antianginal drugs 抗心绞痛药 antianginal drugs. what’s angina pectoris cause and the...
Post on 27-Dec-2015
263 Views
Preview:
TRANSCRIPT
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
Thanks!
top related