浙江大学医学院：心血管系统药理学 Pharmacology for cardiovascular system（抗高血压药物 Antihypertensive Drugs）

Pharmacology for cardiovascular system Part 3 Antihypertensive Drugs Weiping Zhang, MD PhD. Associate professor Dept Pharmacology, Medical schooL, Zhejiang University weiping601@zju.edu.cn 2010.6.21

Weiping Zhang, MD. PhD. Associate professor Dept. Pharmacology, Medical School, Zhejiang University weiping601@zju.edu.cn 2010.6.21 Part 3 Antihypertensive Drugs Pharmacology for cardiovascular system

Antihypertensive Drugs Overview I. Basic pharmacology of antihypertensive drugs 1. Drugs that alter sodium water balance 2. Drugs that alter sympathetic nervous system function; 3. Vasodilators: 4. Agents that block raas II. Clinical pharmacology of antihypertensive agents

Blood Pressure and risk for Coronary Heart Disease in Men 60 60 50 50 E豆 40 40 Age65-94 Age65-94 30 30 320 Age 35-6. 0g 10 10 A9e35-64 三0 <120120-140-160-180+ <7575-85-95-105 139159179 8494104 Systolic blood pressure(mmHg Diastolic blood pressure(mmHg) Based on 30 year follow-up of Framingham Heart Study subjects free of coronary heart disease (CHD) at baseline Framingham Heart Study, 30-year Follow-up NHLBI, 1987

0 10 20 30 40 50 60 <120 120- 139 140- 159 160- 179 180+ 0 10 20 30 40 50 60 <75 75- 84 85- 94 95- 104 105+ A g e - a d j u s t e d a n n u al in cid e n c e o f C H D p e r 1 0 0 0 Based on 30 year follow-up of Framingham Heart Study subjects free of coronary heart disease (CHD) at baseline Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Framingham Heart Study, 30-year Follow-up. NHLBI, 1987

JNC-7 Definitions(2003) Systolic Diastolic Category (mm Hg)(mm Hg) Twice as likely Normal <120 <80 to progress to Prehypertension 120-139<80-89 hypertension Hypertension 140-159 90-99 (Stage D) Hypertension 160 (Stage D) 100 JnC-8 Expected Availability for Public Review and Comment: Spring 2011 Expected Release date: Fall 2011

Category Systolic (mm Hg) Diastolic (mm Hg) Normal < 120 < 80 Prehypertension 120 – 139 < 80 – 89 Hypertension (Stage I) 140 – 159 90 – 99 Hypertension (Stage II)  160  100 JNC－8 Expected Availability for Public Review and Comment: Spring 2011 Expected Release Date: Fall 2011

Causes of death in patients with htn Kidney Other MI or che F allure Stroke 15% ■ Kidney failure ■ Other MI or che Stroke 33%

MI or CHF 50% Stroke 33% Kidney Failure 15% Other 2% MI or CHF Stroke Kidney Failure Other

The goal of treatment: Lower the blood pressure; Protect the target organ Reduce the morbidity and mortality rates Best therapy and minimal risk

The goal of treatment: • Lower the blood pressure; • Protect the target organ; • Reduce the morbidity and mortality rates; • Best therapy and minimal risk;

Hypertension regulation of blood pressure Normal regulation of blood pressure BP CO PVR Arterial blood C arenac Peripheral arterio pressure output Vascular resistance tone Blood HeartContractility Filling volume rate pressure Venous tone Baroreceptors and sympathetic nervous system Renin-angiotention-aldosterol system(RAAS)

BP CO PVR

Hypertension regulation of blood pressure 2. CAPACITANCE Baroreflexes(mediated by Venules 3. PUMP OUTPUT Heart autonomic nerves) CNS Humoral mechanisms Sympathetic nerves 4. VOLUME (include: RAAS system and 1. RESISTANCE Kidneys local release of hormones from vascular endothelium Renin such as, NO, endothelin 1) Aldosterone -+ Angiotensin Anatomic sites of blood pressure control Anatomic sites of blood pressure control

Anatomic sites of blood pressure control Baroreflexes (mediated by autonomic nerves) Humoral mechanisms (include: RAAS system and local release of hormones from vascular endothelium, such as, NO, endothelin 1)

Hypertension regulation of blood pressure A Postural baroreflex: responsible for rapid, moment to moment adjustments in blood pressure. Sense the stretch of the vessel walls from a reclining to an upright posture; 2. Nucleus of the tractus solitarius reduction of peripheral vacular resistance; Reduction in intravascular volume: Brain stem Sensory fiber 1. Baroreceptor in carotid sinus Inhibitory interneurons Arterial blood pressure 3. Vasomotor Motor fibers 4. Autonomic 5. Sympathetic nerve ending 6.aor阝 receptor Figure 11-2. Baroreceptor reflex arc

Sense the stretch of the vessel walls • from a reclining to an upright posture; • reduction of peripheral vacular resistance; • Reduction in intravascular volume; - A. Postural baroreflex: responsible for rapid , moment to moment adjustments in blood pressure

Hypertension regulation of blood pressure B. Renin-Angiotensin-Adolsteron (RAAS AngiotensinⅡ Adrenal cortex Aldosterone Systemic arteries Vasoconstriction 2. CAPACITANCE Venules 3. PUMP OUTPUT Kio Increase Nat and H2o reabsorption pressure CNS- 4. VOLUME Kidneys Redistribution of renal blood flow 1. RESISTANCE Arterioles This is responsible for Renin long-term blood pressure Aldosterone-+ Angiotensin control Anatomic sites of blood pressure control

B. Renin-Angiotensin-Adolsteron (RAAS) This is responsible for long-term blood pressure control. Redistribution of renal blood flow Angiotensin II