Drugs for Angina Pectoris

Card Set Information

Author:
meganc0201
ID:
39926
Filename:
Drugs for Angina Pectoris
Updated:
2010-10-05 15:12:41
Tags:
Drugs Angina Pectoris
Folders:

Description:
Pharm: Drugs for Angina Pectoris
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user meganc0201 on FreezingBlue Flashcards. What would you like to do?


  1. Angina Pectoris
    • the principle symptom of ischemic heart disease
    • it is a pain felt right int he middle of the chest, behind the sternum (not generally on the side)
    • sensation of tightness, yet some people describe it as only midly painful discomfort
    • can spread toward the neck or the jaw, the arm and the wrist, most often on the left side
    • sometimes situated lower down, towards the pit of the stomach
  2. Categories of Angina Pectoris:
    Stable
    predictable in response to exertion, stress, etc; there is a fixed block that permits adequate flow under basal conditions but impedes higher levels of flow
  3. Categories of Angina Pectoris:
    Unstable
    • manifests as symptoms of angina at rest or worsening of exeritonal angina due to vasospasm, platelet aggregation, thrombus formation, and/or emboli transiently blocking downstream vessels
    • has increased risk of myocardial infarction and/or death in comparison to stable angina pectoris
    • need to use therapy in addition to that discussed below such as antiplatlet therapy (e.g. aspirin), oxygen, morphine for pain
  4. Categories of Angina Pectoris:
    Vasopastic
    • aka Printzmetal's angina
    • angina caused by coronary artery spasm
    • in contrast to stable angina, can produce pain at anytime including while asleep
    • between attacks, there may be little to no evidence of coronary flow impairment
  5. The ischemic condition results from
    • an imbalance between myocardial oxygen demand and myocardial oxygen supply
    • this imbalance may be due to a decrease in myocardial oxygen supply, an increase in myocardial oxygen demand or both
  6. Factors that affect myocaridal oxygen demand
    • contractility
    • heart rate
    • ventricular wall tension
  7. Ventricular Wall Tension
    • Preload:
    • the pressure that distends the ventricular wall during diastole
    • some antianginal drugs increase venous capacitance which causes venous pooling, decreases venous return, decreases ventricular end-diastolic pressure, reduces cardiac work and thus decreases oxygen demand
    • Afterload:
    • the force distributed in the ventricular wall during ejection of blood (ventricular systolic wall tension) (it has to be greater than diastolic blood pressure to open the valves)
  8. Factors that affect myocardial oxygen supply:
    Coronary Blood Flow
    a function of aortic diastolic blood pressure and coronary vascular resistance
  9. Factors that affect myocardial oxygen supply:
    Regional blood flow distribution
    • subendocardial regions of the heart are more poorly perfushed than the subepicaridal regions
    • decreasing preload decreases intraventricular pressure which allows for greater subendocaridal perfusion
  10. Organic nitrates
    • –organic nitrates have been used for over 100 years, and are still primary drugs for the treatment of angina pectoris
    • –cellular mechanism of action :
    • organic nitrates are converted to nitric oxide (NO)
    • -->stimulates guanylate cyclase to cause an increase in the formation of cyclic GMP
    • -->dephosphorylates myosin light chains and causes vascular relaxation
  11. Organic nitrates
    Pharmacological actions to reduce myocardial ischemia:
    • venous and arterial dilation, with dilation of veins predominating over that of arteries.
    • •decreased preload and afterload results in decreased myocardial work and decreased oxygen demand.
    • •the organic nitrates do not directly alter the inotropic (force of contraction) or chronotropic (rate) state of the heart.
    • effects on coronary blood flow
    • •organic nitrates dilate large epicardial coronary arteries and collateral vessels to provide some increase in oxygen delivery to the ischemic myocardium
    • •reduced preload decreases diastolic intraventricular pressure which favors subendocardial perfusion
  12. Mechanism of pain relief in angina for organic nitrate drugs
    • –cause a marked reduction in myocardial work and concomitant reduction in oxygen demand
    • –there may be some improvement in perfusion of the heart
  13. Nitrate pharmacokinetics
    • –differences exist in the pharmacokinetics of the various organic nitrates
    • –have low oral bioavailability due to extensive first-pass metabolism in the liver.
    • oral isosorbide dinitrate is completely absorbed, but only about 25% of the absorbed dose enters into the systemic circulation as intact drug
  14. Nitrate routes of administration
    –the sublingual route of administration of organic nitrates is most useful for the treatment of acute attacks of angina pectoris

    • –the oral (swallowed) and transdermal preparations have a slow onset and a long duration of action
    • used to provide prophylaxis against anginal attacks
    • must be given in sufficient dosage to saturate the liver’s capacity to degrade them
  15. Nitrate tolerance
    –tolerance is apparent when repeated administration of a given dose of an organic nitrate produces a decreased effect or when increasingly larger doses must be taken to obtain the effects observed with the original dose

    –the magnitude of tolerance is a function of the dose and frequency of administration of the nitrate, with frequent exposure to high oral or transdermal doses of organic nitrates leading to the development of tolerance
  16. Nitrate adverse effects
    –generally, the acute adverse effects are direct extensions of the pharmacological effects of these drugs, and include:

    • •vasodilatation – severe headache, facial flushing,
    • •hypotension – dizziness, weakness
    • •orthostatic hypotension
    • •reflex tachycardia
  17. Nitrate use in angina pectoris
    •sublingual and other rapid acting nitrates are used to treat acute attacks of angina

    –will help for both stable and vasospastic forms of angina

    • –if 2-3 sublingual pills taken at 5 min intervals fail to alleviate symptoms, head to ER for thrombolytic therapy (i.e., it’s a myocardial infarction)
    • long acting oral and transdermal nitrates are used prophylactically to prevent angina
  18. Antianginal Drugs: b-Adrenergic receptor antagonists
  19. •These drugs bind to b-adrenergic receptors and reduce the response caused by the activation of these receptors by the sympathetic nervous system, thereby inhibiting many of the cardiovascular effects
    • •b1-adrenergic receptors act:
    • –on the heart muscle to increase contractility
    • –on the cardiac conduction system to increase heart ratein the kidney to increase renin secretion
  20. Hemodynamic effects of b blockers in treating angina pectoris
    • –the b blockers antagonize the actions of epinephrine and norepinephrine released by sympathetic stimulation during stress or exercise, reducing both heart rate and contractility
    • –arterial blood pressure is also reduced by b blockers
    • –the three major determinants of myocardial oxygen demand—heart rate, contractility and systolic wall tension—are reduced.
  21. Adverse effects of b blockers
    • •respiratory - wheezing, bronchoconstriction in patients with airway disease, b2 > b1
    • •cardiovascular – bradycardia, AV block in patients with conduction disturbances; abrupt withdrawal of b blockers can worsen angina
  22. Use and beneficial effects of b blockers in the treatment of angina pectoris
  23. • decrease frequency of anginal attacks
    • • decrease nitroglycerin consumption
    • • increase exercise tolerance
    • •b blockers are used prophylactically to prevent exertional angina.
    • –are NOT useful for vasospastic angina
    • –most useful in patients whose attacks of angina are frequent and unpredictable
  24. Antianginal Drugs: Calcium Channel Blockers (CCB)aka CEB [calcium entry blockers])
    Drug classes used to treat angina pectoris include:
    • •phenylalkylamines: verapamil
    • •benzothiazepines: diltiazem (effects lie between extremes of other 2 classes, we will not discuss further)
    • •dihydropyridines: nifedipine, amlodipine, nicardipine, nimodipine, felodipine, isradipine
  25. Major therapeutic uses of calcium channel blockers include treatment of
    • •angina pectoris
    • •essential hypertension
    • •cardiac arrhythmias
  26. Calcium effects on vascular smooth muscle
  27. •vascular smooth muscle contraction is dependent upon an increase in intracellular Ca2+
    • •Ca2+ channel blockers bind to and inhibit L-type voltage-dependent Ca2+ channels in arterial smooth muscle.
    • •CCB have little or no effect on the entry of calcium into the cell via other mechanisms
    • •decreased intracellular Ca2+ in arterial smooth muscle results in coronary and peripheral vascular relaxation and a decrease in blood pressure (afterload)CCB have little or no effect on the veins and no effect on cardiac preload
  28. Class of Ca2+ channel blocker: verapamil (and diltiazem)
    • –affects the SA node and AV conduction system, exerting effects that slow the heart rate
    • –also causes a greater decrease in myocardial contractility (inotropy) than the dihydropyridines; can worsen heart function in a failing heart
  29. Class of Ca2+ channel blocker:
    nifedipine and related dihydropyridines
    • –do NOT have significant direct effects on the atrioventricular conduction system or the sinoatrial node that would slow heart rate
    • –moreover, these drugs are better vasodilators than verapamil… this peripheral vasodilatation leads to a reflex increase in sympathetic tone, which increases heart rate à i.e., causes a reflex tachycardia
  30. Ranolazine (Renexa®)
  31. •Initially approved for treatment of refractory angina
    • •New class, definitely does exert beneficial antianginal effects –
    • –~No effect on HR, BP or rate-pressure product… ?
    • –Initially thought to work by modifying fatty acid metabolism
    • –Now thought to work primarily by blocking a Na+ channel responsible for a late phase of influx (less Nai = greater driving force for Ca2+ extrusion via Na/Ca exchanger)
    • –Prolongs QT interval, so fear was that it could trigger torsades de pointes
    • •MERLIN-TIMI36 trial failed to demonstrate added benefit in non-ST elevated MI patients, its initial main target
    • –Oops… fire 1/4 of employees
    • –Oops again… noted that patients receiving ranolazine had significantly lower incidence of arrhythmias and no torsades
    • •Recently approved as initial therapy for chronic angina
    • •Testimonials suggest it is a miracle drug for some patients…

What would you like to do?

Home > Flashcards > Print Preview