CVS Drugs Flashcards
List some conditions that cardiovascular drugs treat
– Arrhythmias
– Heart failure
– Angina
– Hypertension
– Risk of thrombus formation
How can drugs affect the CVS?
– The rate and rhythm of the heart
– The force of myocardial contraction
– Peripheral resistance and blood flow
– Blood volume
Some drugs can act on multiple sites
What are some causes of arrhythmias?
Ectopic pacemaker activity:
– damaged area of myocardium becomes depolarised and spontaneously active
– latent pacemaker region activated due to ischaemia and dominates over SA node
Afterdepolarisations:
– abnormal depolarisations following the action potential (triggered activity)
Re-entry loop:
– conduction delay
– accessory pathway
What are delayed after-depolarisations?
What are early after-depolarisations?
What is the re-entrant mechanism for generating arrhythmias?
It is possible to get several small re-entry loops in the atria, leading to atrial fibrillation
What classes of drugs affect the rate and rhythm of the heart?
- Drugs that block voltage-sensitive sodium channels
- Antagonists of β-adrenoreceptors
- Drugs that block potassium channels
- Drugs that block calcium channels
What class of drug is lidocaine and how does it work?
It is a drug which blocks voltage-dependant Na+ channels (class I)
- Typical example is the local anaesthetic lidocaine (class Ib)
- Only blocks voltage gated Na+ channels in open or inactive state
- Dissociates rapidly in time for next AP
- Little effect in normal cardiac tissue
- Use-dependent block
When is lidocaine used in relation to heart pathology?
Sometimes used following MI:
– only if patient shows signs of ventricular tachycardia – given intravenously
Damaged areas of myocardium may be depolarised and fire automatically
More Na+ channels are open in depolarised tissue – lidocaine blocks these Na+ channels (use-dependent)
– prevents automatic firing of depolarised ventricular tissue
Not used prophylactically following MI
– Even in patients showing VT may use other drugs
What are beta-adrenoceptor antagonists?
Examples: propranolol, atenolol (Beta blockers)
- Block sympathetic action by acting at β1-adrenoreceptors in the heart
- Decrease slope of pacemaker potential in SA
How do beta-blockers work?
Used following myocardial infarction
– MI causes increased sympathetic activity
– β-blockers prevent ventricular arrhythmias
– Arrhythmias may be partly due to increased sympathetic activity
Also reduces O2 demand:
– Reduces myocardial ischaemia
– Beneficial following MI
β-blockers slow conduction in AV node
– Can prevent supraventricular tachycardias
– Slows ventricular rate in patients with AF
How do drugs that block K+ channels work
- Class III anti-arrhythmics
- Prolong the action potential
– mainly by blocking K+ channels
- This lengthens the absolute refractory period
- In theory prevents another AP occurring too soon
– In reality can be pro-arrhythmic
Drugs that block K+ channels aren’t generally used as anti-arrythmic. What is the exception?
One exception – amiodarone
Included as a type III anti-arrhythmic, but has other actions in addition to blocking K+ channels
Used to treat tachycardia associated with Wolff- Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
How do drugs that block Ca2+ channels work?
Example: verapamil
- Decreases slope of action potential at SA node
- Decreases AV nodal conduction
- Decreases force of contraction (negative inotropy). Also some coronary and peripheral vasodilation
- Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias, but do act on vascular smooth muscle
Examples: Amlopidine, felopidine, nicardipine etc
How does adenosine work?
Produced endogenously:
- Can also be administered pharmacologically
- Acts on A1 receptors at AV node
• Enhances K+ conductance
– hyperpolarises cells of conducting tissue
• Anti-arrhythmic
– administered intravenously
– doesn’t belong in any of the classes mentioned
What is heart failure and its features?
– Chronic failure of the heart to provide sufficient output to meet the body’s requirements
Features:
– Reduced force of contraction
– Reduced cardiac output
– Reduced tissue perfusion
– Oedema
What drugs are used in the treatment of heart failure?
Positive inotropes increase cardiac output:
– cardiac glycosides
– β-adrenergic agonists
- dobutamine
- Drugs which reduce work load of the heart – reduce afterload and preload
What are cardiac glycosides?
Have been used to treat heart failure for over 200 years. They improve symptoms but not long term outcome
Digoxin is the prototype. Extracted from leaves of the foxglove digitalis purpurea or digitalis lanata
– Blocks Na+/K+ ATPase
How do cardiac glycosides work?
Ca2+ is extruded via the Na+-Ca2+ exchanger which is driven by Na+ moving down concentration gradient.
Cardiac glycosides block Na+/K+ ATPase so there is a rise in [Na+] intracellularly.
Rise in intracellular Na+ leads to decrease in activity of Na+-Ca2+ exchanger which causes increase in [Ca2+] intracellularly.
There is more Ca2+ stored in SR and an increased force of contraction
Cardiac glycosides also cause increased vagal activity: – action via central nervous system to increase vagal activity
– slows AV conduction
– slows the heart rate
What kind of drug increases myocardial contractility?
β–adrenoreceptor agonists – eg dobutamine
– act on β1 receptors
Uses:
- cardiogenic shock
- acute but reversible heart failure (eg following cardiac surgery)
How do ACE inhibitors work?
- Prevent the conversion of angiotensin I to angiotensin II.
- Angiotensin II acts on the kidneys to increase Na+ and water reabsorption.
- Angiotensin II is also a vasoconstrictor
- Very valuable in treatment of heart failure
- Decrease vasomotor tone (blood pressure)
- Reduce afterload of the heart
- Decrease fluid retention (blood volume)
- Reduce preload of the heart
- Reduce work load of the heart
What types of drugs can reduce the workload of the heart?
β–adrenoceptor antagonists (β-blockers)
Diuretics:
– reduce blood volume
– more to follow in Urinary module
ACE inhibitors
How is angina treated?
• Reduce the work load of the heart
– β-adrenoreceptor blockers
– Ca2+ channel antagonists
– organic nitrates
• Improve the blood supply to the heart – organic nitrates
– Ca2+ channel antagonists
How does NO exert its vasodilatory effects?
Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released.
• NO2- is reduced to NO (Nitric Oxide)
- NO activates guanylate cyclase
- Increases cGMP
- Lowers intracellular [Ca2+]
- Causes relaxation of vascular smooth muscle
Examples of Organic Nitrates;
- glyceryl trinitrate
- isosorbide dinitrate
