Flashcards in cardiovascular pharmacology Deck (31):
What are the vascular smooth muscle innervated by?
What is vascular tone?
The degree of constriction experienced by a blood vessel relative to its maximally dilated state.
What is the mechanism of vascular smooth muscle contraction?
1) Stimulation of angiotensin II type 1 receptors and alpha adrenergic receptors --> Activates phospholipase C.
2) This produces the 2nd messenger IP3
3) IP3 stimulates release of ca2+ from the sarcoplasmic reticulum --> raised conc of ca2+
4) Raised ca2+ activates calmodulin --> which activates myosin light chain kinase (MLCK)
5) MLCK phosphorylates myosin light chain (myosin - LC)
6) Phosphorylated myosin -LC interacts with actin-myosin cross-bridges - INITIATES VASCULAR SMOOTH MUSCLE CONTRACTION
List some types of vasodilators
ACE inhibitors, AT1R antagonists, calcium channe; blockers, potassium channel blockers
How do ace inhibitors cause vasodilation?
inhibits the formation of angiotensin II
How is angiotensin II formed?
Kidney secretes renin, renin cleaves the prohormone angiotensinogen to angiotensin I
Ang I is then converted to angiotenin II by angiotensin converting enzymes (ace) - CAUSES VASOCONTRICTION AND RAISES BP
What do ace inhibitors do?
They inhibit the renin- angiotensin system by inhibiting the conversion of angiotensin I to angiotensin II
They also decrease the breakdown of bradykinin causing vasodilation as a result
What does increase in bradykinin do?
What are some of the effects of angiotensin AT1 stimulation?
- Aldosterone secretion from adrenal glands
- Renal NaCl reabsorption
-Stimulation of thirst
What are the effects of angiotensin AT2 receptor
vasodilation through bradykinin and NO release
What do ACEi end in?
PRIL e.g ramipril
What do angiotensin II receptor blockers do?
Inhibit the binding of ang II to the AT1 receptor, promoting vasodilation.
What is the name of the other pathway that produces angiotensin II
What do angiotensin II receptor blockers end in?
SARTAN e.g losartan
Describe the mechanism of smooth muscle relaxation (WITH Nitric oxide)
NO increases the level of cGMP within the cell.
What is glyceryl trinitrate
a prodrug - used to treat MI and pulmonary oedema. CAUSES VASODILATION
How does vasodilation occur?
1) Agonist stimulation of beta-2-adrenergic receptors --> lead to activation of adenylate cyclase --> producing the second messenger cAMP.
2) cAMP activates protein kinase A which has several effects such as reducing calcium conc and reducing myosin light chain phosphorylation
Give an example of Beta-2- agonist
Salbutamol - used in asthma
What is arterial thrombosis?
Atherosclerosis plaque ruptures, activating coagulation and platelets which form big clot/ thrombus.
What is percutaneous coronary intervention?
Non-surgical widening of the coronary artery - using balloon stent - used in MI, angina.
What is thromboxane?
Induces platelet aggregation
What is cox enzyme?
Cyclooxygenase - its responsible for the production of thromboxane
How does aspirin work as antiplatelet?
Inactivates COX 1 enzymes - suppressing production of thromboxane.
What are ADP receptors?
These are found on the surface of platelets - activate them
How does phioenopyridines act as antiplatelets?
works by inhibiting the p2y12 adp receptor - forming a disulfide bridge with the platelet adp receptor
What are the two main types of anticoagulants?
Vitamin K antagonists and heparins
What is warfarin?
very commonly used anticoagulant - used in the treatment of thrombosis and embolism
How does it work?
it is structurally similar to vitamin K, and it inhibits vitamin K epoxidide reductase
What is heparin?
it is a blood thinner
What are the two clinically used heparins?
low molecular weight and unfractioned