Pharmacology of the heart Flashcards
How can the heart be targeted and what will it affect?
Directly by targeting SANodal cells to alter rate, rhythm and force.
Indirectly by affecting vasculature to alter blood volume and composition.
What is an arrhythmia?
Abnormal generation or conduction leading to an abnormal rhythm or disruptive rate. Classified by location and rate. Improved by directly affecting the SANodal cells.
What is the effect of anti-arrhythmic drugs?
To change the ion currents to modify the membrane potential and control the rate and rhythm.
What is a class I anti-arrhythmic drug and what is its mechanism?
Voltage gated Na channel blockers e.g. Lidocaine
Reduce rate of depolarisation and slow HR
What is a class II anti-arrhythmic drug and what is its mechanism?
Beta Blocker e.g. propanolol
Reduces sympathetic effect and slow HR and targets the pacemaker potential to reduce the rate at which it reaches the threshold.
What is a class III anti-arrhythmic drug and what is its mechanism?
K channel blockers e.g. aminodarone, sotalol
Prolong the AP by preventing repolarisation to create a longer refractory period.
What are the side effects of using aminodarone?
Contains iodine so can alter thyroid function as an off target effect.
What is a class IV anti-arrhythmic drug and what is its mechanism?
L-type Ca channel blocker e.g. Verapamil
Affects the depolarisation of SA and AV nodal cells which require Ca for depolarisation. Cardioselectivity to L-type.
What is a class V anti-arrhythmic drug and what is its mechanism?
Non classified drugs
e. g. Adenosine = Acts at receptors on nodal cells to open K channels for hyperpolarisation and a longer refractory period to slow conduction
e. g. Cardiac glycosides - Digoxin targets CNS to increase vagal activity and reduce AV conducting rate and ventricular rate. Decreased the rate to normalise rhythm.
What is the main use of digoxin?
Atrial fibrillation
Why does caffeine cause palpitations?
It is an adenosine antagonist, exciting the cells
What is the s.e of all anti-arrhythmic drugs?
Can cause arrhythmias themselves
When are drugs that alter inotropy required?
For a pt in heart failure or during anaphylaxis using autonomic drugs e.g. Ad
What determines the force of contraction?
Extracellular Ca influx causes release of Ca from SR. Actin-myosin interactions are Ca dependent. Both extracellular and SR act as a source.
What happens to the Ca after a contraction?
Some Ca is resequesterd and some is excreted by Na/Ca antiporter.
What is the aim of an inotropic drug?
To increase contractility, by increasing [Ca] during cardiac failure
Name the 3 main inotropic drugs.
Sympathomimetics
Cardiac glycosides
Phosphodiesterase inhibitors
What is the mechanism of action of cardiac glycosides?
e.g. Digoxin partially inhibits Na/K ATPase to slow the mechanism and increase intracellular Na and therefore reduce the gradient for the Na/Ca antiporter. Ca remains in the cell, creating an inotropic effect.
What are the s.e of glycosides?
Cause ionic disturbance for increased excitation = arrhythmias
Can affect nervous system Na/K ATPase = neurological disturbances
Affect GIT smooth muscle
Gynaecomastia in an off target affect by activating oestrogen receptors.
What are the contraindications for glycosides?
Interacts with diuretics to cause hypokalaemia by competing with the K at the ATPase and increasing the digoxin effect even further.
What is the mechanism of action of phosphodiesterase inhibitors?
e.g. Milrinone, enoximone
Inhibiting cAMP breakdown allows Ca channels to stay open for longer. More cAMP = more force of contraction as more intracellular Ca.
What is the cardioselectivity of phosphodiesterase inhibitors?
PDE 3 is specific to cardiac myocytes so target their cAMP without affecting other cell types.
What are the adverse effects of phosphodiesterase inhibitors?
Arrhythmias from increased excitability
Only given in emergencies due to its short half life.
What drugs are used for cardiac failure?
ACEi beta Blockers (redued HR) ARBs Diuretic (reduce blood volume) Vasodilator (increase systemic volume) Ivabradine (reduce HR by targeting pacemaker channels)
