Flashcards in Session 7 Deck (36):
What does initial polarisation in ventricular cells cause?
Voltage gated sodium channels open and depolarise the membrane rapidly
What occurs after immediately depolarisation of a ventricular cell?
- Outward flow of potassium causes brief repolarisation
Why is there a delay in repolarisation of ventricular cells?
Voltage gated calcium channels take time to activate so the repolarisation is delayed
What does initial influx of calcium into a ventricular cells due to the opening of voltage gated calcium channels cause?
- Further calcium is released from cellular stores in the mitochondria and SR
- Calcium causes contraction of the ventricular cells, producing contraction
What repolarises ventricular cells to their resting membrane potential?
Potassium efflux from the cell
Why is the membrane potential of pacemaker cells persistently less negative than the membrane potential of ventricular muscle cells?
To ensure fast sodium channels remain inactivated
What is the funny current in pacemaker cells?
Spontaneous, gradual depolarisation caused by the movement of sodium ions through slow sodium channels which open during repolarisation when potential reaches its most negative values
What occurs in pacemaker cells when the cell reaches threshold voltage?
Calcium channels open to create a relatively slow depolarisation
How do pacemaker cells repolarise?
After calcium channels close, potassium efflux repolarises the cell
What happens to the membrane potential changes in pacemaker cells if heart rate increases?
Interval between contractions, and therefore depolarisations, shortens so the funny current becomes steeper
What effect does activating baroreceptors have on the membrane changes in pacemaker cells?
If stretch sensitive baroreceptors are activated (due to increased arterial blood pressure) they send signals to the medulla oblongata to increase parasympathetic innervation to the heart so the funny current becomes shallower and heart rate slows
What can cause cardiac arrhythmias?
- Ectopic pacemaker activity
- Abnormal depolarisations following an action potential (after-depolarisations)
- Re-entry loop
What causes ectopic pacemaker activity?
Damaged areas of myocardium can become spontaneously active when depolarised so a latent pacemaker region is activated and dominates over the SA node causing abnormal pacemaker activity
What causes after-depolarisations?
High intracellular calcium levels
What causes a re-entry loop in the heart?
Damaged area of the myocardium prevents normal spread of excitation so there is a delay in conduction
What are class 1 anti-arrhythmic drugs?
Voltage gated sodium channel blockers: blocks sodium channels that are open or inactive and rapidly dissociates so normal firing isn't prevented, only over-firing is prevented
Give an example of a type 1 anti-arrhythmic drug
What is a class 2 anti-arrhythmic drug?
Beta-receptor antagonist: blocks sympathetic action by acting on beta1 receptors so funny current slope is decreased and inotrophy is decreased
Give an example of a type 2 anti-arrhythmic drug
Propranolol or atenolol
Why are type 2 anti-arrhythmic drugs used after a MI?
To combat increases in sympathetic activity and reduce oxygen demand of the heart
What are type 3 anti-arrhythmic drugs?
Drugs which block potassium channels: prolongs the action potential and lengthens the absolute refractory period so further action potentials are delayed
Why are type 3 anti-arrhythmic drugs not generally used?
They can also be pro-arrhythmic
What are class 4 anti-arrhythmic drugs?
Drugs which block calcium channels: decreases the slope of the funny current at the SA node; decreases AV node conduction and decreases force of contraction of the heart. Also causes some coronary and peripheral vasodilation
Give an example of a class 4 anti-arrhythmic drug
What is the function of adenosine in the heart?
- Produced endogenously
- Acts on A1 receptors at the AV node to enhance potassium conductance and hyperpolarise cells
- Acts as an anti-arrhythmic as it can act to reset the heart
What are inotrophic drugs?
Drugs which affect the force of contraction of the heart
When are negative inotrophic drugs used?
In circumstances where it is beneficial to reduce the workload of the heart; e.g. After a MI so oxygen requirement is reduced and further damage is limited
Give an example of a negative inotrophic drug
When are positive inotrophic drugs used?
In circumstances where the heart needs to beat more strongly; e.g. In cardiogenic shock or acute (but reversible) heart failure
Give an example of a positive inotrophic drug
Beta receptor agonists; e.g. Doubutamine
How are drugs used in the treatment of heart failure?
- ACE-inhibitors prevent formation of vasoconstrictor angiotensin2 so vasodilation of arteries and veins is promoted and after-load and pre-load decrease
- ACE-inhibitors also have diuretic action as angiotensin2 promotes aldosterone release which leads to sodium and water retention, therefore it causes blood volume and pre-load to decrease
How are drugs used in angina treatment?
Treated with drugs that reduce the workload of the heart: beta-blockers, calcium channel blockers and organic nitrates
- Organic nitrates and calcium blockers also improve blood supply to the heart
Describe the action of organic nitrates on the CVS
- Organic nitrates in vascular smooth muscle cause NO2- to be released which is reduced to NO
- NO acts as a powerful vasodilator by activating guanylate cyclase, increasing cGMP and lowering intracellular calcium levels to cause vascular smooth muscle to relax
- Venous pressure lowers so pre-load lowers and force of contraction reduces
- Can also acts on coronary arteries to improve oxygen delivery to ischaemic areas of myocardium
How is increased risk of thrombus formation treated?
- Anti-thrombotic drugs, e.g. Warfarin can be used
- Aspirin is used following MI or in coronary artery disease to reduce the risk of platelet-rich arterial clots forming as it is an anti-platelet drug
How can drugs be used to treat hypertension?
Drugs act to reduce cardiac output and/or peripheral resistance, e.g. ACE-inhibitors, diuretics, adrenoceptors blockers and calcium channel blockers