《CHFlecture藥理》PPT課件_第1頁
《CHFlecture藥理》PPT課件_第2頁
《CHFlecture藥理》PPT課件_第3頁
《CHFlecture藥理》PPT課件_第4頁
《CHFlecture藥理》PPT課件_第5頁
已閱讀5頁,還剩70頁未讀, 繼續(xù)免費閱讀

下載本文檔

版權(quán)說明:本文檔由用戶提供并上傳,收益歸屬內(nèi)容提供方,若內(nèi)容存在侵權(quán),請進行舉報或認領(lǐng)

文檔簡介

1、Overview of congestive heart failureCongestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of body. CHF can be increased workload imposed on the heart. CHF is accompanied by abnormal increases in blood volume and interstitial fluid; the

2、heart, veins, and capillaries are therefore generally dilated with blood. Hence the term “congestive(充血性)” heart failure, since the symptoms include pulmonary congestion with life heart failure, and peripheral edema with right heart failure. Underlying causes of CHF include arteriosclerotic heart di

3、sease, hypertensive heart disease, valvular heart disease(心瓣膜病), dilated cardiomyopathy(擴張性心肌病), and congenital heart disease(先天性心臟病). Left systolic dysfunction secondary to coronaryartery disease is the most common cause of heart failure. Treatment of congestive heart failure1醫(yī)學(xué)PPTHeart FailureFina

4、l common pathway for many cardiovascular diseases whose natural history results in symptomatic or asymptomatic left ventricular dysfunctionCardinal manifestations of heart failure include dyspnea, fatigue and fluid retentionRisk of death is 5-10% annually in patients with mild symptoms and increases

5、 to as high as 30-40% annually in patients with advanced disease2醫(yī)學(xué)PPTMain causesCoronary artery diseaseHypertensionValvular heart disease (心瓣膜病) Cardiomyopathy (心肌病)Cor pulmonale3醫(yī)學(xué)PPTCompensatory changes in heart failureActivation of SNSActivation of RASIncreased heart rateRelease of ADHRelease of

6、 atrial natriuretic peptide心鈉素Chamber enlargement 心室腔擴大Myocardial hypertrophy 心室肥厚4醫(yī)學(xué)PPTClassification of heart failureClass I: No limitation of physical activityClass II: Slight limitation of physical activityClass III: Marked limitation of physical activityClass IV: Unable to carry out physical ac

7、tivity without discomfort5醫(yī)學(xué)PPTNew classification of heart failureStage A: Asymptomatic with no heart damage but have risk factors for heart failureStage B: Asymptomatic but have signs of structural heart damageStage C: Have symptoms and heart damageStage D: End stage diseaseACC/AHA guidelines, 2001

8、6醫(yī)學(xué)PPT心功能障礙收縮功能舒張功能輸出量神經(jīng)激素心肌1受體RAACA心縮力順應(yīng)性 心肌肥大、重構(gòu) 鈉水潴留血容量靜脈淤血血管收縮阻抗順應(yīng)性后負荷血管肥厚、重構(gòu) 前負荷抗RAA系統(tǒng)藥改善舒張功能藥正性肌力藥受體阻斷藥利尿藥減前負荷藥減后負荷藥恢復(fù)心血管病理形態(tài)的藥 CHF的病理生理過程及可能治療的環(huán)節(jié)長期病情心率7醫(yī)學(xué)PPTStrategy of treatment of CHFThe therapeutic goal for CHF is to increase cardiac output. Inotropic agents that increase the strength of c

9、ontraction of cardiac musclePDEI (phosphodiesterase inhibitors) agents that increase cAMP to induce systoles and vasodilatationCalcium sensitizers extracellular fluid volumeb adrenergic agonistb adrenergic antagonistVasodilators: Calcium channel blocker Decreasing RAS activity: ACEI and AT1 antagoni

10、st Diuretic agents8醫(yī)學(xué)PPTTreatment of congestive heart failureClassification1 Positive inotropic drugsCardiac glycosides-adrenergic agonists (New dopamine receptor agonist)phosphodiesterase inhibitors Calcium sensitizers2 Diuretics3 VasodilatorsCalcium channel blocker Nitryl-vasodilatorsHydralazine4

11、RAAS inhibitors: antiotensin converting enzyme inhibitor and AT1 antagonist5 -receptor blocker9醫(yī)學(xué)PPTClassification1 Positive inotropic drugsCardiac glycosides/強心苷類 structure-activity relationship A cardiac glycoside molecule consists of an aglycone苷元 or genin配基, which possesses the same pharmacologi

12、c activity as the whole molecule combined chemically with one or more sugars.10醫(yī)學(xué)PPTCardiac glycosidesOOOHCH3CH3HOC18 H31O912ACBD173DigitoxinDigoxin= H at 12 C= OH at 12 CSugars- 3 mols. of digitoxose 3分子洋地黃毒糖Aglycones苷元Unsaturated lactone不飽和內(nèi)酯環(huán)steroid nucleus甾核Convey the pharmacological activityCon

13、vey cardiotonic activityModulate potency and pharmacokinetic distribution11醫(yī)學(xué)PPTOOOHCH3CH3HOC18 H31O912ACBD173 1. The relationship between structure and effectsThe Indispensable parts of activityC14CCThe number of -OH and glycose will decide water-solubility and lipid-solubility活性基團activity :C17 不飽和

14、內(nèi)酯環(huán)Unsaturated lactone 、C14羥基OH、C3 洋地黃毒糖digitoxose脂溶性lipid-solubility: C3 洋地黃毒糖;水溶性water-solubility :C12及其他位點的羥基數(shù)12醫(yī)學(xué)PPTClassification of cardiac glycosides1. grade 1: in plant, cedilanide 2. grade 2: extract of digitalis Digitoxin(洋地黃毒苷), Digoxin(地高辛), Deslanoside (旋花毛地黃苷), Strophanthin K(毒毛旋花子苷K)3

15、.地高辛和洋地黃毒苷C3位均聯(lián)結(jié)3個洋地黃毒糖,地高辛C12位多一個羥基,毒毛花苷K的甾核上有多個羥基,所以脂溶性:洋地黃毒苷地高辛毒毛花苷K。13醫(yī)學(xué)PPTProcess of drug through bodyDrugAbsorption rate (%)Protein-binding (%)Heptoenteral-circulation (%)Biotransformation (%)Kidney excretion (%)T1/2digitoxin90100972730701057 daydigoxin6085306.851060903336 hCedilanide20405Few

16、Quite few9010033 hStrophanthin K255Few 0901001219 h14醫(yī)學(xué)PPTPharmacologic actionI. Action of cardiac glycosides on the heartPositive inotropic action:Increasing contractility of cardiac muscle in heart failure. (1) characteristic:myocardiac quick contraction, Q-T period rate of force time to peak tens

17、ion 15醫(yī)學(xué)PPTB. no increase oxygen consumption: the increase in output is not accompanied by an equivalent increase in oxygen consumptionFactors of oxygen consumption: 1)Myocardia contractility 2)Heart rate 3)Myocadiac fiber length and tone16醫(yī)學(xué)PPTFactors affect consumption of oxygenThe force of cardia

18、c contractionHeart rateVolume of ventricular17醫(yī)學(xué)PPTC. Effect of positive inotropic act cardiac output is increased compensatory sympathetic tone is reduced cardiac preload and afterload is decreased heart rate is reduced myocardiac fiber tone and oxygen consumption is decreased increasing stroke vol

19、ume causes a decrease in end-systolic volume18醫(yī)學(xué)PPT(2) Machanism of cardiac glycoside on positive inotropic actionA. Inhibiting Na+-K+-ATPase in therapeutic dose:B. Increasing of calcium inward and induce the releasing of calcium from sarcoplasmic reticulum ( internal stores, by CICR)19醫(yī)學(xué)PPTglycosid

20、eStructure changesEnzyme activity Na+, K+ in cellCa2+Na+exchange in cell)Na+-K+-ATPase is a recetor of glycosideMechanism of pharmacological act20醫(yī)學(xué)PPTNa+-K+-ATPase is the receptor of cardiac glycosides , so cardiac glycosides act by inhibiting the membrane Na+-K+-ATPase pump Na+ i Na+ i21醫(yī)學(xué)PPT Bidi

21、rectional exchange Na+ enter Ca2+ outer Na+ outer Ca2+ enterby Na/Ca 2+exchanger Ca2+ i22醫(yī)學(xué)PPTCa2+ -induced Ca2+ release Sarcoplasmic reticulum release Ca 2+Enhance the increased cytosolic calcium concentration Sarcoplasmic reticulum Ca 2+ i23醫(yī)學(xué)PPT2.Negative chronotropic actionA. Continuous effect o

22、f positive inotropic action decreasing sinus rate heart rate is decreased24醫(yī)學(xué)PPTHeart rate is decreased,Atropine can antagonize (block) B. Increasing sensibility of myocardia to vagus nerve (increasing of potassium outward and resting potential, reducing of automaticity).25醫(yī)學(xué)PPT3. Affects of glycosi

23、des to conductive tissuesA. Increasing conduction of the atrial muscle fibers, because increasing excitation of vagus nerve (increasing of potassium outward). Increasing resting potential. Elevating rate of phase-0 depolarization. Acceleration rate of depolarization phase-0 and atrial fibers conduct

24、ion.26醫(yī)學(xué)PPTB. Slowing (depress) conduction at the atrioventricular (A-V) node (inhibiting Na-K-ATPase, reducing resting potential), and increase effctive refractory period atrial fibrillation, atrial flutter, paroxymal (and) or supraventricular tachycardiaC. Increasing automaticity of Purkinjie fibr

25、es: toxicity27醫(yī)學(xué)PPTIf Na+-K+-ATPase was inhibited more than 30%, cardiac glycosides would induce toxicity by the overload of intercellular free calcium concentration in myocardiac. (decreasing inotropic action)If intercellular potassium concentration was lower level, cardiac glycosides would easily

26、induce toxicity in myocardiac. (arrhythmia)Mechanism of toxicity act28醫(yī)學(xué)PPT4. Affects of cardiac glycasides to ECG (electrocardiography)A. Therapeutic dose:T-wave can become low, flat, isoelectric or invertedS-T segment falls below the isoelectric lineP-R interval is lengthened, which is associated

27、with slower or delayed A-V conductionQ-T interval is shortened, ERP and APD is shortened in Purkenje fibersB. Higher dose: arrhythmias29醫(yī)學(xué)PPTThe affects on ECGT waveIt is characterized by an descend ST segment on the ECG P-R Q-T P-P30醫(yī)學(xué)PPT Directly inhibit or reflected decrease sympathetic activity

28、Exciting increase the vagal activity Inhibit RAAS system, promote the excrete of ANP cause arrhythmias (toxic doses)II. Action of cardiac glycosides on vascular and kidney Vasoconstriction, increase in peripheral vascular resistance Diuretic,increase the blood flow through kidney and inhibit Na+-K+-

29、ATPase Na decreased re-absorbnewII. Action of cardiac glycosides on neural and hormone31醫(yī)學(xué)PPTClinical usesCardiac glycosides are given for CHF Effects: Best go with atrial fibrillation Better hypertension congenital heart disease not good anaemia lack of vitamin B1 not useful pericarditis 心包炎Some ki

30、nds of arrhythmias Atrial fibrillation Atrial flutter Supraventricular Tachycardia32醫(yī)學(xué)PPTToxic effectsResponses of stomach-intestines : Anorexia 厭食, nausea,vomiting , Abdominal pain and diarrhoeaCNS: visual disturbacesArrhythmia: 1) Tachycardia 2)AV block 3)Bradycardia 60 beat/min33醫(yī)學(xué)PPTProphylaxis

31、and treatment of the toxicity Clear the signal of toxic and the indication of withdraw Inspect the concentration of digoxin (3ng/ml), digitoxin(45ng/ml) If necessary ,potassium supplements and antiarrhythmic drugs ( phenytoin ,lidocaine,atropine )administered For severe intoxication ,antibodies spec

32、ific to cardiac glycosides are available 34醫(yī)學(xué)PPTMethod of administration Classical :whole effect dose quick or slow (have use digoxin within two weeks) The suitable dose to the patients Maintain :45 t Digoxin 0.25mg/day , 67 day ( t 3336 hours)35醫(yī)學(xué)PPT Classification1 Positive inotropic drugs -Adreno

33、ceptor agonists They are used intravenously in CHF emergenciesExample of -Adrenoceptor agonists :Dobutamine (多巴酚丁胺) Exciting 1 Adrenoceptor positive inotropic action the volume of output Exciting 2 Adrenoceptordilate the vascular afterload have benefits within short time36醫(yī)學(xué)PPTClassification1 Positi

34、ve inotropic drugs Phosphodiesterase- inhibitorsInodilator / inodilating drugsInhibiting the activity of PDE cAMP causes an increase in myocardial contractility and vasodilatation total peripheral resistance cardiac output Examples: Armirinone(氨力農(nóng)): Inhibits the excess product of NO, TNF and affects

35、 the neurohormone, anti-the forming of thrombus milrinone(米力農(nóng)): stronger 20 time vesnarinone(維司力農(nóng)): myocardial contract elements the sensitivity to calcium37醫(yī)學(xué)PPTClassification1 Positive inotropic drugs Calcium sensitizersPimobendan 匹莫苯: Inhibit PDE ; increase TnCs sensitivity to calciumTn troponin肌

36、鈣蛋白;myosin肌球蛋白;tropomyosin原 ;Actin 肌動蛋白38醫(yī)學(xué)PPTClassification 2 DiureticsDiuretics inhibit sodium and water retention, reduce the volume of blood, venous pressure and the thus cardiac preload are reduced, increasing the efficiency of the heart as a pump cardiac output , so reduce oedema due to heart

37、failure Heart failure Low-grade : Thiazides hydrochlorothiazide 氫氯噻嗪 Higher-grade : Acute left heart failure loop diuretics - furosemide 呋塞米(速尿) Spironolacton 螺內(nèi)酯 (anti-aldosterone ,keep potassium and diuretics)39醫(yī)學(xué)PPTAntiotensin converting enzyme inhibitor (ACEI) and AT1 antagonistCalcium channel b

38、locker Nitryl-vasodilatorsHydralazineClassification 3 Vasodilators40醫(yī)學(xué)PPTbradykininaldosteroneACEI and AT blocker41醫(yī)學(xué)PPTClassification 3 VasodilatorsAngiotensin-converting-enzyme inhibitor (ACEI )Captopril EnalaprilMethanism of anti-CHF:Humour: Inhibit ACEangiotensin and aldosterone levels, reduce s

39、odium retention, increase bradykinin levels , ANP、 NO、PGI2, reduce the release of NA ET and renew the expression of receptor This therefore causes vasodilatation (include coronary artery) reduction in peripheral resistance increase the cardiac output, Increase the blood flow of kidney so Improve the

40、 function of kidney3) Prevent the remodel of the heart 42醫(yī)學(xué)PPTAT1 antiagonistsLosartan (氯沙坦)The function just like ACEIt dosent influence bradykinin levelsClinical utilize: CHF Protection of kidney43醫(yī)學(xué)PPTCalcium-channel blockersAmlodipine 氨氯地平Dilate arteryDilate the coronaryAlleviate the LV Wall Ten

41、sionVessel44醫(yī)學(xué)PPTDilatation of the veins decreases preload Dilatation of the artery decreases afterload Decrease the oxygen demand of the heartmechanismOthers - VasodilatorsNitrate esters: nitroglycerin , nitroprusside sodium 硝普納Hydralazine 肼屈嗪 direct dilate the vascularPrazosin 哌唑嗪 - receptor block

42、er45醫(yī)學(xué)PPTClassification 4 receptor blockerCarvedilol 卡維地洛labetalol 拉貝洛爾Bisoprolol 比索洛爾Carvedilol 卡維地洛mechanism Anti RAAS system Anti-arrthymias Anti-myocardial ischemia Cardiomyopathy 心肌病46醫(yī)學(xué)PPT Thanks ! Good Luck!47醫(yī)學(xué)PPT 二 other action of cardiac gylcosides Nerve system Toxic concentration:enhancin

43、g sympathetic activity increasing sympathetic impulse of preganglial and afterganglial fibers, can cause atrial fibrillation and ventricular tachycardia.48醫(yī)學(xué)PPTTherapeutic dose: increasing parasympathetic center in brain stem excitation-slowing rate of heart,inhibiting conduction49醫(yī)學(xué)PPT2. Effect of

44、cardiac glycosides to kidneyincreasing renal blood flow and filtering rate of glomeruluscompetitive antagonism with aldosterone in proximal tubule50醫(yī)學(xué)PPTClinical uses1. Congestive heart failure *Depends in part on the cause of the failure *Depends in part on the severity of cardiac damage51醫(yī)學(xué)PPTA. T

45、he best therapeutic effect is the chronic, low-output formSuch as: heart failure with atrial fibrillation an rapid heart rate52醫(yī)學(xué)PPTB. The better therapy is heart failure caused by hypertension, heart disease caused by coronary atherosclerosis Valvular stenosis(瓣膜狹窄) Rheumatic valvulitis(風濕性瓣膜炎)53醫(yī)學(xué)

46、PPTC. No better Thyrotoxicosis(甲狀腺中毒癥)Thyroidism(甲狀腺功能亢進) Serious anemia Vitamin B deficiency Advanced valvular stenosis54醫(yī)學(xué)PPTD. No use pulmonocardiac disease activity carditis serious myocardia injured Activity rheumatic other forms of infectious or toxic myocarditis , pulmonocardiac disease advan

47、ced cardiomyopathy心肌病 badly damaged hearts cardiopericarditis 心包炎55醫(yī)學(xué)PPTE. Acute heart failureiv.Use strophanthin K cedilanide56醫(yī)學(xué)PPT2. Atrial fibrillantionVentricular rate Atrial rate :400650/min Circulative blood flow Heart failure57醫(yī)學(xué)PPTCardiac gylcosidesventricular rate (atrial fibrillation)Circ

48、ulative blood flow volume (relive) sysptoms of heart failure58醫(yī)學(xué)PPTIn atrial fibrillation, the same vagomimetic action helps control ventricular rate, thereby improving ventricular filling and increasing cardiac output.Slowing conduction in A-V node,increasing concealed conduction(隱匿性傳導(dǎo)),slowing ven

49、tricular rate.59醫(yī)學(xué)PPTConcealed conductionThe impulses arriving at the AV node are rapid and random in time. Most of these impulses either fail to enter the AV node because it is refractory or propagate only partway through it and give rise to the phenomenon of concealed conduction.60醫(yī)學(xué)PPT3. Atrial f

50、lutteratrial rate : 320360 beats/min, rapid and regular In atrial flutter, the depressant effect of the drug on atrioventricular conduction will help control an excessively high ventricular rate. The effects of the drug on the atrial musculature may convert flutter to fibrillation, with a further de

51、crease in ventricular rate61醫(yī)學(xué)PPTTherapeutic action:Increasing block and ERP in atrioventricular (AV) node heart rate decrease (ventricular rate)(2) Shortening ERP of atrium(convert) atrial flutter atrial fibrillation62醫(yī)學(xué)PPT(3) After withdrawal cardiac glycosides, sinus rhythm may return, ERP increa

52、se (prolong ERP of shortened ERP in atrium)(4) Quinidine may convert atrial flutter to sinus rhythm , but may increase the risk of cardiac glycosides toxicity. 63醫(yī)學(xué)PPT3. Paroxysmal supraventricular tachycardiaIncreasing function of vagal nerveEnhance vagal activityDecrease excitation of atriumNo use

53、: supraventricular tachycardia caused by glycosides-intoxication64醫(yī)學(xué)PPTToxicity of cardiac glycosides1. Gastrointestinal and centre nerve systom occasions sickness , vomiting , purging泄瀉 , giddiness眩暈 , confused vision , green vision or yellow vision , anorexia厭食 , nausea , diarrhea , abdominal discomfort or pain , headache , fatigue the drugs may stimulate the chemo

溫馨提示

  • 1. 本站所有資源如無特殊說明,都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請下載最新的WinRAR軟件解壓。
  • 2. 本站的文檔不包含任何第三方提供的附件圖紙等,如果需要附件,請聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
  • 3. 本站RAR壓縮包中若帶圖紙,網(wǎng)頁內(nèi)容里面會有圖紙預(yù)覽,若沒有圖紙預(yù)覽就沒有圖紙。
  • 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
  • 5. 人人文庫網(wǎng)僅提供信息存儲空間,僅對用戶上傳內(nèi)容的表現(xiàn)方式做保護處理,對用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯,并不能對任何下載內(nèi)容負責。
  • 6. 下載文件中如有侵權(quán)或不適當內(nèi)容,請與我們聯(lián)系,我們立即糾正。
  • 7. 本站不保證下載資源的準確性、安全性和完整性, 同時也不承擔用戶因使用這些下載資源對自己和他人造成任何形式的傷害或損失。

最新文檔

評論

0/150

提交評論