Drugs on heart

Question 1

What does high HR do?

Answer 1

• Increases myocardial O2 consumption
• Reduces coronary circulation perfusion time (only perfuses during diastole)
• Increases arrhythmia risk
• Linked to atherosclerosis/coronary artery plaque disruption

Question 2

What HR shows greater risk to CVD?

Answer 2

Resting rate > 70 bpm

Question 3

What’s the central treatment for angina, heart failure, post-MI treatment, arrhythmias?

Answer 3

drugs that lower HR

Question 4

Why lower HR

Answer 4

High HR is predictor of morbidity + mortality from CVD

Question 5

How to lower HR?

Answer 5

Decrease initiation + frequency of pacemaker potentials by:

• Inhibit vgcc: reduce phase 0, slower upstroke
• Inhibit If channels: increase Phase 4, slower diastolic depolarisation before reaches threshold, slower to activate vgcc

Question 6

What are Ca2+ channel blockers (CCB)?

Answer 6

Drugs that site in channel pore blocking Ca2+ entry into SA cells reducing HR

Question 7

Why do CCB need to selectivity target Ca2+ channels in SAN?

Answer 7

Ca2+ channels also in cardiac myocytes (phase 2, plateau phase) + vascular smooth muscle
providing Ca2+ influx for contraction

Question 8

Subtypes of CCB?

Answer 8

vascular = Dihydropyridines
cardiac = Diphenylalkyamines
vascular+cardiac = Benzothiazepines

Question 9

What’s Amlodipine?

Answer 9

Dihydropyridine

vascular selective CCB

Question 10

What’s Verapamil?

Answer 10

Diphenylalkyamine

cardiac selective CCB

Question 11

What’s Diltiazem?

Answer 11

Benzothiazepine

vascular+cardiac selective CCB

Question 12

How can CCBs cause heart block?

Answer 12

Non-selective blocking actions on:
Ca2+ channels in cardiac myocytes for contractility
AVN for conduction

Question 13

What’s Ivabradine?

Answer 13

Selective inhibitor of If channel in SAN
Decreases pacemaker potential frequency
Decreases HR to reduce myocardial O2 demand
Used in heart failure, angina

Question 14

Describe how If channel blockers work?

Answer 14

• inhibits If
• inhibits diastolic depolarisation
• slows unstable membrane potential from reaching threshold
• slower to activate vgcc
• slower upstroke of phase 0
• reduction in pacemaker frequency potentials
• decrease HR

Question 15

How sympathetic increases HR?

Answer 15

NA binds to β1 adrenoceptor (Gs) - stimulate adenyl cyclase producing cAMP from ATP which increases If channel activity

Question 16

How para decreases HR?

Answer 16

Ach binds to M2 (Gi) - inhibit adenyl cyclase so no cAMP from ATP which decreases If channel activity

Question 17

Affect of β1-adrenoceptor blockers (antagonists)?

Answer 17

reduce sympathetic NA/A on SAN reducing HR

Question 18

What’s Atenolol?

Answer 18

β1-adrenoceptor blockers (antagonists)

reduce sympathetic NA/A on SAN so increase in HR/contractility subdued which reduces work / O2 demands on heart

Question 19

Why isn’t β1-adrenoceptor blockers used with CCB?

Answer 19

reduce contractility too much + produce too much bradycardia

Question 20

Why isn’t β1-adrenoceptor blockers used on asthmatic patients?

Answer 20

can affect β2 on lungs so less bronchial dilation

Question 21

Why can β1-adrenoceptor blockers cause fatigue?

Answer 21

can’t increase HR enough, less blood flow

Question 22

Affect of Mus receptor blockers (antagonists)?

Answer 22

reduce para vagus/Ach on SAN so removal of inhibitory influence on HR – vagal tone which increase HR

Question 23

What treatments are Mus blockers used for?

Answer 23

COPD, IBS, overactive bladder

Question 24

What’s Atropine?

Answer 24

Mus receptor blockers (antagonists)

increase HR creating stable CO

Question 25

Adverse effect of Mus blockers?

Answer 25

tachycardia increases O2 demands on heart | Important in patients w co-morbidities (COPD + angina)

Question 26

What happens during heart failure?

Answer 26

CO unmaintained – poor blood flow so end organs poorly perfused

Question 27

How to maintain CO in heart failure?

Answer 27

Increase: contractility, ejective force, SV - CO = HR x SV

Question 28

eg of acute heart failure?

Answer 28

cardiac arrest, anaphylaxis, sepsis

Question 29

eg of chronic heart failure?

Answer 29

cardiomyopathy, chronic hypertension, valve disease

Question 30

What are drug targets to increase contractility (inotropic agents)?

Answer 30

Gs coupled receptor agonists - bind to receptors linked to Gs (β1, glucagon receptor) PDE inhibitors - less cAMP -> AMP, build up of cAMP driving PKA Other Ca2+ rising processes

Question 31

What's phosphodiesterase (PDE)?

Answer 31

cause breakdown cAMP -> AMP

Question 32

What are β1-adrenoceptor agonists + eg?

Answer 32

Gs coupled receptor agonists A, dobutamine, dopamine Used in acute heart failure

Question 33

eg of other Gs coupled agonist?

Answer 33

Glucagon – glucagon receptors in heart muscle

Question 34

What's used for acute heart failure when the patient is on β blockers?

Answer 34

Gs coupled agonist GLUCAGON | A, dobutamine, dopamine won't work

Question 35

Why isn't Gs coupled agonists used in chronic heart failure?

Answer 35

increase: HR (proarrhythmic), myocardial work, O2 demand

Question 36

What are PDE inhibitors + eg?

Answer 36

Gs coupled receptor agonist Amrinone – phosphodiesterase III inhibitor (PDE3 is heart specific) Used in severe + chronic cases - waiting for heart transplant

Question 37

Describe how PDE inhibitor Amrinone work

Answer 37

build up of cAMP, activates PKA, increase vgcc + Ca2+ influx

Question 38

What are cardiac glycosides + eg?

Answer 38

other Ca2+ rising process : increases contractility by reducing Ca2+ extrusion - but high toxicity Digoxin

Question 39

Describe how cardiac glycosides Digoxin work

Answer 39

- Digoxin inhibits Na+/K+ ATPase on cardiomyocyte surface - No 3Na+ out , 2K+ in - build up of Na+ - less Ca2+ out, 3Na2+ in by Na/Ca exchanger (NCX) - more Ca2+ uptake into stores so greater CICR - greater contraction

Question 40

What are Ca2+ sensitizers + eg?

Answer 40

other Ca2+ rising process used in decompensated heart failure - condition w poor outcome Levosimedan, Omecamtiv

Question 41

Disadvantage of Gs coupled agonist + alternative?

Answer 41

induced rise in Ca2 requires Ca2+-ATPase for reuptake into stores so more O2 consumption, stresses heart, increase HR - pro-arrhythmogenic Ca2+ sensitizers

Question 42

Describe how Ca2+ sensitizers work

Answer 42

- no effect on Ca2+ - increase contractile sensitivity (troponin) to Ca2+ - contraction at lower Ca2+ - no increase O2 consumption or pro-arrhythmogenic

Question 43

Describe how Levosimedan works

Answer 43

Ca2+ sensitizer - bind to troponin C - increase binding of Ca2+ to TnC

Question 44

Describe how Omecamtiv works

Answer 44

Ca2+ sensitizer | -increases actin-myosin interactions

Question 45

Why use β blockers in chronic heart failure?

Answer 45

To prevent: - overworking by slowing HR increases diastolic time - increases coronary perfusion - overworking by reducing contractility reduces O2 demand - desensitization of βadrenoceptors caused by excess compensatory sympathetic in heart failure - so available for contractility - βadrenoceptor associated arrhythmias

Question 46

Describe how Diuretics work

Answer 46

-excrete more fluid -reducing blood volume -reducing central venous pressure + SV (via Starling’s law) -reduces CO -reduces BP BP=CO (blood volume) x TPR (blood vessel constriction)

Question 47

What are Diuretics + eg?

Answer 47

reduces afterload | loop, thiazide, K+ sparing

Question 48

What are ACEi, ARB + eg?

Answer 48

reduces afterload | ramipril, losartan

Question 49

Describe how ACEi, ARB work

Answer 49

- reduce Ang II-induced vasoconstriction : reduces TPR | - reduce Ang II-induced aldosterone : reduces blood volume - reduces CO

Question 50

What's the cardiac pain in angina caused by?

Answer 50

occlusion of coronary arteries, poor perfusion of heart, produces acid, stimulates sensory nerves

Question 51

What's a nitrate donor + eg?

Answer 51

dilates coronary arteries to increase blood flow, relieves cardiac pain from angina Glyceryl tri-nitrate (GTN) : spray under tongue

Question 52

What's nitric oxide (NO)?

Answer 52

- continually produced/released | - lipophilic, soluble gas, freely diffusible out of endothelium into surrounding VSMCs