Pharmacology of the CVS Flashcards
What is angina?
Angina is chest pain or pressure, usually due to not enough blood flow to the heart muscle.
What are some symptoms of angina?
- crushing chest pain, also in the jaw, shoulders, arms, etc.
- shortness of breath
- sweating
- nausea
What increases the risk of angina attack?
- INCREASED SYSTOLIC BLOOD PRESSURE (AFTERLOAD): the heart has to work harder to eject blood and so requires more oxygen
- INCREASED SYMPATHETIC NERVE ACTIVITY: this increases heart rate, increases contractility and increases vasoconstriction
What are the different types of angina?
- STABLE ANGINA (MOST COMMON): exercise-induced - predictable, relieved by rest and medications
- UNSTABLE ANGINA (ACUTE CORONARY SYNDROME, MORE SERIOUS): exercise-induced - unpredictable, may indicate thrombosis or plaque rupture
- VARIANT (PRINZMETAL) ANGINA: symptoms present at rest
Describe how an atheroma can lead to an angina during exercise.
In a normal heart, the resistance is low in the large coronary artery, and high in the arterioles. During exercise, metabolic vasodilation of the arterioles reduces the total resistance. This means that there is increased blood flow to meet the increased O2 demands.
In a heart with an atheroma, there is stenosis in the large coronary artery, increasing the resistance. This means that metabolic hyperaemia occurs at rest, so that the blood flow meets the O2 needs.
During exercise, arterioles will further dilate to reduce resistance, but the total resistance is still too high to dominate the stenosis.
This means that the O2 demand cannot be met, and angina develops.
What are the aims of the treatment for an atheroma?
IMPROVE THE PROGNOSIS:
- prevent MI and death
- reduce plaque progression
- stabilise plaque
- prevent thrombosis
MINIMISE SYMPTOMS:
- improve quality of life
What drugs can be used to treat angina?
- nitrates
- calcium-blockers
- β-blockers
How do β-blockers work in treating angina?
They reduce the actions of sympathetic activity (noradrenaline and adrenaline) on β1 adrenoreceptors in the heart.
- they slow the heart rate and AV conduction; this increases diastolic time, which increases coronary artery perfusion
- they reduce the force of contractility; this reduces myocardial work and oxygen consumption
How do calcium-blockers work in treating angina?
They reduce the Ca2+ entry into cardiac myocytes/ vascular smooth muscle cells; this reduced contractility.
- they can cause direct coronary vasodilation so there is more coronary blood flow
- they reduce TPR/ BP/ afterload, so the heart works less to eject blood
- they reduce the force of contraction, so there is less O2 consumption
What are the three subtypes of calcium-blockers (with examples of each)?
- dihydropyridines (vascular): Amplodipine, Nifedipine
- benzothiazepines (cardiac): Verapamil
- diphenylalkyamines (both): Diltiazem
List some side effects of dihydropyridines.
- lower limb oedemas (because of the increased capillary pressure in the lower limbs)
- flushing and headache (caused by excess vasodilatation)
- reflex tachycardia (increased vasodilation causes increased baroreflex, so increased sympathetic activity)
Describe how nitric oxide is made in the body, and how it affects it.
Stimulated by shear stress, acetylcholine, hitamine, bradykinin, etc., an enzyme called endothelium NO synthase (eNOS) converts L-Arginine to NO.
This NO diffuses from the endothelial cell to the vascular smooth muscle cell, where it will stimulate Guanylyl Cyclase to make more cGMP from GTP. cGMP activates Protein Kinase G.
Protein Kinase G reduces smooth muscle tone by:
- myosin light chain dephosphorylation
- increasing uptake of Ca2+ by the SR, causing a decrease in cytoplasmic levels
- activating K+ channels, causing hyperpolarisation and closing of the VGCCs
Where does vasodilatation occur?
1) coronary artery dilatation: increases collateral arteriole dilation to shunt blood from areas of good perfusion to poor perfusion (between functional end-arteries)
2) venodilatation: decreases venous return and preload
3) arteriole dilatation: decreases TPR and afterload
Decreased preload and afterload reduces the myocardial O2 demand, so will relieve symptoms.
List some commonly prescribed anti-angina drugs.
ASPIRIN: inhibits COX, decreasing thrombane A2 and platelet aggregation (GPIIb/IIIa expression)
CLOPIDOGRAL: inhibits ADP receptors on platelets
(both the above drugs can be used together because they use different mechanisms)
NICORANDIL: potassium channel activator, causing hyperpolarisation, leading to decreased VGCC activation and decreased Ca2+ entry
STATINS: HMG Co-A reductase inhibitor, so reducing cholesterol levels
IVABRADINE (PROCORALAN) - IN DEVELOPMENT: a selective inhibitor of the If channel in the SAN, so decreases pacemaker potential frequency, so decreases HR (HR is a risk factor for CVD)
