drugs on blood vessels Flashcards
Why do we need appropriate blood pressure?
what is the issue with too low?
issue with too high? (3)
what is it important in treating?
Too low – systolic <60 mmHg, poor drive for end organ perfusion
Too high – damage blood vessels, and produces afterload which reduces cardiac output, increasing O2 demand of the heart which also alters end organ perfusion
Regulation of blood pressure and blood flow are important clinical objectives in treating cardiovascular disease, e.g. sepsis, hypertension
What effect does regulation of vascular tone have?
controls 2 things?
Regulation of vascular tone (controlling blood vessel radius) is central for controlling blood pressure and blood flow
What is vascular tone?
describes the degree of constriction of a blood vessel relative to maximum dilation
effect of increasing and decreasing vascular tone
Increasing vascular tone will increase blood vessel constriction and increase blood pressure
Reducing vascular tone will induce blood vessel dilation and reduce blood pressure
Effect sepsis has on the body
what does it cause excessive of? effect of this?
why is it a very complex condtion?
systemic infection, causes systemic excessive vasodilatation, decreases TPR, large drop in BP, no drive for end organ perfusion, end organ damage, very serious, ITU support
Very complex condition – potential involvement of all those endothelium-mediated vasodilation pathways
Effect of anaphylaxis has on the body
what type of reaction is it?
what does it cause and effect?
hypersensitivity reaction, systemic vasodilatation, poor end organ perfusion
Effect of heart failure on the body
3 main effects
Poor cardiac output, poor blood pressure and poor end organ perfusion
Vasoconstrictor mechanisms
receptors for NA /AD? Ang II? Vasopressin? ET-1? TXA2? what also activates these receptors? what is this response called?
what pathways does it activate and what does this produce?
what effect do these molecules have? (2 molecules with different effects)
Receptors NA / Ad : α1 Ang II : AT1 Vasopressin : V1 ET-1 : ETA TXA2 : TP Stretch also activates these receptors – Myogenic response
activates the Gq pathway so PiP2 becomes DAG and IP3 via PLC
DAG increase membrane permeability leading to depolarisation which leads to the Activation of voltage-gated Ca2+ channels (VGCCs) which induces Ca2+ influx
IP3 acts on the IP3 receptor on SR to release Ca2+ from stores which leads to contraction via the MLCK pathways
Using noradrenaline and adrenaline will drive these mechanisms to increase vasoconstriction
What are the different responses adrenaline have on resistance vessels?
most tissues?
muscle + heart?
Most tissues e.g Gi tract, skin -> vasoconstriction
skeletal muscle + coronary circulation -> vasodilation
What are the different responses noraadrenaline have on resistance vessels?
most tissues?
muscle + heart?
Most tissues e.g Gi tract, skin -> vasoconstriction
skeletal muscle + coronary circulation -> vasoconstriction
why are there different responses?
what receptor does adrenaline have higher affinity for?
what receptor does noradrenaline have higher affinity for?
what effect does a1 receptors have?
what effect does B2 receptors have?
what does skeletal muscle + heart tissues have more receptors of?
where does adrenaline mainly act and where does noradrenaline mainly act?
Adrenaline higher affinity for B over a adrenoceptors
Noradrenaline higher affinity for a over B adrenoceptors
a1 adrenoceptors produce contraction, B2 receptors produce relaxation
Skeletal muscle and coronary arteries have more B2 than a1 adrenoceptors
Giving adrenaline mainly acts at B2 to dilate vessels
Giving noradrenaline mainly acts at a1 receptors to constrict vessels
Effect of adrenaline on circulation
what will increase? what will it decrease? why?
effect on BP? why?
effect on CO? why?
will increase HR but tpr decreases due to vasodilation (B2 receptors) hence only small increase in BP
rise in hr will increase CO
Effect of noradrenaline on circulation
what happens to tpr and BP? why?
what happens to heart?
what happens to HR and why?
hence why give NA?
de increase in tpr due to vasoconstriction (a1 receptors) so BP will increase
As heart is B1 receprots, nto much effect by NA
baroreceptor stimulation - increase BP recognised by receptor leading to decrease in HR via vagus nerve
hence give NA – increase BP whilst protecting heart
Physiologically what does sympathetic nerve stimulaton do? (2 things)
noradrenaline (synapses) + adrenaline (adrenal gland) are both released
Pharamacological effects of NA
where does it primarily act? what 2 key effects does it have? effect on heart? clinical importance? important in which conditions?
NORAD is given to primarily act at a1-adrenoceptors on VSMCs
to increase TPR and increase blood pressure
Without having significant actions on heart (B1) – cardiac protective, doesn’t make the heart work hard to increase BP, blood flow
e.g. important in conditions such as sepsis, severe heart failure
