Drugs and the heart

Question 1

Recall the ion channels that influence heart rate

Answer 1

If (VGSC)
It (VGCC)
Il(VGCC)
Ik(VGPC)

Question 2

Recall the roles of the sodium and calcium channels in depolarisation

Answer 2

If kickstarts depolarisation by allowing Na+ to move into cell
It (transient) begins to propagate AP
Il (long-lasting) produces the real upstrike of the AP

Question 3

How does the SNS affect ion channels in the heart?

Answer 3

Linked to cAMP to increase opening of VGSCs and VGCCs

Question 4

How does the PNS affect ion channels in the heart?

Answer 4

Increases Ik opening to prolong repolarisation

Question 5

Describe the effect of beta-receptor activation on cardiac myocytes

Answer 5

PKA activated –>

1. Contractility increase
2. Reduced Ca++ reuptake into SR

Question 6

What is the target of ivabradine?

Answer 6

If channel

Question 7

Recall the 2 classes of calcium antagonists and their comparative tissue specificities

Answer 7

Rate-slowing: cardiac and SMC effects

Non-rate slowing: Just SMC, and more powerful on SMCs that rate-slowers

Question 8

What is the main risk associated with non rate-slowing calcium antagonists?

Answer 8

Reflex antagonists: profound vasodilation leads to overstimulation of baroreceptors

Question 9

Recall 2 classes of drug that act as rate-slowing calcium-antagonists

Answer 9

Phenylalkylamines

Benzothiapenes

Question 10

Give an example of a non rate-slowing calcium antagonist

Answer 10

Amlodipine

Question 11

What classes of drug can act as influencers on myocardial oxygen supply/ demand?

Answer 11

Organic nitrates

K+ channel openers

Question 12

How do organic nitrates decrease the work burden of the heart?

Answer 12

NO –> more GTP converted to cGMP –> vasodilation

Question 13

Describe the effects of vasodilation and venodilation on cardiac work

Answer 13

Vasodilation –> decreased AFTERload

Venodilation –> decreased PREload

Question 14

What are organic nitrates/ K+ channel-openers most frequently used to treat?

Answer 14

Angina

Question 15

Describe the instructions for administration of organic nitrate drugs

Answer 15

These are short acting, and so are used as opportunistic symptomatic relief

Question 16

In which group of people are K+-channel-openers most frequently prescribed and why?

Answer 16

Asthmatics

Contra-indicted for beta-blockers

Question 17

Systematically address the possible side-effects of a beta-blocker

Answer 17

Beta-1 side-effects: slow heart, care not to ppt heart block
Beta-2 SEs: bronchoconstriction (caution asthmatics), hypoglycaemia (caution: diabetics), cold extremities (caution, raynaud’s)

Question 18

What sort of drug is verapamil?

Answer 18

Calcium channel antagonist

Question 19

Recall 3 possible side effects of calcium channel antagonists

Answer 19

ABC:
AV block
Bradycardia
Constipation

Question 20

Recall and justify 3 possible side effects of dihydropiridenes

Answer 20

Ankle oedema (vasodilation puts pressure on capillaries)
Headache/ flushing (vasodilation)
Palpitations (Ca++ channel interference)

Question 21

What sort of drugs are dihydropiridenes?

Answer 21

Calcium channel antagonists

Question 22

Recall the possible classifications of arrhythmias

Answer 22

Supraventricular
Ventricular
Complex

Question 23

What tissue is affected by a supraventricular arrhythmia?

Answer 23

Atria/ nodal tissue

Question 24

Recall 2 drugs implicated in supraventricular arrhythmia

Answer 24

Amiodarone

Verapamil

Question 25

Recall 2 drugs implicated in ventricular arrhythmia

Answer 25

Lidocaine | Flecainide

Question 26

Recall a drug implicated in complex arrhythmia

Answer 26

Disopyramide

Question 27

Recall the Vaughan Williams classification of arrhtyhmia

Answer 27

``` I = SODIUM channel blockade II = BETA-adrenergic blockade III = Prolonged repolarisation (VGPC BLOCKADE) IV = CALCIUM channel blockade ```

Question 28

Recall the method of administration of adenosine

Answer 28

IV

Question 29

Why is adenosine generally seen as safer than verapamil?

Answer 29

Short-lived action so less concerned about long-term SEs

Question 30

Recall the twofold mechanism of action of adenosine

Answer 30

1. Effect on SMCs in heart and vasculature = stimulation of cAMP to increase RELAXATIOn 2. Effect on NODAL tissue = REDUCES cAMP --> decreased ICa opening, increased Ik opening

Question 31

What sort of arrythmia is verapamil particularly useful for treating?

Answer 31

Atrial arrhythmias - it reduces the ventricular response

Question 32

What sort of arrythmia is amiodarone particularly useful for treating?

Answer 32

Re-entry rhythms caused by tissue block

Question 33

Describe how a re-entry rhythm might arise

Answer 33

Normally if 2 APs coming down purkinje fibres meet at apex they cancel each other out + ensure the Aps continue up both sides. In re-entry, goes back up and re-activates tissue to cause consistent contraction of ventricular muscle

Question 34

What effect needs to be produced in the heart to combat reentry rhythms?

Answer 34

Prolonging of repolarisation so that tissue hit by re-entering AP is not depolarised again

Question 35

How does amiodarone treat re-entry rhythms?

Answer 35

Blocks multiple ion channels to prolong repolarisation

Question 36

Why has amiodarone got so many side effects? Recall some of these

Answer 36

Really long t1/2: Skin rashes Hypo/hyperthyroidism Pulmonary fibrosis

Question 37

What sort of drug is digoxin? Summarise its mechanism of action

Answer 37

Anti-arrhythmic: | Blocks Na+/K+ATPase

Question 38

Recall the 2 sites of action of digoxin

Answer 38

``` Ventricles (improves contraction) Vagus nerve (increases refractory period) ```

Question 39

Why is digoxin used for AF? (2 reasons)

Answer 39

1. Improves ventricular filling | 2. Combats ventricular tachycardia

Question 40

When should you NOT give digoxin and why?

Answer 40

In hypokalaemia: | Digoxin competes with K+