Flashcards in Anti-Anginal Deck (42):
1. occurs if the coronary artery is narrowed
2. the reduced blood flow through narrowed arteries can't meet the increased O2 demand-->
3. Symptoms occur with increased emotional or physical exertion.
Variant Angina aka Prinzmetal's angina
1. results from a reversible spasm of large coronary arteries, usually at the site of atherosclerotic plaque
2. can occur at rest or irrespective of the amount of physical or emotional exertion
acute coronary syndrome aka unstable angina
1. characterized by increased frequency and severity as a result of combo of atherosclerotic plaques and vasospasm
2. symptoms occur even at rest
3. might signal an impending MI-->treat as medical emergency
2 strategies for treatment of angina
1. increase O2 delivery: Nitrates & Ca Channel Blockers
2. Reduce O2 requirement: beta blockers
3. anti platelet drugs (i.e. low dose aspirin, abciximab) are also used
Which anti anginal meds work to increase Oxygen delivery to tissues?
Nitrates & Calcium Channel Blockers (CCB)
Which anti anginal meds work to reduce the oxygen requirement?
beta adrenergic blockers
a newer drug that works to increase the efficiency of oxygen utilization by partial fatty acid oxidation inhibitors (pFOX inhibitors)
1. a pFOX inhibitor (partial fatty acid oxidation inhibitor) in myocardium
2. primary mechanism of action involves reduced contractility
3. action results from blockade of a late sodium current that facilitates calcium entry via the sodium-calcium exchanger
Examples of Nitrates
1. Nitroglycerine (GTN)
2. Isosorbide dinitrate
3. Isosorbide mononitrate
1. powerful vasodilators
2. act by releasing NO
3. NO--> smooth muscle relaxation
4. effectiveness due to action on capacitance vessels to reduce cardiac pre-load: Dilation of collateral coronary vessels
1. NO formation is triggered by Ach, Bradykinin, histamine & serotonin
2. NO activates Guanylyl Cyclase (GC) to form cGMP--> smooth muscle relaxation
1. Contraction of vascular smooth muscle is triggered by influx of calcium
3.. Ca combines with calmodulin & converts enzyme myosin light chain kinase to its active form (MLCK)
3. MLCK phosphorylates the myosin light chains-->initiates interaction btw myosin & actin
4. Nitrates dephosphorylate Myosin light chains to prevent their interaction with actin
5. phosphodiesterase breaks down cGMP. a phosphodiesterase inhibitor (i.e. Sildenafil) results in an increase in the amount of cGMP-->more dephospho rylation of MLC-->more muscle relaxation
Combining nitrates with sildenafil-->sudden severe hypotension
phosphodiesterase breaks down cGMP. a phosphodiesterase inhibitor (i.e. Sildenafil) results in an increase in the amount of cGMP-->more dephospho rylation of MLC-->more muscle relaxation
Glyceryl trinitrate (GTN)
1. given sublingually to avoid 1st pass metab; also rapidly absorbed
2. also available in transdermal patch & via IV
How do nitrates work?
Any other uses?
they decrease the cardiac preload by preferentially dilating veins
Other uses: cyanide poisoning (sodium nitrite, amyl nitrite with sodium thiosulfate)
NITRITE used in cyanide bc converts Hb to MetHb, which has higher affinity for cyanide.
Adverse effects of nitrates
1. severe headache (from vasodilation of extracerebral bv)
2. Tolerance occurs with long term use (need higher doses)
3. Postural hypotension & reflex tachycardia
4. Methemoglobinemia caused by NITRITES, not nitrates
"monday disease" in production of substances involving nitrates is an example of the tolerance (build it up over the week) & the symptoms (headache)
Nitrates have an interaction with? How?
1. these agents inhibit a phosphodiesterase isoform (PDE5) that metabolizes cGMP in smooth muscle
2. the increased cGMP in erectile smooth muscle relaxes it, allowing for greater inflow of blood & more effective & prolonged erection
3. this effect also occurs in vascular sm. as a result the combo of nitrates (via increase in cGMP production) & a PDE5 inhibitor (through decreased breakdown of cGMP) --> synergistic relaxation of vascular sm with potentially dangerous HYPOTENSION & inadequate perfusion of critical organs
Calcium Channel Blockers block what type of channel? where is it located?
CCB block voltage-gated L-type calcium channels in cardiac & smooth muscle
Examples of CCB
a) Dihydropyridines (DHP):
1. nifedipine, amlodipine, nicardipine, nimodipine
b) Verapamil, diltiazem
Examples of Dihydropyridines (DHP)
Important differences in vascular selectivity between CCB
in general, DHPs have a greater ratio of vascular smooth muscle effects compared to cardiac effects than either diltiazem or verapamil
Nimodipine is particularly selective for
cerebral blood vessels-->used to treat subarachnoid hemorrhage
Verapamil & Diltiazem function & use
block calcium-dependent conduction in the AV node & are used to treat AV nodal arrhythmias
How do CCB work to treat angina?
They decrease both preload and after load--> decreasing workload on the heart!
1. what is it?
1. mainly arteriolar vasodilator
2. minimal effect on cardiac conduction or HR-->NOT USED FOR ARRHYTHMIAS
3. useful to treat varying angina
4. peripheral edema
All the ADR are results of the vasodilation
ADR of Nifedipine
4. peripheral edema
All the ADR are results of the vasodilation
What? Use? Interactions/toxicities?
More selective for cardiac calcium channels (but will also affect bv)
1. slows cardiac conduction
2. decreases HR & O2 demand
3. causes more negative inotropic effect than nifedipine
4. Weaker vasodilator than nifedipine--DIP always more powerful
5. Drug interaction: with digoxin (increases digoxin levels)
same as verapamil--More selective for cardiac calcium channels (but will also affect bv)
1. has specific coronary vasodilating effect relieving coronary vasospasm
2. particularly useful in variant angina
3. ADR: low
ADR of CCB (generally)
1. cause hypotension due to vasodilation
2. peripheral edema
3. overdose leads to cardiac arrest (bc blocked channels--> decreased FOC), bradycardia, AV block & Heart Failure
What condition is contraindicated against CCB?
Heart Failure! IN heart failure the cardiac output isn't sufficient to meet the body's demands. CCB will further decrease the heart's FOC--> further decreasing it's CO.
How are Beta blockers used to treat angina?
1. work by opposing the action of adrenaline on the heart
2. block B1 receptors present in the heart--> results in unopposed alpha effects-->vasoconstriction
3. results in a decrease in HR, BP & contractility
4. this decreases the myocardial oxygen requirements at REST & DURING EXERCISE
5. they do NOT HAVE ANY EFFECT ON MYOCARDIAL O2 SUPPLY!
6. they are used in combo with other anti-anginal drugs
ie beta blockers + nitrates bc nitrates -->vasodilation + reflex tachycardia but the beta blockers will help prevent the tachycardia
When are beta blockers contraindicated in treating angina
in vasospastic angina, bc beta blockers will cause further vasoconstriction
block B1 receptors present in the heart--> results in unopposed alpha effects-->vasoconstriction
DOC in acute relief of symptoms in all types of angina
What is used as prophylactic therapy in vasospastic/variant/Prinzmetal's angina?
Ca channel blockers
they're also useful in angina of effort
When should you use beta blockers to treat angina?
ONLY for prophylaxis of angina. They're effective in preventing EXERCISE-INDUCED angina
Nitrates have a preference for?
How do nitrates treat angina?
release NO-->sm relaxation through activation of cGMP--> ultimate reduction in preload
How do you overcome the reflex tachycardia associated with nitrates?
Give them in conjunction with beta blockeres
Nifedipine has a preference for?
Nimodipine has a preference for
cerebral blood vessels
decreases HR, BP & contractility
reducing these-->decreases myocardial oxygen requirements at rest & during exercise
blocks AV nodal conduction
verapamil & diltiazem
anti platelet effect; used like aspirin in treatment of angina