Flashcards in Drugs in the CVS Deck (29):
Give two examples of an arrhythmia/dysarrhythmia
Describe how ectopic pacemaker activity can be triggered.
Damage to myocytes so they spontaneously depolarise, or in an MI where there is activity surrounding the site due to ischaemia (may dominate over the SAN).
What is after depolarisation?
State the two types.
Abnormal depolarisation after an action potential has fired (triggered action potential).
Delayed/early after depolarisation
Describe delayed after depolarisation and what intracellular condition can predispose it.
Initiate after repolarisation has finished, but before another should occur. If they reach the threshold they can trigger another action potential.
More likely with high intracellular calcium.
Describe early after depolarisation.
When action potentials occur before another has finished.
More likely with a long action potential.
What can cause a re-entry loop?
Conduction delay or accessory pathway
If a unidirectional block causes a re-entry loop, what effect does this have on excitation?
It can take a long route to spread the wrong way around the circuit.
If there are a few in the atria they can cause atrial fibrillation.
What are the four classes of anti-arrhythmics?
Block voltage sensitive Na+ channels
Beta adrenoceptor antagonists
Inhibit potassium channels
Inhibits calcium channels
When are class I anti-arrhythmics (block voltage-sensitive Na+ channels) used?
Following a MI if the patient shows signs of ventricular tachycardia.
(not used prophylactically)
Describe how class I anti-arrhythmics (block voltage-sensitive Na+ channels) work.
Block voltage-sensitive Na channels when they are open or inactive (use-dependent).
It dissociates rapidly for the next action potential, so stops multiple ones occurring in quick succession, but allow normal contraction.
What are class II anti-arrhythmics (beta adrenoceptor antagonists) used for?
Prevents supraventricular tachycardia
Decrease O2 demand in MI
How do class II anti-arrhythmics (beta adrenoceptor antagonists) work?
Inhibit beta-1 adrenoceptors in the heart, decreasing the slope of the pacemaker potential in the SAN as the HCN channel is inhibited. This reduces heart rate.
Can also decrease conduction in the AVN
How do class III anti-arrhythmics (inhibit K+ channels) work?
Prolong the action potential, lengthening the absolute refractory period.
Theoretically prevent an action potential occurring too soon, but in reality are pro-arrhythmic and are therefore not generally used.
Amiodarone is an exception in class III anti-arrhythmics. What is it used to treat?
Tachycardia associated with Wolff-Parkinson-White syndrome.
How does a class IV anti-arrhythmic (Ca2+ channel inhibitor) work?
Decreases the slope of the pacemaker action potential at the SAN and decreases AVN conductivity (has negative ionotrophy).
Causes some coronary and peripheral vasodilation
What are class IV anti-arrhythmics (Ca2+ channel inhibitor) used for?
They are generally not effective in preventing arrhythmias but can be used to treat hypertension.
How can pharmacological adenosine be used to treat a serious arrhythmia?
Acts on A1 receptors at the AVN. The gamma subunit increases potassium conductance, hyperpolarising cells of conducting tissue.
Resets the rhythm by momentarily causing the heart to stop. Has a very short half life so doesn't have a prolonged effect.
What are the features of heart failure?
Decreased force of contraction
Decreased cardiac output
Reduced tissue perfusion
Oedema (peripherally or in the lungs)
Give a class of drug which can be used to increase cardiac output in heart failure.
Cardiac glycoside (rarely used)
Describe how cardiac glycosides work.
Block Na/K ATPase.
As Ca is usually removed by NCX (driven by the concentration gradient of sodium), calcium in the cell will increase. This means that more is stored in the SR and released on initiation by an action potential, increasing the force of contraction.
They also increase vagal activity by acting at muscarinic receptors.
Also slow AV conduction and heart rate.
Give an example of a condition which can be treated by cardiac glycosides.
What are beta-adrenoreceptor agonists used to treat?
Cardiogenic shock (sudden drop in CO)
Acute and reversible heart failure
How do ACE inhibitors work?
Inhibit angiotensin converting enzyme which converts inactive angiotensin I to active angiotensin II. This would normally increase aldosterone release from the kidneys and vasopressin from the brain.
They therefore decrease blood volume (and therefore pressure) and lower vasomotor tone.
How can organic nitrates be used to treat angina?
Convert NO2- to NO which is a powerful vasodilator.
It activates guanylate cyclase which increases cGMP production, upregulating PKG. This decreases calcium concentration
Primary action on the venous system which decreases preload, and has a secondary effect on collateral coronary arterys which increases delivery to the ischaemic myocardium.
In what conditions are antithrombotics important prophylactically?
Mechanical prosthetic heart valves
Describe how heparin works as an antithrombotic.
Inhibits thrombin, is an anticoagulant.
Describe how warfarin works as an antithrombotic
Anticoagulant by inhibiting vitamin K action.
Describe how aspirin works as an antithrombotic.