PHAR232 - Pharmacological tools in HF 1 Flashcards
What are key things that SNS does on the cardiovascular system?
- Increase HR
- Vasoconstriction
- Increase contraction force
- Activate RAAS
In RAAS, what is the major vasoconstrictors?
Angiotensin II
Aldosterone = increased H20 retention = Increase BP
Heart failure
What is forward heart failure?
Inability of heart to pump blood FORWARD to meet metabolic demands of body
What is backward heart failure?
Cardiac pressure too high
Thick blood
(thick smoothie, causes straw issues)
Heart failure pathophysiology revision
Wha happens with a reduction in baroreceptor integrity on HR?
- Blunts PNS activity
- Increased constant HR
- Increased vascular tone
- Increased heart overload
What are catecholamines?
NA and adrenaline
How much higher is NA in CHF patients?
2-3x
What is the number 1 vasoconstrictor ?
Angiotensin II
+ increases NA + aldosterone
What does aldosterone do?
Holds H20 = increase BP
Revision
Is nitric oxide a vasodilator or vasoconstrictor?
Vasodilator
What is the number 1 vasodilator in the cardiovascular system?
Nitric oxide
Purpose = decrease Ca++
What is eccentric (elongated) myocardial hypertrophy due to?
Volume overload
- Insufficient muscle to contract around increased volume
What is concentric (compact) myocardial hypertrophy de to?
Excessive muscle
- Compromises ventricular capacity
- Causes inefficient contraction
What are 2 extremely key treatment interventions for HF?
- B1 adrenergic receptors e.g. beta blockers
- Angiotensin II type 1 receptor (AT1R) e.g. ACE inhibitors
What is the rationale for b1 ad receptors?
Overexcitation of SNS accompanies by electated ciruclating catecholamines
What does increased HR do to blood volume?
Reduces capacity to fill
= low BV
B1 adrenergic receptors info - KNOW
What is the goal for b1 adrenergic receptor blockers?
Block B1 receptors in heart
- REduce HR
- Optimise contraction force
Problem with beta blockers in HF
What are the only beta blocker drugs (3 key ones) with vasodilatory effects effective for HF?
Carvedilol
Bisoprolol
Metoprolol
Special beta blockers
Use of beta blockers in heart failure
Goal = improve myocyte Ca++ availability and utilisation
- Improves LV remodelling
- Improvement of ion channels
- Improved heart sensitivity to SNS activation
= improvement in overall heart function
= Improved cardiac output (CO)
MUST KNOW THIS SLIDE!!!!!
Adrenergic receptors as research targets
Microscopic review of myocytes after NA exposure
Hypercontraction association with increased cAMP
What does long term NA do to myocytes?
Excitotoxicity
kills cells
Catecholamines as growth factors
What does PLC create?
IP3 = increase Ca++
DAG = activates PKC
What is MAPK associated with?
growth
What does CREB stand for?
CAMP
Response
Element
Binding
Protein
What does CREB do when it’s become phosphorylated?
Dimerises
Binds to cAMP response element on DNA
Regulates RNA transcription
Controls number and identity of proteins in cells
Catecholamines as growth factors
Potential mechanisms underlying value of special beta blockers
Where is angiotensin-converting enzyme found (ACE)
Lungs
Role of ACE
ACE = increases bradykinin
= increases NO release
= increases prostaglandins
Too much vasodilation = other enzymes creating ACE
Blocking ACE = increased bradykinin
Angiotensin II and it’s receptors
What type of receptor is angiotensin II, type 1 receptor (AT1-Rs)
GPCR
Quetions regarding AngII
review and understand why has B-arrestin
-
Abbreviation definitions
