Drugs and the CVS: vasculature Flashcards
what is released by the SNS to cause vasoconstriction?
noradrenaline
name examples of VSM mediators that cause contractions by increasing [ca2+]
o AngII –>AT1r
o PGG2, PGH2 –>TP (T-prostanoid receptor).
o ET1 –> ETA/B
name examples of endothelial cell agonists that stimulate relaxation by increasing [ca2+]
o NO.
o CNP – C-Type Naturietic Peptide.
o PGI2.
o EDHF – Endothelial Hypopolarising Factor.
state the BP formula
CO x TPR
what vessel contributes the greatest to BP regulation?
arterioles
these exhibit vascular tone and are in a partial state of constriction
what state are arterioles in hypertensive patients in?
raised base vascular tone that increases TPR and therefore BP
what is hypertension the most important risk factor in?
stroke
main risk factor in MI and CKD
what is the overview of hypertension treatment?
o Step 1 – Single Therapy: Under 55 – ACEi or ARB (Angiotensin Receptor Blocker). Over 55, Afro-Caribbean – CCB or Thiazide diuretic.
o Step 2 – Dual Therapy:
ACEi and CCB.
ACEi and thiazide diuretic.
o Step 3 – Triple Therapy:
ACEi, CCB and thiazide diuretic.
o Step 4 – Symptomatic Relief:
- Low-dose spironolactone (diuretic therapy).
- alpha -blockade or beta-blockade.
how is hypertension defined?
a BP consistently higher 140/90 or higher
what stimulates the production of renin?
- reduced sodium reabsorption
- reduced renal perfusion pressure
- increased SNS stimulation
how does ANGII contribute to blood pressure?
- increases thirst sensation (so you drink more)
- activates the SNS
- vasoconstrictor
- salt +H20 retention via aldosterone
what drug eliminates ANGII? what also does it do?
ACEi e.g. enalapril
decreases ANGII production and increases Bradykinin (stops it breakdown by ACE)
less ANGII–> less vasoconstriction
more bradykinin–> more vasodilation
what are the uses of ACEi?
o Hypertension. o Heart failure. o Post MI. o Diabetic nephropathy. o Progressive renal insufficiency. o High CVS-disease-risk patients.
what is the suffix for ACEi?
-pril
what are the main two effect of ACEi in reducing hypertension?
(1) reduction of TPR
(2) reduction of sodium retention
how do ACEi reduce TPR in hypertension ?
accumulation of bradykinin and reduction in ANGII:
- less AT1R mediated vasoconstriction
- more bradykinin mediated vasodilation
how does ACEi reduce sodium retention in hypertension?
less Na+ retained:
- via blocked actions of ANGII on AT1R in the kidney
- therefore less aldosterone secretion due to blocked AT1R in the adrenal medulla
what are the effects of ACEi in heart failure?
(1) reduce TPR
(2) reduce preload
how do ACEi reduce preload in heart failure?
venodilation reduces preload
how do ACEi reduce TPR in heart failure?
- less vasoconstriction via AT1R in peripheral vasculature
- reduced TPR
- decreased after load on the heart so inotropic effects decreased
what drug stops ANGII having its effects?
Angiotension Receptor Blockade (ARB) e.g. losartan prevents binding to AT1 receptors on arteries, kidneys and adrenal cortex
what are the uses of ARBs?
- hypertension
- heart failure
why would an ARB be used over an ACEi?
ARB does not affect ACE so bradykinin is not spared:
- Bradykinin induces cough
- ACEi causes Bradykinin to accumulate causing the cough
what are the side effects of ACEi and ARBs?
Cough – ACEi increased bradykinin Urticaria/angioedema – ACEi rarely. Hypotension Hyperkalaemia Foetal injury Renal failure (in patients with renal artery stenosis)
