7: Drugs affecting cardiac rate and force Flashcards
Cardiac rate and force are mainly regulated by the ___ nervous system.
autonomic
Sympathetic regulation of cardiac rate and force depends on a transmitter and a hormone - what are they called?
Adrenaline (hormone released from the adrenal medulla)
Noradrenaline (post-ganglionic transmitter)
Which type of receptor do adrenaline and noradrenaline activate?
ß1 adrenoceptors
In the context of cardiac rate and force, where are ß1 adrenoceptors found?
1) AV/SA nodal cells
2) Myocardial cells
ß1 are coupled to what kind of protein?
G protein
The activation of ß1 adrenoceptors by (nor)adrenaline triggers the activation of which enzyme?
Adenylyl cyclase
What does adenylyl cyclase do?
Increases the concentration of cAMP
What is the effect of sympathetic stimulation on heart rate, and what is another name for this effect?
Increases heart rate
‘Positive chronotropic effect’
What is the effect of sympathetic stimulation on force of contraction, and what is another name for this effect?
Increased force of contraction
‘Positive inotropic effect’
What effect does sympathetic stimulation have on the conduction velocity of the AV node?
Increased velocity of conduction
therefore increases heart rate
What is the name given to increasing mass of cardiac muscle caused by long-term sympathetic stimulation?
Cardiac hypertrophy
Which neurotransmitter is involved in parasympathetic regulation of cardiac rate and force?
Acetylcholine
What kinds of neurotransmitter are noradrenaline and acetylcholine? Which divisions of the nervous system are they part of?
Noradrenaline (post-ganglionic)
Acetylcholine (post-ganglionic, pre- too sometimes)
Noradrenaline - sympathetic
Acetylcholine - parasympathetic
In parasympathetic regulation of cardiac rate and force, which receptor is activated by acetylcholine?
M2 muscarinic receptors
Where are M2 muscarinic receptors usually found?
Which neurotransmitter binds to them?
On behalf of which nervous system does this neurotransmitter act?
Nodal cells
Acetylcholine
Parasympathetic
Which type of protein are M2 muscarinic receptors bound to?
G protein
Activated M2 muscarinic receptors reduce the activity of which enzyme?
Adenylyl cyclase
Adenylyl cyclase activity is reduced by the activation of which G-protein-coupled receptor?
M2 muscarinic receptors
What does adenylyl cyclase help synthesise?
What is the effect of sympathetic stimulation on the concentration of this chemical?
And parasympathetic stimulation’s effect?
cAMP
Increased [cAMP]
Decreased [cAMP]
Apart from decreasing [cAMP], the activation of M2 muscarinic receptors has another effect - what is it?
Opens potassium channels (GIRK) to hyperpolarise SA node cells (this reduces heart rate because the rate of action potentials decreases)
What effect does parasympathetic stimulation have on heart rate, and what is another name for this effect?
Decreases heart rate
Negative chronotropic effect
What effect does parasympathetic stimulation have on force of contraction, and what is another name for this effect?
No effect
sry
What effect does parasympathetic stimulation have on AV node conduction? Why?
Reduced AV node conduction
Opening of GIRK potassium contraction causes hyperpolarisation
Parasympathetic stimulation may causes ___ to develop in the atria.
Arrythmias
Which maneouvres increase parasympathetic output and may be employed in atrial tachycardia?
Vagal maneouvres
Give an example of a vagal maneouvre which can be used to increase parasympathetic output.
Valsalva maneouvre - activates aortic baroreceptors
Massage of the bifurcation of the carotid artery - activates carotid baroreceptors
i.e massage of the baroreceptors found in aorta and carotid artery
Blocking HCN channels ___ the slope of pacemaker potential and ___ heart rate.
decreases , reduces
What increases the activation of HCN channels?
Cyclic AMP
Name a drug which is a selective blocker of HCN channels and can be used to reduce O2 consumption in heart disease (reduced HR = reduced “).
Ivabradine
During excitation of cardiac muscle, Ca2+ release from the sarcoplasmic reticulum is said to be what kind of release?
Calcium dependent/induced calcium release
During relaxation of cardiac muscle, which channel is responsible for calcium efflux? What are the numbers of ions involved in this transport?
Na+ / Ca2+ exchanger 1 (NCX1)
1 calcium out, 3 sodiums in
ß1 adrenoceptor activation increases heart rate and force of contraction. ___ acts on the enzyme ___ ___ _ to enhance contractility of muscle.
cAMP , Protein kinase A
Cardiac muscle relaxation is dependent on Ca2+ being pumped out of the cell. Which enzyme performs which reaction on the protein that facilitates this?
Protein kinase A
Phosphorylation
Phospholamban
Name two ß adrenoceptor agonists used in treatment of heart conditions.
Dobutamine
Adrenaline
What are the pharmacodynamic effects of ß adrenoceptor agonists on the heart?
Increased force of contraction, heart rate and therefore cardiac output
Reduced cardiac efficiency (O2 consumption increases more than the cardiac work itself)
ß adrenoceptors can cause disturbances in cardiac ___, also known as ___.
rhythm , arrythmias
Adrenaline is commonly used clinically. Name two conditions in which it is used, and the route of administration.
Cardiac arrest - IV
Anaphylactic shock - IM
Dobutamine is another ß adrenoceptor which is used clinically. When?
During acute heart failure which may be reversible (e.g cardiac surgery, shock)
Name two ß adrenoceptor antagonists.
Propranolol (ß1 and ß2)
Atenolol, bisoprolol, metoprolol (ß1)
Name a clinical effect of a non-selective ß adrenoceptor blocker such as atenolol, bisoprolol or metoprolol.
Reduces exercise tolerance
Reduces myocardial O2 requirement, allowing for better oxygenation of the myocardium
What can ß adrenoceptor antagonists be used to treat clinically?
Arrhythmias (decrease excessive sympathetic drive and help to restore sinus rhythm)
Atrial fibrillation and superventricular tachycardia (delay conduction through AV node and help to restore sinus rhythm)
Angina
Low dose ß blockers are used in compensated heart failure. Just remember this.
lol
Name a couple of adverse effects of ß blockers as a class.
Bronchospasm
Aggravation of cardiac failure
Bradycardia
Hypoglycaemia (glucose release from liver is controlled by ß2 adrenoceptors in diabetics)
Fatigue and cold extremities
Name a muscarinic ACh receptor antagonist.
Atropine
Atropine blocks muscarinic ACh receptors. Which division of the nervous system are these receptors associated with?
What does increased parasympathetic discharge cause in a patient?
What will the effect of atropine administration be in a patient?
Parasympathetic
Bradycardia
Increased heart rate
Give in low doses, atropine causes (increased / decreased) heart rate.
Decreased heart rate
(In higher doses it increases heart rate.)
Name a cardiac glycoside which increases the contractility of the heart.
Digoxin
What is heart failure?
A cardiac output insufficient to provide adequate tissue perfusion
Name two inotropic drugs which enhance contractility.
Digoxin
Dobutamine
Inotropic drugs increase stroke volume at any given __ __ __.
end diastolic volume
Which membrane transporter does digoxin block?
Na+/K+ ATPase
(sodium-potassium pump)
