angina Flashcards
how do you treat variant/angiospastic/prinztmetals angina
nitrates, CCB
O2 demand depends on —— which is determine by —–?
cardiac workload which is determined by: 1. HR 2. contractility 3. Ventricular wall tension
What does wall tension represent and how is it increased
wall tension = force developed during contraction
*increase wall tension by increasing pressure and/or increasing volume
any increase in HR or contractility will cause what
increase the need for O2
O2 supply depends on
myocardial delivery and extraction
heart normally extracts 75% of O2 in blood so how can you increase O2 available to tissues
only way is to increase O2 delivery through coronary blood flow
Coronary blood flow is directly proportional to
perfusion pressure
duration of diastole
Coronary flow may be decreased by
- shortening diastole (due to ^HR) (this decreases filling time)
- Increased vendtricular end diastolic pressure
- reduced diastolic arterial pressure
* prevents pressure gradiant that is conducive to blood flow
MOA of nitrates/nitrite
vasodilation via NO that stimulates cGMP (dephos Myosin LC) = relax
describe the vasodilation that occurs with nitrates/nitrites
UNEVEN: veins more dilated = increase venous capacitance = decreased preload
*arterioles dilated less but still decrease afterload
Nitrates are DOC for
acute angina attack
What makes nitrates good/bad
good: decrease cardiac workload bc decrease preload and afterload
BAD: increase cardiac workload: bc the dec BP stimulates baroreflex to increase HR an contractility thus decreasing diastolic perfusion time
what makes for anginal relief
Predominant: decrease myocardial O2 requirement
Secondary: redistribution of coronary blood flor to ischemic areas
*also relax SM in bronchi, GI and GU
pharmacokinetics of oral organic nitrates
rapid hepatic metab with high first pass
what are the fastest acting nitrites
inhaled: amyl nitrite
IV: nitroprusside
benefits to SL nitrite
avoids hepatic damage!
rapid absorption
immediate anginal relief (1-3 min onset, lasts 10-30min)
amyl nitrite form
volatile liquids, inhaled
Isosorbide dinitrate form
solid, SL or oral tab
Adverse effects of nitrates
acute toxicity, pronounced vasodilation causes:
orthostatic hypotension, tachycardia, HA
*not suitable for long term
what is mondays disease
explosive manufacturers w/ chronic exposure
friday sx disappear bc tolerance
monday: HA/dizzy
How do CCB work
relax all SM dependent on Ca
*differences in tissue selectivity can result in opposite effects on HR (dipines increase HR, verapamil decreases HR)
when is slow release nifedipine indicated
ONLY in HTN
*may provoke angina (bc increase HR)
what type of tx are CCB good for (re angina)
chronic angina, not for immediate angina relief
Nifedipine benefits
coronary vasodilation increases myocardial O2 supply, decreases afterload
Nifedipine harmful effect
enhanced development of MI
*rapid hypotension –> baroreflex –> increase cardiac workload
Verapamil/diltiazem benefit
decreased cardiac workload: decrease myocardial contractility, bradycardia (bc dec SA and AV node)
harmful effect of Verapamil/diltiazem
potential to cause serious cardiac depression –> cardiac arrest, AV block, CHF
BB major effects are..
both cardiac and vascular
3 organs BB has CV effect on
heart: decrease CO
Kidney: decrease renin
CNS: decrease SNS
how do BB cause anginal relief
decrease SNS = dec cardiac activity and dec vasoconstriciton = hypotension, dec HR = decreased cardiac workload = decreased myocardial O2 demand
*also, dec HR increases myocardial perfusion time
can BB produce coronary vasodilation?
NO NO NO… BB do not cause direct vasodilation thus are NOT indicated for variant angina
what type of angina should we use BB for
CLASSICAL - not variant bc BB do not cause direct vasodilation
adverse effects of BB include
bronchoconstriciton (bad for asthma)
^ TAG: bad for hyperlipidemics
^ Glu intolerance: bad for DM
CNS SE: fatigue/depression/sleep disturbances
*potentially harmful if used in variant angina bc slows HR, prolongs ejection time = increase LV end diastolic volume = increase myocardial O2 requirement
MOA of Fanolazine and indication
PFox inhibitor (decrease O2 consumption in ischemic tissue, decrease contractility) *use only when others don't work
why are BB potentially harmful in variant angina
*potentially harmful if used in variant angina bc slows HR, prolongs ejection time = increase LV end diastolic volume = increase myocardial O2 requirement
effective tx of angina will..
increase exercise tolerance
decrease freq and duration of myocardial ischemia
tx for variant
nitrates and CCB
*but slow release nifedipine may worsen angina, better for nitrate + cardio CCB ie verapamil
*BB will not cause vasodilation of spastic coronary vessels
Most effect drug combo for classic angina
BB and vasodilator
how can you minimize the harmful effects of CCB or BB
by combing with nitrates and vice versa
how can you minimize reflex tachy
combine nitrates with CCB or BB
preferred for asthma angina pt
CCB (verapamil) and nitrate
least: BB
DM angina pt tx
CCB (verapamil) and nitrate
least: BB
CHF angina pt tx
nitrate
least: BB, CCB (verapamil, diltiazem)
HTN angina pt tx
BB, CCB
least: nitrate
PUD angina pt tx
BB, nitrate
least: CCB
Sildenafil MOA and use
selective inhibitor of cGMP PDE5
*intended for angina but found to be better for ED
indication for sildenafil
ED, pulm HTN
PK of sildenafil
oral, rapid absorption, 40% bioavailable
Max concentration: 30-120 min, t1/2 4 hr
how is sildenafil metab
CYP3A4 major
CYP2C9 minor
Adverse effects of Sildenafil
mild/mod: HA, flushing, dyspepsia, nasal congestion, UTI, blue color tinge to vision/ blurred vision
When should you not rx sildenafil
pregnant/lactating, pt currently on nitrates, pt on alpha blockers (double hypotension effect)
other contraindication for sildenafil
inhibitors of CYP3A4 and 2CP: increase sildenafil
*ketoconazole, erythromycin, quinidine, Cimetidine/omeprazole
*note omeprazole also increases toxicity of quinidine and warfarin and clopidogrel
other PDE5 inhibitors and MOA
Vardenafil and Tadalafil
*more selective for PDE5 than PDE6, less visual blue tinge
Vardenafil benefits
faster onset than sildenafil or tadalafil
Tadalafil benefits
longer duration (24-36 hours) = spontaneity
