Drugs of the Cardiovascular System – The Vasculature Flashcards
Name three drug classes that interfere with the renin-angiotensin system.
Renin inhibitors
ACE inhibitors
Angiotensin receptor blockers
Describe the action of aldosterone in collecting duct tubule cells.
Aldosterone passes through the plasma membrane and binds to mineralocorticoid receptors intracellularly and increases the synthesis of Na+ channels and Na+/K+ pumps
This causes an increase in sodium reabsorption and potassium excretion. (increased intracellular K+ due to Na+/K+ pump, the K+ then diffuses out passively on the tubular fluid side via K+ channels)
What are the uses of ACE inhibitors?
Hypertension Heart Failure Diabetic Nephropathy Post-MI Progressive Renal Insufficiency Patients at high risk of cerebrovascular disease
Give an example of an ACE inhibitor.
Enalapril
Ramipril
drugs that end in ‘-pril’ are normally ACE inhibitors
What are the main actions of angiotensin II?
How do ACEi treat hypertension and heart failure?
A2 actions:
- intrinsic salt retention ability
- Salt retention via aldosterone
- Vasoconstriction
- SNS activation
Hypertension:
Reduce TPR, less fluid retention and hence less venous return
Heart failure:
reduced TPR=lower afterload
reduced venous return= less preload
What law links venous return to contractility?
Starling’s Law
What is diabetic nephropathy caused by?
It is due to significant damage to the kidney glomerulus because of toxic products building up at the glomerulus
NOTE: hyperglycaemia increases the risk of exposure to oxygen free radicals
Why are ACE inhibitors used in diabetic nephropathy?
ACE inhibitors reduce the angiotensin II-mediated vasoconstriction of the efferent arteriole
This reduces the blood pressure at the glomerulus and hence reduces the accumulation of toxic products at the glomerulus
Give an example of an angiotensin receptor blocker.
Losartan
ARBs end in ‘sartan’
What is the most common side effect of ACE inhibitors?
COUGH
due to bradykinin build up
Which 2 group of patients do you have to be careful of when thinking of prescribing ARBs or ACEi ? Think of its potential side effects
- Hyperkalaemia (aldosterone causes increased potassium excretion). So NOT given to patients on K supplement or K sparing diuretics
- Patients with renal failure as a result of renal artery stenosis (stenosis reduces blood flowing into glomerulus, so low pressure and low GFR. A2 normally constricts efferent arteriole. If you stop this then the pressure is reduced further in the glomerulus)
Describe the excitation-contraction coupling of vascular smooth muscle cells.
Deplarisation causes the opening of voltage-gated calcium channels (VGCC)
This leads to calcium influx
The calcium then binds to calmodulin forming a Ca2+-CaM complex
This complex activates Myosin Light Chain Kinase (MLCK), and the MLCK-mediated phosphorylation leads to smooth muscle contraction
What type of calcium channel blocker is more selective for blood vessels? Give an example.
Dihydropyridines – nicardipine
(non rate limiting CCB)
dipine = dihyropyridines
Give 4 examples of non-rate slowing CCBs.
Nicardipine
Nitrendipine
Amlodipine
Nisoldipine
Which part of the calcium channel do the different CCBs bind to?
Dihydropyridines bind to the extracellularly component of the calcium channel
Diltiazem and verapamil binds to the intracellular component so for a CCB to have an effect on the heart it needs to be able to penetrate the membrane and act on the receptor inside the cell
