L50 – Treatment of Angina Flashcards Preview

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Flashcards in L50 – Treatment of Angina Deck (75):
1

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

Fixed narrowing / obstruction of epicardial coronary arteries by atheromatous obstruction

2

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

Aortic dissection
Granulomas
Tumours
Congenital anomalies

(+ myocardial bridges
Scarring from trauma/radiation )

3

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

4

What is the major cause of Unstable angina?

 increase epicardial coronary artery tone
(vasoconstriction)

 Formation of unstable non-occlusive thrombi

5

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

6

What is the major cause of Variant/ angiospastic angina?

spasm in coronary artery (contract and relax)

7

Is variant/ angiospastic angina associated with underlying atheromas?

may or may not

Could be non-pathological

underlying atheromas may release mediators to stimulate spasm

8

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

Stress
Vasoconstriction medication
Cold weather
Smoking
Cocaine

9

Which type of angina lasts the longest?

Variant angina

10

What are the 2 goals of antianginal drugs?

Increase perfusion of myocardium by coronary vessel dilation

Decrease metabolic demand by reducing cardiac workload

11

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

Coronary Steal Phenomenon

12

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

13

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

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

14

What are the 6 antianginal drugs? NICBMD

-Nitrates
-Inhibitors of slowly inactivating sodium current
-CCB

-B-Adrenergic receptor blockers
-Metabolic modulators
-Direct bradycardiac agents

15

Name two commonly used Nitrates

Nitroglycerin
Isosorbide dinitrate

16

Which type of angina is Nitrates used for?

Effective against Variant angina

17

What is the action of nitrates?

Effective vasodilators of Veins, Large arteries, Collateral coronary artery

18

How does dilation of vein improve angina?

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

19

How does dilation of large arteries improve angina?

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

20

How does dilation of collateral coronary artery improve angina?

Improve distribution of coronary flow

21

Mode of Action of nitrate causing vasodilation?

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

22

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

Rapid onset/ immediate relief but short duration of action

23

How is nitrates metabolized in body?

Rapid metabolism in liver > First pass effect

Excretion by kidneys

24

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

Oral = low bioavailability, need larger dose

Sublingual = preferred to avoid excessive effect

25

What are the 2 main unwanted effects of nitrates?

Dependence
Tolerance/ Tachyphylaxis

26

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

27

What forms of administering nitrate can lead to tachyphylaxis?

Long acting isosorbide dinitirate

Prolonged infusion or slow release of short-acting nitroglycerin

28

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

29

What are some common adverse effects to nitrates?

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

30

How can high dose of nitrate exacerbate angina?

High dose > sudden drop in BP > reflex tachycardia

31

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

32

What are the 5 ways ot administer nitrate? SCOTI

Sublingual
Cutaneous
Oral
Transmucosal/ Buccal
IV

33

When is sublingual nitrate administration chosen?

Fast, short-acting.

Given for fast relief/ prevent angina before exercise

34

When is oral nitrate administration chosen?

Prophylaxis/ Prevention against angina in patients with frequent angina

(high dose, sustained release)

35

When is cutaneous nitrate administration chosen?

Slow onset
Controlling nocturnal angina

36

When is Transmucosal/ buccal nitrate administration chosen?

short term prevention of angina

gradual release

37

When is IV nitrate administration chosen?

Allow rapid and safe titration

Emergency relief of coronary vasospasm

38

Name some common CCBs?

Nifedipine, amlodipine, diltiazem, verapamil

39

How does CCB help treat angina?

Decrease force of contraction of heart

Vasodilate arteries and arterioles

Decrease coronary artery spasm

40

What type of angina is CCB effective against?

Variant angina

41

What are some common adverse effects of vascular selective CCB?

Headache
Flushing
Peripheral oedema

Reflex tachycardia
Decrease coronary perfusion

42

What do the adverse effects of CCBs depend upon?

Cardiac selective or vascular selective

43

What are some adverse effects of cardiac selective CCB?

Atroventricular block > Heart failure

44

Name common B-blockers

propranolol
Metaprolol

45

How does B-blocker help angina?

Decrease rate and force of heart contraction

46

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

Variant angina

because it increases coronary artery vasospasm

47

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

48

Which 3 drugs are 1st line antianginal drugs?

CCB
B-blocker
Nitrate

49

Which drugs are 2nd line antianginal drugs? TRI

Trimetazidine

Ranolazine

Ivabradine

50

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

51

Can trimetazidine be used in patients with low HR or BP?

Yes

No major effect on HR or BP (unlike B-blocker )

52

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.

53

What are some mild trimetazidine side effects?

GI discomfort
cramps
dizziness

54

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

55

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.

56

Can ranolazine be used in patients with low HR or BP?

Yes

No major effect on HR or BP

57

What are some mild adverse effects of Ranolazine?

nausea
Dizziness
headache
constipation

58

Why is Ranolazine not used in liver failure patients?

Metabolized by liver cytochrome P450 3A4 pathway

Hepatic dysfunction = cannot metabolize = high conc. = arrhythmia

59

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

60

What drugs contraindicate Ranolazine?

Strong CYP3A4 inhibitors

e.g. azole, macrolide, clarithromycin, erythromycin

61

What patients must not use Ranolazine?

Patients with cirrhosis

62

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

63

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

64

What are some adverse effects of Ivabradine? (slow, tense, fibrillating flashes)

Bradycardia

Phosphene (flashes of light), blurred vision

Atrial fibrillation

Hypertension

65

Which patient groups must not take Ivabradine?

Taking CCB
Arrhythmia
QT-prolonging drugs
Hypokalemia-causing drugs

66

Name some drugs that cannot be used with Ivabradine?

Quinidine
Thiazide
Loop D.
Verapamil
Diltiazem

67

Which type of patient is Ivabradine designed for?

Resting HR of at least 70 bpm

Chronic stable angina with normal sinus rhythm

68

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

69

What are some common synergistic combos involving nitrates?

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

70

What are some common synergistic combos involving dihydropyridines?

B-blocker
cardiac selective CCB

71

What is the avoided combo that can worsen angina?

Nitrate + dihydropyridine

72

What are some common synergistic combos involving b-blockers? (everything but CCB)

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

73

What are some common synergistic combos involving CCB?

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

74

What surgery can be done for angina ?

Coronary artery bypass grafting (CABG)

Percutaneous transluminal coronary angioplasty (PTCA)

75

What are other pharmacological therapy of angina?

Anti-coagulant
Anti-platelet
Lipid-lowering drug

Prevent thrombi formation, unstable angina and atheroma deposition

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