1、Antianginal Drugs,Zhu Yi Zhun, Dept. of Pharmacology, SPFDU Email: ,Hypertension,Therefore, it is important to treat hypertension and reduce mortality and morbidity of these conditions,End organ damage,is associated with increased risk from ischemic heart disease, cerebrovascular accidents, heart an
2、d renal failure.,Complications of untreated hypertension,Hypertensive cardiovascular disease Hypertensive cerebrovascular disease and dementia Hypertensive renal disease Aortic dissection Atherosclerotic complication,Myocardial infarction ( MI ) is one of the most common diagnoses occurring in the w
3、orld. Its mortality is approximately 30%. Although the survival following treatment has improved in the last two decades, the morbidity and mortality of MI still remain high.,MYOCAIDIAL INFARCTION,LEADING CAUSES OF MORTALITY IN WHO REPORT,The mortality of ischaemic heart disease is ranked first amon
4、g other diseases in the WHO statistics,MYOCARDIAL INFARCTION,Myocardial Infarction generally occurs with the abrupt decrease in coronary blood flow that follows a thrombotic occlusion of a coronary artery leads to irreversible myocardial cells damage and necrosis.,Angina pectoris,Is the most common
5、condition involving in tissue ischemia,Vasodilator drugs are commonly used (e.g. nitroglycerin, calcium channel blocker),-blockers are also useful,Vasodilators,Calcium channels blockers: arteriodilator (e.g. Nifedipine硝苯地平, verapamil异搏定, diltiazem硫氮卓酮),Nitrites (increase NO): venodilator (+), Arteri
6、oles (+), ischemic zone (+).,ACE inhibitors (e.g. Captopril开普通) and angiotensin II receptor antagonists (Losartan氯沙坦): mixed,Cause,Atheromatous obstructionmost frequent Primary cause: imbalance between the oxygen required by the heart and oxygen supplied to it by the coronary artery.,O2 required,O2
7、supplied,Nitrates & Nitrites (硝酸盐& 亚硝酸盐),Mechanisms of action in Angina: * Endothelial-derived relaxation factor (EDRF内皮衍生的松弛因子)nitric oxide (NO): induces coronary vasodilation,* Nitrates dilate coronary arteries to:,1) redistribute blood flow from epicardial to endocardial regions.,2) relieve coron
8、ary spasm and dynamic stenosis,* Reduce oxygen demand,Nitrates/Nitrites NO Relaxation,Drugs used to treat Angina,Nitrates: Nitroglycerin (glyceryl trinitrate),Pentaerythritol tetranitrate,Isosorbide dinitrate,硝酸甘油,硝酸异山梨酯,硝酸戊四醇酯,Drugs used to treat Angina,Nitrites: Amyl Nitrite,(戊基亚硝酸盐),Indications,S
9、hort-acting nitrates for acute effort angina: sublingual nitroglycerin (0.3 to 0.6 mg) every 5 minutes until pain goes or a max. of 4 to 5 tablets to be taken. Nitroglycerin spray is an alternative mode of oral administration.,Long acting nitrates for angina prophylaxis: Oral preparation of nitrate
10、is frequently given for the prophylaxis of angina. Long-acting nitrates are not continuously effective if regularly taken over a prolonged period, unless allowance is made for a nitrate-free or -low interval.,Side-effects of Nitrates,Headache-most common side-effect,with long-acting preparations: th
11、e development of tolerance, worsening of the underlying diseases process.,Failure of nitrate therapywith short-acting preparations: noncompliance (headache), loss of potency of the tablets, and incorrect timing,Hypotension-most serious side-effect,Other drugs used to treat angina,Calcium channel blo
12、ckers,-blockers,Indications:chronic stable angina, unstable anginaHypertensionSuperaventricular ArrhythmiasOthers: hypertrophic cardiomyopathy, migraine and atherosclerosis. Side-effectsHeadache, facial flushing, dizziness, and constipation (but Nifedipine not ),Calcium channel blocking drugs,Effect
13、s of calcium channel blocking drugs,Indications:Ischemic heart diseaseHypertension Cardiac arrhythmiasOthers cardiovascular disorders: increasing stroke volume (in patients with obstructive cardiomyopathy), congestive heart failure (in certain carefully selected patients)Glaucoma, Hyperthroidism, Ne
14、urologic diseases. Side-effectsWorsening of preexisting asthma and other forms of airway obstruction (nonselective agents due to 2 blockade); Rash, fever, sedation, sleep disturbance, and even depression,-adrenoceptor blocking drugs,Drugs for Atherosclerosis,Zhu Yi Zhun, Dept. of Pharmacology, SPFDU
15、 Email: ,Hyperlipidemia: Lipoprotein,Agents for hyperlipidemia,Acute pancreatitis,Atherosclerosis,(LDL) (HDL),Cholesterol level,mg/dL(mmol/L),Metabolism of cholesterol,3-hydroxy-3-methyl- glutaryl-coenzyme A 3-羟-3-甲戊二酰辅酶,-statin,Lovasatin Atorvastatin Fluvastatin Pravastatin Simvastatin Rosuvastatin
16、,LDL,Oxidative stress,Lovastatin,Prodrug,Active form,Daily dose: 10-80 mg, evening administration,Absorbtion: 40-75% T1/2: 1-3 h,Other cholesterol lowing agents: Niacin, Ezetimibe etc.,Vasodilators,Calcium channels blockers: arteriodilator (e.g. Nifedipine硝苯地平, verapamil异搏定, diltiazem硫氮卓酮),Nitrites
17、(increase NO): venodilator (+), Arterioles (+), ischemic zone (+).,ACE inhibitors (e.g. Captopril开普通) and angiotensin II receptor antagonists (Losartan氯沙坦): mixed,Nitrates & Nitrites (硝酸盐& 亚硝酸盐),Mechanisms of action in Angina: * Endothelial-derived relaxation factor (EDRF内皮衍生的松弛因子)nitric oxide (NO):
18、 induces coronary vasodilation,* Nitrates dilate coronary arteries to:,1) redistribute blood flow from epicardial to endocardial regions.,2) relieve coronary spasm and dynamic stenosis,* Reduce oxygen demand,Nitrates/Nitrites NO Relaxation,Indications,Short-acting nitrates for acute effort angina: s
19、ublingual nitroglycerin (0.3 to 0.6 mg) every 5 minutes until pain goes or a max. of 4 to 5 tablets to be taken. Nitroglycerin spray is an alternative mode of oral administration.,Long acting nitrates for angina prophylaxis: Oral preparation of nitrate is frequently given for the prophylaxis of angi
20、na. Long-acting nitrates are not continuously effective if regularly taken over a prolonged period, unless allowance is made for a nitrate-free or -low interval.,Nitrates & Nitrites,Mechanisms of action in Angina: * Endothelial-derived relaxation factor (EDRF)nitric oxide (NO): induces coronary vaso
21、dilation,* Nitrates dilate coronary arteries to:,1) redistribute blood flow from epicardial to endocardial regions.,2) relieve coronary spasm and dynamic stenosis,* Reduce oxygen demand,Nitrates/Nitrites NO Relaxation,Metabolism of cholesterol,3-hydroxy-3-methyl- glutaryl-coenzyme A 3-羟-3-甲戊二酰辅酶,-statin,Lovasatin Atorvastatin Fluvastatin Pravastatin Simvastatin Rosuvastatin,LDL,Oxidative stress,END!,
