Drugs Affecting the Heart Flashcards
How can drugs affect the heart?
Directly - affects rate/rhythm and force of contraction
Indirectly - vasculature (+blood volume/composition - renal)
Why do we need drugs that affect rate/rhythm?
arrhythmias
= disorders of rate or rhythm (or both)
What are the types of arrhythmias?
Define by location - atrial, junctional, ventricular
Define by rate - tachycardia, bradycardia
How are antiarrythmic drugs classified?
Classified by mechanism of action Class I, II, III, IV Sometimes those without a class are said to be in Class V but they all have different mechanisms of action
Give examples of drugs in class I and their mechanism of action.
Class I e.g. Lidocaine, Flecainide
- blocks voltage gates sodium channels
- all affect depolarisation phase
- shifts tilt of ventricular action potential to the right
Give examples of drugs in class II and their mechanism of action
Class II e.g. propanolol
- beta blockers
- decreases sympathetic affect
- targets pacemaker potential
- takes longer to get to threshold
- decreases excitability
Give examples of drugs in class III and their mechanism of action
Class III e.g. amiodarone (can affect thyroid function), sotalol (also a beta-blocker but this is main action)
- prolongation of AP
- could be due to K+ channel block
- shifts ventricular action potential right and so increases refractory period
Give examples of drugs in class IV and their mechanism of action
Class IV e.g. verapamil
- blocks Ca2+ channels (L-type)
- relative cardio-selectivity –> targets cardiomyocytes
- shifts ventricular action potential to the right
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Give 2 examples of none classified antiarrythmic drugs and their mechanism of action
- Adenosine (caffeine has similar action –> palpitations)
- K+ channel opens, receptors for adenosine on SA/AV
- hyperpolarisation, further from threshold
- increased refractory period, nodal conduction slowed - cardiac glycosides e.g. digoxin
- CNS - increase vagal activity
- decreases AV conduction rate
- decreases ventricular rate
What are the adverse effects of antiarythmic drugs?
can cause arrhythmias! Because they are so diverse with so many mechanisms. Each arrhythmia is due to a particular ion so need to ensure correct drug is chosen.
Dose? needs to be carefully controlled
Pharmacokinetic issues - interactions with other drugs, affect metabolic enzymes e.g. in liver
Why might we need drugs to affect force of contraction?
- anaphylaxis - CV collapse
- heart failure? - cardiac output is insufficient for the metabolic needs of the body
- many therapeutic options
How is the force of cardiac muscle contraction usually determined?
- multiple determinants
- Starling forces, stretch, venous return
- Intracellular Ca2+
What are inotropic drugs?
Work to increases contractility
+ve inotropic drugs increase intracellular calcium and subsequently increase force of contraction
What are the three classes of inotropic drugs?
sympathomimetics (autonomic lecture)
cardiac glycosides
phosphodiesterase inhibitors
What is the mechanism of action of digoxin?
CARDIAC GLYCOSIDE Partial inhibition of Na+K+ATPase Increases intracellular Na+ Reduces gradient for sodium exit Na+/Ca2+ transporter works less Ca2+ is retained Intracellular Ca2+ is increased
State and explain the adverse effects of cardiac glycosides such as digoxin.
Ionic disturbance - increase excitability –> arrhythmias
Neurological disturbance, GIT disturbance (smooth muscle)
Gynaecomastia - off target effect, nothing to do with action on Na+K+ATPase, drug has large steroid component. In a few patients this can trick oestrogen receptors
Is there a clinical use for digoxin?
Only used in a subset of heart failure of patients
Needs individual dose tailoring
High incidence of drug interaction
- some diuretics decrease potassium, this increases effect of digoxin due to competition for receptor –> increased adverse effects
Give examples of phosphodiesterase inhibitors
What is their mechanism of action?
e.g. milrinone, enoximone
Phosphodiesterase breaks down cAMP and cGMP (signalling molecules)
Normally NorArenaline acts on B1 receptors and increases cAMP via a G-protein, this increases Ca2+ influx.
Phosphodiesterase inhibitors prolong action of g protein.
Increase cAMP –> increase inotropy
–> increase force of contraction
What are the side effects of PDE inhibitors?
Do they have a clinical use?
increased excitability can lead to arrythmias
PDE type 3 are specific to the heart so systemic effects are decreased
Clinically
- emergencies only
- some studies suggest decreased survival in heart failure
- short half life
What other drugs can be used for cardiac failure?
diuretics - blood volume vasodilators - systemic volume ACE inhibitors - blood pressure beta blockers - decrease heart rate ivabradine - targets PMP channels
