Drugs Affecting Heart Rate
Beta-blockers
Propranolol + Timolol + Pindolol – These are non-specific beta-blockers
Atenolol + Bisoprolol – These are specific beta-1-receptor blockers
The beta-blockers work by inhibiting sympathetic stimulation on the heart to reduce the heart rate and force of contraction, reducing cardiac demand for oxygen.
They give a sustained reduction in peripheral vascular resistance and decreases renin release.
N.B. If you take a beta-blocker overdose –> 1st line = Atropine, 2nd line = Glucagon.
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 + verapamil
If channel blockers
e.g Ivabradine
This blocks the If funny current – mixed Na-K inward current in the SAN
It lowers pacemaker activity in SAN, slowing the heart rate down and so is used in angina.
Side effects
Luminous phenomenon (as retinal Ih channels are similar to cardiac If channels)
Drugs Affecting Heart Contractility
a) Increase contractility
These drugs aim to increase Ca2+concentrations in cardiac muscle, which allows for stronger force of contraction. As such they are often used in heart failure, to increase cardiac output.
Cardiac glycosides
e.g Digitoxin + Digoxin
These inhibit the Na+/K+ – ATPase, which increases intracellular Na+
– It reduces the concentration gradient for the NCX exchanger which removes Calcium
– Leads to a build-up of Calcium in the cell, increasing force of contraction next time.
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
e.g Dobutamine
These act by mimicking sympathetic stimulation on B1 receptors increasing heart rate + force
They are often given IV for quick effect in severe acute cardiac failure.
Gives greater inotropic than chonotropic effects
Side effects
- May precipitate hypertension
- May precipitate dysrhythmias (tachycardia)
Inodilators
e.g. Milrinone + Inamrinone
These are phosphodiesterase inhibitors which inhibit PDE type 3 in the heart and smooth muscle
– In the heart, it mimics sympathetic stimulation to increase rate and force of contraction.
– In smooth muscle, rise in cAMP –> PKA –> phosphorylation of MLCK –> causes vasodilation
– Use is limited to heart failure unresponsive to other therapies, as it can cause dysrhythmias.
b) Drugs which decrease contractility
L-type Calcium Channel blockers
e.g. Verapamil + Diltiazem
These have high use dependence which gives them more selectivity for cardiac channels
– This is because channels in the heart are constantly opening and closing with each heartbeat, whereas in smooth muscle they remain open or closed for longer
– They prevent calcium entry which reduces the force of contraction in cardiac myocytes
– They also prolong the action potential slowing the heart rate down
Side effects
Bradycardia
Hypotension
Worsen heart failure
Ankle swelling
Verapamil also causes constipation
Contraindications
- Not used with Beta-blockers as will cause a profound bradycardia
Beta-Blockers
e.g. Propranolol + Bisoprolol
These are also used to decrease heart contractility by blocking sympathetic stimulation
Ranolazine
In the heart, a late inward Na+ current causes increased [Na+] i
– This reduces the driving force for the NCX, which leads to increased Ca(2+) impairing relaxation
– This increases ventricular wall stiffness compressing coronary arteries
– The drug therefore blocks late inward Na+ allowing the cell to get rid of more Ca(2+)
– This reduces Ca(2+) overload –> reduces compression on coronary arteries –> increases blood flow
– Used to improve blood flow to the heart in ischaemia
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