Drugs of the Cardiovascular System – The Vasculature Flashcards
Name the first line treatments for hypertension
<55: ACE inhibitors or Angiotensin Receptor Blockers
>55 or afrocarribean: Calcium channel blockers or Thiazide like diuretics
What are the second, third and fourth line treatments for hypertension?
2nd: CCB/ Thiazide like diuretic + ACEi/ ARB
3rd: ACEi/ ARB + CCB + Thiazide like diuretic
4th: = resistant hypertension. Consider spironolactone or A- or B-blocker
Name 3 things that drive renin production in the kidney
Decreased Na+ reabsorption
Decreased renal perfusion pressure
Increased sympathetic activity
Give an example of an ACE inhibitor.
Enalapril
What are the anti-hypertensive effects of ACE inhibitors?
Reduce production of AII, thus inhibiting its effects of: Vasoconstriction Increased thirst SNS activation Increased salt retention in kidney Increased aldosterone secretion
What law links venous return to contractility?
Starling’s Law
How can blockade of vasoconstriction and decreased salt and water retention caused by ACEi be used in treating hypertension?
Vasoconstriction increases TPR
Increased TPR increases BP + venous return
Increased venous return increases contractility + CO
Blockade decreases TPR + BP
Decreased salt + water retention decreases volume in blood system, so BP deceases
How can blockade of vasoconstriction and decreased salt and water retention caused by ACEi be used in treating heart failure?
Increased vasoconstriction increases afterload + cardiac work.
Increased venous return causes congestion + oedema.
Blockade reduces afterload.
Decreased salt + water retention means less volume is returned to the heart, thus decreases cardiac work
Give an example of an angiotensin receptor blocker. How do these drugs work?
Losartan
Antagonists of type 1 AII receptors
Prevent renal + vascular actions of AII
What is the most common side effect of ACE inhibitors? Why?
COUGH
Breakdown of bradykinin is inhibited
Bradykinin is pro-cough
State 3 other side effects of ACE inhibitors and ARBs.
Hypotension
Hyperkalaemia
Renal failure in patients with renal artery stenosis
Describe the excitation-contraction coupling of vascular smooth muscle cells.
Depolarisation causes opening of VGCC
Allows Ca2+ influx
Ca2+ binds to calmodulin forming a Ca2+-CaM complex
This complex binds to + activates Myosin Light Chain Kinase (MLCK)
MLCK-mediated phosphorylation leads to smooth muscle contraction
What type of calcium channel blocker is more selective for blood vessels? Give an example.
Dihydropyridines e.g. Amlodipine (does not cause negative inotropy)
How do calcium channel blockers reduce blood pressure?
Blockade of channels inhibits entry of Ca2+ into vascular smooth muscle cells
Allows vasodilation
Decrease in TPR results in decrease in BP
What may be an unwanted result of CCB usage?
Powerful vasodilation can lead to reflex tachycardia + increased inotropy, thus increasing myocardial oxygen demand
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
Why might alpha adrenoceptor antagonists be used as anti-hypertensives?
Blockade of A1 receptors blockades vasoconstriction
Lowers TPR
Lowers BP
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
What is spironolactone?
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 + fatigue
Which 4 drugs are normally used on patients with chronic heart failure?
ACEi
ARB
Beta-blockers
Spironolactone
How do arterioles contribute to blood pressure?
Arteriole contraction decreases the radius, so there is less space for blood to pass through thus resistance increases
What defines hypertension?
Sustained BP >140/90 mmHg
How can ACEi and ARBs cause hyperkalaemia?
Inhibition of Na+ reabsorption means K+ exchange is reduced
Thus K+ accumulates in blood instead of being excreted in urine
How can ACEi and ARBs cause renal failure in patients with renal artery stenosis?
Blocking ability of AII to constrict the efferent arteriole in the glomerulus means a fall in GFR can’t be recovered from
Exacerbates failure
Why is first line treatment of hypertension different in the elderly?
Hypertension is more likely to be associated to atherosclerosis or other issues
Thus, targeting the RAAS system would have little effect
(low plasma renin activity)
