Drugs to treat arrhythmia and congestive heart failure Flashcards
What are some characteristics of HF?
Progressive cardiac dysfunction Raised CVP Tiredness Breathlessness Oedema Sudden cardiac death
What are some physiological compensation methods for heart failure?
Heart failure = decreased CO.
Decreased CO means increased TPR to increase BP, as BP = CO x TPR. Increase TPR by increased sympathetic tone to arterioles.
Also increase activation of the renin angiotensin aldosterone system in order to raise blood pressure and filling pressures.
How does increased RAP (right atrial pressure) lead to dilatation of the heart?
Increased filling pressure means increased volume in the right atrium.
Would mean that there is a increased CO due to length tension relationship in myocardium of ventricle however due to weak heart, cant pump all blood out so some is left in the ventricle.
Ventricle fills up again and puts more stress on the heart walls and they dilate further which leads to even less contraction strength and more blood in the ventricle at the end of systole.
What are some causes of heart failure
Volume overload - valve regurgitation
Pressure overload - Systemic hypertension
Loss of muscle (post MI, chronic ischaemia)
Restricted filling (pericardial disease)
Chronic heart failure
What drugs are usually used in order to improve symptoms of heart failure?
Diuretics
ACE inhibitors or ATI antagnists
Digoxin
What drugs are usually used in order to improve survival of heart failure?
ACE inhibitor or ATI inhibitor
B blockers
Spironolactone
Name two ACE inhibitors?
Captopril
Enalapril
What is the function of ACE inhibitors?
Inhibit production of AIi
Inhibit aldosterone production
Vasodilation
What are ACE inhibitors useful for?
Controlling K+ loss
Hypertension
What are some side effects of ACE inhibitors?
hyperkaleamia
Hypotension
Cough (inhibition of bradykinin breakdown).
What is an example of an ATII receptor blocker?
Losartan
Why use ATII over ACE inhibitor?
No cough , better tolerated.
What are some side effects ofATII inhibitors?
birth defects
Give an example of a loop agent
Furosemide
Where do loop agents act in the nephron?
Act at thick ascending limb of loop of henle Na/K/2CL transporter.
What are the side effects of furosemide?
Hypokaleamia
Hypovolaemia
Hypomagnesia
Ototoxicity
How much of filtered NA+ are furosemide responsible for?
30%
Where do thiazides act
distal convoluted tubule Na/Cl transporter
What is another effect that thiazides have?
Vasodilators of smooth muscle.
What are some side effects of thiazides?
K loss, hypotension
Where does Spironolactone act
Convoluted tubule
What is the method of action of spironolactone
It is an aldosterone antagonist.
What is spironlactone useful for
Controlling K+ loss
What are some potential side effects of spironolactone?
hyperkalaemia.
What are the actions of cardiotonic steroids
F orce increae
E xcitability increase
A a-v conduction decrease
R rate decrease
Name two cardiotonic steroids
Digitoxin, Digoxin
What are the properties of digitoxin
Long duration
Slow onset - half life 5-7 days
High affinity for serum proteins with strong binding
What are the properties of Digoxin
Rapid onset
Low oral activity
Low affinity for serum proteins
What is the mechanism of action of cardiotonic steroids?
Cardiotonic steroids inhibit the Na/k atpase
Increasing intracellular Na+
Meaning more Activity for the Na+/Ca2+ antiporter
Increasing intracellular Ca2+
Increasing Ca2+ released from sarcoplasmic reticulum
Increased contraction strength.
What are side effects of cardiotonic steroids
Arrhythmias
Gastrointestinal
Narrow theraputic range. - risk of toxicity
What is the use of digitalis?
To treat heart failure in old sedentary patients.
How can nitrates be used to treat congestive heart failure?
GTN (glycerol trinitrate ) spray can be administered to release NO which is a vaso dilator.
It therefore reduces the amount of preload and afterload
How can GTN be administered?
Sublingual or injection
When is GTN spray mostly used in heart failure?
Acute HF collapse due to tolerance
What are some side effects of nitrates?
Headache
Dizziness
Give an example of a sympathomimetic inotrope
Milrinone, Dopamine (IV)
When are sympathomimetic ionotropes usually used for HF?
Reversible heart failure
What does the first class of antiarrhythmatic drugs target?
Na channel blockade
Reduce phase 0 slope & AP peak
What does the second class of antiarrhythmatic drugs target?
B-blockers
Block sympathetic drive, reduce rate, conduction & excitability
What does the third class of antiarrythmatic drugs target?
K+ channel blockers
Delay repolarisation
What does the fourth class of antiarryhthmatic drugs target?
Ca 2+ blockers
Reduce rate & conduction
Give an example of a class 1a antiarrythmatic drug?
Quinidine
What is the mechanism of action of Quinidine
Prolong AP durating and reduce upstroke
Decrease sodium entry into cell
What is quinidine used for?
Ventricular arrhythmias
What is an example of a class 1b antiarrhythmatic drug?
Lignocaine
Lidocaine
What is the mechanism of action of lignocaine?
Decrease AP duration and reduce upstroke
Prolong refractory period by binding to inactivated Na+ channels so they cant be opened again.
Decrease Na+ influx
What is lignocaine used for
Treatment during and immediately after myocardial infarction.
What is an example of a class 1c anti arrythmatic drug
Flecainide
What is the mechanism of action of flecainide?
No change in APD.
Blocks sodium entry
Supress Automaticity
Increases refractory period
Give an example of a class II anti arythmatic drug
atenolol
How does atenolol work to treat anti arrhythmias
B blocker
Reduces the effect of sympathetic drive
Lengthens action potential duration
Prolong refractory period
Decrease conduction + excitability + rate
When is atenolol used?
superventricular tachycardia
Give an example of a class III anti arrhythmic drug?
amiodarone
How does amiodarone work?
K+ channel blocker
Prolong APD
Prolong ERP
What is amiodarone used to treat?
V tachycardia
Atrial fibrillation
Give an example of a Ca2+ channel blockers which is used to treat arrhythmias
Diltiazem
How does Dilitiazem work?
Selectivity for cardiac muscle (verapamil & diltiazem)
Block AV node ( good for supraventricular trachyarrythmia)
What are the uses of dilitiazem?
Supraventricular tachycardia
Reduce ventricular rate in patients with atrial fibrillation.
Give an example of a class V anti arrythmatic drug?
Dixogin
How does Digoxin work to treat arrythmias?
Decreases A-V conduction
Decreases ventricular contraction rate.
What is digoxin mainly used for?
Supraventricular tachyarrhythmias
What drug can be used to turn atrial flutter to atrial fibrillation?
Digoxin
- As decreases A-V conduction and rate of heart.
Need to be careful to control clotting via the use of warfarin/heparin.
What is the role of magnesium in the control of arrhythmias?
Decreases calcium entry into the sarcolemma, therefore less calcium released from sarcoplasmic reticulum.
Regulates metabolic processes in intracellular space by binding to ATP
Valuable in ventricular arrythmias in ischeamic cells especially if there is hypomegnesemia.
