Drugs Affecting The Heart
Beta-blockers
These drugs are antagonists of beta receptors. They inhibit sympathetic stimulation of the heart to reduce both the heart rate and the force of contraction, reducing cardiac demand for oxygen.
They also have secondary effects of causing a sustained reduction in peripheral vascular resistance and inhibiting renin release.
Non-specific – Propranolol, timolol
These are non-specific beta-blockers.
Specific – Atenolol, bisoprolol
These are specific beta-1-receptor antagonists.
Side effects
Bronchoconstriction
Fatigue
Sleep disturbance/nightmares
Coldness of extremities
Impotence
Decreased hypoglycaemic awareness
Contraindications
Uncontrolled heart failure
Asthma
Sick sinus syndrome
Don’t co-prescribe beta-blockers and verapamil
If channel blockers – Ivabradine
This medicine blocks the If funny current, a mixed Na-K inward current in the SAN.
It lowers pacemaker activity in the SAN, which slows the heart rate down.
It is primarily used in angina but can also be used in heart failure.
Side effects
Luminous phenomenon (as retinal Ih channels are similar to cardiac If channels)
Cardiac glycosides – Digoxin
These inhibit the Na+/K+ – ATPase, which increases the intracellular Na+ concentration.
It reduces the concentration gradient for the NCX exchanger which removes Ca2+ ions from the cell.
This leads to a build-up of Ca2+ in the cell, increasing the force of muscle contraction next time.
Digoxin also increases vagal activity, which helps to slow the heart down.
It is mainly used clinically to slow down the heart rate in atrial fibrillation.
It is also an old heart failure treatment that has been shown to reduce hospitalisations in the pre-ACE-inhibitor era, although not mortality.
Side effects
Seen in digoxin toxicity (digoxin has narrow therapeutic index)
Increased vagal activity – arrhythmias, conduction disturbances
GI upset (nausea, vomiting, diarrhoea)
Dizziness
Blurred or yellow vision
Gynaecomastia (with long-term use)
Factors Increasing the risk of digoxin toxicity
a) Older age
b) Hypokalaemia – Digoxin binds to the K+ site of the sodium pump.
Hence in hypokalaemia, glycosides have greater effect as less competition, so decrease dose
c) Decreased renal clearance – this is because digoxin is excreted by the kidneys
– Hence higher risk in renal failure + drugs which compete for secretion in the DCT (Ciclosporin + Amiodarone + Verapamil)
To manage digoxin toxicity: Give digoxin-specific antibody fragments + correct K+ abnormalities
B1 agonists – Dobutamine
These are agonists of the B1 receptor which mimic sympathetic stimulation.
They cause an increase in contractility as well as heart rate.
They are known as inotropes and given to ill patients in settings like intensive care units for those who have acute cardiac failure and hypotension.
Side effects
May precipitate hypertension
May precipitate dysrhythmias (tachycardia)
Inodilators – Milrinone, inamrinone
These are phosphodiesterase inhibitors which inhibit the enzyme PDE type 3 in the heart as well as in smooth muscle.
In the heart, they mimic sympathetic stimulation which leads to an increase in the heart rate and the force of contraction.
In smooth muscle, they lead to a rise in cAMP which activates protein kinase A.
This leads to inhibition of myosin light chain kinase which leads to vasodilation.
Their use is limited to heart failure unresponsive to other therapies, as they can cause dysrhythmias.
Calcium Channel blockers – Verapamil, diltiazem
These are inhibitors of voltage gated calcium channels, which are found in the heart and the smooth muscle of artieroles.
These drugs have high use dependence which gives them more selectivity for cardiac channels than in smooth muscle.
This is because the channels in the heart are constantly opening and closing with each heartbeat, whereas in smooth muscle they remain open or closed for longer.
They inhibit calcium entry at the SAN and AVN, which slows the heart rate down.
They also lead to smooth muscle dilation, and so can be used to decrease blood pressure and dilate coronary blood vessels in angina.
Verapamil can also be used for prophylaxis of cluster headaches.
Side effects
Bradycardia
Hypotension
Worsen heart failure
Ankle swelling
Verapamil also causes constipation
Ranolazine
Towards the end of the action potential, there is a late inward sodium current.
Increased intracellular [Na+]i reduces the driving force for the NCX exchanger.
This leads to increased intracellular calcium which impairs ventricular relaxation.
Less relaxation increases wall tension, which compromises myocardial blood flow.
This drug blocks the late inward Na+ current allowing the cell to get rid of more Ca2+, reducing Ca2+ overload.
It improves left ventricular relaxation in diastole increasing coronary blood flow.
It is used in angina, which is refractory to other treatments.
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