Anti-Anginal Agents Flashcards
angina pectoris
Angina is the primary symptom of ischemic heart disease
temporary and reversible imbalance between myocardial O2 supply and demand
increased demand - from HR, ventricular contraction, and ventricular wall tension
decreased supply – from coronary blood flow, O2 carrying capacity of blood, or both
coronary artery disease (CAD) usually the underlying cause
sensation of angina?
Heavy pressing substernal discomfort (rarely called pain)
Often radiating to left shoulder, flexor aspect of left arm, jaw, or epigastrium
typical angina
= exertional angina
Usually fixed atherosclerotic narrowing of an epicardial coronary artery on which exertion or emotional stress superimposes an increase in myocardial O2 demand
Hx = angina induced by exercise, relieved by rest and/or nitroglycerin (NTG)
lasts no longer than 15 min,
5 - 15 episodes/wk
ST segment depression
atypical angina
= angina at rest
(other names: variant, vasospastic, prinzmetal’s)
- Focal or diffuse coronary vasospasm episodically reduces coronary flow
- Transient ST segment elevation during angina
unstable angina
Rupture of an atherosclerotic plaque, with consequent platelet adhesion and aggregation decreased coronary blood flow
Abrupt decreases in blood flow due to thrombus or embolus signals impending myocardial infarction (MI)
If symptoms not relieved by 3 NTG tablets within 15 minutes should call 911 or get to nearest ED immediately
agents used to tx angina?
- Beta blockers: decrease HR/contractility
- Ca channel blockers: some decrease HR/contractility, others affect preload/afterload
- vasodilators: increase coronary blood flow
- statins/anti-thrombotics: increase regional myocardial blood flow
how to tx exertional angina?
decrease work on heart: decrease HR and contractility
- Beta blockers + aspirin
- Beta blockers + aspirin + long acting nitrates
- nitrate for acute attacks
- ACEI’s for DM or left ventricular dysfunction
how to tx unstable angina?
increase blood flow and decrease work of heart
Acute: MONA: morphine, O2, nitroglycerine, aspirin
+ Beta blocker
If b blocker contraindicated –verapamil or diltiazem if no LV dysfunction
increase blood flow – antiplatelet agent (aspirin) + heparin to decrease thrombus
Percutaneous coronary interventions (PCI) - Angioplasty, placement of stents
Coronary bypass grafts (CBG) (“cabbage”)
Thrombolytics (Alteplase, Reteplase, Tenecteplase, Streptokinase)
how to treat prinzmental’s angina?
relax the vasculature
mechanism of organic nitrates
they are the source of nitric oxide
- NO decreases both preload and afterload by relaxing vascular smooth muscle
- relaxation of large vv –> decrease venous return–> decreased preload –> decreased O2 demand
- directly dilate coronary arteries
nitrates and exertional angina?
can’t directly infuse NTG into heart, does not relieve exertional angina
- must take sublingual NTG (because it must be converted to nitric oxide first)
how is NTG activated?
nitrates + endothelial cells result in NO
NO converts guanylyl cyclase –> which converts GTP to cGMP
cGMP increases mosin LC –> relaxation
*** NOTE: phosphodiesterase inactivates cGMP
Nitroglycerin (NTG)
= nitrate vasodilator
Sublingual tablet or spray (PRN), sustained-release oral capsules BID/QID, buccal tablets or gel Q3-5hr, ointment Q4-8 hr, dermal patch 12-16 hr/day
isosorbide dinitrate
long acting nitrate vasodiator
SE’s of nitrates?
headaches, facial flush, dizziness, orthostatic hypotension (worsened by alcohol)
limitations of nitrates?
- can develop tolerance, resulting in diminished effectiveness
CI’s or nitrates?
In acute MI – avoid nitrates if right ventricular infarction: because higher right-sided filling pressures are needed
** patients on erectile dysfunction drugs: these work to elevate cGMP, resulting in synergistic effects with NO —> can cause potentially fatal decrease in BP (Sildenafil, Tadalafil, Vardenafil = Viagra, cialis, levitra)
how do CCB’s work?
Ca2+ activates Calmodulin which increases MLCK –> causes increased Myosin LC –> increased relaxation
CCB’s with primary cardiac effects?
The non DHPs:
Verapamil , diltiazem
CCB’s with mostly arterioloar vasodilator effects?
dihydropyridines: Nifedipine, amoldipine, felodipine (all end in -pine)
- with DHPs see vasodilation and reflex tachycardia
PD of CCB’s in Angina
blocks Ca2+ entry through L-type slow channels –> relaxation of arterioloar smooth mm
–> decreased afterload and decreased O2 demand
- increases supply of blood to heart due to dilation of coronary aa.
mechanism of CCBs on smooth mm. cells
Voltage-sensitive (L-type) Ca++ channels mediate entry of Ca++ into smooth muscle, cardiac myocytes, SA & AV nodal cells in response to electrical stimulation
Ca++ triggers contraction of vascular smooth muscle
CCBs block channel and produce relaxation of arterioles, little effect on veins
Mostly decreased afterload, little effect on preload
mechanism of CCBs on cardiac cells?
In myocytes, Na+ entry through “fast” channels is the primary carrier of current in the depolarization event, but Ca++ entry through slow channels is an additional component
Ca++ entry may also induce Ca++ release from SR
Ca++ binds to troponin- relieves inhibition of troponin on contractile apparatus – allows actin-myosin contraction
**CCBs block Ca++ entry, cause negative inotropic effect –but concurrent decrease in vascular resistance causes decreased BP and baroreceptor reflex which negates negative inotropic effect
how do CCB’s affect SA and AV nodes?
- Depolarization is largely through L-type Ca++ current
- DHPs block channel but do not effect recovery of channel & are not “frequency (use) dependent”
***Verapamil & diltiazem block channel, delay recovery of channel, & are frequency dependent
*** Therefore, verapamil & diltiazem decrease the rate of SA node depolarization + slow AV nodal conduction
*These properties makes them useful for treatment of supraventricular tachyarrhythmias!
DHPs vs NON-DHPs?
Dihydropyridine (DHP) CCBs tend to be more potent vasodilators
non-dihydropyridine (non-DHP) agents, have more marked negative inotropic effects.
Both subclasses have a similar capacity to lower BP; however, non-DHPs appear to offer potential advantages in the management of patients with chronic kidney disease and diabetic nephropathy.
effects of CCBs on hemodynamics?
**All CCBs decrease coronary vascular resistance + increase coronary blood flow
DHPs are more potent (arteriolar) vasodilators than verapamil which is >diltiazem
DHPs decrease arterial P, slight reflex increase HR & contractility, CO increase, ventricular function improved, peripheral blood flow improved, venous tone unchanged
Verapamil – reflex tachycardia due to arterial dilation is blunted by direct negative inotropic effect
Diltiazem – same as verapamil but less negative HR
toxicity of CCBs?
can cause Excessive vasodilation – dizziness, hypotension, headache, flushing, nausea
“Coronary steal” worsens angina
Constipation (esp., verapamil), peripheral edema, coughing, wheezing, pulmonary edema
SE of verapamil?
constipation
what not to use with beta blocker?
don’t use verapamil/diltiazem - b/c can potentially cause AV block
should also not use these in in pts with ventricular dysfunction, SA or AV nodal conduction defects and systolic BP< 90 mm Hg
how do beta blockers tx angina?
- cause decrease in HR
- decrease in contractility to lesser extent
= decreased CO and decreased O2 - see decreased peripheral resistance in the long term which also decreased O2 demand
most effective beta blockers?
atenolol and metoprolol are beta selective and preferred
propanolol is nonselective and cheaper
Beta blockers and chronic stable angina?
Indications:
- monotherapy for mild to moderate angina of effort (not for Prinzmetal’s)
- combination therapy with long acting nitrate or DHP CCB (typical exertional angina)
- after MI – should be used in every patient
Limitations:
- Bradyarrhythmias or AV block
- Compensated congestive heart failure
- Asthmatics and diabetics use with extreme caution
aspirin
- antiplatelet
- clearly demonstrated to ¯decrease mortality in patients with unstable angina, reducing incidence of MI and death
- see decreased incidence of MI in chronic stable angina
- effect due to inhibition of platelet aggregation
how does aspirin work?
Blocks production of prostaglandins
Irreversibly inhibits cyclooxygenase
clopidogrel (plavix)
Selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex
Irreversible, long-term inhibition of platelet aggregation
Useful for unstable angina, prophylaxis and treatment of TIA and completed stroke
Standard practice to treat for patients undergoing stent placement
abciximab
used during angioplasty
Monoclonal antibody against glycoprotein IIb/IIIa receptor; thus, inhibits platelet aggregation
Tirofiban and eptifibatide inhibit ligand binding to IIb/IIIa receptor
approved for treatment of unstable angina when angioplasty or atherectomy planned within 24 hrs.
how to tx single attacks?
NTG is mainstay Onset: 1-3 min, duration:20-30 min
how to tx chronic stable angina?
b blockers, Ca++ channel blockers, or long duration nitrates or combination
how to tx vasospastic angina?
Ca++ channel blockers or nitrates
