Flashcards in CVS Session 9 Deck (94):
What are CVS drugs used to treat?
High risk of thrombus formation
What main methods of action can CVS drugs use?
Alter heart rhythm
Alter force of myocardial contraction
Act on arterioles to alter TPR and blood flow
Alter blood volume
Can CVS drugs act at more than one site?
What is bradycardia?
What is atrial flutter?
Rapid depolarisation rate of atria
What is atrial fibrillation?
Unidentifiable depolarisation of atria on ECG
How does atrial fibrillation appear on an ECG?
What is tachycardia?
Fast HR coupled with low BP as there is not enough time for filling of ventricles
What two types of tachycardia can occur?
What causes supraventricular tachycardia?
Something in the atria causing rapid ventricular contraction e.g. Extra conduction loop, fast atrial contraction
What does ventricular fibrillation cause?
A severely reduced cardiac output which is incompatible w/life
What are the three causes of arrhythmias?
Actio is pacemaker activity due to damage
Afterdepolarisations (triggered activity)
How do damaged myocytes cause ectopic pacemaker activity?
They depolarise and become spontaneously active
How can an MI lead to tachycardia?
If area of ischaemia around infarct depolarises and becomes spontaneously active at a rate faster than the SAN
What is triggered activity?
Abnormal depolarisations after a normal AP
In what conditions are afterdepolarisations more likely?
If intracellular calcium is high
What can cause the firing of an early AP?
NCX or calcium-activated chloride conductance
When is an early after-depolarisation more likely?
In a long AP
What does a long QT make a cardiac myocyte more susceptible to?
Sodium channels recovered from inactivation
V-G calcium channels triggered
What causes oscillatory activity in early after-depolarisation?
Recovery of sodium channels and triggering of V-G calcium channels
What is a re-entry loop?
Accessory pathway - 2 paths b/w atria and ventricles or damaged area which causes condition delay
How does incomplete conduction damage cause a re-entry loop to form?
Unidirectional block formed which forces excitation to take long route to spread wrong way through damaged area
What circumstances must be present in order for a re-entry loop to exist normally in a person?
No delay in conduction and circuit set up
What can multiple re-entry loops around the pulmonary vein spread to give?
What method of action do Class I anti-arrhythmics use?
Block V-G sodium channels
What mechanism of action do Class II anti-arrythmics use?
What method of action do Class III anti-arrhythmics use?
Block potassium channels
What method of action do Class IV anti-arrythmics use?
Block calcium channels
Give an example of a Class I anti-arrhythmic.
Why is lidocaine described as 'use-dependent'?
Can only block sodium channels when they are open/inactive
Do Class b V-G sodium channel blockers affect normal AP firing?
No, they do not affect the upstroke
Do Class b V-G sodium channel blockers dissociate rapidly or slowly?
Why are V-G sodium channel blockers given IV in ventricular tachycardia following MI?
Sodium channels are open in the damaged tissue so can be blocked to prevent automatic firing and therefore prevent ventricular fibrillation
Is lidocaine still used prophylactically after MI?
What other name are beta-adrenoreceptor antagonists known by?
Give two named examples of beta-adrenoreceptor antagonists.
How do beta-blockers reduce heart rate?
Alter cAMP levels --> decrease funny current --> decrease slope of pacemaker potential --> slow SAN firing
Slow conduction at AVN
What neurotransmitter action do beta-blockers oppose at beta1 receptors?
How do beta-blockers prevent supraventricular tachycardia?
Slow conduction at AVN
Why are beta-blockers used after MI to prevent ventricular arrythmias?
To oppose the increased sympathetic activity
What effect does decreasing the oxygen demand of the heart by beta-blockers have on cardiac workload?
Why are potassium channel blockers used to prolong AP?
To lengthen absolute refractory period to prevent another AP from being fired too soon
In reality, why can potassium channel blockers be very pro-arrythmic?
Lengthening AP leads to early after depolarisations
The method of action of which class of anti-arrythmics is screened for in drugs testing as an unwanted side-effect?
III - potassium channel blockers
What additional action to blocking potassium channels does the class III drug Amiodarone have?
Blocks sodium channels
What is Wolff-Parkinson-White-Syndrome?
Re-entry loop due to extra conductional pathway
What method of action does a pharmacological dose of adenosine follow?
Act on A1 receptors at AVN --> enhance potassium conductance --> hyperpolarises cell of conducting tissue --> stops heart and allows regular rhythm to be re-established
Which G-protein subunit is stimulated by a pharmacological dose of adenosine?
What is the half life of adenosine?
What is heart failure?
Chronic failure of cardiac output to meet body's requirements
What type of drugs increase cardiac output?
When are beta-adrenergic agonists used to increase cardiac output?
Acute but reversible heart failure e.g. In surgery
What class of receptor do beta-adrenergic agonists act on?
What neurotransmitter do beta-adrenergic agonists such as Dobutamine mimic?
What type of positive inotropes improve the symptoms of heart failure but not the long-term outcome?
How do cardiac glycosides work?
Block sodium-potassium ATPase --> increase intracellular sodium --> impairs NCX function --> more calcium in SR w/every AP --> more calcium released in CICR --> stronger contraction
Why are cardiac glycosides used in arrhythmia caused by increased vagal activity?
Activate muscarinic receptors which slows AVN conduction causing a decrease in HR
How is heart failure treated in most people?
Decrease cardiac workload by decreasing afterload and preload
What do ACE inhibitors inhibit?
Angiotensin converting enzyme converting angiotensin I to angiotensin II
How does the action of angiotensin I compare to angiotensin II?
Angiotensin I is not active, angiotensin II is
What does angiotensin II do?
Acts on kidneys to retain sodium
Why is angiotensin II bad for heart failure?
Increases blood volume which increases preload
Increases TPR which increases cardiac workload
How do ACE inhibitors indirectly decrease afterload of heart?
Decrease blood volume and TPR which decreases BP
How do ACE inhibitors decrease preload?
Decrease fluid retention therefore decrease heart filling
Why are diuretics used to treat heart failure?
Act at kidneys to decrease blood volume therefore decrease preload
Why are beta-blockers used in heart failure?
Reduce oxygen demand of heart therefore decrease cardiac workload
What four things can contribute to heart failure?
Reduced force of contraction
Reduced cardiac output
Reduced tissue perfusion
Peripheral or pulmonary oedema
How does increased venous pressure cause peripheral or pulmonary oedema?
Increases capillary hydrostatic pressure
How is angina treated?
Decrease workload of the heart with:
Calcium channel antagonists
Which angina treatments improve blood supply to the heart?
Calcium channel antagonists
How do organic nitrates cause nitric oxide release?
React with thiols in vascular smooth muscle
How is nitric oxide released?
Endogenously by endothelial cells
How does nitric oxide cause vasodilation?
Activates guanylate cyclase --> increases cGMP --> decreases intracellular calcium --> relaxation of vascular smooth muscle
Give two examples of organic nitrates and compare their speed of action.
Glyceryl trinitrate - rapid admission so fast acting
Isosorbide dinitrate - slower acting
What is the primary action of organic nitrates?
How does the primary action of organic nitrates lower oxygen demand of the heart?
Venodilation lowers preload therefore reduces workload of heart as more blood is stored in veins --> less venous return --> less filling
What is the secondary action of organic nitrates?
Act on coronary arteries to improve oxygen delivery
Why do organic nitrates only give a minor contribution to improving coronary artery oxygen delivery?
Act in collateral arteries NOT arterioles and there are only a few of these present
What can happen to collateral artery number in long term ischaemia?
What heart conditions increase the risk of thrombus formation?
Mechanical prosthetic heart valves
How does atrial fibrillation increase risk of thrombus formation and subsequent stroke?
Stasis of blood in appendages
How is heparin used as an anticoagulant?
IV to inhibit thrombin for acute use
SC fractionated heparin also used
Describe the use of warfarin as an anticoagulant.
Orally administered to antagonise vitamin K action
Can be used long term
Why is aspirin used following acute MI or in high risk of an MI?
Antiplatelet drug so prevents clot formation
What two things cause hypertension?
Increase in blood volume
Increase in TPR
What is targeted when treating hypertension?
Decrease blood volume
Decrease cardiac output
How can diuretics be used to treat hypertension?
Decrease sodium and therefore water retention by kidney which decreases blood volume
How can ACE inhibitors treat hypertension?
Decrease sodium and water retention which decreases blood volume
Decreases TPR by vasodilation
Why can beta-blockers be used to treat hypertension?
Decrease cardiac output
Are beta-blockers used clinically as hypertensives currently?
Why can calcium channel blockers be used to treat hypertension?
Selective for vascular smooth muscle receptors causing vasodilation
Give an example of calcium channel blockers that are used to treat hypertension.
Why can alpha 1-adrenoreceptor antagonists be used to treat hypertension?
Block NA therefore cause vasodilation