drugs抗高血压药ppt课件

Antihypertensive drugs Study guideline 1.Mechanisms for normal blood pressure regulation including an understanding of major determinants of blood pressure. 2.Baroreceptor related to regulating blood pressure. 3.Classification of antihypertensive agents . 4.The mechanisms of different antihypertensive drugs 5.Pharmacological actions，adverse effects and precautions of each drug. Section one：introduction What is hypertension？ Hypertension is defined as an arterial pressure greater than or equal to 140/90mmHg for an extended period of time. BP140/90 mmHg Morbidity:15%-20% DiagnosisDiagnosis Lead to Hypertension systolic blood pressure140 diastolic blood pressure 90 Either of them Danger Zone systolic blood pressure120 diastolic blood pressure 80 Both of them Normal blood pressure正 常血压范围 A warning sign If your BP are 120/80 or higher but below 140/90 It is called Pre-hypertension Hypertension Essential Hypertension 90 95% Secondary Hypertension 510% primary or essential hypertension: high blood pressure with no obvious underlying medical cause. Secondary Hypertension: High blood pressure that is caused by another medical condition or medication. Classification Of HypertensionClassification Of Hypertension Primary (essential ) hypertension Nearly 90% of patients have no specific cause. Elevated blood pressure is usually caused by several abnormalities such as genetic inheritance, psychological stress, dietary factors. Treatment: such hypertension can be controlled by some combination of antihypertensive drugs and changes in daily habits. prevention measuresprevention measures One is to feel comfortable, to avoid sadness. It will cause hypertension. Second, life regularly. A regular life, the prevention of hypertension is very important. Third, reasonable diet and avoid obesity. Fourth, to actively participate in sports. In addition, according to the characteristics of their hobby. We can Often listen to beautiful music. Treatment of hypertension Diet Loss weight Exercise Antihypertensive drugs Pathophysiology of hypertension Genetic factor Activation of sympathetic nervous system Activation of RAAS (renin-angiotensin- aldosterone system) Na+ Dysfunction of vascular endothelium Normal regulation of blood pressure Response mediated by the sympathetic nervous system antihypertensive drugs Renin-angiotensin system inhibitor ACE inhibitor：captopril receptor blocking agent：losartan Calcium channel blockers：nifedipine Emictory：hydrochlorothiazide Sympathetic inhibitor 1Antihypertensive drugswith central action: clonidine 2Ganglionic blocking agent：trimetaphan camsilate 3Noradrenergic nerve blocking drugs：reserpine 4Adrenoreceptor blocking drugs： （1）1 receptor blocker：prazosin （2） receptor blocker：propranolol （3） and receptor blocker：labetalol Vasodilator （1）Direct vasodilator：hydralazine、sodium nitroprusside （2）Potassium channel openers：pinacidil Traditional Chinese medicine antihypertensive drugs：Niuhuang Jiangya pill Section II basic antihypertensive drugs I.Diuretics 1.Thiazide Diuretics（moderate efficacy diuretics ） hydrochlorothiazide chlorothiazide Characteristics： Mildness，lasting，no tolerance . decrease morbidity and mortality of hypertension complications after long-term use. The mechanism for reduction of BP 1.Early：Na+ and H2O excretion， extracellular volume and blood volume ， cardiac output 2.Long：Na+ of vessel wall， Na+-Ca2+ exchange, intracellular Ca2+ sensitivity of VSM to vasoconstrictors (NE) 3.Dilate VSM directly The mechanism for reduction of BP of thiazide diuretics Thiazide diuretics Na+ in vessel wall Na+-Ca2+ exchange Ca+ in smooth musclecell peripheral resistance sodium, water retention blood volume cardiac output Decrease in BP Long-term initial Clinical uses and evaluation Low-dose of thiazide diuretic therapy is safe , effective and cheap for hypertension. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension , particularly elderly patients. Low doses of hydrochlorothiazide(25-50mg/d) exert as much antihypertensive effect as do higher doses. Adverse effect 1.Thiazide diuretics induce electrolyte disturbance : hypokalemia, hypomagnesaemia, hyposodium et al. 2.Thiazide diuretics can increase TC,TG,LDL level and renin activity , impair glucose tolerance. Therefore diuretics should be avoided in treatment of hypertensive diabetics or patients with hyperlipidemia. Indapamide Increase in renal Na+ excretion diuresis Dilate the vascular smooth muscle. Have no effect on the serum lipids. Loop diuretics （high efficacy diuretics） furosemide ，etacrynic acid. The loop diuretics act promptly and can be used in hypertensive emergencies or failure hypertension combined with renal function. Potassium-sparing diuretics （low efficacy diuretics） Spironolactone，amiloride Potassium-sparing diuretics are useful both to avoid excessive potassium depletion and to enhance the natriuretic effect of other diuretics. II Adrenergic receptor blockers 1. -receptor blockers propranolol metoprolol atenolol The mechanism of action （1）Blocking 1-R of heart， cardiac output （2）Blocking 1-R of kidney，inhibit renin release， RAS activity. （3）Blocking peripheral sympathetic presynaptic 2-R， NA release. （4）Blocking -R of CNS, peripheral sympathetic activity. （5）Increase synthesis of PGI2. Clinical uses and evaluation All types of hypertension ，especially in high renin activity and high cardiac output. The -blockers are useful in treating conditions that may coexist with hypertension，such as superventricular tachyarrhythmia ，previous myocardial infarction，angina pectoris，migraine headache. Adverse effects： (1)Common effects： CNS side effects：fatigue，lethargy， insomnia Sexual dysfunction（impotence）can severely reduce patient compliance. （2）Alteration in serum lipid patterns： decrease HDL and increase plasma triacylglycerol（TG） （3）Drug withdrawal：abrupt withdrawal may cause rebound hypertension，probably as a result of up regulation of receptor. Application attention （1）Be avoided in treating patients with (contraindication) Serious AV conduction block, bradycardia , bronchial asthma, peripheral vascular disease, et al. (2) Beginning with small dose (individual variation is larger) (3) Combining with diuretics 1-adrenoreceptor antagonist Prazosin Terazosin Pharmacological Action Blocking 1-R selectively Dilate A and V vessel BP Merit: Do not reduce the renal blood flow Do not increase renin activity Do not reflex increase in heart rate TG,TC,LDL-C,HDL-C Clinical uses All types hypertension，be united with -R blockers and diuretics. Prostate hypertrophy Untoward reactions 1.First dose phenomenon 2. Retention of salt and fluid and -receptor antagonist Labetalol Carvedilol Blocking 1=21 Blocking 1 and -R，BP Light effect on heart rate and cardiac output Used for all types of hypertension Calcium channel blockers Nifedipine Amlodipine Verapamil Diltiazem Mechanism of antihypertension Calcium antagonists block the entry of calcium into the smooth muscle of the blood vessels，causing it to dilate Certain types such as verapamil and diltiazem can also slow the heart rate and inhibit cardiac contractility. Therapeutic uses Calcium channel blockers are useful in the treatment of hypertensive patients who also have asthma，diabetes，angina，and/or peripheral vascular disease. Nifedipine 1.Action of dilating vessel is stronger than other calcium antagonist. 2.Treatment of all types hypertension. 3.Reflex increase in sympathetic activity： tachycardia，CO，renin activity. 4.Short action，can increase mortality if used for long time. Amlodipine Amlodipine belongs to long-acting calcium channel blockers which are better than nifedipine. （1）It takes effect slowly （1-2w），lower BP steadily and continuously. （2）It does not affect heart obviously. （3）It can reverse myocardial hypertrophy. Inhibitors of RAS Angiotensin converting enzyme inhibitors（ACEI） Catopril Enalapril Cilazapril Benazapril Ramipril The mechanism of action 1.Inhibit ACE that cleaves Ang I to form the potent vasoconstrictor Ang both in circulating system and local tissue. 2.Diminish the degradation of bradykinin increase bradykinin levels increase the release of NO,PGI2 3.Inhibit NA release，inhibit RAS in CNS, and decrease central and peripheral sympathetic nerve activity. The mechanism of action 4.Inhibit generation of Ang II in local tissue, inhibit or reverse myocardial and vascular remodeling. 5.Decrease the secretion of aldosterone , result in decreased sodium and water retention. 6.Protect vascular endothelial cell. The merits of treatment of hypertension 1.Have no tachycardia 2.Prevent or reverse and hypertrophy of VSMC and myocardial cells 3.Increase renal blood flow and protect renal function 4.Have no electrolyte disturbance and lipid metabolism disturbance 5.Improve life quality, mortality Clinical use 1.The ACE inhibitors are appropriate for most patients with mild or moderate hypertension, particularly hypertension with high renin activity. 2.The ACE inhibitors are useful in treating conditions that may coexist with hypertension, such as CHF, myocardial ischemia, diabetes. Adverse reactions Hypotension(2%) Dry cough(5-20%) Angioedema Hyperkalemia Influence on development of fetus 2.Angiotensin II receptor antagonist (AT1- receptor blocking agents) Losartan Valsartan Irbesartan Pharmacological actions Arrest Ang II combine with ATIR 1.More selective blockers of Ang II effects than ACEI 2.No effect on bradykinin metabolism Clinical use and evaluation 1.The action is similar to that of ACEI 2.Does not cause cough and angioedema Other hypotensors 1.centrally-acting sympathoplegic drugs 2.vasodilators 1.Centrally acting sympathoplegic drugs Clonidine Pharmacological action 1.Antihypertensive effect （iv or oral） 2.Sedative effect 3.Inhibit gastrointestinal secretion and motion The mechanism of action 1.Excite 2-R of medulla oblongata 2.Activate type 1 imidazoline receptor （I1）of rostral ventrolateral medulla (RVLM) 3.Excite 2-R and I1 receptor of peripheral sympathetic presynaptic membrane- decrease release of NA Clinical use 1.Moderate hypertension: appropriate for patients with peptic ulcer 2.Morphine addiction: increase the release of endogenous opioid peptides, such as enkephalin. Adverse effects 1.Dry mouth, sedation, headache, sexual dysfunction, constipation. 2.Withdrawal reaction, tachycardia, sweating, acute rising in BP Rilmenidine Moxonidine They belong to secondary central hypotensor, mainly excite I1 receptor of RVLM. Actions on central and peripheral 2-R are very weak, so the adverse reaction is rare. They also have no withdrawal reaction. vasodilators Hydralazine 1.Mainly dilate small arteriols. 2.Reflex sympathetic and renin activi