B4.050 - Treatment of Angina Flashcards
what are the 3 risk factors for CAD
High BP High LDL Smoking
how many americans have one of the 3 risk factors for CAD
50%
what medical conditions increase risk of heart disease
DM Obesity Poor diet Physical inactivity Excessive alcohol
what is angina pectoris
chest pain when amount of blood delivered to heart cannot supply enough oxygen to satisfy myocardial requirement
what is the primary symptom of heart disease
angina pectoris
what is used for immediate relief of angina pectoris
organic nitrates (Nitroglycerin)
what is used as prophylaxis for angina pectoris
CCB and Beta blockers
how is angina pectoris pain described
strangling, vise like, constricting, suffocating. crushing, heavy, sqeezing
how is angina pectoris described in vague situations
only mild pressure, numbing, nausea, sweating, SOB
what is the site of chest pain in angina pectoris
usually retrosternal often radiating down the left arm or may also involve the right or both arms
etiology of classic atherosclerotic angina of effort
atheromatous obstruction of large coronaries especially with exercise
what is the treatment for angina of effort
if uncontrolled by drugs may require coronary bypass or angioplasty
what is variant or angioplastic prinzmetals angina
spasms or constriction in atherosclerotic coronary vessels
what is the treatment for prinzmetals angina
relieved by nitrates or CCBs
what does oxygen demand depend on
cardiac workload which is determined by
1. contractility (major det of O2 consumption)
- heart rate
- wall stress
cornerstone drugs for angina
CCBs and beta blockers
what is the main source of energy in the heart
fatty acid oxidation
what does trimetazidine do
shifts myocardial metabolism towards greater use of glucose to potentially reduce oxygen demand without affecting hemodynamics
what is a pFOX inhibitor
inhibits fatty acid oxidation to try and shift energy use from fatty acid oxidation to glycolysis
Trimetazidine
what is O2 delivery directly related to
perfusion pressure and duration of diastole
what happens with increased diastole time
increased O2 delivery
what is vascular bed resistance determined by
metabolic products
autonomic activity
various drugs
damage to endothelium of coronary vessels causes what
increase in vascular resistance
what can increase O2 supply
mechanical intervention
Stents
Angioplasty
Coronary bypass surgery
what to beta adrenergic antagonists and some Ca entry blockers affect
affect heart rate and contractility
what do organic nitrates and calicum entry blockers affect
preload and afterload
what do vasodilators, statins, and anti-thrombolytics affect
coronary blood flow, regional myocardial blood flow
what are the primary sites of action of pharmacological agenst
reduce O2 demand or enhance O2 supply
what do CCBs do
decrease intracellular Ca
Blocks calmodulin cascade that leads to contraction of vascular smooth muscle
what do beta 2 agonists do
increases cAMP
increase cGMP which causes muscle relaxation
what does NO do
activator of soluble guanylyl cyclase leading to smooth muscle relaxation
what are the 4 drug classes used in angina
- organic nitrates
- CCBs
- beta blockers
- investigative ones
what is ranolazine
reduces intracellular calcium concentration and thus reduces cardiac contractility and work
what is allopurinol
inhibits xanthine oxidase which contributes to oxidative stress and endothelial dysfunction
which drug prolongs exercise time in patients with angina
allopurinol
wht is ivabradine
direct bradycardic agent
inhibits hyperpolarization activated sodium channel in sinatrial node
what is fasudil
Rho-kinase inhibitor reduces coronary vasospasm in experimental animals
where do organin nitrates vasodilate
use enzymes found predominantly on venous side or vasculature, preferentially vasodilates veins
what is the one drug that vasodilates both veins and arteries and why
sodium nitroproside
does not need enzymes
what are the short acting nitrates used for angina
Amyl nitrite - inhalant
Nitroglycerin - sublingual
Isosorbide dinitrate - sublingual
what are long acting nitrates used for angina
Nitroglycerin, oral sustained action
Nitroglycerin - 2% ointment
Nitroglycerin - slow release, buccal
Nitroglycerin - slow release, transderma
isosorbide dinitrate - oral
isosorbide mononitrate - oral
what is sildenafil and why is it important
inhibitor of PDE-5
Can potentiate action of NO in angina –> sever hypotension, MI
Nitrate ion reactis with what and can be used for what type of poisoning
hemoglobin –> methemoglobin –> can be used to treat cyanide poisoning because methemoglobin regenerates cytochrome oxidase
beneficial effectso of nitrate therapy
- pronouced dilation of large veins - reduced preload, O2 demand, cardiac work
- redistribution of regional coronary artery blood flow - from normal to ischemic areas due to perferential dilation of large epicardial arteries
- mild arteriolar dilation to reduce afterload and O2 demand in heart
harmful nitrate effects and their results
reflex increases in HR and contractility - increased myocardial O2 demand
Reflex tachycardia - reduced perfusion due to shorter diastole
what can you combine NO with to prevent reflex tachycardia
CCB
where is NO metabolized
liver
why are inhaled or sublingual nitrates quicker
they bypass liver and dissolve right into blood stream
routs of administration of NO for acute treatment
inhalation
sublingual
routes of administratin of NO for chronic treatment
oral
transdermal
prefered ROA for nitroglycerin and isosorbide dinitrate
sublingual
what does sodium notroprusside do
dilates arteries and veins equally
can you use sublingual NO for chronic therapy
no
how do you minimize tolerance of NO
chronic treatmen use this is common
lowest effective dose with nitrate free intervas 10-12 hrs daily
acute toxicity of nitrates
strong vasodilation
orthostatic hypotension
tachycardia
throbbing headache
what is monday disease
people chronically exposed to nitrates at work would become less tolerant over the weekend and monday would all have headache
what type of channel do CCBs block
L type channels in the myocardium and vascular smooth muscles
how are calcium channels opened
stimulation of beta receptors
what blood vessels are most sensetive to CCBs
arterioles more sensetive than veins
what are dihydropyridines
nifedipine - binds 1A, tissue selectivity is vascular
what does the chemical class benzothiazepine consist of and (CCB)
diltiazem 1B tissue selectivity in between
what does the chemical class phenylalkylamine do
verapamin - 1C - myocardial tissue selectivity
major effects of CCBs
Mainly cardiac effects
Decreased contractility,
Decreased SA node impulse generation
Decreased AV node conduction
which CCB has the strongest cardiac effect
Verapamil
which CCB is the strongest vasodilator
Nifedipine
which CCB has reflex tachycardia
Nifedipine
rank order nifedipine, diltiazem and verapamil in their effect on vasodilation (RT) and myocardial depression
harmful effects of verapamil and diltiazem
serious cadiac depression could result in
cardiac arrest
AV block
CHF
which drug class can affect insulin secretion
CCB
what are CCB harmful effects other than mycardial depression and RT
inhibition of insulin secretion
interference with platelet aggregation
verapamil and diltiazem may reduce digoxin renal clearance
they should not be used in patients with ventricular dysfunction or SA/AV node disturbances
what are beta blockers often used for treatment of angina
atenolol
metoprolol
propranolol
nadolol
how do beta blockers work
decreasing sympathetic tone to decrease CO
what are beta blockers especially useful for
angina associated with effort, reduce myocardial oxygen requirements at rest and during exercise
do beta blockers or CCBs produce better outcomes and symptomatic treatment
beta blockers
do beta blockers dilate coronary arteries
no
what are beta blockers valuble to treat other than exercise induced angina
silent or ambulatory ischemia detected by ECG
what drug class reduces amount of ischemic time per day
beta adrenergic blockade
harmful effects of beta adrenergic blockade
may induce or worsen CHF whe sympathetic activity is critical to support cardiac performance
why are beta blockers potentially harmful in variant angina
slowing HR and prolonging ejection time might increase O2 requirement
what drug class may increase plasma TGs and decrease HDL cholesterol
beta blockers
which drug class can predispose to diabetes
beta blockers
first line therapy for angina pectoris
modify risk factors and add atiplatelet drugs
eg. aspirin/clopidogrel plus statins and weight loss
effective antianginal therapy will
increase exercise tolerance
decrease frequency and duration of myocardial ischemia
for variant or angioplastic angina what drugs are most effective
nitrates and CCBs
NOT beta blockers
drugs for hypertensive pt
CCB or beta blocer
normotensive pt drug choice
long actinge nitrate
effective drug combos for angina pectoris
beta adrenergic blockers and CCBs
2 CCBs
potentially harmful effects of CCBs or beta blockers can be prevented by
combined treatment with nitrates
how can reflex tachycardia be minimized
combining nitrates with CCBs or Beta blockers
