Drugs and the heart

Question 1

What are the different ways drugs can affect the heart

Answer 1

Direclety
- can actually affect cardiomyocytes
- Can affect rate/rhythm
- force of contraction

Indirectly

• can influence by vasculature
• Blood volume and the composition of blood

Question 2

What are arrythmias

Answer 2

when the heartbeat’s rhythm is irregular or abnormal

Question 3

what can be the difference disorders of rate or rhythm

Answer 3

• rhythm could be too fast or slo
• abnormal generation/conduction
• disruption of how cardiac action potentials

Question 4

What are the causes of arrhythmias?

Answer 4

• Pathology (is it due to nodes or conducting tissue)
• Drug-induced (taking particular drugs for therapeutic or recreational)
• Congenital

Question 5

How do we name arrhythmias

Answer 5

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

Question 6

How do anti-arryhtmatic drug work?

typically how do they target the heart

Answer 6

can focus on cardiac action potential

they act on different parts of the action potential graph

Question 7

How many classes of antiarrhythmic drugs work

Answer 7

4

Question 8

Name a drug in class 1

Answer 8

lidocaine, flecainide

Question 9

How do class 1 drugs work

Answer 9

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

Question 10

Name some class 2 antiarryhmic drugs

Answer 10

• beta blockers
• Eg metoprolol, propanolol

Question 11

How do class 2 anti-arrhythimcs work

Answer 11

• decreases sympathetic effect by blocking beta 1 receptors
  
  • increases slope of the action potential

Question 12

Name some class 3 antiarrhytmics

Answer 12

amiodarone (Idoine molecule, used in thyroid action), sotalol (has some beta blocker action)

Question 13

How do class 3 antiarrhytmics work

Answer 13

• they prolong the action potential
• by blocking potassium channels involved in repolarisation (primary for antiarrhythmics )
• but these drugs do act on other receptors

Question 14

Name a class 4 anti-arrhythmic

Answer 14

Verapamil

Question 15

How do class 4 anti-arrhythmics work

Answer 15

• 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

Question 16

Non classifeid drugs

Name some anti-arrhythmics that aren’t part of the classification

Answer 16

adenosine
cardiac glycosides

Question 17

How does adenosine work

Answer 17

• 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

Question 18

Name a cardiac glycosides

Answer 18

digoxin

most commonly used

Question 19

How do cardiac glycosides usually work

Answer 19

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

Question 20

What are the general side effects of antiarrhythmic drugs

Answer 20

• 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

Question 21

Why might we need drugs to affect the force of contraction?

Answer 21

• Anaphylaxis
  
  • massive reduction in blood pressure
• Heart failure
  
  • Cardiac Output is insufficient for the metabolic needs of the body

Question 22

How is he force of contraction normally determined

what ion is involved

Answer 22

intracellular calcium i

Question 24

How can drugs work to increase the contractility?

generally what can they do

Answer 24

• Inotropic effects
• change muscle fibres

Question 25

What do negtative ionotropic drugs do usually

Answer 25

decreases intracelluar calcium so they decrease force of contraction

Question 26

What classes of drugs cause a positive ionotropic effect

Answer 26

- Sympathomimetics - Cardiac glycosides - Phosphodiesterase inhibitors

Question 27

How do poisitive ionotropic drugs work generally

Answer 27

they increase intracelluar calcium, which increases force of contraction

Question 28

How does digoxin work

Answer 28

-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 ## Footnote Na+/K+ ATPase normally maintains ion concentration gradient inside/outside cells.

Question 29

What will happen if we fully inhibit the Na+/K+ ATPase

Answer 29

if we fully inhibit the sodium pottassum atpase we will die

Question 30

What are the Side effects of cardiac glycosides

Answer 30

- 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 ## Footnote 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

Question 31

What are the clinical use of digoxin

Answer 31

-heart failure patients ## Footnote wrong dose of digoxin ca cause arrhmias

Question 32

What drugs can interact with digoxin

Answer 32

- 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

Question 33

Name some Phosphodiesterase inhibitors (PDEs)

Answer 33

Eg milrinone, enoximone

Question 34

How do Phosphodiesterase inhibitors (PDEs) work

Answer 34

-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

Question 35

What are the side effects of PDE inhibitors

Answer 35

-increased excitability as PDE type 3 inhibition adjust Ca2+ levels in cardiac myocytes -may result in arrhythmias at the wrong doses

Question 36

What are the other drugs not mentioned that can be used for cardiac failure

Answer 36

- You can decrease Heart rate - for example beta blockers - ivabradine Can be used, but don't affect the heart - Diuretics (decreases blood volume) - Vasodilators (increases systemic volume) - ACE inhibitors