Treatment of Angina Flashcards
the heart itself requires more blood when…
- its workload increases
- O2 consumption increases
- there is dilation of coronary arteries
what is angina
O2 deprivation to the heart causes imbalance between O2 supply and demand, leads to chest pain
what happens when coronary blood flow to the heart is insufficient
O2 deprivation, decreased muscle strength - leads to acute heart failure because we can’t supply the heart with the energy needed to contract
what do drugs that treat angina do
fix the imbalance between O2 supply and demand
angina can be a symptom of…
coronary artery disease
risk factors for angina
diabetes
hypertension
high cholesterol
obesity
sedentary lifestyle
tobacco use
stress
family history
symptoms of angina
chest pain
pain in shoulders
nausea
shortness of breath
fatigue
excess sweating
dizziness
what are the 3 types of angina pectoris
atherosclerotic
vasospastic
unstable
atherosclerotic angina
- most common form
- due to irreversible atherosclerotic obstruction of coronary arteries
- precipitated by exertion
vasospastic angina
- spasm of part of coronary vessel (usually at site of plaque)
- can occur at any time
unstable angina
atherosclerotic plaque + platelet aggregation + vasospasm
what are the 3 determinans of cardiac O2 consumption
- preload - blood volume + venous tension
- heart rate and contractility
- afterload - peripheral resistance
what are treatment strategies to fix oxygen demand for the heart
- decrease demand by decreasing blood pressure
- use these drugs: nitrates, B-blockers, Ca2+ blockers
what are treatment strategies for fixing oxygen supply for the heart
- increase supply by increasing coronary blood flow
- use these drugs: nitrates, Ca2+ blockers
which drugs to treat angina are considered vasodilators
nitroglycerin (nitrate)
verapamil (Ca2+ channel blocker)
which drugs to treat angina are considered sympatholytics
propanolol (B-blocker)
metoprolol (B-blocker)
pharmacokinetics of nitroglycerin
- metabolized by the liver - low oral bioavailability
- subligual form has higher bioavailability and rapid onset
- transdermal not used as often because onset takes long
Nitroglycerin - mechanism
- nitrate groups converted to NO (the EDRF)
- casues relaxation of SM cells = vasodilation
- affects veins and coronary arteries (also arteries at high doses)
- also acts on SM in bronchioles
Nitroglycerin - effect on body
- decreased venous return to heart
- decreased PVR (therefore BP)
- dilation of coronary arteries
- overall O2 requirment is decreased and O2 delivery is increased
toxicity and tolerance of nitroglycerin
toxicities = hypotension, tachycardia (reflex in SNS activity), headaches
tolerance = reduced effectiveness of same dose - less NO released, increased cGMP metabolism, increased SNS retention of salt and water
how can the drug combination of nitrates + sildenafil trigger a heart attack
elevated cGMP levels cause extreme hypotension and lead to myocardial infarction bc of decreased bloodflow to myocardium
what happens when you give nitroglycerin to treat angina to a patient who has been administered sildenafil (viagra)?
- viagra inhibits phosphodiesterase, therefore inhibits breakdown of cGMP
- causes relaxation
- potenates the effects of nitrates - causes severe hypotension and myocardial infraction
- can also alter vision
Verapamil - mechanism
- inhibits Ca2+ influx into blood vessel SM - causes dilation
- inhibits Ca2+ influx into cardiac muscle - decreased cardiac contractility
verapamil - effects
decreased O2 requirement for smooth muscle and the heart
verapamil - toxicities
hypotension and cardiac depression - can lead to bradycardia and heart failure
why does less Ca2+ to arterial smooth muscles cause vasodilation
less myosin is able to be phosphorylated to allow for SM contraction
sympatholytics to treat angina - propanolol and metoprolol
- decrease rate and force of contraction
- decreases myocardial O2 requirement
- at SA node: decreased heart rate and O2 demant
- at ventrivular myocardium: decreased contractility and O2 demand
clinical management of angina
- for acute attacks - use sublingual nitrates
- for maintenance monotherapy in hypertensive patients - Ca2+ channel or B blocker
- for maintenance monotherapy in normotensive patients - long-acting nitrate
- combination therapy: Ca2+ blocker + B-blocker (and possibly nitrate)
