Drugs and the heart

Question 1

What are the ‘funny’ channels in the heart? - I f channels

Answer 1

Hyperpolarization activated cyclic nucleotide gated channels - switch on during hyperpolarised states and utilise cyclic AMP and drive sodium entry to initiate depolarisation. On their own they do not produce enough to complete depolarissation, but it starts it

Question 2

What is the predominant channel that drives depolarisation in Heart rate

Answer 2

Calcium channels - transient t type calcium channels or long lasting l type

Question 3

What channels repolarise the cells controlling heart rate

Answer 3

-potassium channels

Question 4

What is phase 4 in heart rate regulation

Answer 4

Spontaneous depolarization that triggers an action potential

Question 5

Mechanism regulating heart contractility - describe the steps

Answer 5

1. signal promotes calcium entry
2. calcium activates RyR receptor
   - 25% of calcium comes from outside, 75% from sarcoplastic reticulum
3. calcium promotes troponin binding and causing contraction
4. repolarisation via sodium exchanging for calcium to export calcium out of cell and sodium potassium atpase maintains sodium levels in cell

Question 6

What mechanisms increase the myocardial oxygen demand

Answer 6

An increase in:
heart rate
preload
afterload
contractility

Question 7

What are factors that can increase the myocardial oxygen supply

Answer 7

Increase in:
Coronary blood flow
Arterial O2 content

Question 8

What drugs mainly effect rate of heart

Answer 8

Beta blockers and

Question 9

What beta blockers effect on the heart rate

Answer 9

Sympathetic NS increases nodal activity, and therefore affects funny current and ca2+ channels
Therefore a beta blocker will stop the sympathetic NS therefore decrease If and Ica

Question 10

Calcium antagonist effect on heart rate

Answer 10

Block Ca2+ therefore slow heart down

Question 11

What affect ivabradine on heart rate

Answer 11

Block funny current therefore decreasing heart rate as spacing out the time between each depolarisation starting

Question 12

What affect beta blockers and calcium channel blockers on contractility

Answer 12

decrease calcium entry therefore decrease contractility

Question 13

What are the different types of calcium antagonists

Answer 13

there are two classes - rate slowing that have cardiac and smooth muscle actions and non rate slowing that only have smooth muscle actions, but these are more potent

Question 14

What are examples of rate slowing drugs

Answer 14

Phenylalkylamines eg verapamil

Benzothiazepines eg diltiazem

Question 15

What are examples of non rate slowing drugs

Answer 15

Dihydropyridines eg amlodipine

Question 16

What effect do organic nitrates and potassium channel openers have on the heart and how does it do this?

Answer 16

It increases cyclic GMP therefore causing smooth muscle relaxation and hyperpolarisation (due to potassium efflux) of the cells making it harder to contract. K+ channel openers mainly just cause potassium efflux causing hyperpolarisation of the cell

Question 17

What two different effects of nitrates and potassium channel openers influence preload and afterload? What is a consequence of this?

Answer 17

It causes vasodilation therefore decreasing afterload
Venodilate causing a decrease in preload
Therefore a decrease in myocardial oxygen demand

Question 18

What is a stable angina

Answer 18

A cardiac stitch where the heart doesn’t receive enough oxygen during exercise causing pain

Question 19

What is the first line treatment of a stable angina? What is the problem of this treatment

Answer 19

Beta blockers or calcium channel blocker by reducing HR and contractility but make it harder to exercise as less response to sympathetic stimuli and therefore less Ca2+ influx

Question 20

beta blocker side effects

Answer 20

It can worsen heart failure as it makes your tissues less able to match CO to tissue needs, which is already a problem in heart failure.
It also increases vascular resistance by blocking dilating of vessels. This will make HF even worse as have to work harder to push blood around the body
Also causes bradycardia, and if a patient has conduction problems then this will be even worse

Question 21

What are examples of beta blockers used on the heart

Answer 21

Pindolol - an equal affinity for beta1 and beta 2 receptors with intrinsic sympathetic activity
Carvediol that causes an alpha 1 blockade causing additional vasodilator properties (alpha 1, beta 1 and 2)

Question 22

What kind of patients can you NOT use beta blockers for and why

Answer 22

Asthmastics and diabetics
They block B2 receptors in lungs therefore make asthma attacks worse
It also interferes with liver control of glucose and masks hyperglycaemia effects

Question 23

What is a common side effect of beta blockers that really bothers patients

Answer 23

Cold extremities (also a worsening peripheral artery disease) due to a loss of beta 2 receptor mediated cutaneous vasodilation in extremities therefore no blood in extremities

Question 24

Side effects of calcium channel blocker

Answer 24

they are ‘safer’ than beta blockers but they can cause bradycardia and constipation (can affect people from taking a drug)

Question 25

What are side effects of dihydropyridines

Answer 25

Ankle oedema due to vasodilation meaning more blood in capillaries causing fluid coming out Headache/flushing due to vasodilation Palpitations due to reflex tachycardia due to vasodilation of vessels

Question 26

What are the different arrythmias simply classified between

Answer 26

Supreventricular - above the ventricles Ventricular Complex ( a mix of both supra and ventricular)

Question 27

What is the vaughn williams classification

Answer 27

A classification of anti arrhythmic drugs: seperating the drugs into: Class 1- sodium channel blockers Class 2 - beta adrenergic blockade Class 3 - prologation of repolarisation (membrane stabilisation mainly due to potassium channel blockade) Class 4 - calcium channel blockade

Question 28

What drugs are used to treat supraventricular arrythmias and how does it do this?

Answer 28

Adenosine, binding to adenosine receptors having an inhibitory effect on adenylate cyclase and therefore inhibiting cyclic AMP therefore decrease funny current therefore reducing depolarisation via AV node (less importantly also has effect on SM and promote relaxation)

Question 29

How does verapamil work

Answer 29

Block Ca2+ channels therefore decreasing ability to depolarisation therefore causing a longer time between the depolarisations therefore increases chances of normal rhythm starting

Question 30

How does amiderone work

Answer 30

Blocks re-entry arrhythmias This is done by a potassium channel blockade therefore prolonging the repolarisation state

Question 31

What is a reentry rhythm

Answer 31

Where areas of damaged or dead tissue due to heart attack etc that causes a signal for a heart to contract coming back up the heart to cause a contraction instead of going as it would do, down the heart and cause contraction down the heart

Question 32

What are the effects of digoxin/.

Answer 32

Decrease stroke risk by inhibiting the Na K ATPase pump Digoxin also increases refractory period and reduces rate of conduction through the AV node, therefore more time between heart contractions

Question 33

What effect does digoxin have on inotropy

Answer 33

Blocks Na K ATPase therefore blocking Na+ movement into the cell. This means that Na+ can't be exchanged for Ca2+ successfully therefore more Ca2+ in cardiac muscle as it can't move out. Therefore making cardiac muscle contractions more powerful.

Question 34

When is digoxin used

Answer 34

In AF and Atrial flutter particularly when worry about stroke

Question 35

Side effects of digoxin

Answer 35

Dysrhythmias due to AV conduction block

Question 36

What can make digoxin toxicity threshold worse therefore make effects worse and why

Answer 36

Hypokalaemias eg due to diuretic use due the digoxin binding to the potassium binding site. Potassium competes with digoxin for this site, and if K+ levels decrease then more digoxin binds to the target so has a more powerful effect