antianginal drugs 抗心绞痛药 antianginal drugs. what’s angina pectoris cause and the...
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抗心绞痛药Antianginal DrugsAntianginal Drugs
• What’s Angina pectoris• Cause and the classification of angina pectoris :– Atheromatous obstruction of the large coronary vessels (atherosclerotic a
ngina, classic angina); 劳累性心绞痛:稳定型,初发型,恶化型– Transient spasm of localized portions of the large coronary vessels (angi
ospastic or variant angina); 自发性心绞痛:卧位型,变异型,急性冠脉功能不全,梗死后心绞痛– Both causes 混合性心绞痛
Unstable angina pectoris:Unstable angina pectoris: initial onset type; accelerated type; spontaneous typeinitial onset type; accelerated type; spontaneous type associated with atheroscleosis plaque and thrombus formationassociated with atheroscleosis plaque and thrombus formation may lead to myocardial infarctionmay lead to myocardial infarction
OverviewOverview
Coronary vessels:Coronary vessels: blood supply for the blood supply for the heartheart
OverviewOverview
Coronary atherosclerosis:Coronary atherosclerosis:
cause of cardiac ischemiacause of cardiac ischemia
OverviewOverview
Distribution of coronary arteries in the heartDistribution of coronary arteries in the heart
• Primary cause of angina pectoris:
– In classic angina, the imbalance occurs when the myocardial oxygen requirement increases; “angina of effort”
– In variant angina, oxygen delivery decreases as a result of reversible coronary vasospasm. “vasospastic or Prinzmetal's angina”
oxygen requirement
oxygen supply imbalance
OverviewOverview
preloadpreloadafterloadafterload
Myocardial Myocardial oxygen demandoxygen demand is is diminisheddiminished by:by:• Reducing contractilityReducing contractility• Reducing heart rate Reducing heart rate • Reducing the preloadReducing the preload• Reducing the afterloadReducing the afterload
Myocardial Myocardial oxygen supply oxygen supply is is increasedincreased by:by:• Dilating conduct coronary arteries Dilating conduct coronary arteries ( ( coronary blood flow) coronary blood flow)• Promoting regional distribution Promoting regional distribution ( ( in ischemic regions) in ischemic regions)
Treatments:• Non-drug treatment:经皮冠状动脉成形术 (percutaneous transluminal coronary angioplasty, PTCA), 冠脉搭桥术 ( coronary artery bypass graft surgery, CABG )• Drug treatment
Wall tension Wall tension
OverviewOverview
Antianginal DrugsAntianginal Drugs
Antianginal drugs:Antianginal drugs:• Organic nitratesOrganic nitrates• receptor blockersreceptor blockers
• Calcium channel blockersCalcium channel blockers • Anti-platelet agents• ACEIs• Fish oil
Effects of antianginal drugs:Effects of antianginal drugs:
• Reducing oxygen demandsReducing oxygen demands
• Increasing oxygen supplyIncreasing oxygen supply
• Others:Others: Anti- platelet coagulation and thr Anti- platelet coagulation and thrombus formation ombus formation
Nitrates & Nitrites
• Quick tolerance and cross-tolerance;• Pharmacokinetic factors determine the selection;
nitroglycerin
- Pharmacokinetics• Low oral bioavailability (eg, nitroglycerin and isosorbide dini
trate, typically < 10–20%).• Sublingual is normally used. Transdermal and buccal absorpt
ion from slow release preparations.• Amyl(戊基 ) nitrite and related nitrites can be used with inhal
ation route.• Duration of effect is very brief (Unchanged nitrate t1/2=2-8 minu
tes, partially denitrated metabolites longer t1/2= 3 hrs). So micro-pump is very common in hospital usage.
Nitrates & Nitrites
- Pharmacological actions- Pharmacological actions• Dilating vessels and reducing heart loadsDilating vessels and reducing heart loads wall tension wall tension ; reflex tachycardia; reflex tachycardia• Redistribution of coronary circulationRedistribution of coronary circulation
dilating conduct artery:dilating conduct artery: collateral circulation collateral circulation reducing wall tension:reducing wall tension: blood flow in ischemic subendocardial area blood flow in ischemic subendocardial area • Alleviating ischemic injuryAlleviating ischemic injury• Anti- platelet coagulationAnti- platelet coagulation
Nitrates: Nitrates: NitroglycerinNitroglycerin (( 硝酸甘油硝酸甘油 ))
Influence of organic nitrates and dipyridamole Influence of organic nitrates and dipyridamole on the blood supply of ischemic areaon the blood supply of ischemic area
Nitrates: Nitrates: NitroglycerinNitroglycerin (( 硝酸甘油硝酸甘油 ))
Intracellular Ca2+ release↓ , extracellular Ca2+ influx↓
Intracellular [Ca2+] ↓
The production of PGE or PGI2 and membrane hyper-polarization may also be involved.
Mechanism of the Mechanism of the effect of effect of nitroglycerin and nitroglycerin and other nitratesother nitrates
- Clinical uses- Clinical uses• Angina pectoris: Angina pectoris: all kinds, especially stable typeall kinds, especially stable type• Heart failureHeart failure
- Adverse reactions- Adverse reactions• Symptoms due to vasodilation:Symptoms due to vasodilation: headache, postural headache, postural hypotension, hypotension, etcetc..• Increase in heart rate and contractilityIncrease in heart rate and contractility• Others:Others: methaemoglobinaemia methaemoglobinaemia (高铁血红蛋白)(高铁血红蛋白)• Tolerance : avoiding steady-state plasma concentration; avoiding steady-state plasma concentration; supplement of agents containing –SHsupplement of agents containing –SH (captopril, NAC), VitC(captopril, NAC), VitC
Nitrates: Nitrates: NitroglycerinNitroglycerin (( 硝酸甘油硝酸甘油 ))
Other nitrates Isosorbide dinitrate (( 硝酸异山梨酯硝酸异山梨酯 ))
Isosorbide-5-mononirate (5-(5- 硝酸异山梨酯硝酸异山梨酯 )) Compared with nitroglycerin:Compared with nitroglycerin:• Similar but weaker effect
• Acting slowly but lasting longer
• Larger individual variation and more adverse effects
NitratesNitrates
- Pharmacological action- Pharmacological action• Reducing oxygen demand:Reducing oxygen demand: heart rate and contractility heart rate and contractility • Increasing oxygen supply:Increasing oxygen supply: diastolic period diastolic period : : perfusion time perfusion time
vascular tone in normal regions vascular tone in normal regions : : blood flow in ischemic regions blood flow in ischemic regions
• Others:Others: Improving myocardial metabolismImproving myocardial metabolism Increase oxygen supplyIncrease oxygen supply Inhibiting coagulation of plateletsInhibiting coagulation of platelets
receptor blockersreceptor blockers
- Clinical uses- Clinical uses stablestable and and unstableunstable pectoris, pectoris, especially associated with especially associated with
hypertension or arrhythmias, even with myocardial infarctionhypertension or arrhythmias, even with myocardial infarction; ; but not but not used forused for variant angina pectorisvariant angina pectoris
- Notes- Notes• Dose individualization:Dose individualization: starting from small dosestarting from small dose • Withdraw gradually and slowly:Withdraw gradually and slowly: symptomsymptom reboundrebound
• Cardiac depressionCardiac depression• Inducing asthmaInducing asthma• Combination with nitroglycerinCombination with nitroglycerin
receptor blockersreceptor blockers
- Pharmacological actions- Pharmacological actions
• Reducing myocardial oxygen remand:Reducing myocardial oxygen remand: heart loads heart loads : : nifedipinenifedipine heart rate and contractilityheart rate and contractility :: verapamil and diltiazemverapamil and diltiazem
• Increasing myocardial blood supplyIncreasing myocardial blood supply• Inhibiting coagulation of plateletsInhibiting coagulation of platelets• Protecting ischemic myocardial cellsProtecting ischemic myocardial cells
- Clinical uses- Clinical uses
stable and variant type:stable and variant type: nifedipine, verapamil, diltiazemnifedipine, verapamil, diltiazem
unstable type:unstable type: verapamil, diltiazemverapamil, diltiazem
Calcium channel blockersCalcium channel blockers
- Toxicity• Cardiac depressionCardiac depression, including cardiac arrest, bradycardia, atriove
ntricular block, and heart failure.• Relatively short-acting calcium channel blockers have the potential
to enhance the risk of adverse cardiac events.• Slow-release and long-acting vasoselective calcium channel blocke
rs are usually well tolerated.
• Patients receiving -adrenoceptor-blocking drugs are more sensitive to
the cardiodepressant effects of calcium channel blockers.
• Tolerable toxicity: flushing, dizziness, nausea, constipation, and peripheral edema.
Calcium channel blockersCalcium channel blockers
Other drugsOther drugsAngiotensin converting enzyme inhibitors (ACEI)Angiotensin converting enzyme inhibitors (ACEI)
Nicorandi Nicorandi ((尼可地尔尼可地尔 ))
• a potassium channel opener
Molsidomine Molsidomine (吗多明)(吗多明)• Producing NO → stimulate guanylyl cyclase (GC) →increase cGMP → relaxes vascular smooth muscle
Dipyridamole Dipyridamole (双嘧达莫,潘生丁)(双嘧达莫,潘生丁)
• Inhibiting adenosine uptake and cAMP degradation Inhibiting adenosine uptake and cAMP degradation • Inhibiting pletelet aggregationInhibiting pletelet aggregation
nitroglycerinnitroglycerin blockers blockers CaCa2+2+ antagonists antagonists combination*combination*
Heart rateHeart rate Contractility Contractility //Wall tensionWall tension // //
Oxygen demandOxygen demand Blood pressureBlood pressure
: increase, : increase, : markedly increase; : markedly increase; : decrease, : decrease, : markedly decrea: markedly decrease; se; : variable according to the dose and effect of each drug ; : variable according to the dose and effect of each drug ; * * bl bl
ockersockers combined with nitroglycerin or Cacombined with nitroglycerin or Ca2+2+ antagonists ( antagonists (nifedipine; combinifedipine; combination with verapamil/diltiazem not be recommendatednation with verapamil/diltiazem not be recommendated))
Caution:Caution: Combination may potentiate the antianginal effects,Combination may potentiate the antianginal effects, but may induce severe hypotension but may induce severe hypotension
Summary of antianginal drugsSummary of antianginal drugs
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