L50 – Treatment of Angina Flashcards by Max Kam

What is the major cause of stable/ classic/atherosclerotic angina?

Fixed narrowing / obstruction of epicardial coronary arteries by atheromatous obstruction

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Name some secondary non-atherosclerotic causes of stable angina. (ATCG)

Aortic dissection
Granulomas
Tumours
Congenital anomalies

(+ myocardial bridges
Scarring from trauma/radiation )

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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

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What is the major cause of Unstable angina?

 increase epicardial coronary artery tone
(vasoconstriction)

 Formation of unstable non-occlusive thrombi

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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

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What is the major cause of Variant/ angiospastic angina?

spasm in coronary artery (contract and relax)

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Is variant/ angiospastic angina associated with underlying atheromas?

may or may not

Could be non-pathological

underlying atheromas may release mediators to stimulate spasm

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What is variant angina triggered by? (stressfully smoking cocaine in the cold)

Stress
Vasoconstriction medication 
Cold weather 
Smoking 
Cocaine

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Which type of angina lasts the longest?

Variant angina

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What are the 2 goals of antianginal drugs?

Increase perfusion of myocardium by coronary vessel dilation

Decrease metabolic demand by reducing cardiac workload

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Why is non-selective vasodilator not used to increase perfusion of myocardium? Name the phenomenon.

Coronary Steal Phenomenon

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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

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What vessel does antianginal drug dilate vs non-selective vasodilators?

Collateral vessel, leading blood from vessel with more blood to one with less

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What are the 6 antianginal drugs? NICBMD

Nitrates
Inhibitors of slowly inactivating sodium current
CCB
B-Adrenergic receptor blockers
Metabolic modulators
Direct bradycardiac agents

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Name two commonly used Nitrates

Nitroglycerin

Isosorbide dinitrate

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Which type of angina is Nitrates used for?

Effective against Variant angina

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What is the action of nitrates?

Effective vasodilators of Veins, Large arteries, Collateral coronary artery

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How does dilation of vein improve angina?

Dilate vein > lower venous return > lower cardiac workload > lower myocardial O2 demand

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How does dilation of large arteries improve angina?

Decrease peripheral vascular resistance > lower BP > lower cardiac workload > decrease myocardial O2 demand

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How does dilation of collateral coronary artery improve angina?

Improve distribution of coronary flow

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Mode of Action of nitrate causing vasodilation?

Nitrate > NO > increase production of cGMP > dephosphorylate MYOSIN LIGHT CHAIN > relaxation

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Why can’t nitrates be used as long-term management of angina?

Rapid onset/ immediate relief but short duration of action

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How is nitrates metabolized in body?

Rapid metabolism in liver > First pass effect

Excretion by kidneys

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What is the bioavailability of nitrates in oral or sublingual route?

Oral = low bioavailability, need larger dose

Sublingual = preferred to avoid excessive effect

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What are the 2 main unwanted effects of nitrates?

Dependence | Tolerance/ Tachyphylaxis

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?

Tachycardia Postural hypotension (like B-blockers, due to vein vasodilation) Headache

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) e.g. riociguat

What are the 5 ways ot administer nitrate? SCOTI

``` Sublingual Cutaneous Oral Transmucosal/ Buccal IV ```

When is sublingual nitrate administration chosen?

Fast, short-acting. 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?

Slow onset | Controlling nocturnal angina

When is Transmucosal/ buccal nitrate administration chosen?

short term prevention of angina gradual release

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?

Variant angina

What are some common adverse effects of vascular selective CCB?

Headache Flushing Peripheral oedema Reflex tachycardia 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

propranolol | Metaprolol

How does B-blocker help angina?

Decrease rate and force of heart contraction

Which type of angina is B-blockers not used in?

Variant angina 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?

CCB B-blocker Nitrate

Which drugs are 2nd line antianginal drugs? TRI

Trimetazidine Ranolazine Ivabradine

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?

Yes 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?

GI discomfort cramps dizziness

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?

Yes No major effect on HR or BP

What are some mild adverse effects of Ranolazine?

nausea Dizziness headache constipation

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)

Bradycardia Phosphene (flashes of light), blurred vision Atrial fibrillation Hypertension

Which patient groups must not take Ivabradine?

Taking CCB Arrhythmia QT-prolonging drugs Hypokalemia-causing drugs

Name some drugs that cannot be used with Ivabradine?

``` Quinidine Thiazide Loop D. Verapamil Diltiazem ```

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?

``` Nitrates + cardiac selective CCB or + B-blocker or + Trimetazidine or +Ranolazine ```

What are some common synergistic combos involving dihydropyridines?

B-blocker | 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)

``` B-blockers + Trimetazidine Ranolazine Dihydropyridine Nitrates Ivabradine (only if HR >60) ```

What are some common synergistic combos involving CCB?

``` CCB (cardiac-selective) +nitrate +dihydropyridine +trimetazidine +Ranolazine ```

What surgery can be done for angina ?

Coronary artery bypass grafting (CABG) Percutaneous transluminal coronary angioplasty (PTCA)

What are other pharmacological therapy of angina?

Anti-coagulant Anti-platelet Lipid-lowering drug Prevent thrombi formation, unstable angina and atheroma deposition

L50 – Treatment of Angina Flashcards

(75 cards)