Drugs & CVS

Question 1

What are the 4 classifications of anti-arrhythmic drugs?

Answer 1

1. Class 1 : drugs that block voltage sensitive sodium channels
2. Class 11 : antagonists of beta-adrenoreceptors
3. Class 111: drugs that block potassium channels
4. Class 1V: drugs that block calcium channels

Question 2

Give an example of a class 1 drug

Answer 2

Lidocaine

Question 3

Explain how a class 1 drug works eg lidocaine

Answer 3

Loclass 1 drugs blocks voltage gated Na+ channels in open or inactive state.

Damaged myocardium can spontaneously depolarise causing arrhythmia’s eg AF. Lidocaine works in this condition by blocking Na+ channels after an action potential , therefore preventing the initiation of another action potential.

Sometimes used after an MI. INTRAVENOUSLY

Question 4

Give examples of class 11 drugs

Answer 4

Propranolol , atenolol ( BETA BLOCKERS j

Question 5

Outline the mechanism of action of class || drugs

Answer 5

1. They block the sympathetic action by blocking B1 receptors in the heart to slow the heart rate ( negative chronotropy).
2. Blocking the b1- receptors causes a reduced heart rate due to a decreased slope of the pacemaker potential in the SA node as the SA nodes increases the time taken to initiate an action potential
3. AND slows conduction in the AV node to increase the time between depolarisation of the atria and the ventricles.

Question 6

When are beta blockers used ?

Answer 6

1. Used following an MI. This is because MI often causes increased sympathetic activity and arrhythmia may be partly due to the increased sympathetic activity. Beta blockers prevent ventricular arrythmias.
2. Can prevent supraventricular tachycardia as beta blockers slow conduction in the AV node. It also slows ventricular rate in patients with AF.
3. Reduce myocardial ischaemia by reducing oxygen demand.
4. In heart failure

Question 7

Give an example of a class ||| drug

Answer 7

Amiodarone

Question 8

Outline the mechanism of action of class 111 drugs

Answer 8

They block potassium channels which prolongs the action potential and lengthens the absolute refractory period to slow the heart rate down. This prevents another action potential from forming. However , these drugs can actually be pro-arrhythmic as they promote early after depolarisations.

Question 9

Why is amiodarone considered a good class 111 drug ?

Answer 9

Because it has other actions in addition to blocking K+ channels for example it is also a beta blocker and calcium channel blocker.

Question 10

When do we use class 111 drugs ?

Answer 10

1. Can be used to treat most arrhythmias , however it is not first line in most cases due to side effects .
2. Treat tachycardia associated with Wolff-Parkinson white syndrome.
3. Suppress ventricular arrhythmias post MI.

Question 11

Give examples of class 1V drugs ?

Answer 11

Verapamil ( act on the heart to give negative chronotropic and inotropic effects )

Diltiazem ( act on the heart to give negative inotropic and chronotropic effects )

Dihydropyridine eg Amlodipine which work on smooth muscle vasculature by promoting systemic vasodilation. These are NOT effective in preventing arrhythmias.

Question 12

What is the mechanism of action of class 1V drugs ?

Answer 12

1. Can act on the myocardium to decrease the slope of the action potential at the SA node and decrease AV node conduction by blocking calcium channels
   This leads to negative inotropic and negative chronotropic effects.
2. Class 1V drugs can also block calcium channels on smooth muscle cells to reduce contraction. This leads to the dilation of blood vessels to reduce total peripheral resistance. Which then decreases arterial blood pressure. And reduces the workload of the heart by reducing afterload.

Question 13

What is Adenosine ? And what is its importance

Answer 13

An endogenous substance that is produced in our body in small amounts at psychological levels.

It can be given IV which acts on a1 receptors to enhance potassium conductance and hyperpolarised cells. This hyperpolarisation inhibits the movement fo calcium and essentially re sets the SA node. It has a very short half life.

The patient will feel like their heart has stopped when adenosine is given.

It is important because it is an anti-arrhymic drug but does not belong to any of the classes. It is useful for terminating re entrant SVT.

Question 14

What are ACE-inhibitors ( ACEi) ?

Answer 14

Very important in reducing hypertension and heart failure.

They inhibit the action of angiotensin converting enzyme. This , this would prevent the conversion of angiotensin 1 to angiotensin 11.

This is important because angiotensin 11 acts on the kidneys to increase Na+ and water reabsorption. Angiotensin 11 is also a vasoconstrictor. And angiotensin 11 also stimulates release of aldosterone from the adrenal cortex.

Question 15

What are the common side effects on patients who take Angiotensin converting enzyme inhibitors ?

Answer 15

CNS cause a dry cough due to excess bradykinin building up in the lungs this is because ACE is used to break down bradykinin but now that it is inhibited , bradykinin builds up.

Question 16

Why are ACE-inhibitors important in the treatment of heart failure ?

Answer 16

,this is because ACEi decrease vasomotor tone which means they decrease blood pressure.

This reduces the afterload of the heart. And reduces pre load of the heart.

Both effects reduce the work load of the heart.

Question 17

In a patient who cannot toleratte ACEi eg due to build up of bradykinin , what is an alternative ?

Answer 17

Angiotensin 1 receptor blockers which block angiotensin 1 receptors which prevents angiotensin 11 from binding. This leads to a reduced effect of Angiotensin 11.

They have the same effect as ACEI but ACE enzyme is not affected so bradykinin can still be broken down.

Question 18

Ca2+ channel blockers are useful in which problems ?

Answer 18

Hypertension

Angina

Coronary artery spasm

Supraventricular tachycardia

Question 19

What are the two types of positive inotropic ?

Answer 19

1. Cardiac glycosides

2. Beta-adrenergic agonists

Question 20

Give an example of cardiac glycosides

Answer 20

Digoxin

Question 21

Outline the mechanism of action of cardiac glycosides such as digoxin

Answer 21

1. Blocks Na+/K+ ATPase
2. This causes an increase in intracellular Na+
3. This leads to a decrease in activity of the nA+/Ca2+ exchanger. Which leads to more Ca2+ stored in the SR.
4. This leads to an increased force of contraction

IMPROVES SYMPTOMS IN PATIENTS WITH HEART FAILURE BUT NO LONG TERM ACTION

Question 22

Outline the action of cardiac glycosides on heart rate

Answer 22

Cardiac glycosides also cause increased a gala activity. This slows AV conduction and slows the heart rate.

May be used in heart failure when there is an arrythmia such as AF

Question 23

Give examples of beta-adrenoreceptors agonist

Answer 23

Dobutamine

Question 24

Summarise the way to treat heart failure.

Answer 24

Cardiac glycosides will relieve symptoms by making the heart contract harder , however there is no long term benefits as making the heart work harder is not good in the long run. It is better to reduce workload.

Therefore ACEi or ARB or diuretics are better for heart failure as they reduce the workload of the heart. Beta blockers can also reduce workload of the heart

Question 25

What is angina?

Answer 25

When o2 supply to the heart does not meet its demands. This is of a limited duration and does not result in death of myocytes. When ischaemia of heart tissue occurs , chest pain arises.

Question 26

How can we treat angina ?

Answer 26

Organic nitrates

Question 27

What is the mechanism of action of nitrates ?

Answer 27

1. Organic nitrates react with thiols ( SH) in vascular smooth muscle which causes NO2- fo be released. 2. NO2- is reduced for NO ( nitric oxide ) 3. Nitric oxide is released endogenously from endothelial cells. 4. Nitric oxide is most effective on VEINS - less of an effect on arteries 5. Nitric oxide causes venodilation of veins. 6. Venodilation of veins lowers pre load , which reduces work load of the heart. The heart fills less therefore force of contraction reduced. This lowers O2 demands.

Question 28

How does nitric oxide cause vasodilation ?

Answer 28

Nitric oxidie activates guanylate cyclase. This catalyses the formation of cGMP from GTP. CGMPthen goes off to activate protein kinase G. Protein kinase G then works by lowering intracellular Ca2+ Which causes relaxation of vascular smooth muscle

Question 29

What heart conditions increase the risk of thrombus formation ?

Answer 29

AF acute myocardial infarction Mechanical prosthetic heart valves

Question 30

What drug is commonly given as an anti thrombotic drug to someone with AF ?

Answer 30

Warfarin ( orally) which antagonises the action of vitamin K Direct oral thrombin inhibitors such as dabigatran are more commonly used now , where you don’t have to check their INR.

Question 31

How is heparin given usually ?

Answer 31

IV - it inhibits thrombin used acutely for short term action Fractioned heparin is given using a subcutaneous injection.

Question 32

Give an example of an anti platlet drug

Answer 32

Aspirin Clopidogrel Used following acute MI or high risk MI