Drugs and the heart Flashcards
What are the different ways drugs can affect the heart
Direclety
- can actually affect cardiomyocytes
- Can affect rate/rhythm
- force of contraction
Indirectly
- can influence by vasculature
- Blood volume and the composition of blood
What are arrythmias
when the heartbeat’s rhythm is irregular or abnormal
what can be the difference disorders of rate or rhythm
- rhythm could be too fast or slo
- abnormal generation/conduction
- disruption of how cardiac action potentials
What are the causes of arrhythmias?
- Pathology (is it due to nodes or conducting tissue)
- Drug-induced (taking particular drugs for therapeutic or recreational)
- Congenital
How do we name arrhythmias
Classify based on where the origin is from (so is it atrial, ventricular or nodal)
and the effect it has on heart rate (normal HR, tachycardia bradycardia)
for example ventricular tachycardia
How do anti-arryhtmatic drug work?
typically how do they target the heart
can focus on cardiac action potential
they act on different parts of the action potential graph
How many classes of antiarrhythmic drugs work
4
Name a drug in class 1
lidocaine, flecainide
How do class 1 drugs work
they target voltage-gated sodium channels
which….
increase the refractory period →which reduce the general exictbity of cardiomyocytes
-so the cells are less likley to fire
Name some class 2 antiarryhmic drugs
- beta blockers
- Eg metoprolol, propanolol
How do class 2 anti-arrhythimcs work
- decreases sympathetic effect by blocking beta 1 receptors
- increases slope of the action potential
Name some class 3 antiarrhytmics
amiodarone (Idoine molecule, used in thyroid action), sotalol (has some beta blocker action)
How do class 3 antiarrhytmics work
- they prolong the action potential
- by blocking potassium channels involved in repolarisation (primary for antiarrhythmics )
- but these drugs do act on other receptors
Name a class 4 anti-arrhythmic
Verapamil
How do class 4 anti-arrhythmics work
- they are calcium ion channel blockers
- they specfically block the L-type calcium channels
- found in muscle cells to determine intracellular calcium levels
- this decreases the rate of depolarisation (targets AVN)
- so blocks how fast deporlrisation happens
- ## can slow conduction increasing the refraction period, so stops some APs in atria from being translated to the ventricles
these drugs have relative cardomyocselectivity
Non classifeid drugs
Name some anti-arrhythmics that aren’t part of the classification
adenosine
cardiac glycosides
How does adenosine work
- Acts on adenosione receptors on SA/AV → causes opening of k+ channel
- this causes the membrane to hyperpolarise
- so we get a delay in the next action potential, so the membrane potential is further away from threshold
- so binding of adenosine causes an increase in the refractory period
- and nodal condition is slowed
caffine is an anatgonist for adensoine receptors
so drining caffine my cause heart palpatations, so the nodal cells are closer to threshold hold, so they are more likley to fire -> so HR increases
Name a cardiac glycosides
digoxin
most commonly used
How do cardiac glycosides usually work
They have some CNS action → Increases vagal activity,
-means there’s an increase in PNS activity
-therefore, we get a decrease in AV conduction rate
-and decreases ventricular rate too
What are the general side effects of antiarrhythmic drugs
- Can cause arrhythmias
- when fiddling with ion levels can make things work
-They have -ve inotropic action - can affect contraction, so if you decrease force of contraction, it wont help if somoen is has cardiac compromise
- when fiddling with ion levels can make things work
Why might we need drugs to affect the force of contraction?
- Anaphylaxis
- massive reduction in blood pressure
- Heart failure
- Cardiac Output is insufficient for the metabolic needs of the body
How is he force of contraction normally determined
what ion is involved
intracellular calcium i
How can drugs work to increase the contractility?
generally what can they do
- Inotropic effects
- change muscle fibres
What do negtative ionotropic drugs do usually
decreases intracelluar calcium
so they decrease force of contraction
What classes of drugs cause a positive ionotropic effect
- Sympathomimetics
- Cardiac glycosides
- Phosphodiesterase inhibitors
How do poisitive ionotropic drugs work generally
they increase intracelluar calcium, which increases force of contraction
How does digoxin work
-Digoxin binds to and results in the partial inhibition of Na+/K+ ATPase
-when we inhibit the Na+/k+ ATPase there is an acculmation of intracelluar sodium
-if that happens this impacts the sodium calcium exchnager,
-think about it, if theres more sodium inside the cell, the conc gradient is not gradienting, so it will be worse at letting sodium in, and worse at letting calcium out,
-which means well get an acculmation of extrecelluar calcium (since there;s less activity)
which increases the force of contraction
Na+/K+ ATPase normally maintains ion concentration gradient inside/outside cells.
What will happen if we fully inhibit the Na+/K+ ATPase
if we fully inhibit the sodium pottassum atpase we will die
What are the Side effects of cardiac glycosides
- can cause Ionic disturbance
- this can affect excitability
- potentially cause arrhythmias -neuronal disturbances
- and smooth muscles might manifest in GIT
- Rare complication: gynecomastia (breast growth)
- digoxin can fool estrogen receptors, which can cause breast growth
Digoxin can cross the BBB and therefore impact neurones in CNS in a similar way. At a high toxic level, Digoxin can cause neurological disturbance
What are the clinical use of digoxin
-heart failure patients
wrong dose of digoxin ca cause arrhmias
What drugs can interact with digoxin
- Diuretics
- this is bad because diruretics decreases K+
- so these potassium ions bind to the sodium-potassium ATPase, at the same place that digoxin does
- so they compete with each other
- so all in all, if theres less pottasium ions, its easier for digoxin to bind
- which means your more likley to get adverse effects
Name some Phosphodiesterase inhibitors (PDEs)
Eg milrinone, enoximone
How do Phosphodiesterase inhibitors (PDEs) work
-typically phosphodiesterase causes cAMP/cGMP breakdown
-If we inhibit this enxyme we can increase cAMP/cGMP
- if we inhibit PDE we can increase cAMP, which means increase in calcium levels, which increases force of contraction
- this is a positive iontropic effect
What are the side effects of PDE inhibitors
-increased excitability as PDE type 3 inhibition adjust Ca2+ levels in cardiac myocytes
-may result in arrhythmias at the wrong doses
What are the other drugs not mentioned that can be used for cardiac failure
- You can decrease Heart rate
- for example beta blockers
- ivabradine
- Diuretics (decreases blood volume)
- Vasodilators (increases systemic volume)
- ACE inhibitors
