高血压英文ppt精品课件drugsaffecting the cardiovascular

Drugs Affecting the Cardiovascular System Ion Channels Blockers Antihypertension Drugs The Treatment of Congestive Heart Failure Antiarrhythmic Drugs Antianginal Drugs Antihyperlipidemic Drugs and Anti-artherosclerosis Drugs Antihypertensive Drugs OVERVIEW Hypertension is defined as a sustained diastolic blood pressure greater than 90 mmHg (mercury) accompanied by an elevated systolic blood pressure(140 mmHg). Hypertension results from increased peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system. Elevated blood pressure is an extremely common disorder, affecting approximately 10-15% of the population. Although many of these individuals have no symptoms, chronic hypertension- either systolic or diastolic can lead to congestive heart failure, myocardial infarction, renal damage, and cerebrovascular accidents. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. ETIOLOGY OF HYPERTENSION Essential/primary hypertension: more than 90% of patients have essential hypertension, a disorder of unknown origin affecting the blood pressure-regulating mechanism. A family history of hypertension in creases the likelihood that an individual will develop hypertensive disease. Essential hypertension occurs more often among middle-aged males than among middle-aged females. Environmental factors such as a stressful lifestyle, high dietary intake of sodium, obesity, and smoking all further predispose an individual to the occurrence of hypertension. ETIOLOGY OF HYPERTENSION Secondary hypertension: occurs in 5-10% of patients. The cause is usually one of the following: Renal disease which activates the Renin- Angiotensin-Aldosterone System (RAAS) Endocrine disease, steroid-secreting turmour of the adrenal cortex, adrenaline- secreting tumour of the adrenal medulla. Arterial blood pressure is regulated within a narrow range to provide adequate perfusion of the tissues without causing damage to the vascular system, particularly the arterial intima. Arterial blood pressure is directly proportional to the product of the blood volume, cardiac output and the peripheral vascular resistance. In both normal and hypertensive individuals, blood volume cardiac output and peripheral resistance are controlled mainly by two overlapping control mechanisms: the baroreflexes mediated by the sympathetic nervous system, and the renin-angiotensin-aldosterone system (RAAS). Most antihypertensive drugs lower blood pressure by reducing cardiac output and /or decreasing peripheral resistance. MECHANISMS FOR CONTROLLING BLOOD PRESSURE Classification of Antihypertension： I. Sympatholytic drugs II.Vasodilators III. Inhibitors of RAS IV. Diuretics Classification I ： Sympatholytic drugs (drugs that alter sympathetic nervous system function) Classification I ： Sympatholytic drugs (drugs that alter sympathetic nervous system function) 1.central antihypertensive drugs Clonidine可乐定 , Methyldopa甲基多巴 2.ganglion-blocking agents( ganglionic blocking drugs) Mecamylamine美加明 3.adrenergic neuron blocking agents( antipostganglionic sympathetic neurons) reserpine利血平 , guanethidine 胍乙啶 4.adrenoceptor antagonists (adrenergic receptor blocking agents) -adrenoceptor-blocking agents propranolol普萘洛尔， -adrenoceptor-blocking agents prazosin哌唑嗪 and -blockers labetalol 拉贝洛尔 Classification II ： Vasodilators 1. direct vasodilators hydralazine 肼苯哒嗪 sodium nitroprusside 硝普钠 2. calcium channel blockers( calcium antagonists) nifedipine 硝苯地平 nitrendipine 尼群地平 3. potassium channel openers minoxide 米诺地尔（长压定） diazoxide 二氮嗪 pinacidil 吡那地尔 Classification III ： Inhibitors of RAS 1.angiotensin converting enzyme inhibitors. ACEI captopril 卡托普利 enalapril 依那普利 2.angiotensin receptor-blocking agents losartan 氯沙坦 valsartan 缬沙坦 3. renin inhibitors: Enalkiren(依那吉仑 ) , Remikiren(瑞米吉仑 ) Classification VI ： Diuretics hydrochlorothiazide 氢氯噻嗪 indapamide 吲达帕胺 Classification I. Sympatholytic drugs Normal regulation of blood pressure in CNS: Vasomotor centers Center nervous system controls peripheral sympathetic activity in brain stem Inhibiting neurons:2 receptor resulting in blood pressure lowering bradycardia vasodilatation Exciting neurons: receptors resulting in blood pressure enhancing tachycardia Subtype 1. Central antihypertensive drugs Clonidine可乐定 and Methyldopa甲基多 巴 may stimulate inhibiting neurons of central adrenoceptors-2 receptor, resulting in vasodilation, blood pressure lowers. Drug 1. Clonidine（ 可乐定） 又称氯压定， 2- imidazoline derivation Pharmacokinetics: Lipid-soluble, rapid absorption by oral administration F, 75% t1/2 812 hours 30% 50% metabolisms in liver Others are eliminated unchanged in urine Mechanism of action: 1.stimulating postsynaptic 2 adrenoceptors in brain stem peripheral sympathetic activity blood pressure producing sedation 2.stimulating 1-imidazoline咪唑啉 receptor in rostral ventrolateral medulla oblongata (RVLM 延髓腹外侧核吻侧端 )peripheral sympathetic activity lowering 3.stimulating opium receptor relieving abstinence syndrome戒断症状 Pharmacodynamics: 1. Relaxation of arterial vessels reduction in peripheral vascular resistance blood pressure lowers 2. Contracting force of cardiac muscule reduction of cardiac output heart rate decreases 3. Decreased renal vascular resistance and maintenance of renal blood flow 4. Inhibiting movement and secretion of gastrointestinal tract hypertensive patients with ulcer is the better Adverse reaction: 1.dry mouth/ xerostomia (dry nasal mucosa, dry eyes), nausea, dizziness头晕 , sedation嗜睡 , parotid gland swelling and pain腮腺肿痛 ,sleep disturbances with vivid dreams or nightmares 噩梦 2.water and sodium (Na+) retention 3.withdrawal syndrome停药反应 headache apprehension(恐惧忧虑 ), tremors(震 颤 ),abdominal pain, sweating, tachycardia treatment: -adrenergic blocker (phentolamine) continuative administration clonidine Drug 2. Methyldopa 1.center antihypertension drug 2.treatment: mild to moderately severe hypertension with renal failure 3.reducing peripheral vascular resistance, with a variable reduction in heart rate and cardiac output 4.no decreasing renal blood flow and glomerular filtration rate Clinical uses: 1.moderate hypertensive disease 2.iv drop, therapy of hypertensive crisis高 血压危象 3.controlling abstinence syndrome of opium Subtype 2. ganglion-blocking agents( ganglionic blocking drugs) Drug: Mecamylamine美加明 Subtype 3. Adrenergic neuronblocking agents Pharmacological action: 1. lower blood pressure, with long-term therapy with reserpine cardiac output peripheral vascular resistance heart rate rennin secretion falls salt and water are retained 2. sedative and neuroleptic （ 精神安定） effect reserpine depletes catecholamine(儿茶酚胺 ) and 5- hydroxytryptamine (5-HT) Drug 1. Reserpine利血平 Mechanism of action: Reserpine can remain bound to amine pump of vesicular membranes in central and peripheral adrenergic neurons for prolonged periods of time. The storage vesicles are destroyed as a result of their interaction with reserpine and nerve endings lose their ability to concentrate and store norepinephrine and dopamine. Catecholamines leak into the cytoplasm, where they are destroyed by intraneruronal monoamine oxidase (MAO), depressing the ability to uptake norepinephrine Reserpine -induced depletion of biogenic amines correlates with evidence of sympathetic dysfunction and antihypertensive effects. Recovery of sympathetic function requires synthesis of new storage vesicles, which takes days to weeks after discontinuation of the drug, so effect of reserpine is slow and persistent. Clinical uses: Mild hypertension Cooperative administration Adverse effects: Sedation and inability to concentrate or perform complex tasks are the most common adverse effects. More serious is the occasional psychotic depression. Drug 2. Guanethidine 胍乙啶 Mechanism and sites of action: Guanethidine inhibits the release of norepinephrine from sympathetic nerve endings. Guanethidine nerve concentration in transmitter vesicles replaces norepinephrine causes gradual depletion of norepinephrine stores in the nerve ending -adrenoceptor-blocking agents propranolol普萘洛尔， -adrenoceptor-blocking agents prazosin哌唑嗪 and -blockers labetalol 拉贝洛尔 Subtype 4. adrenoceptor antagonists (adrenergic receptor blocking agents) Drug1.-adrenoceptor-blocking agents 1.Mechanism and sites of action blocking -receptor in heart, decreasing cardiac output depressing secretion of rennin, inhibiting the rennin- angiotensin-aldosterone system, decreasing level of angiotersin in plasm -blockers may also block -receptor of presynaptic membrane in peripheral prejunctional to reduce sympathetic vasoconstrictor nerve activity decreasing secretion of norepinephrine in never center, affecting sympathetic regulation changing sensitivity of baroreceptor increasing synthesis of prostaglandin Drugs 普萘洛尔 propranolol 1 2 美托洛尔 metoprolol 1 intrinsic sympathetic mimetic activity 阿替洛尔 atenolol 1 intrinsic sympathetic mimetic activity Clinical uses: Moderate hypertension or severe hypertension of therapeutic ineffective with other antihypertensive drugs. Adverse reaction: Postural hypotension, dizziness, nausea, vomiting, diarrhea Contraindications: Severe diseases accompanied heart, brain, kidney, arteriosclerosis, dysfunction of circulation Drug 2. 1-adrenoceptor-blocking agents 1. Mechanism: 1). blocking selectively postsynaptic 1 receptors in arterioles and venules 2). dilating both resistance and capacitance vessels 2. Drugs: 1). prazosin 哌唑嗪 2). terazosin 特拉唑嗪 3). urapidil 乌拉地尔 1.Mechanism: Blocking 1 and receptors Blocking action of R blocking action of 1 R 2.Drugs: labetalol 拉贝洛尔 Drug 3. and adrenoceptor -blocking agents Classification II. Vasodilators Summary of the Action and Mechanism 1. Dilating directly arterioles but no veins, lowering blood pressure, relaxing smooth muscle of arterioles. 2. Eliciting compensatory responses, mediated by baroreceptors压力感受器 and the sympathetic nervous system, as well as rennin, angiotension and aldosterone opposing the antihypertensive effect of vasodilator such as： tachycardia心动过速 ; cardiac output; plasma rennin activity; retention of salt and fluid. 3. Vasodilators are used common by combination with other antihypertensive drugs that oppose the compensatory cardiovascular response. Drugs: 1.hydralazine肼屈嗪，肼苯哒嗪 Action: relaxing smooth muscle in arterioles via release of nitric oxide (NO) in vascular interfere with Ca2+ entering into cell 2.sodium nitroprusside 硝普钠 .treating hypertensive emergencies and severe cardiac failure, crisis .dilating both arterial and venous vessels decreasing cardiac preload and afteroad Subtype1. direct vasodilators Subtype 2. Calcium channel blockers Action: Antianginal effects抗心绞痛 Antiarrhythmic effects抗心律失常 Dilating peripheral arterioles扩张外周血管 Reducing blood pressure Mechanism of action: inhibiting calcium influx into arterial smooth muscle cells Drugs: 1.Nifedipine硝苯地平 ,Verapamil维拉帕米 ,Diltiazem地尔硫 卓 2. Dihydropyridine family: amlodipine, felodipine, isradipine, nicardipine, nifedipine, misolipine, more selective as vasodilators treating selectively angina or coronary spasm prolong effect, slow, persist, smoother, reflex sympathetic activation with slight antiarteriosclerosis Subtype 3. potassium channel openers Drugs: minoxide 米诺地尔（长压定） diazoxide 二氮嗪 pinacidil 吡那地尔 Classification III. Inhibitors of RAS NO PGI2 bradykinin aldosterone ACEI and AT blocker Subtype I. Angiotensin converting enzyme inhibitors ACEI Mechanism of action: 1.inhibiting ACE angiotensin -angiotensin ACE (-) inhibitors 2.inhibiting RAS( rennin- angiotensin system) in local tissue 3.inhibiting the kalliurein-kini system(激肽释放酶 -激肽系 统 ) Drugs: Captopril, 卡托普利 4.Accelerating release of prostacyclin(PGI2) vasodilatations decreased peripheral vascular resistance decreased blood pressure 5.accelerating release of nitric oxide (NO) 6.improving myocardial hypertrophy of left ventricle, inhibiting hyperplasia of vascular smooth muscles. decreasing formation of Ang , inhibiting remodeling of my