7: Drugs affecting cardiac rate and force

Question 1

Cardiac rate and force are mainly regulated by the ___ nervous system.

Answer 1

autonomic

Question 2

Sympathetic regulation of cardiac rate and force depends on a transmitter and a hormone - what are they called?

Answer 2

Adrenaline (hormone released from the adrenal medulla)

Noradrenaline (post-ganglionic transmitter)

Question 3

Which type of receptor do adrenaline and noradrenaline activate?

Answer 3

ß₁ adrenoceptors

Question 4

In the context of cardiac rate and force, where are ß₁ adrenoceptors found?

Answer 4

1) AV/SA nodal cells

2) Myocardial cells

Question 5

ß₁ are coupled to what kind of protein?

Answer 5

G protein

Question 6

The activation of ß₁ adrenoceptors by (nor)adrenaline triggers the activation of which enzyme?

Answer 6

Adenylyl cyclase

Question 7

What does adenylyl cyclase do?

Answer 7

Increases the concentration of cAMP

Question 8

What is the effect of sympathetic stimulation on heart rate, and what is another name for this effect?

Answer 8

Increases heart rate

‘Positive chronotropic effect’

Question 9

What is the effect of sympathetic stimulation on force of contraction, and what is another name for this effect?

Answer 9

Increased force of contraction

‘Positive inotropic effect’

Question 10

What effect does sympathetic stimulation have on the conduction velocity of the AV node?

Answer 10

Increased velocity of conduction

therefore increases heart rate

Question 11

What is the name given to increasing mass of cardiac muscle caused by long-term sympathetic stimulation?

Answer 11

Cardiac hypertrophy

Question 12

Which neurotransmitter is involved in parasympathetic regulation of cardiac rate and force?

Answer 12

Acetylcholine

Question 13

What kinds of neurotransmitter are noradrenaline and acetylcholine? Which divisions of the nervous system are they part of?

Answer 13

Noradrenaline (post-ganglionic)

Acetylcholine (post-ganglionic, pre- too sometimes)

Noradrenaline - sympathetic

Acetylcholine - parasympathetic

Question 14

In parasympathetic regulation of cardiac rate and force, which receptor is activated by acetylcholine?

Answer 14

M₂ muscarinic receptors

Question 15

Where are M₂ muscarinic receptors usually found?

Which neurotransmitter binds to them?

On behalf of which nervous system does this neurotransmitter act?

Answer 15

Nodal cells

Acetylcholine

Parasympathetic

Question 16

Which type of protein are M₂ muscarinic receptors bound to?

Answer 16

G protein

Question 17

Activated M₂ muscarinic receptors reduce the activity of which enzyme?

Answer 17

Adenylyl cyclase

Question 18

Adenylyl cyclase activity is reduced by the activation of which G-protein-coupled receptor?

Answer 18

M₂ muscarinic receptors

Question 19

What does adenylyl cyclase help synthesise?

What is the effect of sympathetic stimulation on the concentration of this chemical?

And parasympathetic stimulation’s effect?

Answer 19

cAMP

Increased [cAMP]

Decreased [cAMP]

Question 20

Apart from decreasing [cAMP], the activation of M₂ muscarinic receptors has another effect - what is it?

Answer 20

Opens potassium channels (GIRK) to hyperpolarise SA node cells (this reduces heart rate because the rate of action potentials decreases)

Question 21

What effect does parasympathetic stimulation have on heart rate, and what is another name for this effect?

Answer 21

Decreases heart rate

Negative chronotropic effect

Question 22

What effect does parasympathetic stimulation have on force of contraction, and what is another name for this effect?

Answer 22

No effect

sry

Question 23

What effect does parasympathetic stimulation have on AV node conduction? Why?

Answer 23

Reduced AV node conduction

Opening of GIRK potassium contraction causes hyperpolarisation

Question 24

Parasympathetic stimulation may causes ___ to develop in the atria.

Answer 24

Arrythmias

Question 25

Which maneouvres increase parasympathetic output and may be employed in **atrial tachycardia?**

Answer 25

Vagal maneouvres

Question 26

Give an example of a vagal maneouvre which can be used to increase parasympathetic output.

Answer 26

**Valsalva maneouvre** - activates aortic baroreceptors **Massage** of the bifurcation of the carotid artery - activates carotid baroreceptors i.e massage of the baroreceptors found in aorta and carotid artery

Question 27

Blocking HCN channels ___ the slope of pacemaker potential and ___ heart rate.

Answer 27

**decreases** , **reduces**

Question 28

What increases the activation of HCN channels?

Answer 28

Cyclic AMP

Question 29

Name a drug which is a selective blocker of HCN channels and can be used to reduce O₂ consumption in heart disease (reduced HR = reduced ").

Answer 29

**Ivabradine**

Question 30

During excitation of cardiac muscle, Ca²⁺ release from the sarcoplasmic reticulum is said to be what kind of release?

Answer 30

**Calcium dependent/induced calcium release**

Question 31

During relaxation of cardiac muscle, which channel is responsible for calcium efflux? What are the numbers of ions involved in this transport?

Answer 31

**Na**⁺ / **Ca²**⁺ **exchanger 1** (NCX1) ## Footnote **1 calcium out, 3 sodiums in**

Question 32

ß₁ adrenoceptor activation increases heart rate and force of contraction. ___ acts on the enzyme ___ \_\_\_ _ to enhance contractility of muscle.

Answer 32

**cAMP , Protein kinase A**

Question 33

Cardiac muscle relaxation is dependent on Ca²⁺ being pumped out of the cell. Which enzyme performs which reaction on the protein that facilitates this?

Answer 33

**Protein kinase A** **Phosphorylation** **Phospholamban**

Question 34

Name **two** ß adrenoceptor agonists used in treatment of heart conditions.

Answer 34

**Dobutamine** **Adrenaline**

Question 35

What are the pharmacodynamic effects of ß adrenoceptor agonists on the heart?

Answer 35

**Increased force of contraction, heart rate** and therefore **cardiac output** **Reduced cardiac efficiency** (O₂ consumption increases more than the cardiac work itself)

Question 36

ß adrenoceptors can cause disturbances in cardiac \_\_\_, also known as \_\_\_.

Answer 36

**rhythm** , **arrythmias**

Question 37

**Adrenaline** is commonly used clinically. Name two conditions in which it is used, and the route of administration.

Answer 37

**Cardiac arrest** - IV **Anaphylactic shock** - IM

Question 38

**Dobutamine** is another ß adrenoceptor which is used clinically. When?

Answer 38

During acute heart failure which may be reversible (e.g cardiac surgery, shock)

Question 39

Name two ß adrenoceptor antagonists.

Answer 39

**Propranolol** (ß₁ and ß₂) **Atenolol, bisoprolol, metoprolol** (ß₁)

Question 40

Name a clinical effect of a non-selective ß adrenoceptor blocker such as **atenolol, bisoprolol** or **metoprolol**.

Answer 40

**Reduces exercise tolerance** **Reduces myocardial O₂ requirement**, allowing for **better oxygenation of the myocardium**

Question 41

What can ß adrenoceptor antagonists be used to treat clinically?

Answer 41

**Arrhythmias** (decrease excessive sympathetic drive and help to restore sinus rhythm) **Atrial fibrillation** and **superventricular tachycardia** (delay conduction through AV node and help to restore sinus rhythm) **Angina**

Question 42

Low dose ß blockers are used in **compensated heart failure.** Just remember this.

Answer 42

lol

Question 43

Name a couple of **adverse effects** of ß blockers as a class.

Answer 43

**Bronchospasm** **Aggravation of cardiac failure** **Bradycardia** **Hypoglycaemia** (glucose release from liver is controlled by ß₂ adrenoceptors in diabetics) **Fatigue** and **cold extremities**

Question 44

Name a **muscarinic ACh receptor** antagonist.

Answer 44

**Atropine**

Question 45

Atropine blocks muscarinic ACh receptors. Which division of the nervous system are these receptors associated with? What does increased parasympathetic discharge cause in a patient? What will the effect of atropine administration be in a patient?

Answer 45

**Parasympathetic** **Bradycardia** **Increased heart rate**

Question 46

Give in **low** doses, **atropine causes** (increased / decreased) heart rate.

Answer 46

**Decreased heart rate** (In higher doses it increases heart rate.)

Question 47

Name a **cardiac glycoside** which **increases the contractility** of the heart.

Answer 47

**Digoxin**

Question 48

What is heart failure?

Answer 48

**A cardiac output insufficient to provide adequate tissue perfusion**

Question 49

Name **two inotropic drugs** which enhance contractility.

Answer 49

**Digoxin** **Dobutamine**

Question 50

Inotropic drugs increase **stroke volume** at any given __ \_\_ \_\_.

Answer 50

**end diastolic volume**

Question 51

Which membrane transporter does **digoxin** block?

Answer 51

Na⁺/K⁺ ATPase | (**sodium-potassium pump**)