Cardiac Drugs Flashcards
What are the four basic phenomena that underlie disturbance to cardiac rhythm?
(1) Delayed after-depolarisation
(2) Re-entry
(3) Ectopic pacemaker activity
(4) Heart block
Explain after-depolarisation.
After-depolarisation is caused mainly by abnormally raised intracellular calcium ion concentration. This increase in calcium ions inside the cell activates Na+/Ca2+ exchange, where 1 calcium ion is transferred out of the cell in exchange for 3 sodium ions. This increases the positive charge inside the cell, causing depolarisation.
Explain re-entry.
Normally, the cardiac action potential dies out after it has activated the ventricles because the tissue is refractory. In re-entry, the impulse re-excites the myocardium, causing continuous circulation of an action potential.
What factors control coronary blood flow?
(1) physical factors
(2) metabolites
(3) neural and humoral factors
How do physical factors control coronary blood flow?
During systole, the pressure exerted by the contracting myocardium on vessels passing through it is greater than perfusion pressure –> blood is only able to flow during diastole.
How does tachycardia affect the ability to perfuse the heart?
With tachycardia, diastole is shortened more than systole –> there is reduced ability to perfuse the heart because blood can only flow through coronary blood vessels during diastole.
What are the MOA of the four classes of antidysrhythmic drugs?
Class I = sodium channel block
Class II = beta-adrenoceptor antagonists
Class III = potassium channel block
Class IV = calcium channel block
What is the difference between class Ia, Ib and Ic antidysrhythmic drugs?
The speed at which they dissociate.
Ia = intermediate dissociation
Ib = fast dissociation
Ic = slow dissociation
Explain ‘use dependence’ in relation to Class I antidysrhythmic drugs.
Sodium channels exist in three states: resting, open and inactivated. These drugs bind to channels more strongly when they are either open or inactivated –> this means that the more frequently the channels are activated, the greater the degree of block that is produced.
What are the effects of the sympathetic nervous system on the heart?
(1) increased heart rate
(2) increased force of contraction
(3) increased automaticity (i.e. tendency for ectopic beats)
(4) reduced cardiac efficiency (oxygen consumption increased > cardiac work increased)
(5) cardiac hypertrophy
What is the molecular MOA of the sympathetic nervous system on the heart?
The effects of the SNS are the result or B1-adrenoceptor activation. This has several effects:
(1) Beta1-adrenoceptor activation –> activates adenylyl cyclase –> increased cAMP –> activates protein kinase A –> phosphorylates calcium channels –> increased probability that they will open –> increases inward calcium current.
(2) Beta1-adrenoceptor activation also increases sensitivity of the contractile machinery to calcium ions (possibly by phosphorylation of troponin C).
(3) Beta1-adrenoceptor activation facilitates capture of calcium ions by the sarcoplasmic reticulum –> more calcium is available for release with each action potential.
(4) B1-adrenoceptor activation stimulates the Na/K-ATPase pump –> repolarises damaged/hypoxic myocardium –> can restore cardiac function after asystole has occurred
What is the effect of the parasympathetic nervous system on the heart?
(1) Reduces heart rate
(2) Reduces conduction through the AV node
(3) Reduces automaticity
BUT has little effect on contractility (because the ventricles are only sparsely innervated by parasympathetic fibres)
What is the main cardiac glycoside in clinical use?
Digoxin
What is the effect of digoxin on the heart?
(1) Increased force of contraction
(2) Slowed conduction through the AV node
Explain the effects of digoxin on the heart.
(1) Increased force of contraction is due to inhibition of the Na/K-ATPase pump –> increases intracellular Na+ concentration –> slows the extrusion of Ca2+ from cell by the Na/Ca exchanger (because the gradient that drives this exchange has been affected) –> more calcium is stored in the SR –> increased calcium is released by the action potential;
(2) Slowed conduction through the AV node: because digoxin increases vagal outflow.
