Heart rate and contractility Flashcards
What is the equation for cardiac output?
Cardiac output(CO)=Heart rate(HR) x Stroke volume(SV)
What is the sympthateic control of heart rate at SAN?
- Noradrenaline binds to beta-1 adrenoceptor
- Stimulates Galphas pathway which stimulates adenylate cyclase.
- This increases cAMP levels
- Ultimately leads to:
-Increase in If channel activity
-Increase pacemaker potential frequency
-Increase in heart rate
Overall a positive chronotropic effect
What is the parasympathetic control of heart rate at SAN?
- Acetylcholine binds to M2 receptors
- this stimulates the Galphai pathway which inhibits adenylate cyclase
- This reduces cAMP levels
- Ultimately leads to:
-Decreased If channel activity
-Decreased pacemaker potential frequency
-Decreased heart rate
Overall a negative chronotropic effect
What do beta 1 adrenoceptor blockers reduce and do?
Beta 1-adrenoceptor reduces action of sympathetic nervous system on SAN
-Reduces heart rate
What do muscarinic receptor blockers reduce and do?
Muscarinic receptor blockers (antagonists) – e.g., atropine
will reduce action of parasympathetic nervous system (vagus nerve) on SAN
-Increases heart rate
What are concerns associated with beta 1-adrenoceptor blockers?
Avoid in asthma patients (may block β2-adrenoceptor)
Not given with Ca2+ channel blockers – reduce heart rate/contractility too much
Can produce fatigue
What are concerns associated with muscarinic receptor blockers?
Muscarinic blockers are used to treat many different conditions
e.g., COPD, IBS, overactive bladder
-Muscarinic receptors increase heart rate and tachycardia increases O2 demands on heart and is significant if patients have comorbidities like COPD and angina
What needs to be decreased to reduce heart rate?
Decrease initiation and frequency of pacemaker potentials to reduce heart rate
How does decreasing initiation and frequency of pacemaker potentials reduce heart rate?
-Inhibit voltage-gated Ca2+ channels: Reduce Phase 0, slower upstroke
-Inhibit If channels: Increase Phase 4 time, slower to activate Ca2+ channels
What are calcium channel blockers and what do they do?
Drugs that sit in pore of channel - block Ca2+ entry into SAN
Reduce heart rate
Why do Ca2+ channel blockers need to be selectively targeted?
Ca2+ channels also found in cardiac myocytes (phase 2, plateau phase)
and vascular smooth muscle
Provide Ca2+ influx involved in cardiac and smooth muscle contraction
What are the 3 subtypes of Ca2+ channel blockers?
- Dihydropyridines
- Diphenylalkyamines
- Benzothiazepines
What do Dihydropyridines target and give an example?
-Vascular selective
E.g. Amlodipine
What do Diphenylalkyamines target and give an example?
-Cardiac selective
E.g. Verapamil
What do Benzothiazepines target and give an example?
-Vascular+cardiac selective
Diltiazem
Why can CCB’s make heart failure worse and eventually cause heart block?
There’s Non-selective blocking actions on Ca2+ channels in cardiac myocytes
(needed for contractility) and at AVN needed for atria-ventricle conduction which can make heart failure worse and cause heart block
What is an example of If channel blockers?
Ivabradine
What does Ivabradine inhibit?
-Selective inhibitor of If channel in the SAN
What does Ivabradine reduce?
Reduces pacemaker potential frequency