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Flashcards in Drugs affecting cardiac rate and force Deck (27):

How does NA cause increased HR?

Coupling through Gs protein activates adenylyl cyclase to increase [cAMP]i;
(i) an increase in the slope of phase 4 depolarization (‘the pacemaker potential’) caused by enhanced If and ICa
(ii) reduction in the threshold for AP initiation caused by enhanced ICa


Describe the sympathetic effects on the heart?

increased HR

increased contractililty

increased conduction velocity

increased automaticity
decreased duration of systole

increased activity of Na/K-ATPase

increased mass of cardiac muscle


describe the parasympathetic effects on the heart?

decreased HR
decreased contractility
decreased conduction in AV node
parasympathetic stimulation


How does ivabradine work?

Selective blocker of HCN channels, used to flow heart rate in angina


Describe the steps in excitation contraction coupling in cardiac muscle

1. ventricular action potential
2. opening of voltage activated Ca channels during phase 2
3. ca influx into cytoplasm
4. CICR caused by ryanodine type 2 channel
5. Ca binds to troponin C ans shift tropomyosin out of the actin cleft
6. cross bridge forms resulting in contraction


Describe the steps in muscle relaxation

1. depolarise in phase 3 to phase 4
2. voltage activated L type channels close
3. Ca influx ceases Ca efflux occurs via the Na.Ca exchanger (NCX1) a plasma membrane ATPase
4. Ca release from sarcoplasmic reticulum ceases. active sequestration of Ca via SERCA
5. ca dissociated from troponin C
6. cross bridge between actin and myosin break


How does B1 adrenoreceptor activation modulate cardiac contractility?

formation of cAMP and activation of protein kinase A


Name some B agonist ligands used on the heart



What do B agonist ligands do to the heart

increased force, rate and cardiac output

decreased cardiac efficiency


Clinical uses of adrenaline

cardiac arrest (IV), as part of the Advanced Life Support (ALS) treatment algorithm.

anaphylactic shock (IM, not IV unless cardiac arrest occurs), very important in immediate management


Clinical uses of dobutamine

acute, but potentially reversible, heart failure (e.g. following cardiac surgery, or cardiogenic, or septic, shock).

For reasons unknown, causes less tachycardia than other β1 agonists


Effect of b adrenoreceptor antagonists on the heart

depend upon the degree to which the sympathetic nervous system is activated

At rest (normal subjects) - little effect on rate, force, CO, or MABP (agents with partial agonist activity increase rate at rest, but reduce

During exercise, or stress, rate, force and CO are significantly depressed – reduction in maximal exercise tolerance

Coronary vessel diameter marginally reduced, but myocardial O2 requirement falls, thus better oxygenation of the myocardium


non-selective b blockers

β1 and β2, e.g. propranolol


selective b blockers

β1, e.g. atenolol, bisoprolol, metoprolol


Uses of B adrenereceptor antagonists

Treatment of disturbances of cardiac rhythm (arrhythmias)

Treatment angina

Treatment of heart failure (compensated)

Treatment of hypertension (HT)


Adverse effects of B blockers

Aggravation of cardiac failure
Cold extremities


pharmacodynamic effect of atropine

>Increase in HR in normal subjects (at all but low doses) – more pronounced effect in highly trained athletes (who have increased vagal tone)
>No effect upon arterial BP (resistance vessels lack a parasympathetic innervation)
>No effect upon the response to exercise


effect of atropine on heart

First line in management of severe, or symptomatic bradycardia, particularly following myocardial infarction (in which vagal tone is elevated). In MI given IV (with caution) in incremental doses*. Monitoring is required. Glycopyrronium is an alternative

In anticholinesterase poisoning (to reduce excessive parasympathetic activity, e.g. bradycardia


Use of digoxin

Heart failure – a CO insufficient to provide adequate tissue perfusion

Inotropes cause an upward and leftward shift of the ventricular function curve, such that SV increases at any given EDP


How does digoxin work?

Block sarcolemma ATPase


Indirect effects of digoxin

Slows SA node discharge
Slows AV node conduction; increases refractory period


Direct effect of digoxin

Shortens the action potential and refractory period in atrial and ventricular myocytes (which is pro-arrhythmic); toxic concentration cause membrane depolarization and oscillatory afterpotentials- likely due to Ca2+ overload


Clinical use of digoxin

IV in acute heart failure, or orally in chronic heart failure, in patients remaining symptomatic despite optimal use of other drugs (e.g. ACE inhibitors, diuretics)
Particularly indicated in heart failure with atrial fibrillation (AF)


Levosinedan function

Binds to troponin C in cardiac muscle sensitizing it to the action of Ca2+

Additionally opens KATP channels in vascular smooth muscle causing vasodilation (reduces afterload and cardiac work)


Use of levosimedan

in treatment of acute decompensated heart failure (IV)





How do inodilators work?

Inhibit phosphodiesterase (PDE) in cardiac and smooth muscle cells and hence increase [cAMP]i

Increase myocardial contractility, decrease peripheral resistance (haemodynamic indices are improved), but worsen survival – perhaps due to increased incidence of arrhythmias