Flashcards in L50 – Treatment of Angina Deck (75):
What is the major cause of stable/ classic/atherosclerotic angina?
Fixed narrowing / obstruction of epicardial coronary arteries by atheromatous obstruction
Name some secondary non-atherosclerotic causes of stable angina. (ATCG)
(+ myocardial bridges
Scarring from trauma/radiation )
Explain how obstructed coronary blood flow causes discomfort in chest in stable angina?
insufficient coronary blood flow for oxygen demands of the myocardium > myocardial ischemia DURING INCREASE DEMAND FOR O2 (e.g. exercise, emotional stress) > discomfort in chest
What is the major cause of Unstable angina?
increase epicardial coronary artery tone
Formation of unstable non-occlusive thrombi
Explain how obstructed coronary blood flow causes discomfort in chest in unstable angina?
insufficient coronary blood flow to meet the oxygen demands of the myocardium > TRANSIENT myocardial ischemia > discomfort at rest
What is the major cause of Variant/ angiospastic angina?
spasm in coronary artery (contract and relax)
Is variant/ angiospastic angina associated with underlying atheromas?
may or may not
Could be non-pathological
underlying atheromas may release mediators to stimulate spasm
What is variant angina triggered by? (stressfully smoking cocaine in the cold)
Which type of angina lasts the longest?
What are the 2 goals of antianginal drugs?
Increase perfusion of myocardium by coronary vessel dilation
Decrease metabolic demand by reducing cardiac workload
Why is non-selective vasodilator not used to increase perfusion of myocardium? Name the phenomenon.
Coronary Steal Phenomenon
Explain coronary steal phenomenon.
Heart automatically compensates for lack of perfusion due to atheroma by dilating arterioles downstream from occlusion
Non-selective vasodilator dilates all vessels except collateral vessels > would direct blood to least resistance vessel
Further decrease in blood supply to ischaemic area > exacerbate angina
What vessel does antianginal drug dilate vs non-selective vasodilators?
Collateral vessel, leading blood from vessel with more blood to one with less
What are the 6 antianginal drugs? NICBMD
-Inhibitors of slowly inactivating sodium current
-B-Adrenergic receptor blockers
-Direct bradycardiac agents
Name two commonly used Nitrates
Which type of angina is Nitrates used for?
Effective against Variant angina
What is the action of nitrates?
Effective vasodilators of Veins, Large arteries, Collateral coronary artery
How does dilation of vein improve angina?
Dilate vein > lower venous return > lower cardiac workload > lower myocardial O2 demand
How does dilation of large arteries improve angina?
Decrease peripheral vascular resistance > lower BP > lower cardiac workload > decrease myocardial O2 demand
How does dilation of collateral coronary artery improve angina?
Improve distribution of coronary flow
Mode of Action of nitrate causing vasodilation?
Nitrate > NO > increase production of cGMP > dephosphorylate MYOSIN LIGHT CHAIN > relaxation
Why can't nitrates be used as long-term management of angina?
Rapid onset/ immediate relief but short duration of action
How is nitrates metabolized in body?
Rapid metabolism in liver > First pass effect
Excretion by kidneys
What is the bioavailability of nitrates in oral or sublingual route?
Oral = low bioavailability, need larger dose
Sublingual = preferred to avoid excessive effect
What are the 2 main unwanted effects of nitrates?
What is tachyphylaxis in nitrate usage? How can this be improved?
Tachyphylaxis = lower response to nitrates
due to frequently repeated or continuous exposure
Improved with "nitrate-free" period (8-12 hours/day)
At night with low physical activity/ low demand for O2
What forms of administering nitrate can lead to tachyphylaxis?
Long acting isosorbide dinitirate
Prolonged infusion or slow release of short-acting nitroglycerin
What is the effect of sudden withdrawal of nitrate from a patient after chronic use?
Dependence- never abruptly withdraw nitrates from chronic use
Sudden Withdrawal > increase risk of coronary and digital arteriospasm
What are some common adverse effects to nitrates?
Postural hypotension (like B-blockers, due to vein vasodilation)
How can high dose of nitrate exacerbate angina?
High dose > sudden drop in BP > reflex tachycardia
Which two drugs is carefully used with nitrates?
PDE 5 inhibitor (PAH) e.g. sildenafil
Stimulators of soluble guanylyl cyclase (Type 4 PH)
What are the 5 ways ot administer nitrate? SCOTI
When is sublingual nitrate administration chosen?
Given for fast relief/ prevent angina before exercise
When is oral nitrate administration chosen?
Prophylaxis/ Prevention against angina in patients with frequent angina
(high dose, sustained release)
When is cutaneous nitrate administration chosen?
Controlling nocturnal angina
When is Transmucosal/ buccal nitrate administration chosen?
short term prevention of angina
When is IV nitrate administration chosen?
Allow rapid and safe titration
Emergency relief of coronary vasospasm
Name some common CCBs?
Nifedipine, amlodipine, diltiazem, verapamil
How does CCB help treat angina?
Decrease force of contraction of heart
Vasodilate arteries and arterioles
Decrease coronary artery spasm
What type of angina is CCB effective against?
What are some common adverse effects of vascular selective CCB?
Decrease coronary perfusion
What do the adverse effects of CCBs depend upon?
Cardiac selective or vascular selective
What are some adverse effects of cardiac selective CCB?
Atroventricular block > Heart failure
Name common B-blockers
How does B-blocker help angina?
Decrease rate and force of heart contraction
Which type of angina is B-blockers not used in?
because it increases coronary artery vasospasm
In which patients is B-blocker not used ? (Heart, vessels, glucose, brain)
Diabetes > hypoglycaemia
Asthma/ COPD > bronchospasm
Severe peripheral vascular diseases/ vasospastic disorders > vasospasm
Psychiatric disorders > CNS disturbance
Arrhythmia/ heart failure
Which 3 drugs are 1st line antianginal drugs?
Which drugs are 2nd line antianginal drugs? TRI
What is the mode of action of Trimetazidine? (metabolic modulator)
Inhibit long-chain mitochondrial 3-ketoacyl coenzyme A thiolase (3-KAT) enzyme
> inhibit myocardial FA oxidation > shift to glucose oxidation > less O2 needed > increase efficiency of cardiac oxygen use
Can trimetazidine be used in patients with low HR or BP?
No major effect on HR or BP (unlike B-blocker )
What are the contraindications of trimetazidine? (shaky kidneys)
Not used in:
1) parkinson diseases/ movement disorders > block dopamine receptors at high dose
2) Severely reduced kidney function > high plasma conc.
What are some mild trimetazidine side effects?
What is the action of Ranolazine under normal clinical use?
Late sodium current inhibitor in heart
Decrease sodium influx > less activation of Na/Ca exchanger > less intracellular Ca overload > lower contractility
Lower risk of Ca overload > diastolic relaxation failure & ishemia
What is the action of Ranolazine at very high doses/ not in clinical dosage?
Decrease O2 demand by inhibiting FA oxidation in myocardium> efficient use of O2
Increase coronary perfusion by inhibiting sodium channels in vascular SM > lower intracellular Ca conc.
Can ranolazine be used in patients with low HR or BP?
No major effect on HR or BP
What are some mild adverse effects of Ranolazine?
Why is Ranolazine not used in liver failure patients?
Metabolized by liver cytochrome P450 3A4 pathway
Hepatic dysfunction = cannot metabolize = high conc. = arrhythmia
Why cant ranolazine be used in patients with long QT syndrome?
Risk of increased duration of AP
Due to inhibition of K- current in cardiomyocytes
What drugs contraindicate Ranolazine?
Strong CYP3A4 inhibitors
e.g. azole, macrolide, clarithromycin, erythromycin
What patients must not use Ranolazine?
Patients with cirrhosis
What is the action of Ivabradine?
Inhibit HCN (hyperpolarization-activated cyclic nucleotide-gated) channels
Selectively inhibit funny current in SA node > decrease rate of spontaneous depolarisation > decrease HR
What is the target dose for Ivabradine ?
To maintain 50-60 bpm
>60 bpm = increase dose by 2.5mg (up yo 7.5mg twice/day)
<50 = decrease dose by 2.5mg twice/day
What are some adverse effects of Ivabradine? (slow, tense, fibrillating flashes)
Phosphene (flashes of light), blurred vision
Which patient groups must not take Ivabradine?
Name some drugs that cannot be used with Ivabradine?
Which type of patient is Ivabradine designed for?
Resting HR of at least 70 bpm
Chronic stable angina with normal sinus rhythm
Which type of patient is Ivabradine not designed for?
Resting HR <60bpm
BP < 90/50mmHg
SA node dysfunction, decompensated HF, pacemaker dependent
Taking CYP3A4 inhibitors
Pregnant, lactating, non-contraceptive fertile women
What are some common synergistic combos involving nitrates?
+ cardiac selective CCB
What are some common synergistic combos involving dihydropyridines?
cardiac selective CCB
What is the avoided combo that can worsen angina?
Nitrate + dihydropyridine
What are some common synergistic combos involving b-blockers? (everything but CCB)
Ivabradine (only if HR >60)
What are some common synergistic combos involving CCB?
What surgery can be done for angina ?
Coronary artery bypass grafting (CABG)
Percutaneous transluminal coronary angioplasty (PTCA)