Action of Drugs on the CVS -- 7.2 Flashcards
What do drugs for the CVS have an effect on?
- rate and rhythm of heart
- force on contraction
- peripheral resistance and blood flow
- blood volume
Define arrhythmia
an abnormality of heart rate or rhythm
Give 5 types of arrythmia
- Bradycardia
- Atrial flutter
- Atrial fibrillation
- Tachycardia (ventricular and supraventricular)
- Ventricular fibrillation – no coordinated electrical activity so no coordinated contraction
What are the 3 causes of arrhythmias?
- Ectopic pacemaker activity – pacemaker activity not where it is meant to be
- Afterdepolarizations
- Re-entry loop – problem with conduction
- Sarah’s Doctor Who Uno
Define afterdepolarisations
- anything that prolongs the duration of the AP
- can trigger a premature action potential
- longer AP so longer QT interval
- could be due to increased intracellular calcium
GIve an example of re-entry loop and describe it
problem with conduction e.g. conduction delay
There is a block of a branch of purkinje fibre
Incomplete conduction damage
– unidirectional block
– excitation takes the long route to spread the wrong way setting up a circus of excitation
– can get several small re-entry loops in the atria which can cause atrial fibrilation
Describe ectopic pacemaker activity
Damaged area of myocardium because depolarised and spontaneously active.
Latent pacemaker region activated due to ischaemia
Dominate over SA node
What are the 4 basic classes of anti-arrhythmic drugs?
- Drugs that block voltage gated Na+ channels
- Antagonists of β-adrenoceptors
- Drugs that block K+ channels
- Drugs that block Ca2+channels
Give an example of a drug that blocks voltage-gated Na channels and what they do
lidocaine
They block channels in open or inactive state
– are able to dissociate rapidly before the next AP
– Prevents firing of AP too close to each other
When are class I drugs used and why?
After MI w/ ventricular tachycardia
– prevents the automatic firing of the depolarised, damaged area of the myocardium
Give an example if antagonists of B-adrenoceptors and what they do
Propranolol, atenolol
– block sympathetic action (B-1 adrenoceptors in heart) and decrease slope of pacemaker potential in the SA
When are class II drugs used?
Used after MI –> decreased sympathetic activity which prevent ventricular arrhythmias.
– reduces O2 demand to reduce the risk of myocardial ischaemia
– slows AV node conduction (prevents supraventricular tachycardias)
What do drugs that block K+ channels do?
– prolong the AP to lengthen the absolute refractory period
– should prevent and AP from occurring too soon, but can be proarrhythmic
Are not generally used
What class III drug is used regularly?
Amiodarone
– used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop due to extra conduction pathway)
GIve an example of a drug which blocks calcium channels and what they do
Verapamil
- Decreases the slope of pacemaker action potential at SA node and decreases AV node conduction.
- This causes a decrease in the force of contraction (negative ionotropy)
- Can cause coronary and peripheral vasodilation
What is adenosine?
Acts on A2 receptors at AV node to enhance K+ conductance (prevents conduction through the AV node)
– inhibits adenylyl cyclase
Does not fit into the classes
– short half life of ~ 10 seconds
– Allows heart to get back to a synchronous rhythm h
What are the features of heart failure that have to be combatted?
– Reduced force of contraction – Reduced cardiac output
– Reduced tissue perfusion
– Oedema
What are positive ionotropes used for?
Give an example of a positive ionotrope
Increase the cardiac output
Cardiac glycosides
What are the general actions of cardiac glycosides?
Improve the symptoms of heart failure
Are not good in the long term
What is the molecular action of cardiac glycosides?
- -> blocks Na+/K+ ATPase so increases intracellular Na conc as well as intracellular Ca as the Na/Ca exchanger is inhibited
- -> increase vagal activity via CNS (slows AV conduction and heart rate
Give an example if antagonists of B-adrenoceptors and what they do
Propranolol, atenolol
– block sympathetic action (B-1 adrenoceptors in heart) and decrease slope of pacemaker potential in the SA
What is the effect of cardiac glycosides?
- -> blocks Na+/K+ ATPase
- -> Na/Ca exchanger still works so [Na] increases
- -> increased [Na] causes Na/Ca to exchange less, so [Ca] increases
- -> increase [Ca] increases the force on contraction (positive ionotropic effect)
INCREASE CARDIAC OUTPUT
Also cause increase vagal activity
(slows AV conduction and HR)
What class of drugs increase myocardial activity and give an example
Beta-adrenoceptor agonist
Dobutamine
When are drugs which increase myocardial activity used?
- Cardiogenic shock
2. Acute but reversible heart failure, for example after heart surgery
What are ACE-inhibitors?
drugs which inhibit the action of angiotensin converting enzyme
What do ACE-inhibitors do?
They prevent the conversion of angiotensin I to angiotensin II
– angiotensin II acts on the kidneys to increase Na+ and H20 reabsorption. It is also a vasoconstrictor.
– decrease Na+ and water retention by kidney (decrease blood volume)
– decrease total peripheral resistance due to vasodilation
- decrease blood pressure by decreasing vasomotor tone, reducing afterload
What does angiotensin II stimulate the release of?
Aldosterone from the adrenal cortex
Define angina
Occurs when O2 supply to the heart does not meet its need
Causes Ischaemia of heart tissue
Usually causes chest pain upon exertion which is due to narrowing of the coronary arteries
What are the general ways of treating angina
Reduce the work load of the heart
and
Improve the blood supply to the heart
What drugs reduce the work load of the heart?
– β-adrenoreceptor blockers
– Ca2+ channel antagonists
– organic nitrates
What drugs improve the blood supply of the heart?
– organic nitrates
– Ca2+ channel antagonists
What is the general action of organic nitrates?
Reduce venous pressure due to venodilation and dilate the coronary arteries
Describe the molecular action of organic nitrates
The react with -SH groups in vascular smooth muscle causing the release of NO (powerful vasodilator)
NO activates guanylate cyclase. This converts GTP to cGMP to lower [Ca].
Lower [Ca] relaxes the vascular smooth muscle –> venodilation
What is the primary action of organic nitrates?
Cause venodilation which lowers preload
– reduces work load, lowers force on contraction and lowers O2 demand
What is the secondary action of organic nitrates?
Acts to dilate the coronary arteries so improves O2 supply to ischaemic myocardium
– usually collateral arteries rather than arterioles to bypass atheromatous plaque
Which conditions carry an increased risk of a thrombus forming?
– Atrial fibrillation
– Acute myocardial infarction
– Mechanical prosthetic heart valves
What are the two classes of drugs that are antithrombitic drugs?
Anticoagulants and anti-platelet drugs
Give three anticoagulants and what they do
- Heparin (given intravenously)
- - inhibits thrombin and is used acutely (short term action) - Fractionated heparin (subcutaneous injection)
- Warfarin (given orally)
- - antagonises action of vitamin K so can be used long term
Give an antiplatelet drug
Aspirin
– taken following an acute MI of if someone has a high risk of an MI
What are possible treatments for hypertension?
– diuretics – ACE-inhibitors – β-blockers – Ca2+ channel blockers which act at vascular smooth muscle – α1-adrenoceptor antagonists
What characteristics are associated with hypertension?
Increased blood volume
Increased TPR
What do diuretics do?
decrease Na+ and water retention by kidney therefore decrease blood volume
What do beta-blockers do?
Decrease the cardiac output
What do drugs that are Ca2+ channel blockers selective for vascular smooth muscle do?
Cause vasodilatation
What do alpha-one adrenoceptor antagonists do?
Cause vasodilation
What is the equation the links BP, TPR and CO?
BP = CO x TPR
What do organic nitrates not dilate?
Arterioles
