A glycoside extracted from the leaves of foxglove (digitalis lanata). Available as oral (tablets 62.5mcg-250mcg, elixir 50mcg/ml) and IV 100-250mcg/ml.
Widely used for treatment of A fib and A flutter. Should be avoided in patients with ventricular ectopics as it may precipitate VF.
Treatment starts with loading dose of 1-1.5mg over 24hours then maintenance dose of 125-500mcg/day.
Digoxin mechanism of action
Direct - binds to and inhibits Na+/K+ ATPase. Increases IC sodium, decreases IC potassium. Increased IC sodium causes increased exchanged with EC calcium resulting in increased IC calcium. This has a positive inotropic effect. Also increases refractory period of AV node.
Indirect - increased release of ACh at cardiac muscarinic receptors and slows conduction. Further prolonging refractory period.
In AF the atrial rate is too high for 1:1 conduction. By slowing conduction through AV node the rate of ventricular response is reduced = increased coronary blood flow and increased ventricular filling.
Digoxin Side effects
Cardiac - arrhythmias and conduction disturbances (PVC’s, bigemin, AV block etc).
Non-cardiac - annorexia, nausea, vomiting, lethargy. Visual disturbance (deranged red-green colour perception included) and headache are common.
Variable absorption from the gut but oral bioavailability >70%.
25% protein bound. Vd 5-10L/kg.
Excreted mainly unchanged by filtration at glomerulus and active tubular secretion therefore half life significantly increased in the presence of renal failure.
T1/2 normally 35 hours.
Plasma conc. >2.5mcg/L are associated with toxicity. Serious > 10mcg/L.
Due to Na/KATPase inhibition hyperkalaemia may be a feature and should be treated. If bradycardic atropine or pacing is preferred as catecholamines may induce further arrhythmias.
If plasma levels >20mcg/L, life threatening arrhythmias or hyperkalaemia uncontrolled digoxin specific antibody is indicated. This is IgG fragments which directly bind digoxin and essentially remove it from its site of action. Digoxin-Fab complex removed by kidneys.
A naturally occuring purine nucleoside which is present in all cells.
Presented as a colourless solution in vials containing 3mg/mL. Stored at room temperature.
Used to differentiate between SVT (where the rate is transiently slowed) and VT where the rate does not slow.
If SVT due to re-entry circuits that involve AV node adenosine may convert the rhythm to sinus.
AF and flutter are not converted to sinus as they are not generated by re-entry circuits but its use in this setting will slow ventricular response and aid in ECG diagnosis.
Adenosine mechanism of action
Specific actions on SA and AV node mediated by adenosine A1 receptors that are not found elsewhere within the heart.
Adenosine sensitive K+ channels are opened causing membrane hyperpolarisation and G-proteins cause a reduction in cAMP.
–> Result in a dramative negative chronotropic effect
Adenosine side effects
Short half life means side effects are very short lived.
Cardiac - may induce Af or flutter as it decreases atrial refractory period.
Non-cardiac - chest discomfort, shortness of breath and facial flushing. Can precipitate bronchospasm.
Given in incremental doses from 3 to 12mg as an IV bolus.
Rapidly deaminated in the plasma and taken up by RBC so t1/2 is less than 10 seconds.
Verapamil class and presentation
Competitive calcium channel antagonist. Class IV anti-arrhythmic.
Presented as film coated and modified release tablets and as a solution for IV injection containing 2.5mg/mL
Used to treat SVT, AF and A flutter which it may slow or convert to sinus rhythm.
Also used in prophylaxis of angina and treatment of hypertension
Verapamil mechanism of action
Prevents the influx of calcium through slow voltage gated L-Type calcium channels in SA and AV node thereby reducing automaticity (by reducing phase 0 of AP).
Cause a decreased rate of conduction (negative dromotropy) and coronary artery dilatation.
Verapamil side effects
Cardiac - If used to treat WPW can precipitate VT due to increased conduction across accessory pathway. If given with other agents that slow AV node conduction may cause severe bradycardia. Increases serum levels of digoxin. Although relatively selective for myocardium may cause hypotension
Non-cardiac - cerebral artery vasodilation.
Oral - 90% absorbed by the gut but high first-pass metabolism reduces its oral bioavailability to about 25%. Approx 90% bound to plasma proteins.
Metabolised by liver to inactive metabolites that are excreted in the urine.
Vd 3.5L/Kg. Elimination half life 3-7 hours.
B-blocker mechanism of action and uses
Drugs that bind to beta-adrenoreceptors and block the binding of noradrenaline and adrenaline. These receptors are located in nodal tissues, conducting system and contracting myocytes.
B-adrenoreceptors are coupled to G proteins which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates L-type calcium channels and causes increased calcium entry into cell. Increased calcium induced calcium release from SR.
= increased inotropy, chronotropy, dromotropy (electrical conduction) and lusitropy (relaxation).
Used in the treatment of HTN (reduce CO and renin release long term), Angina (decreased HR, inotropy and MAP reduce 02 demand) and SVT/AF/sinus tachy due to increased levels of catecholamines.
Esmolol selectivity and presentation
Relatively cardioselective b blocker with rapid onset and offset
Presented as a clear liquid with either 2.5g or 100mg in 10mL. The former should be diluted before being administered as an infusion (50-200mcg/Kg/min) and the latter given as 5-10mg boluses to effect
Used in short term management of tachycardia and hypertension in the peri-operative period. Also used for acute SVT.
Esmolol side effects
Although relatively cardioselective it does display b2 receptor antagonism at high doses so should be used with caution in asthmatics.
Irritant to veins and extravasation can lead to tissue necrosis.
Like other b blockers can precipitate heart failure.
Only available IV. 60% protein bound.
Rapidly metabolised by RBC esterases to an inactive metabolite - this means short half life of 10min.
Can be used to treat SVT including AF and flutter. Less popular now days.
Quinidine class and mechanism of action
Class 1a anti-arrhythmic
It reduces the rate of rise of phase 0 of the action potential by blocking Na + channels. It also raises threshold potential and prolongs refractory period. Does not effect duration of AP
Quinidine side effects
Cardiac - may provoke other arrhythmias including heart block, sinus tachy etc.
Can cause prolonged PR interval, wide QRS and prolonged QT.
Non-cardiac - CNS toxicity (cinchonism) - blurred vision, tinnitus, impaired hearing, headache, confusion
Drug interactions - increase serum conc of digoxin, increased effect of muscle relaxants
Oral bioavailability of 75%. Highly protein bound (90%) and metabolised by liver to active metabolites which are excreted in the urine.
Elimination half life 5-9hrs
Lignocaine class and presentation
Class 1b anti-arrhythmic.
colourless liquid presented as 1 or 2% (10-20mg/mL)
Lignocaine uses and dosage
Used to treat sustained ventricular tachyarrhythmias especially when associated with ischaemia or re-entry pathways. Initial 1mg/kg is followed by IV infusion of 1-3mg/min
Lignocaine mechanism of action
Sodium channel blocker. Reduces the rate of rise of phase 0 of the action potential by blocking inactivated sodium channels and raising the threshold potential. Duration and refractory period of AP are reduced as phase 3 is shortened
Lignocaine side effects
Cardiac - CVS toxicity present at conc >10mcg/ml and manifest as AV block and unresponsive hypotension due to myocardial depression.
Non-cardiac - apparent when plasma levels >4mcg/mL. Initially CNS toxicity = perioral tingling, parasthesia, dizziness. At higher conc get confusion, coma and seizures
33% unionized and 70% protein bound.
Metabolised by hepatic amidases to products that are eliminated in urine.
Elimination half life about 90 min. Clearance reduced in cardiac failure due to reduced hepatic blood flow
Benzofuran derivative. Presented as tablets containing 100-200mg and as a solution containing 150mg per ampoule. Should be diluted before administration
Amiodarone uses and dosage
Used in the treatment of SVT, VT and WPW.
Loading dose of 300mg over 1hour followed by 900mg over remaining 23 hours.
If used orally commence at 200mg tds for one week then 200mg bd for a week and then 200mg daily
Amiodarone mechanism of action
Traditionally desginated as a class III anti-arrhythmic however also have class I, II and IV activity. Blocks K+ channels so slows rate of repolarisation - increases duration of AP. Also increase ERP. Amiodarone also interferes with functioning of beta-adrenergic receptors, sodium channels and calcium channels.
Amiodarone side effects
Many. Affect most patients if given for long enough.
Pulmonary - pneumonitis, fibrosis or pleuritis.
Thyroid - both hyper or hypo have been observed. Prevents conversion of T4 to T3 peripherally
Hepatic - cirrhosis, hepatitis and jaundice. Monitor LFT’s.
Cardiac - bradycardia and hypotension if large doses given rapidly
Neurological - peripheral neuropathy
Dermatological - photosensitivity
Interactions - Effects of other highly protein bound drugs increased and doses should be adjusted. Plasma level of digoxin may be increased and cause toxicity. Should not be given with drugs that prolong Qt for fear of precipitating torsades
Poorly absorbed from the gut. Bioavailability of 50-70%.
Highly protein bound (>95%) and has Vd 2-70L/kg.
Elimination half life is 20 to 100 days.
Hepatic metabolism by CYP3A4 to active metabolite. Excreted by biliary tract, skin and lachrymal glands.
Flecainide presentation and dose
Amide local anaesthetic with class 1c properties. Oral dose is 100mg bd (max 400mg daily). When used IV dose is 2mg/kg over 10-30 min (max 150mg) followed by an infusion.
Flecainide uses and mechanism of action
Useful against atrial and ventricular tachycardias including WPW.
Blocks sodium channels thus prolonging phase 0 of AP
Also blocks ryanodine receptor opening, reducing calcium release from SR which reduces depolarisation of cells.
Flecainide side effects
Cardiac - may precipitate pre-exisiting conduction disorders - care with SA or AV disease or with bundle branch block. Raises pacing threshold. Cardiac failure may complicate treatment due to negative inotropic effect.
Non-cardiac - dizziness, parasthesia and headaches.
Bioavailability 90%. 50% protein bound and large Vd 6-10L/kg.
Hepatic metabolism produces active metabolites excreted in urine along with unchanged drug
A b-blocker (class II) but also has class I and III anti-arrhythmic activity. Available as tablets and as a solution containing 40mg/mL. It is a racemic mixture - D-isomer conferring class III activity and L-isomer conferring both II and III
Indicated to treat life threatening ventricular arrhythmias and maintain normal sinus rhythm in patients with Afib a flutter
Sotalol mechanism of action
Inhibits b1 adrenoreceptors in the myocardium which decreases inotropy and chronotropy Also inhibits rapid potassium channels, thus delaying repolarisation, prolonging AP and ERP (class III action)
Sotalol side effects
Cardiac - most serious is precipitation of torsades - more common in those with prolonged QT and electrolyte imbalance. May precipitate heart failure (decreased inotropy and chronotropy)
Non-cardiac - bronchospasm from B2 antagonism. Masking of symptoms of hypolglycaemia. Visual disturbances and sexual dysfunction are rare.
Oral bioavailability >90%. Not protein bound. Not metabolised.
up to 90% excreted unchanged in the urine with the remainder in bile. Renal impairment significantly reduces clearance.
Half life 10-20 hours
Calcium channel blocker with intermediate specificity to both vascular and cardiac smooth muscle.
Oral use for hypertension and prophylaxis of angina
IV for short term management of A fib or flutter.
Diltiazem mechanism of action
Blocks L-type calcium channels. Thus decreasing phase 0 of AP (both cardiac and smooth muscle). Decreases calcium induced calcium release from SR.
Causes decreased chronotropy, inotropy and systemic vascular resistance thus decreasing myocardial 02 demand.