Drugs affecting cardiac rate and force Flashcards
Dobutamine, adrenaline and noradrenaline are which kind of drug?
b-adrenoceptor agonists
What are the pharmacodynamic effects of b-adrenoceptor agonists upon the heart?
increase force, rate, CO and O2 consumption
decrease cardiac efficiency - O2 consumption increased more than cardiac work does
Which b-adrenoceptor agonists have a plasma half-life of approx. 2 mins?
adrenaline and dobutamine
Why is adrenaline given IV in a cardiac arrest?
positive inotropic and chronotropic actions
redistribution of blood flow to heart (constricts peripheries)
dilatation of coronary arteries
What is the route of administration of adrenaline in an anaphylactic shock?
IM (IV if enter cardiac arrest)
What is the route of administration of dobutamine?
IV infusion
In which condition would dobutamine be used?
acute, but potentially reversible, heart failure
What do the physiological effects of a b-adrenoceptor blockade depend upon?
the degree to which the sympathetic nervous system is activated
Which b-adrenoceptor antagonist is non-selective for b1 and b2 adrenoreceptors?
propranolol
Atenolol, bisoprolol and metoprolol block which adrenoceptor in a competitive manner?
B1
Which b-adrenoceptor antagonist is non-selective and a partial agonist?
alprenolol
What is the effect of non-selective b-adrenoceptor antagonists during exercise?
force and CO are significantly depressed - reduction in maximal exercise tolerance
myocardial O2 requirement falls -> better oxygenation of the myocardium
What are the CVS clinical used of b-adrenoceptor antagonists?
Arrhythmias
Angina
Heart failure
Hypertension
How do b-blockers work in treatment of AF and SVT?
delay condition through the AV node and help restore sinus rhythm
In which condition are b-blockers first line as alternative to CCBs?
angina
In which CVS condition does use of b-blockers seem paradoxical?
heart failure - studies show that low-dose b-blockers improve morbidity and mortality
Which b-blocker is often used in heart failure?
carvedilol - start low, go slow
B-blockers are no longer first line treatment for hypertension, unless…?
co-morbidites (e.g. angina) are present
What are the adverse effects of b-bockers (as a class)?
Bronchospasm Aggravation of cardiac failure Bradycardia Hypoglycaemia Fatigue Cold extremities
Which b-blockers have less associated risk of bronchospasm?
b1-selective agents e.g. atenolol, bisoprolol, metoprolol
If b-blockers can aggravate cardiac failure, why are they used in treatment of heart failure?
studies show that low dose b-blockers are used in compensated heart failure - patients may be relying on sympathetic drive to maintain an adequate CO and b-blockers reduce sympathetic drive so risk of crash - start low, go slow
Which bADR receptors are implicated in fatigue caused by b-blockers?
b1 - cardiac output, and b2 - skeletal muscle perfusion in exercise are regulated by adrenoceptors
Name a non-selective competitive antagonist of muscarinic ACh receptors?
atropine
What is the effect of non-selective muscarinic ACh receptor antagonists?
Increase HR in normal subjects
No effect on arterial BP
No effect on response to exercise
Why is the effect of atropine different in athletes?
SV is larger due to greater mass of cardiac muscle
Highly trained athletes have increased vagal tone
Atropine effect is exaggerated since blocks greater parasympathetic drive
What are the clinical uses of atropine?
First line in severe bradycardia, particularly following MI - vagal tone is elevated.
Anti-cholinesterase poisoning (to reduce excessive parasympathetic activity)
What is an alternative to atropine in severe bradycardia?
Glycopyrronium
What is the name of a cardiac glycoside that increases contractility of the heart?
digoxin
Drugs used in heart failure?
Digoxin
Dobutamine
b-blocker (low dose)
What is the effect of digoxin (and other inotropes) on the Starling curve?
Shift upwards and left on the function curve, such that SV increases at any given EDP
In heart failure, how is the Starling curve changed?
depressed and shifted right - cardiac contractility is reduced
How does digoxin increase contractility of the heart?
blocks the sarcolemma Na/K-ATPase: Increase intracellular Na Increase intracellular Ca Increase Ca storage in SR Increase CICR and therefore, contractility
Which subunit on the Na/K-ATPase does digoxin bind to?
alpha subunit in competition with K+
What can dangerously enhance the effects of digoxin?
low plasma K+ concentration (hypokalaemia)
What are the indirect actions of digoxin on electrical activity?
Increased vagal activity;
slows SA node discharge,
slows AV node conduction - increases refractory period
What are the direct effects of digoxin on electrical activity?
Shortens AP and refractory period in atrial & ventricular myocytes
What effect on the electrical activity does a toxic concentration of digoxin have?
membrane depolarisation and oscillatory after-potentials - likely due to Ca2+ overload
What are the clinical signs of digoxin toxicity?
Nausea, vomiting, anorexia, diarrhoea.
Blurred vision, yellow/green discolouration, haloes.
Palpitations, syncope, dyspnoea.
Confusion, delirium, fatigue
Signs of digoxin toxicity on an ECG?
Down-sloping ST depression = reverse tick/sagging/scooped
Flattened, inverted, or biphasic T waves
Shortened QT interval
Descrive a biphasic T wave and in which leads it would be seen.
initial negative deflection and terminal positive deflection
V4-6 (those with a dominant R wave)
First part is normally continuous with the depressed ST segment
Why is the QT interval shortened due to digoxin toxicity?
it shortens the refractory period
What are the different admin routes for Digoxin and in which scenario would they be used?
IV in acute heart failure
Orally in chronic heart failure
In which arrhythmia is digoxin particularly indicated?
AF
Which new drug would be useful in acute decompensated heart failure?
Levosimendan IV (calcium sensitiser)
How do calcium sensitisers work?
Bind to troponin C in cardiac muscles sensitising it to the action of Ca2+ -> contraction
Also opens K-ATP channels in vasculature -> vasodilation - reduces after load and cardiac work
