Drugs for Heart Failure

Question 1

Describe fibrinolysis

Answer 1

Fibrinogen converted/activated into fibrin by the presence of thrombin
Plasminogen activated into plasmin by Fibrin-Specific Plasminogen Activators
Leads to degradation= Fibrin Degradation Products

Question 2

How does the body control fibrinolysis?

Answer 2

Pro (tissue plasminogen activator) and anti (PAI-1 targeting Fibrin Specific Plasminogen Activator action, antiplasmin in degradation) fibrinolytic mechanisms

Question 3

Describe fibrinolytic ‘clot buster’ drugs

Answer 3

Remove clot and restore blood flow
Most effective to reduce mortality if given immediately (less than 3 hours) after MI or stroke
Accelerates conversion of plasminogen to plasmin, which degrades fibrin in thrombus

Question 4

Name a clot buster drug

Answer 4

Tissue plasminogen activator (tPA.Activase) or streptokinase

Can cause bleeding- reversed by tranexamic acid

Question 5

Describe balloon Angioplasty

Answer 5

PCTA- percutaneous transluminal angioplasty
Stenosis- balloon inflated by catheter insertion
Artery recanalized

Question 6

Describe stenting

Answer 6

Can be carried out as elective procedure to treat angina

Question 7

What occurs after MI?

Answer 7

Heart failure (dysfunction and heart failure in longer term) despite reperfusion of blood after clot removal

Question 8

What is the Frank Starling Law of the Heart?

Answer 8

Increased blood volume= increased stretch of myocardium= increased force to pump blood out
As stroke volume increases, ventricular end-diastole volume increases

Question 9

What is heart failure?

Answer 9

Failure of the heart to meet the demand of the body
Impaired contractility and emptying of ventricle (HF with reduced ejection fraction)- most common/ impaired relaxation and filling of ventricle (HF with preserved injection fraction)- ore common in women, diabetes

Question 10

What are the symptoms of heart failure?

Answer 10

Impaired tissue perfusion, fluid retention, breathlessness, muscle weakness, arrhythmia

Question 11

What are the common causes of heart failure?

Answer 11

• MI= damage to heart muscle after loss of blood supply due to ischaemic heart disease
• Pressure ad overload= due to uncontrolled hypertension and increased afterload
• Volume overload= due to damage to heart valves or increased plasma volume
• Cardiomyopathy= inherited defect in heart muscle structure influencing function
• Myocarditis= bacterial infection of myocardium

Question 12

What are the actions of drugs for heart failure/ types?

Answer 12

• Inotropic agents to increase contractility

- Drugs to unload the heart

Question 13

Examples of inotropic agents to increase contractility

Answer 13

Digoxin

Dobutamine

Question 14

Describe Digoxin

Answer 14

Foxglove- dropsy

Cardiac glycoside- increases force of contraction, positive inotrope therefore increases kidney perfusion and fluid loss

Question 15

How do cardiac glycosides work?

Answer 15

Cardiomyocyte resting membrane potential= -80mV to -90mV
Maintained by the balance of K+ (out), Na+ (in), Cl-, Ca2+ ions across the cell membrane
Inhibit Na+/K+ ATPase- no passive increase of Ca2+ out so increase concentration so increased contractility
Toxic effects

Question 16

Describe dobutamine

Answer 16

Beta 1 adrenoreceptor against IV for rapid response

Increases heart rate and contractility

Question 17

What are the cons to inotropes?

Answer 17

Although provides support in acute heart failure, results in increased oxygen demands and energy demand so not helpful long term in chronic heart failure

Question 18

What is preload determined by?

Answer 18

Preload= volume of blood in the ventricles at the end of diastole, so determined by venous return, the amount of blood entering ventricle during relaxation/diastole
-Plasma volume (kidney)
-Venus tone and capacity to hold blood (SNS)
Energy to empty in systole

Question 19

What is afterload?

Answer 19

The force against which the heart has to pump, determined by tone in resistance arterioles
SNS, circulating hormones and local factors= arteriole constriction so increased energy requirement

Question 20

How is cardiac output and blood pressure maintained?

Answer 20

Homeostatic mechanisms mechanisms activated

Decreased cardiac output (MI)= neuroendocrine activation (carotid sinus)= SNS-RAAS activation

Question 21

Describe the Renin-Angiotensin-Aldosterone system

Answer 21

Pressure detected in juxtaglomerular cells, close to the afferent arteriole, when pressure is low Renin is secreted into plasma
Angiotensinogen- angiotensin 1- angiotensin 2 (angiotensin-converting enzyme in endothelial cells)
Adrenal cortex- aldosterone- Na+ and water retention in renal tubules= blood volume and pre-load increase

Question 22

Describe the role of the SNS in increased preload and afterload

Answer 22

Positive baroreceptor feedback= SNS activation= increased heart rate (beta 1 receptor), activate renin release (beta 1, RAAS)/ smooth muscle constriction (a1) so venoconstriction and arteriolar constriction= increased afterload and increase venous return so preload

Question 23

Describe the cycle of congestive heart failure

Answer 23

Decreased cardiac output (MI)- (baroreceptors in JG cells in kidney)- Neuroendocrine activation- (SNS RAAS)- Vasoconstriction and fluid retention- Increased afterload and preload- (further stress on already malfunctioning heart)- beginning

Question 24

Describe the drugs used in the renin-angiotensin system

Answer 24

Renin inhibitor- aliskiren
ACEi- ACE inhibitor blocks Angiotensin-Concerting Enzyme (ACE breaks down bradykinin so can accumulate bradykinin= cough)
AT receptor antagonists- losartan, valsartan= blocks AT2 receptor

Question 25

Describe drugs to reduce blood volume and preload

Answer 25

``` Loop diuretics (furosemide, bumetamide)= impair Na+/K+/Cl- reabsorption in the ascending loop of Henle Mineralocortoid receptor antagonists (spironolactone, eplerenone)- block effects of aldosterone on Na/K reabsorption ```

Question 26

Describe drugs involved with the SNS

Answer 26

Beta adrenoreceptor antagonists (atenolol, metoprolol- beta 1 selective)- Reduced sympathetic drive to the heart (reduced oxygen demand) Block renin release from the kidney, therefore decrease RAAS activation, decrease preload and afterload Few side-effects, but not useful in asthmatics (especially non-selective)

Question 27

Describe types of vasodilators

Answer 27

-Nitrovaodilators (isosorbide mononitrate)- long acting but risk of tolerance, venous circulation= decrease venous return and preload arterioles= reduce PVR and afterload -Hydralazine= dilator that targets arteries more than veins and reduces afterload Both can be used to treat acute heart failure or in patients with chronic heart failure who fail to respond to other drugs

Question 28

Describe drugs that inhibit structural changes to the heart

Answer 28

ACEi, AT receptor antagonists- block RAAS Mineralocorticoid receptor antagonists- block aldosterone- prevents fibrosis (laying down collagen so stiffening and arrhythmias) Ang2= hypertrophy (increase in cardiomyocyte size)- RAAS Stops ventricle walls becoming thicker and stiffer