Cardiovascular pharmacology tutorial Flashcards
How does smoking, body weight, exercise and salt affect HTN?
Smoking: nicotine causes vasoconstriction
Salt: 30% of HTN salt sensitive (so have low renin) and restriction of salt helps
Exercise: Exercise will help encourage weight loss and has other cardiovascular benefits. Exercise increases circulation to the skin/muscles and widens the arteries. Improves renal function.
Weight: Adipose tissue does contain components of RAS system, and the system is activated in obese individuals despite marked volume expansion.
Why is thiazide best choice
Subtle alterations in the contractile response of vascular smooth muscle.
(after 4-6 weeks, the blood volume is restored)
Why does ACEi work well as a second line treatment to thiazides
GENERAL ATII:
-Vasoconstriction (particularly in the kidney)
- Increased release of NA from sympathetic nerve terminals – reinforcing vasoconstriction
- Stimulation of proximal tubular reabsorption of Na+ – increasing blood volume.
- Secretion of aldosterone from adrenal cortex – further increasing Na+ reabsorption and increased blood volume.
with thiazides, there has been increased renin due to the long term Na+ concentration reduction in the filtrate, so activated RAS, which can actually increase response to ACEi.
Also bradykinin increases which romotes vasodilator activity and may contribute to the overall effectiveness of ACE inhibitors.
Why should afrocarribbeans not be on ACEi
Afro-Caribbeans and elderly individuals, who tend to have low renin hypertension, respond less well to monotherapy with ACE inhibitors.
Why would you give warfarin to someone with AF
Atrial fibrillation has been shown to predispose patients to atrial thrombus formation and subsequent systemic emboli, which commonly cause stroke. Consequently Warfarin, an oral anticoagulant, is given prophylactically to prevent thromboembolism.
Mechanism of digoxin action
DIRECTLY and INDIRECTLY (i.e. via vagus nerve), INHIBIT Na+/K+-ATPase
T/F digoxin currently the main treatment for AF
F
Digoxin currently sidelined due to increased risk of death in patients with atrial fibrillation. Could be due to increase in platelet activity. Currently replaced with beta blockers.
Mechanism of warfarin action
Warfarin blocks the formation of Vitamin K by inhibiting the hepatic reductase enzyme that converts vitamin K to its active (hydroquinone) form. Vitamin K is essential for the formation of the clotting factors II, VII, IX and X. Consequently warfarin affects blood clotting time.
Stable vs unstable angina
Stable angina: ATHEROMA. Predictable pain on exertion and is due to a fixed narrowing of the coronary vessels by atheroma.
Unstable angina: CLOT. Pain following less and less exertion culminating in pain on resting. This is usually associated with a thrombus (derived from an atheromatous plaque) partially occluding the vessel(s)
How do organic nitrates work
release of nitric oxide–> vascular relaxation.
Increases GC, which increases cGMP, which promotes relaxation. In addition, cGMP can open K+ channels which causes hyperpolarisation, which prevents the inward movement of Ca2+.
NO may also directly open K+ channels
Why is hypercholesterolaemia bad
associated with a markedly increased risk of ischaemic heart disease, arising from rupture of atheromatous plaques in the coronary arteries and leading to myocardial infarction.
How do statins work
Inhibiting the enzyme HMG-CoA reductase
The conversion of HMG-CoA to mevalonic acid is the rate-limiting step in cholesterol synthesis in the body and is catalysed by the enzyme HMG-CoA reductase.
The fall in cholesterol synthesis produces a compensatory increase in expression of LDL receptors on the hepatocyte and increased clearance of circulating levels of LDL cholesterol.
When is HMG-CoA reductase active
when blood glucose is high
How does beta blocker used in angina
β-blockers act as competetitive antagonists of catecholamines at β-adrenoreceptors thereby reducing heart rate and contractility. The effects are most marked during exercise.
Decrease If and ICa
Why is aspirin used in angina
Arachidonic acid is converted to thromboxane A2 by the action of cyclooxygenase.
Thromboxane is produced by platelets and promotes platelet aggregation.
Aspirin irreversibly inhibits cyclooxygenase activity thereby reducing the risk of thromboembolism.
Prophylactic use.
TXA2 activation leads to expression of GPIIb/IIIa integrin receptor on platelet surface
GPIIb/IIIa - involved in platelet aggregation
