Pharmacology of the CVS Flashcards
Quantitatively describe the effects of angina pectoris
- 2 million sufferers in the UK
- annual risk of death (usually MI) of 4 - 6%
- Quality of life impacted
What causes angina pectoris?
Caused by local myocardial Ischaemia
- when oxygen demand exceeds supply
- often precipitated by exertion; reversible at rest
Outline the symptoms of Angina Pectoris
- 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
What is the risk of angina increased by?
Increased Systolic BP (afterload)
Increased sympathetic nerve activity
Increased Contractility
Increased vasoconstriction
Explain how increased afterload increases risk of angina
Heart has to work harder to eject blood; requires more oxygen
How does increased sympathetic activity cause angina?
Less diastolic time
Less coronary artery perfusion which only occurs in systole
What causes increased contractility?
exercise
emotion
stress
aortic valve stenosis
=> all increase Oxygen demand
Give an example of how increased vasoconstriction trigger angina?
e. g.
- Redistribution of blood flow in cold weather
- During large meal blood diverted to GI
etc.
=> vasoconstriction in coronary circulation
What are the different types of angina?
Stable Angina
Unstable Angina
Variant (prinzmetal) Angina
Describe the pathology of Stable angina
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
Describe unstable angina
- induced due to minimal exertion; unpredictable
- rest and medications may not relieve symptoms
- may indicate thrombosis / plaque rupture
Outline the features of Variant (prinzmetal) angina
- symptoms at rest
- decreased oxygen supply due to vasospasm
(uncontrolled vasoconstriction decreasing blood flow)
downstream of occlusion
How are the different forms of angina detected?
All linked to acute coronary syndrome (coronary thrombosis)
- ECG will show STEMI
Describe the effect of stable angina during normal activity
In exercise, metabolic vasodilation of arterioles reduces resistance to increase blood flow to meet increased oxygen demand
Describe the effects of stable angina during exercise
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
What are the aims of angina treatment?
Improve prognosis
- prevent MI + death
- reduce plaque progression - stabilise it
- prevent thrombosis
Minimise symptoms
- improve quality of life
What are the approaches to angina treatment?
Vasodilators: Nitrates
Cardiac depressants: Beta Blockers
Both: Ca2+ blockers
Explain how ꞵ Blockers aid angina treatment
Reduce action of sympathetic activity (NA and adrenaline) on ꞵ₁ adrenoceptors in the heart causing:
- Slow HR and AV conduction
- Reduced force of Contractility
What is the effect of slowed HR and AV conduction?
Increased diastolic time - increases coronary artery perfusion
Both of these factors mean more energy is required and ∴ a greater oxygen demand
What is the effect of a reduced force of contractility?
Reduces myocardial work and oxygen consumption
Name an example of a ꞵ-blocker drug used to treat high BP
Atenolol
more ꞵ₁ selective - ꞵ₂ found in vasculature & airways
Describe the side effects of using atenolol
Bronchospasm
Fatigue
Postural hypotension
Evaluate the use of ꞵ₁ selective drugs
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
When is the use of ꞵ blockers such as Atenolol contraindicated?
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
Explain how Ca2+ channel blockers provide anti-anginal effects
Reduces contractility by reducing Ca2+ entry into cardiac myocytes / vascular smooth muscle cells
Describe the effects on the CVS of Ca2+ channel blockers
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
What are the 3 different sub types of Ca2+ channel blockers?
Vascular
- dihydropyridines e.g; amplodipine, nifedipine
Cardiac
- Benzothiazepines e.g; Verapamil
Both
- Diphenylalkyamines e.g; Diltiazem
What are the side effects of dihydropyridines?
lower limb oedema due to increased Pc
Flushing and headaches due to vasodilation
Reflex tachycardia
How do dihydropyridines cause reflex tachycardia?
Dihydropyridine induced vasodilation causes increased sympathetic activity (baroreflex) HR/Contractility - negative in angina
What is a major caution of using Ca2+ channel blockers in the heart?
Blocking Ca2+ channels in the heart may alter electrical conduction and contractility
How is NO produced / donated in the body?
- ENOS - endothelium NO synthesis
- conversion of L-arginine -> NO
- NO donors cause dilation of smooth muscles
- NO -> cGMP -> PKG / GMP via PDE5
What is NO production / donation stimulated?
Shear stress
ACh
Histamine
Bradykinin
Describe some essential features of NO gas
Lipophilic, soluble gas
Continually produced and released
Diffusible endothelium -> surrounding vascular smooth myocytes
What is the effect of Protein Kinase G (PKG) produced from NO on CVS?
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
Where does vasodilation occur?
Coronary artery and veins
What is the effect of coronary artery dilation?
Coronary artery dilation:
- reduces TPR
- decreasing afterload
- increases collateral arteriole dilation
- shunts blood from areas of good perfusion
What is the effect of venodilation?
Decreases intraventricular pressure to decrease cardiac preload
Give examples of drugs used to cause vasodilation
GTN (glyceryl trinitrate)
- spray, sublingual tablets
Isosorbide mononitrate
- oral, longer acting
- high oral dose (1st pass metabolism by liver)
Name other anti-anginal drugs
Nicorandil
Ivabradine
Ranolazine
Explain the effects of Nicorandil
K+ channel activator
causes hyperpolarisation; decreased VGCCs and Ca2+ entry -> coronary vasodilation
Has nitrate moiety ∴ has venodilation action via NO production
Describe the effects of Ivabradine
Specific If current inhibitor in SAN - slows HR
- Decreases pacemaker potential frequency
- Decreases HR reducing myocardial oxygen demand
Explain the effects of anti-anginal drug, Ranolazine
Late Na+ current inhibitor reduces Ca2+ in ischaemic myocardiocytes reduces Oxygen demand reduces compression of small intra-myocardial vessels -> improves myocardial perfusion
Name some prophylactic angina drugs
Aspirin
Clopidogrel
Statins
Explain the effects of Aspirin on Angina
Inhibits COX
Decreases Thromboxane A2 and platelet aggregation (GpIIb/IIIa) expression
How does Clopidogrel prevent angina?
Inhibits ADP receptor on platelets, reducing aggregation
Why are Aspirin and Clopidogrel often used together?
Both reduce thrombosis and can be used together as they have entirely different mechanisms
What is the effect of Statins?
HMG-CoA Reductase inhibitor - decreases cholesterol levels
