Antianginal Drugs Flashcards
most common cause of angina
coronary artery disease
angina that occurs at night due to increase in venous return. Can be vasospastic.
Prinzmetal angina
angina due to imbalance when oxygen demand increases and coronary blood flow doesn’t increase proportionally, especially during exercise leading to pain
classic angina
angina where episodes occur at REST. Increases severity, frequency, duration of chest pain.
Unstable angina
causes of unstable angina
reduced blood flow due to partially occlusive thrombi or fissured/ulcerated plaque.
How do we treat classic angina?
- decrease cardiac work
- shift myocardial metabolism
angina where oxygen delivery decreases as a result of reversible coronary vasospasm
Variant angina
How do we treat variant angina?
- reverse spasm
- treat the atherosclerosis
* these affect the supply**
How do we treat unstable angina?
Treat the SUPPLY (increase)
- reverse spasm
- threat the atherosclerosis
treat the demand (reduce)
- decrease cardiac work
- shift myocardial metabolism
what determines ventricular wall stress?
- intraventricular pressure - increases wall stress
- radius of the ventricle - more filling = increased wall stress
- ventricular wall thickness (h) - hypertrophied heart has LESS wall stress
T=P x r/2h
4 factors that affect myocardial oxygen demand
- ventricular wall stress - influenced by pressure, radius, and wall thickness
- heart rate - increases = increased O2
- contractility - greater force requires more oxygen
- basal metabolism
What determines coronary blood flow?
- perfusion pressure - aortic diastolic pressure SHOULD BE HIGH (flow is ZERO during systole in coronary arteries)
- duration of diastole - limiting factor for perfusion expecially during tachycardia
-
resistance
-
determined by:
- metabolic products
- autonomic activity
- damage - alters ability to dilate (increases R)
-
determined by:
What does arteriolar tone influence and does it control it?
- controls peripheral vascular resistance and arterial BP
- influences systolic wall stress
What does venous tone determine and influence?
- determines the capacity of venous circulation and the location of blood sequestration
- Controls diastolic wall stress
4 factors that influence the supply of the heart tissue=
-
total coronary blood flow
- aortic diastolic pressure - increases increases coronary blood flow
- duration of diastole - increase for increase flow
-
Left ventricular end diastolic P
- ejection fraction
-
pAO2
- hematocrit, saturation, etc. (anemia)
-
Membrane diffusion
- vascular wall thickness
2 factors that affect the demand on the heart :
- Heart rate
-
Intraventricular wall stress
- preload
- afterload
- contractility
- wall thickness
all drugs used for angina pain help to decrease myocardial oxygen demand by:
- decrease HR
- decrease ventricular volume
- decrease BP
- decrease contractility
How do nitrates and nitrites work and what is a side effect?
-
Venodilation > arterial dilation (increases venous capacitance)
- decreases preload (demand component)
- decreases pulmonary vascular resistance
- decrease left ventricular end-diastolic pressure (supply component) - favors distribution of coronary blood flow to endocardium
- MINIMAL CHANGE in coronary blood flow
- REFLEX increase in heart rate & contractility - could actually increase the demand on the heart
Nitroglycerin
- MOA
- Effects
- Applications
- Toxicity
- Interactions
- MOA: release NO in smooth muscle –> activates gCyclase –> increases cGMP –> dephosphorylates myosin –> relaxation
- Effects
- relaxation –> vasodilation –> decreased venous return & heart size
- may increase coronary flow in some areas (but doesn’t change total, just redistributes)
- Used for angina
- sublingual = acute
- oral = prophylaxis
- Tox: hypotension, reflex tachycardia, headache
- Interactions = phosphodiesterase type 5 inhibitors - Viagra, Cialis, Levitra
- due to synergistic hypotension
2 other forms of nitroglycerin
-
Isosorbide dinitrate
- slighltly longer duration of action
-
isosorbide mononitrate
- active metabolite of dinitrate
- used orally for prophylaxis
Metbolism of calcium channel blockers
- high first pass effect
- high plasma protein binding
- extensive metabolism
How do calcium channel blockers affect supply and demand?
- blockade of calcium influx –> muscle relaxation since calcium is needed for contraction of smooth muscle
-
Demand
- decrease heart rate
- decrease contractility
-
Supply
- increase coronary blood flow
-
decrease left ventricle EDP
- could cause REFLEX increase in HEART RATE
Verapamil, Diltiazem
- MOA
- Effects
- Application
- Tox
- interactions
-
MOA
- blocks L type Ca2+ channels in heart and vessels
- Effects
- reduced vascular resistance, heart rate, contractility
- –> reduced o2 demand
- reduced vascular resistance, heart rate, contractility
- Applications
- prophylaxis of angina, hypertension, arrythmias
- Tox - AV block, acute heart failure, constipation, edema
- INT - cardiac depressants & hypotensive drugs
Nifedipine
- MOA
- Effects
- Clinical
- Tox
- INt
- MOA - blocks vascular L type channels
- eff - decreased contractility, HR –> reduced o2 demand
- App - prophylaxis of angina + hypertension
- Tox - excessive hypotension, baroreceptor reflex tachycardia
- INt - all other vasodilators
