Drugs and the Vasculature Flashcards
Hypertension is classified as
raised blood pressure 140/90mmHg.
How does Angiotensin II promote salt and water retention,
via the stimulation of aldosterone secretion, which promotes sodium retention by binding to the kidneys mineralocorticoid receptors
How does Angiotensin II promote increased BP
causes strong vasoconstriction via the AT1 receptor.
What stimulates renin secretion
renal perfusion pressure falling and sodium reabsorption falling
What cells stimulate renin secretion
sympathetic nervous system on JGA cells
MOA of aldosterone?
Aldosterone causes sodium reabsorption and water retention
Aldosterone passes through the cell membrane and binds to the intracellular mineralocorticoid receptor It then upregulates the production of sodium channels and the production of Na+/K+ ATPase The presence of more Na+/K+ ATPase means that you get more sodium reabsorption
uses of ACEi
Hypertension Heart failure Post-MI Diabetic nephropathy Progressive renal insufficiency • Patients at high risk of cerebrovascular disease
What is enalapril
An ACEi
Example of an ACEi
Enalapril
What does ACEi do
Inhibit the somatic form of angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II by ACE
Effect of ACEi?
ACE inhibitors reduce the AT1 dependent vasoconstriction leading to a fall in TPR and a fall in blood pressure
It also reduces the production of aldosterone meaning that you get a decrease in blood volume and a decrease in venous return
How do ACEi effect cardiac output
It also reduces the production of aldosterone (which retains water and Na) meaning that you get a decrease in blood volume and a decrease in venous return
The venous return is also linked, by Starling's Law, to contractility (and cardiac output) Reduced venous return reduces the cardiac output because of the decrease in preload So as anti‐hypertensives, ACE inhibitors have an effect on TPR and cardiac output
What do AT receptor blockers do?
Antagonists of receptors for ATII
Main unwanted effect of ACEi? Why?
Cough because it prevents the breakdown of bradykinin which causes cough
Unwanted effects of ACEi (4)
Cough, hypotension, hyperkalaemia, renal failure
how does ACEi cause hyperkalaemia
because there is less sodium reuptake and less potassium excretion. Aldosterone promotes insertion of Na channels and NaK ATPase into kidney cells to promote Na moving from the tubule into the blood. If you block AT1 receptor, or block ACE, less aldosterone and so fewer of these proteins in the membrane. This means that there is an increased K in the blood as it isn’t lost in the urine. Also may cause hyponatraemia.
How can ACEi cause renal failure
You get poor flow into the glomerulus with poor pressure so GFR isn’t great. ATII one of its roles is to constrict the efferent arteriole and so increase the pressure in the glomerulus. But if you give patients ACEI or ARB you lose the ability to constrict the efferent arteriole so low pressure in glomerulus, GFR goes down, renal failure carries on from there.
Dihydropyridines AKA
Non-rate limiting
Dihydropyridines were more powerful on va. SM or cardiac SM?
va. SM
Are dihydropyridines/non-dyhydropyridine OR rate-limiting/non-rate limiting CCBs used more for hypertension
Dihydropyridines/ non-rate limiting bc they don’t limit heart rate
Are CCBs lipid soluble
Not very
Where do CCBs act
extracellular surface of the protein
What do DHP do regarding Ca
inhibit calcium entry into vascular smooth muscle cells
What can the decreased blood pressure due to DHP cause
reflex tachycardia
