Drugs for Angina Flashcards
CAD
obstruction of coronaries by atheromatous plaques
-high risk, moderate risk, low risk (no, no risk class)
RF for CAD
high bp, high LDL cholesterol, smoking
also- diabetes, overweight, poor diet, inactivity, excessive alcohol use
Angina pectoris
chest discomfort when amt of blood delivered to heart annot supply enough oxygen to satisfy myocardial requirement
-chest pain resulting from myocardial ischemia
Nitroglycerin
immediately relieves angina pain
Classic or atherosclerotic angina
atheromatous obstruction of large coronaries
especially with exercise
-tx with drugs or bypass, angioplasty
Prinzmetal angina
spasm or constriction in atherosclerotic coronary vessels
-relived by nitrates of CCBs
MI pathophys
imbalance between oxygen supply and demand
oxygen demand depends on
cardiac workload which is determined by
-contractility, heart rate, wall stress
main energy source in heart
fatty acid oxidation (requires more oxygen than glycolysis)
Trimetazidine
shifts myocardial metabolism towards greater use of glucose- reduce oxygen demand
-pFOX inhibitors
Increase O2 delivery through coronary blood flow which is
- related to perfusion pressure and duration of diastole
- inversely proportional to coronary vascular bed resistance
- damage to endothelium increases vascular resistance
agents decreasing O2 demand of heart
b adrenergic agonists, organic nitrates, CCB
agents increasing O2 supply
vasodilators, statins, anti thrombotics
drugs can relax vascular smooth muscles by
increasing cGMP
3 drug groups for use in angina
1) organic nitrates
2) CCB
3) b blockers
ranolazine
reduces intracellular calcium concentration and thus reduces cardiac contractility and work
-new drug recently approved for angina
trimetazidine
pFOX inhibitor- metabolic modulator inhibits fatty acid oxidation in myocardium
allopurinol
inhibits xanthine oxidase (contributes to oxidative stress and endothelial dysfunction)
-prolongs exercise time in pts with angina
ivabradine
direct bradycardic agents inhibit hyperpolarization activated sodium channel in SA node
Fasudil
Rho kinase inhibitors reduce coronary vasospasm in experimental animals
Nitrates in angina
Act on guanalyl cyclase to convert GTP–> cGMP which causes relaxation
short acting nitrates
amyl nitrate inhaled, sublingual nitroglycerin or isosorbide dinitrate
-acute events
long acting nitrate
nitroglycerine slow release or oral, isosorbide oral, isosorbide mononitrate oral (10 hrs)
- chronic tx
- can lead to tolerance; have 12 hrs every day w/o nitrate effect
Nitrates act by releasing
- NO
- vascular smooth muscle ccells are relaxed, but vasodilation are uneven
- Large veins markedly dilated, arterioles are dilated less
Other effects of NO
- erection req’s relaxation of smooth muscle (sildenafil)
- inc cGMP in platelets–> decrease aggregation
- nitrate ion reacts with hemoglobin- tx cyanide poisoning
Anginal relief by nitrates
pronounced dilation of large veins- reduce preload, myocardial O2 demand, and cardiac work
- redistribution of regional coronary blood flow from normal to ischemic areas
- mild arteriolar dilation- reduced afterload
IV sodium nitroprusside
dilates arteries and veins equally because does not need activation by enzyme
harmful nitrate effects
reflex increases in hr and contractility leading to inc myocardial O2 demand (combine with beta blocker or CCB)
-reflex tachycardia leads to reduced perfusion due to shorter diastole
nitrate absorption and metabolism
-oral nitrates metabolized by hepatic reductase
-routes are inhaled, sublingual, oral, transdermal
-sublingual nitro- immediate anginal relief, rapid action but short duration
-
nitrate toxicity
acute- strong vasodilation- orthostatic hypotension, tachycardia, headaches
frequent repeated exposure- tolerance or marked reduction in magnitude of most effects
Calcium- cardiovascular actions
- triggers contraction in myocardium and vasc smooth muscles
- req’d for pacemaker activity of SA node and conduction through AV node
- Enters through calcium channel- L channel (long lasting) or T channel (transient)
- opened by stimulation of b-receptors, closed by CCBs
CCBs
- block L type channels in myocardium and vasc smooth muscles
- relax all smooth muscles that depend on calcium for normal resting tone and contraction
Verapamil
CCB with strongest cardiac effects- decreased contractility, reduced SA node impulse generation, slowed AV node conduction–> reduced cardiac workload
- no reflex tachycardia
- can lead to serious cardiac depression- cardiac arrest, AV block, CHF
Nifedipine
CCB dihydropyridine- vascular effect– vasodilation
- most likely to produce reflex tachycardia
- use with verapamil to address cardiac effects
Diltiazem
in between with vascular and myocardial depression effects
- can cause serious cardiac depression
reduction of digoxin renal clearance by
verapamil and diltiazem
-increases plasma digoxin and enhances toxicity
b adrenergic antagonists
atenolol, metoproplol can be used to tx angina
-decreases sympathetic tone to decrease CO (decrease HR) –> dec cardiac workload and O2 demand
-may induce or worsen CHF when sympathetic activity is critical to support cardiac performance
-
AE of b-adrenergic antagonists
- in pts with CHF, exercise tolerance may be decreased by reduction of CO
- potentially harmful in variant angina by slowing HR and prolonging ejection time will increase LV EDV
- may inc plasma triglycerides and decrease HDL cholesterol–> atherogenesis
- delays reccovery of normoglycemia
most effective drug combinations
- b adrenergic blocker and CCB or
- 2 CCBs (nifedipine and verapamil)
reflex tachycardia of nitrates can be minimized by
combining with beta blocker or ccb
Mechanism for nitrates
redistribution of flow leading to increased supply of O2
- arteriodilation leads to reduced afterload and reduced demand
- venodilation leads to reduced preload and reduced demand
Mechanism for CCB
arteriodilation, coronary vasodilation (nifedipine) and reduced cardiac function (verapamil)
Mechanism for b-adrenergic blockers
sympathetic inh, reduced vasoconstriction and reduced cardiac fxn
effective antianginal therapy will
increase exercise tolerance and dec frequency and duration of MI
b adrenergic antagonists used with caution in which pts
- reduced myocardial reserve
- asthma
- peripheral vascular insuff
- diabetes
