Lecture 11 - The Heart Flashcards
What is heart failure?
The output of heart is insufficient to meet the demands of the body
When does Myocardial Ischaemia occur?
When blood flow to your heart is reduced
Not receiving enough oxygen
Where does Myocardial Ischaemia occur from?
Angina
Myocardial Infarction
What is disturbance in cardiac rhythm treated by?
Beta-receptor antagonist
Beta blockers
What can lead to dysrhythmia/ arrhythmia?
Angina
Myocardial infarction
What does Myocardial Ischaemia result from?
Blockage in coronary blood vessel
What is Angina?
Chest pain associated with Myocardial Ischaemia
How can Angina be classified?
Stable
Unstable
Prinzmetals (variant)
What is stable and unstable of angina be due?
Narrowing of blood vessels
Build up of atheromatous plaque = thrombosis
What is stable?
Less serious form of angina
At rest: individual will not experience any chest pain unless acted on oxygen demand of heart increases
What is unstable?
More severe
Continual pain
Whether engaging in exercise or at rest
Greater restriction on blood flow
Prinzmetal (variant)
Smooth muscle contraction in arterial side of circulation
Vasospasm
What is the pharmacological intervention for Angina?
Increase blood flow through coronary vessels
Decrease oxygen demand prophylactically
What are the compounds that treat Angina?
Organic nitrates
Potassium channel activators
Beta adrenoceptor antagonist
Calcium channel antagonist
What can lead to Angina?
Decrease oxygen supply
Increase oxygen demand
What is the effect of decreased oxygen supply?
Decreased coronary blood flow Decrease vessel calibre Increase heart rate Decrease perfusion pressure Increase ventricular wall tension
What is the effect of increased oxygen demand?
Increase heart rate
Increase Myocardial contractility
Increase ventricular well tension
What is nitric oxide taken through?
Sequence of events
Activation of guanylate cyclase —> GT to cyclic cGMP —> activation of protein kinase
Where does nitric oxide come from?
Endothelial cells
What is Increase in blood flow due to?
Vasodilation
What does reduced oxygen demand suggest?
Heart is contracting less forcefully
What does Frank-Starling mechanism of heart suggest?
The relationship between ventricular filling and force of contraction
Greater venous return = greater stretch of myocardium and resulting force of contraction is greater
Greater preload on heart
What are veins referred to as?
Capacitance vessels
Alter proportion of blood in circulation by altering diameter of veins
What does organic nitrates cause?
Both vasodilation on venous and arterial side of circulation
Easier for boood to flow
Reduce cardiac preload
Reduce oxygen demand
What are examples of organic nitrates?
Glyceryl trinitrate
Isosorbide mononitrate
What is Glyceryl trinitrate?
Absorbed quickly across mucosal membrane
Administration: spray/tablet under tongue/patch
Used when there is Angina attack
What is isosorbide mononitrate?
Taken orally
Absorbed in GIT
Longer lasting action
What are the results from cardiovascular point of view?
- Increased blood flow and reduced oxygen demand
- Frank-Starling mechanism
- Dilation in blood vessel = venous side of circulation
- Organic nitrate - venodililation
- Organic nitrate - both vasodilation on venous and arterial circulation
- Relax vascular smooth muscle
- Venous capacitance vessel
- Coronary arteries
- Arterial resistance vessels
Dipyridamole
Dilatory effect on major coronary blood vessel
What does collateral arteries found in cardiovascular circulation allow?
Communication between parts of blood flow
What does organic nitrate have?
Specific dilatory effect which can bring about dilation if collateral vessels
How are organic nitrate administered?
Sublingual
Buccal
Transdermal
Oral
What are the unwanted effects of organic nitrate?
Venodilation Postural hypotension Dizziness Syncope Reflex tachycardia
What can arterial dilation cause?
Throbbing headache and flushing
Asymmetric dosing
Take doses 6 hours apart rather than 12
Most prophylactic effect
Period where concentration of nitrate decreases over period of 24 gods
Reduce incidence of tolerance
Potassium channel Activators
K+ channel opener
Increased membrane K+ permeability with K+ extrusion from cell
Vascular smooth muscle hyperpolarisation
Closure of L-type voltage-dependent Ca2+ channel
Inhibition of intracellular Ca2+ release
Reduced free intercellular Ca2+
Quiescence and protection of cells against hypoxia
Vasodilation
B-adrenoceptor antagonist
Beta blockers
In Angina: reducing oxygen demand of heart
Beta blockers block beta 1 receptors
Beta 1 receptors present on cardiac tissue
When cardiac tissue blocked - reduction in heart rate and reduced force of contraction - lower Bp
What does blockade of B1 receptors act to do?
Reduce heart rate
Reduce force of contraction
Lower blood pressure
What is an example of drug that is cardioseletive?
Atenolol
Lipophilic
Propanolol
Hydrophilic
Atenolol
What are unwanted effects of B-adrenoceptor antagonist?
Precipitation of heart failure/ impairment of blood supply to peripheral tissues
Lowering of HDL
Sleep disturbances
Sudden withdrawal syndrome
What are 3 classes of calcium channel antagonist?
Phenylalkylamine (verapamil)
Dihydropyridine (nifedipine, amlodipine)
Benzothiazepine (diltiazem)
What does the 3 classes of calcium channel antagonist do?
Block cellular entry of calcium through L-type channels
What does cellular entry of Ca2+ blockade result in?
Arteriolar/arterial dilation
Reduction in heart rate and cardiac contractility
What are the side effects of calcium channel antagonist?
Arteriolar dilation: headache, flushing and dizziness and ankle oedema
Reduced cardiac contractility
Verapamil: altered gut motility
Nifedipine: heart burn and nausea
What does formation of clot include?
Fibrinogen
Activated fibrinogen fibrin
What enzyme breaks down blood clots?
Streptokinase
What is the streptokinase enzyme if bacteria origin capable of activating?
Plasminogen into plasmin
What is plasmin involved in?
Breakdown of fibrinogen and fibrin
Dissolving the clot
What does secondary prophylaxis include?
Stop smoking Exercise more Low dose aspirin or warfarin B-adrenoceptor antagonist ACE inhibitors Calcium channel blockers Statins to lower cholesterol
What does ACE inhibitors do?
Angiotensinogen is concerted into Angiotensin 1
Angiotensin 1 is converted into Angiotensin 2
Angiotensin 2: potent vasoconstrictor effect
Ace inhibitors can cause vasodilation - reduce stress on heart by reducing blood pressure
What does peripheral oedema occur?
Swelling in ankles
What are the symptoms associated with reduced cardiac output/ venous congestion?
Breathlessness
Peripheral oedema
Fatigue
What is Digoxin?
Potent inotrope derived from natural sources
Affects how Ca2+ is handled on intracellular part of cardiomyocte
What can diuretics lead to?
Hypokalamia (potassium levels are too low)
What does diuretic influence?
Tubular reabsorption of sodium
Diuretics will increase urine flow at various stages from tubular and water follows by osmotic means
What are examples of Loop Diuretics?
Furosemide
Bumetanide
Torasemide
When is loop diuretics used?
Where oedema is an issue
Clinically used in treatment of salt and water overload
What is salt and water overload associated with?
Acute pulmonary oedema Chronic heart failure Ascites (liver cirrhosis) Nephrotic syndrome Renal failure
where does Thiazide and related drugs act on?
Distal tubule
What are examples of thiazides?
Bendrochlorothiazide
Hydrochlorothiazide
What are other drugs of thiazide?
Chloralidone
Indapamide
Metolazone
What does Thiazide mechanism inhibit?
Na+-Cl- cotransporter
Reduce Na+ reabsorption
Potassium loss
Excretion of Ca2+ and uric acid is decreased
When is Cardiac glycosides good?
Heart failure associated with atrial fibrillation
Rapid heart rate
How do you exacerbate heart failure?
Myocardial depression
Fluid retention
What are primary Myocardial injury?
Secondary Myocardial effect
Neurohormone
Endothelium
