exhibit significant antiarrhythmic properties for more 药剂具有显着的抗心律失常作用
details make sure you check out my video about antiarrhythmic drugs 详情请务必查看我的抗心律失常药物视频
now it's important to remember that even though decreased heart contractions 现在重要的是要记住即使减少心脏收缩
typically result in decreased cardiac output 通常会导致心输出量减少
nondihydropyridines do not significantly decrease cardiac output 非二氢吡啶类不会显着降低心输出量
most likely because of the reflex tachycardia that occurs as a result of 最可能的原因是由于反射性心动过速而发生的反射性心动过速
vasodilation currently there are only two drugs that belong to this group 血管扩张目前只有两种药物属于这一类
namely Diltiazem and Verapamil now when it comes to side-effects nondihydropyridines 即Diltiazem和维拉帕米现在涉及非二氢吡啶的副作用
can cause excessive bradycardia and cardiac conduction abnormalities 可引起过度的心动过缓和心脏传导异常
additionally Verapamil which happens to be the least selective calcium channel 另外维拉帕米恰好是最不具选择性的钙通道
blocker can exert significant inhibition of calcium channels in the smooth muscle 阻滞剂可以对平滑肌中的钙通道产生显着的抑制作用
that lines the GI tract which can lead to constipation 胃肠道可以导致便秘
now the next major class of antihypertensive agents are diuretics there 现在下一个主要类别的抗高血压药物是那里的利尿剂
are three major classes of diuretics that are used in the treatment of 是三种主要的利尿剂类别，用于治疗
hypertension first we have loop diuretics such as Furosemide which 高血压首先我们有呋塞米等袢利尿剂
work by reducing reabsorption of sodium chloride in the kidneys leading to 通过减少肾脏中氯化钠的重吸收而起作用
significant diuresis with less volume in the vascular space less blood returns to 血管空间体积减少，血液回流量减少
the heart so cardiac output decreases this in turn leads to decrease in blood 心脏因此心输出量减少，这又导致血液减少
pressure particularly in patients with volume-based hypertension and chronic 尤其是体积型高血压和慢性高血压患者的压力
kidney disease secondly we have thiazide diuretics such as Hydrochlorothiazide 肾脏疾病其次我们有噻嗪类利尿剂如氢氯噻嗪
which also reduce reabsorption of sodium chloride in the kidneys but to a much 这也减少了肾脏中氯化钠的重吸收，但也减少了很多
smaller degree than loop diuretics this leads to initial decrease in 比袢利尿剂更小的程度导致最初的减少
intravascular volume decrease in cardiac output and ultimately lower blood 心输出量的血管内容量减少并最终降低血液
pressure however the long term effects on blood volume are minimal and 然而，压力对血容量的长期影响很小
sustained antihypertensive effects are thought to be produced by thiazide induced 持续的抗高血压作用被认为是由噻嗪类诱导产生的
vasodilation lastly we have potassium-sparing diuretics such as Triamterene 血管扩张最后我们有保钾利尿剂，如Triamterene
and Spironolactone which increase diuresis by either interfering with the 和螺内酯，通过干扰增加利尿
sodium potassium exchange in the kidneys or by blocking the actions of 肾脏中的钾交换或通过阻断肾脏的作用
aldosterone potassium-sparing diuretics are often used in combination 醛固酮钾保留利尿剂通常联合使用
with loop and thiazide diuretics to reduce loss of potassium that can occur with 用环和噻嗪类利尿剂减少可能发生的钾的流失
the use of these drugs for more details make 使用这些药物了解更多细节
sure you check out my video about diuretics now let's move on to another 确定你现在看看我关于利尿剂的视频，让我们转到另一个
group of antihypertensive agents that is agents that work on the 一组抗高血压药，是一种有效的药剂
renin-angiotensin-aldosterone system so here we have three pharmacological 肾素 - 血管紧张素 - 醛固酮系统所以这里我们有三种药理作用
targets that can be used to reduce the activity of angiotensin II which is 可用于降低血管紧张素II活性的靶点
ultimately responsible for causing blood pressure to increase first we have renin 最终导致血压升高的原因首先我们有肾素
the enzyme responsible for conversion of angiotensinogen to precursor of 负责将血管紧张素原转化为前体的酶
angiotensin II that is angiotensin I so renin is the target of renin inhibitors 血管紧张素II是血管紧张素I，因此肾素是肾素抑制剂的靶标
which selectively inhibit this enzyme thus decreasing production of 它选择性地抑制这种酶，从而减少酶的产生
angiotensin II the example of drug that belongs to this class is Aliskiren 血管紧张素II属于这一类的药物的例子是阿利吉仑
secondly we have angiotensin-converting enzyme that is responsible 其次，我们负责血管紧张素转换酶
for conversion of angiotensin I to angiotensin II this enzyme is the target 为了将血管紧张素I转化为血管紧张素II，该酶是目标
of ACE inhibitors so just like inhibition of renin inhibition of ACE抑制剂就像抑制肾素抑制一样
angiotensin-converting enzyme also leads to decreased production of angiotensin II 血管紧张素转换酶也导致血管紧张素II的产生减少
however what makes ACE inhibitors different is that in addition to 然而，ACE抑制剂的不同之处在于
lowering angiotensin II levels they can also elevate bradykinin levels 降低血管紧张素II水平，他们也可以提高缓激肽水平
bradykinin is a peptide that causes blood vessels to dilate by stimulating 缓激肽是一种通过刺激引起血管扩张的肽
the release of nitric oxide and prostacyclin 一氧化氮和前列环素的释放
however normally angiotensin-converting enzyme inactives bradykinin so it's 然而，通常血管紧张素转换酶使缓激肽失活，所以它是
inhibition leads to bradykinin induced vasodilation the example of drugs 抑制导致缓激肽诱导的血管舒张作用的例子
that belong to this class are Benazepril Captopril Enalapril 属于这一类的是Benazepril Captopril Enalapril
Lisinopril Quinapril and Ramipril finally we have 最后我们有Lisinopril Quinapril和Ramipril
angiotensin II receptors type 1 or AT1 receptors for short so binding 血管紧张素II受体1型或AT1受体短暂如此结合
of angiotensin II to these receptors is actually responsible for most of the 血管紧张素II对这些受体的影响实际上是大多数的
effects of angiotensin II including vasoconstriction and stimulation of 血管紧张素II的作用包括血管收缩和刺激
aldosterone release these receptors are the target of angiotensin II receptor 醛固酮释放这些受体是血管紧张素II受体的靶标
blockers or ARBs for short the example of drugs that 阻滞剂或ARBs简称药物的例子
belong to this class are Candesartan Irbesartan Losartan Olmesartan and 属于这一类的是Candesartan Irbesartan Losartan Olmesartan和
Valsartan so in summary the agents that work on 缬沙坦这样总结了那些工作的代理人
this renin-angiotensin-aldosterone system either block the production of 这种肾素 - 血管紧张素 - 醛固酮系统阻碍了血管生成
angiotensin II or block its actions on the AT1 receptors this in turn leads to 血管紧张素II或阻止其对AT1受体的作用，这反过来导致
decreased systemic vascular resistance but without significant changes in 全身血管阻力降低，但无明显变化
cardiac output additionally these agents reduce the effects of angiotensin II on 另外，这些药物的心输出量减少了血管紧张素II对其的影响
renal hemodynamics specifically angiotensin II constricts the efferent 肾血流动力学特异性血管紧张素II收缩传出
arteriole thereby generating back pressure in the glomerulus which can 因此，小动脉可在肾小球中产生背压
lead to injury so by reducing activity of angiotensin II these agents also 因此通过降低血管紧张素II的活性导致损伤
improve renal blood flow and thereby reduce the risk of renal injury now when 改善肾血流量，从而减少现在肾脏受伤的风险
it comes to side effects because these agents suppress aldosterone release 它会产生副作用，因为这些药物会抑制醛固酮的释放
their use can contribute to development of hyperkalemia furthermore 它们的使用可进一步促进高钾血症的发展
ACE inhibitors in particular may cause dry cough or in rare cases angioedema ACE抑制剂尤其可能导致干咳或极少数情况下引起血管性水肿
which can be life-threatening this is thought to be due to increased 这可能会危及生命，这被认为是由于增加了
levels of bradykinin and substance P now before we end this lecture I wanted to 在我们结束这个讲座之前，我想要的是缓激肽和P物质的水平
briefly discuss few other antihypertensive agents that do not fall 简要讨论一些不会降低的其他抗高血压药物
into any of the classes that we covered thus far so first we have Bosentan 到目前为止我们所涉及的任何课程中，首先我们有波生坦
which is a competitive antagonist of a potent vasoconstrictor called endothelin-1 这是一种强效血管收缩剂的竞争性拮抗剂，称为内皮素-1
which acts on the endothelin-A and endothelin-B receptors located 它作用于内皮素-A和内皮素-B受体
on pulmonary vascular cells by blocking the action of endothelin-1 on 通过阻断内皮素-1对肺血管细胞的作用
these receptors Bosentan leads to vasodilation which decreases pulmonary 这些受体波生坦导致血管舒张，减少肺部
vascular resistance for that reason Bosentan is often a drug of choice for 因此波生坦的血管阻力往往是首选的药物
treatment of pulmonary hypertension next we have Fenoldopam which is a selective 治疗肺动脉高压接下来我们有Fenoldopam这是一种选择性的
dopamine-1 receptor agonist the dopamine-1 receptors are located on the 多巴胺-1受体激动剂多巴胺-1受体位于多巴胺-1受体上
smooth muscle cells in the peripheral vasculature 外周血管系统中的平滑肌细胞
as well as the renal coronary cerebral and mesenteric arteries by stimulating 以及通过刺激引起的肾冠状动脉和肠系膜动脉
dopamine-1 receptors Fenoldopam produces generalized arterial vasodilation 多巴胺-1受体Fenoldopam产生广泛的动脉血管舒张
which leads to decreased peripheral resistance and thus lower blood pressure 这会导致外周阻力降低，从而降低血压
additionally Fenoldopam inhibits tubular sodium reabsorption which 此外，Fenoldopam抑制管状钠重吸收
results in natriuresis and diuresis due to its rapid onset of action and 由于其快速起效，导致尿钠排泄和利尿
short duration of action Fenoldopam is often used in the 动作持续时间短的Fenoldopam常用于
hospitals for short-term management of severe hypertension another fast-acting 医院对于严重高血压的短期治疗是另一种快速作用
agents that are also used for hypertensive emergency are 也用于高血压急症的药剂是
Sodium Nitroprusside and Nitroglycerin which simply serve as a source of nitric oxide 硝普钠和硝酸甘油，它们只是一氧化氮的来源
a potent peripheral vasodilator lastly we have direct acting smooth muscle 一种强效的外周血管扩张剂，最后我们有直接作用的平滑肌
relaxants namely Hydralazine with mechanism of action that has not been 松弛剂即肼苯哒嗪具有尚未作用的作用机制
entirely determined yet and Minoxidil which works by stimulating opening of 完全确定和Minoxidil通过刺激开放工作
ATP-activated potassium channels in the smooth muscle which leads to membrane 平滑肌中ATP激活的钾通道导致膜
stabilization making vasoconstriction less likely while these agents 稳定性使血管收缩不太可能同时使用这些药物
significantly decrease peripheral resistance they also produce significant 显着降低外周阻力他们也产生显着
compensatory reflex tachycardia and renin release for that reason these 由于这个原因补偿性反射性心动过速和肾素释放
drugs are typically administered in combination with a diuretic and a beta 药物通常与利尿剂和β组合施用
blocker on the flip side topical application of Minoxidil promotes hair 在Minoxidil的侧面局部应用阻滞剂促进头发
growth which is why this drug is used more often for treatment of baldness 生长，这就是为什么这种药物更常用于治疗秃头的原因
rather than hypertension and with that I wanted to thank you for watching I hope 而不是高血压，我希望感谢你的观看
you enjoyed this video and as always stay tuned for more 你喜欢这个视频，并一如既往地保持关注更多