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
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
What are the anti-hypertensive effects of ACE inhibitors?
They reduce the production of angiotensin II, which is a potent vasoconstrictor
It also reduces the production of aldosterone, thus reducing salt and water retention
This means that there is a decrease in blood volume, hence a decrease in venous return
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
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
What is the most common side effect of ACE inhibitors?
COUGH
State some other side effects of ACE inhibitors and ARBs.
Hypotension Urticaria/Angioedema (ACEi – very rare) Hyperkalaemia Fetal injury Renal failure in patients with renal artery stenosis (due to both)
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
Give two 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
Why are non-rate slowing CCBs preferred to rate-slowing CCBs in the treatment of hypertension and heart failure?
They have a more powerful effect on vascular smooth muscle
What type of receptor is a beta adrenoceptor?
G-protein coupled receptor (Gs protein linked)
What are the effects of noradrenaline that cause an increase in blood pressure?
Increase in heart rate and cardiac contractility (leads to increase in CO) via beta-1 receptors in the heart
Stimulation of beta-1 receptors in the kidneys promotes renin release –> increase in angiotensin II
What is hypertension in younger patients normally caused by?
Increased sympathetic drive
State some uses of beta-blockers.
Angina Post-MI Cardiac dysrhythmias Chronic heart failure Hypertension Also thyrotoxicosis, glaucoma, anxiety states, migraine prophylaxis, benign essential tremor
Give an example of a cardio-selective beta-blocker.
Atenolol
What are mixed beta-alpha blockers? Give an example.
They are beta-1, beta-2 and alpha-1 blockers
Carvedilol
You get extra vasodilation due to alpha-1 blockade
Give an example of an alpha-1 blocker.
Prazosin
Give an example of a non-selective alpha blocker.
Phentolamine
Why is it important for alpha-1 blockers to be selective?
Alpha-2 receptors are the negative feedback receptors of the SNS
Blocking them will result in enhancement of sympathetic activity
Give an example of a drug that is used to treat migraine and explain how it works.
Sumatriptan
It is a 5-HT (serotonin) receptor agonist, which causes vasoconstriction of some of the large arteries in the brain and inhibits trigeminal nerve transmission
NOTE: painful stimuli is transferred by the trigeminal nerve and profound vasodilation is also associated with migraine
When is sumatriptan contraindicated?
Coronary disease
What are the side effects of sumatriptan?
Dizziness, drowsiness, asthenia/fatigue
What is step 1 in the NICE guidelines for treatment of hypertension?
< 55 years = ACEi + ARB
>55 years or Afro-Caribbean of any age = CCBs + thiazide-type diuretics
What is step 2?
ACEi or ARB
AND CCB or thiazide diuretic
What is step 3?
ACEi/ARB
CCB
Thiazide diuretic
What is step 4?
Further diuretic therapy (low-dose spironolactone)
Alpha or beta-blocker
What is spironolactone?
It is an aldosterone receptor antagonist
What is chronic heart failure?
Impaired cardiac function due to ischaemic heart disease, hypertension or cardiomyopathy that results in fluid retention, oedema and fatigue
Which drugs are normally used on patients with chronic heart failure?
ACEi
ARB
Beta-blockers
Spironolactone
