drugs and the vasculature Flashcards
what does the sympathetic nerve have along its length?
- varicosities
- primarily release NA to stimulate vasoconstriction
name some VSM mediators that can inc. Ca and stimulate VSM contraction? What receptors do they bind to?
- AngII –> AT1r
- PGG2, PGH2 –> T-prostanoid receptor
- ET1 –> ETA/B
name some endothelial cell agonists that can stimulate a relaxation from an inc. in Ca
- NO
- CNP (C type naturietic peptide)
- PGI2
- EDHF (endothelial hyperpolarising factor)
what is BP mediated by?
CO and TPR
BP = CO x TPR
which vessels contribute the most to BP regulation?
- arterioles contribute the greatest to BP regulation
- these vessels have vascular tone
- so always display partial state of constriction
in terms of vascular tone, what do hypertensive patients have?
have a raised base vascular tone
= more TPR
= more BP
define hypertension
> 140/90mmHg
describe the treatment overview
step 1: single therapy (U55 - ACEi or ARB, O55/ Afro-carribbean - CCB or thiazide diuretic)
Step 2: Dual therapy (ACEi and CCB or ACEi and thiazide diuretic)
Step 3: Triple therapy (ACEi, CCB, thiazide diuretic)
Step 4: Symptomatic relief (low dose spironolactone, beta/alpha blockade)
name an ACEi
Enalapril
often have -ipril endings
what is RAS stimulated by?
- low renal Na reabsorption
- low renal perfusion pressure
- High SNS activation
what do ACEi do?
- dec. AngII production
- inc. bradykinin
what are some uses of ACEi?
- hypertension
- HF
- Post MI
- diabetic nephropathy
- progressive renal insufficiency
- high CVS disease risk patients
how are ACEi effective in hypertension treatment?
- reduce TPR (more bradykinin and less AngII –> reduces TPR via less AT1R-mediated vasoconstriction and more bradykinin vasodilation)
- sodium retention (less Na retention in kidneys via blocked actions of AngII and less aldosterone secretion)
- thirst drive (less SNS activation of thirst in brain via AT1R)
how are ACEi used to treat HF?
- reduced TPR (less vasoconstriction via AT1R in vasculature so less afterload = dec. ionotropic effects)
- reduce preload (venodilation means less preload)
what do ARBs (Angiotensin Receptor Blockers) do?
e.g. Losartan
prevent binding of AngII to AT1 receptors
what are the uses of ARBs?
- hypertension
- HF
what are the side effects of ARBs?
- hypotension
- hyperkalaemia (aldosterone promotes K loss so aldosterone inhibtors produce hyperkalaemia)
- foetal injury
- renal failure
what are the side effects of ACEi?
- cough
- urticaria/angiooedema
- hypotension
- hyperkalaemia
- foetal injury
- renal failure
describe the process of smooth muscle contraction
- membrane depolarisation opens VGCC
- Ca enters and binds Calmodulin (CaM)
- Ca-CaM complexes activated MLCk
- MLCk mediated phosphorylation –> VSM contraction
what are the 2 types of CCBs?
- dihydropyridines (DHPs) = non rate limiting
- non-DHPs = rate limiting
name a DHP
amlodipine
no negative ionotropic effect
name a Non-DHP
negative ionotropic effect
which CCB is used to treat hypertension and why?
amlodipine as it doesn’t have an ionotropic effect on the heart
DHPs inhibit Ca entry itno VSMCs so less contraction of cells –> less TPR –> less BP
why are ACE or ARBs first line drugs?
due to good patient adherence
higher adherence = less side effects
why do afro-carribeans have a different drug schedule?
- due to low plasma renin activity
- so ACEi doesn’t work as well
name 2 alpha blockers and what they do
they block alpha 1 mediated vasoconstriction
- prazosin is alpha 2 antagonist
- phentolamine is alpha 1/2 antagonist
how can phentolamine lead to inc. HR (not reflex)?
action against alpha 2 blocks -ve feedback of NA release
so there is ehanced NA release and SNS response
can lead to inc. HR
