Pharmacology of the CVS Flashcards

1
Q

Quantitatively describe the effects of angina pectoris

A
  • 2 million sufferers in the UK
  • annual risk of death (usually MI) of 4 - 6%
  • Quality of life impacted
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2
Q

What causes angina pectoris?

A

Caused by local myocardial Ischaemia

  • when oxygen demand exceeds supply
  • often precipitated by exertion; reversible at rest
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3
Q

Outline the symptoms of Angina Pectoris

A
  • Crushing chest pain (or in jaw, shoulders ,arms)
  • Ischaemic products (H+, lactate)
    -> stimulate nociceptive afferents
  • may be associated with shortness of breath, sweating
    and nausea
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4
Q

What is the risk of angina increased by?

A

Increased Systolic BP (afterload)
Increased sympathetic nerve activity
Increased Contractility
Increased vasoconstriction

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5
Q

Explain how increased afterload increases risk of angina

A

Heart has to work harder to eject blood; requires more oxygen

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6
Q

How does increased sympathetic activity cause angina?

A

Less diastolic time

Less coronary artery perfusion which only occurs in systole

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7
Q

What causes increased contractility?

A

exercise
emotion
stress
aortic valve stenosis

=> all increase Oxygen demand

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8
Q

Give an example of how increased vasoconstriction trigger angina?

A

e. g.
- Redistribution of blood flow in cold weather
- During large meal blood diverted to GI
etc.

=> vasoconstriction in coronary circulation

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9
Q

What are the different types of angina?

A

Stable Angina
Unstable Angina
Variant (prinzmetal) Angina

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10
Q

Describe the pathology of Stable angina

A

most common form
- exercise induced: predictable can work out how much
exertion induces symptoms

  • not able to meet increased oxygen demand due to
    atheroma in coronary arteries
  • relieved by rest and medications
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11
Q

Describe unstable angina

A
  • induced due to minimal exertion; unpredictable
  • rest and medications may not relieve symptoms
  • may indicate thrombosis / plaque rupture
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12
Q

Outline the features of Variant (prinzmetal) angina

A
  • symptoms at rest
  • decreased oxygen supply due to vasospasm
    (uncontrolled vasoconstriction decreasing blood flow)
    downstream of occlusion
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13
Q

How are the different forms of angina detected?

A

All linked to acute coronary syndrome (coronary thrombosis)

- ECG will show STEMI

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14
Q

Describe the effect of stable angina during normal activity

A

In exercise, metabolic vasodilation of arterioles reduces resistance to increase blood flow to meet increased oxygen demand

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15
Q

Describe the effects of stable angina during exercise

A

Stenosis in coronary arteries increases resistance
at rest metabolic vasodilation occurs as normal

However/
during exercise arterioles may attempt further dilation but TPR is still too high - Oxygen demand can’t be met; angina develops

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16
Q

What are the aims of angina treatment?

A

Improve prognosis

  • prevent MI + death
  • reduce plaque progression - stabilise it
  • prevent thrombosis

Minimise symptoms
- improve quality of life

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17
Q

What are the approaches to angina treatment?

A

Vasodilators: Nitrates
Cardiac depressants: Beta Blockers
Both: Ca2+ blockers

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18
Q

Explain how ꞵ Blockers aid angina treatment

A

Reduce action of sympathetic activity (NA and adrenaline) on ꞵ₁ adrenoceptors in the heart causing:

  • Slow HR and AV conduction
  • Reduced force of Contractility
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19
Q

What is the effect of slowed HR and AV conduction?

A

Increased diastolic time - increases coronary artery perfusion
Both of these factors mean more energy is required and ∴ a greater oxygen demand

20
Q

What is the effect of a reduced force of contractility?

A

Reduces myocardial work and oxygen consumption

21
Q

Name an example of a ꞵ-blocker drug used to treat high BP

A

Atenolol

more ꞵ₁ selective - ꞵ₂ found in vasculature & airways

22
Q

Describe the side effects of using atenolol

A

Bronchospasm
Fatigue
Postural hypotension

23
Q

Evaluate the use of ꞵ₁ selective drugs

A

Advantage:
ꞵ₁ selective is better as reduces side effects of ꞵ₂ e.g. bronchospasm (but is still not perfect)

Disadvantage:
Blocking ꞵ₁ causes fatigue as heart rate / force of contraction can’t be increased

24
Q

When is the use of ꞵ blockers such as Atenolol contraindicated?

A

Asthma
- don’t want to block ꞵ₁ as will cause bronchospasm

Heart blockage:

  • already poor perfusion between atria and ventricles
  • don’t want to block AV conduction further via AV node
25
Q

Explain how Ca2+ channel blockers provide anti-anginal effects

A

Reduces contractility by reducing Ca2+ entry into cardiac myocytes / vascular smooth muscle cells

26
Q

Describe the effects on the CVS of Ca2+ channel blockers

A

Direct coronary vasodilation ∴ more coronary blood flow

Reduced TPR/BP/afterload ∴ heart works less hard to eject blood

Reduced force of contraction ∴less oxygen consumption

27
Q

What are the 3 different sub types of Ca2+ channel blockers?

A

Vascular
- dihydropyridines e.g; amplodipine, nifedipine

Cardiac
- Benzothiazepines e.g; Verapamil

Both
- Diphenylalkyamines e.g; Diltiazem

28
Q

What are the side effects of dihydropyridines?

A

lower limb oedema due to increased Pc
Flushing and headaches due to vasodilation
Reflex tachycardia

29
Q

How do dihydropyridines cause reflex tachycardia?

A

Dihydropyridine induced vasodilation causes increased sympathetic activity (baroreflex) HR/Contractility - negative in angina

30
Q

What is a major caution of using Ca2+ channel blockers in the heart?

A

Blocking Ca2+ channels in the heart may alter electrical conduction and contractility

31
Q

How is NO produced / donated in the body?

A
  1. ENOS - endothelium NO synthesis
    • conversion of L-arginine -> NO
  2. NO donors cause dilation of smooth muscles
  3. NO -> cGMP -> PKG / GMP via PDE5
32
Q

What is NO production / donation stimulated?

A

Shear stress
ACh
Histamine
Bradykinin

33
Q

Describe some essential features of NO gas

A

Lipophilic, soluble gas
Continually produced and released
Diffusible endothelium -> surrounding vascular smooth myocytes

34
Q

What is the effect of Protein Kinase G (PKG) produced from NO on CVS?

A

PKG reduces smooth muscle tone:
- via myosin light chain dephosphorylation
- increased Ca2+ uptake by SR, decreasing cytoplasmic
levels
- activates K+ channel s causing hyperpolarisation ->
closing VGCCs

35
Q

Where does vasodilation occur?

A

Coronary artery and veins

36
Q

What is the effect of coronary artery dilation?

A

Coronary artery dilation:

  • reduces TPR
  • decreasing afterload
  • increases collateral arteriole dilation
  • shunts blood from areas of good perfusion
37
Q

What is the effect of venodilation?

A

Decreases intraventricular pressure to decrease cardiac preload

38
Q

Give examples of drugs used to cause vasodilation

A

GTN (glyceryl trinitrate)
- spray, sublingual tablets

Isosorbide mononitrate

  • oral, longer acting
  • high oral dose (1st pass metabolism by liver)
39
Q

Name other anti-anginal drugs

A

Nicorandil
Ivabradine
Ranolazine

40
Q

Explain the effects of Nicorandil

A

K+ channel activator
causes hyperpolarisation; decreased VGCCs and Ca2+ entry -> coronary vasodilation
Has nitrate moiety ∴ has venodilation action via NO production

41
Q

Describe the effects of Ivabradine

A

Specific If current inhibitor in SAN - slows HR

  • Decreases pacemaker potential frequency
  • Decreases HR reducing myocardial oxygen demand
42
Q

Explain the effects of anti-anginal drug, Ranolazine

A
Late Na+ current inhibitor 
reduces Ca2+ in ischaemic myocardiocytes
reduces Oxygen demand 
reduces compression of small intra-myocardial vessels 
-> improves myocardial perfusion
43
Q

Name some prophylactic angina drugs

A

Aspirin
Clopidogrel
Statins

44
Q

Explain the effects of Aspirin on Angina

A

Inhibits COX

Decreases Thromboxane A2 and platelet aggregation (GpIIb/IIIa) expression

45
Q

How does Clopidogrel prevent angina?

A

Inhibits ADP receptor on platelets, reducing aggregation

46
Q

Why are Aspirin and Clopidogrel often used together?

A

Both reduce thrombosis and can be used together as they have entirely different mechanisms

47
Q

What is the effect of Statins?

A

HMG-CoA Reductase inhibitor - decreases cholesterol levels