Drugs for Heart Failure Flashcards
Describe fibrinolysis
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
How does the body control fibrinolysis?
Pro (tissue plasminogen activator) and anti (PAI-1 targeting Fibrin Specific Plasminogen Activator action, antiplasmin in degradation) fibrinolytic mechanisms
Describe fibrinolytic ‘clot buster’ drugs
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
Name a clot buster drug
Tissue plasminogen activator (tPA.Activase) or streptokinase
Can cause bleeding- reversed by tranexamic acid
Describe balloon Angioplasty
PCTA- percutaneous transluminal angioplasty
Stenosis- balloon inflated by catheter insertion
Artery recanalized
Describe stenting
Can be carried out as elective procedure to treat angina
What occurs after MI?
Heart failure (dysfunction and heart failure in longer term) despite reperfusion of blood after clot removal
What is the Frank Starling Law of the Heart?
Increased blood volume= increased stretch of myocardium= increased force to pump blood out
As stroke volume increases, ventricular end-diastole volume increases
What is heart failure?
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
What are the symptoms of heart failure?
Impaired tissue perfusion, fluid retention, breathlessness, muscle weakness, arrhythmia
What are the common causes of heart failure?
- 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
What are the actions of drugs for heart failure/ types?
- Inotropic agents to increase contractility
- Drugs to unload the heart
Examples of inotropic agents to increase contractility
Digoxin
Dobutamine
Describe Digoxin
Foxglove- dropsy
Cardiac glycoside- increases force of contraction, positive inotrope therefore increases kidney perfusion and fluid loss
How do cardiac glycosides work?
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
Describe dobutamine
Beta 1 adrenoreceptor against IV for rapid response
Increases heart rate and contractility
What are the cons to inotropes?
Although provides support in acute heart failure, results in increased oxygen demands and energy demand so not helpful long term in chronic heart failure
What is preload determined by?
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
What is afterload?
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
How is cardiac output and blood pressure maintained?
Homeostatic mechanisms mechanisms activated
Decreased cardiac output (MI)= neuroendocrine activation (carotid sinus)= SNS-RAAS activation
Describe the Renin-Angiotensin-Aldosterone system
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
Describe the role of the SNS in increased preload and afterload
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
Describe the cycle of congestive heart failure
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
Describe the drugs used in the renin-angiotensin system
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
Describe drugs to reduce blood volume and preload
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
Describe drugs involved with the SNS
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)
Describe types of vasodilators
-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
Describe drugs that inhibit structural changes to the heart
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
