i) Na/K ATPase inhibition → ↑ intracell Na → ↓ Na-Ca pump → ↑ intracell Ca → inotropy
ii) direct: ↑ AV node ERP, ↓ V ERP
iii) Indirect: Via Vagus – bradycardia, ↓ A refr. Augmentn of direct ↑ AV node ERP

Non-selective beta adrenergic antagonist
Cause anti-arrhythmic effect by:
--- Decreased pacemaker potential current
--- Decreased slow-inward Ca2+ current
--- Decreased repolarising K+ and Cl- currents
--- Decreased Ca2+ stored in the sarcoplasmic reticulum
--- Increased serum [K+]*

Positive inotropy. Slows sinus rate and AV-nodal conduction and increases AV-nodal refractoriness through direct electrophysiological and vagotonic effects. Rapid IV administration may cause vasoconstriction. Characteristic ECG effects include PR prolongation, ST depression, T-wave flattening and QT shortening. Mild diuresis.

Effects: Inotropy
Direct and indirect effects on refractory period + bradycardia -> treat AF&flutter

CVS
- The main action of digoxin is to increase the force of cardiac contraction; automaticity and contractility also increase.
- The heart rate is slowed due to a combination of improved haemodynamics, depression of sinus node discharge, slowing of AV nodal conduction, an increase in the AV nodal refractory period, and an indirect vagotonic effect.
- Rapid intravenous administration of digoxin may cause vasoconstriction, leading to hypertension and decreased coronary blood flow.
- The characteristic ECG changes produced by the drug include prolongation of the PR interval, ST-segment depression, T-wave flattening, and shortening of the QT interval

GIT - Anorexia/N/V/Diarrhoea (especially if therapeutic range exceeded)

CNS
- Headache, confusion, coma (toxicity)
- Visual disturbances (deranged red-green colour perception)

Renal- Mild diuretic effect

Miscellaneous- Rashes, eosinophilia; Gynaecomastia

Effect: Prolonged Action potential. Reduced Inotropy
Ventricular rate is slowed
QT interval is prolonged

IV, PO BA 60-80%

IV, PO BA 95%

prot bind ~25%; uremia- displaced fm pl prot bind sites

Nil

6-7 L/kg
thyroid (↑ in hyper, ↓ hypo).

1.2—2.4 L/kg

Stomach:Sequential sugar hydrolysis+ redn of lactone ring by intestinal bacteria
min hepatic, most excr unchanged

None

Urine (50% to 70% unchanged)

urine unchanged

36-48 hours

12 hrs

Thyroid-Vd
Narrow therapeutic window -monitoring - 0.5-2mcg/L(~1)
Toxic > 2.5- arrhythmias, AV block.
anorexia,N/V/D, lethargy. Altered Red green colour perception. ECG: ↑ PR, ST dep, T fl-attening, ↓QT. (may not indicate toxicity)

class III: QT prolongation predisposes torsades de pointes (with a risk of 2% in pts with sustained VF/VT). This risk is
increased in electrolyte imbalance.
May precipitate heart failure.
Other:bronchospasm, visual disturbances and sexual dysfunction.

Racemic mixture of d- and l- sotalol
both isomers: similar Class III effects
l-isomer: all of the Class II effect

Antiarrhythmic –
Vaughan Williams Class V
Other

Antiarrhythmic –
Vaughan Williams Class III
K channel blocker

used in AF and atrial flutter, SVT and in heart failure

used for the prevention of SVT and in the
treatment of ventricular tachyarrhythmias

glycoside derived from the dried leaves of the foxglove

Block Na-K-ATPase pump

beta blocker but it also has class III effects and is
often categorised in this class

Level 1

Level 3

Level 3

onset / duration Oral: 1-2 hours; I.V.: 5-60 mins / 3-4 days

Onset IV: 5-10mins, PO 1-2hrs
Duration 8-16hrs

PO: tablets 62.5mcg or 250mcg. IV:25-250mcg/ml.
Narrow therapeutic window. Monitoring necessary - 0.5-2mcg/L(~1)

PO: 80 or 160mg tablets. IV: clear liquid 10mg/ml

IV/PO.
loading 250-500mcg QID then 62.5-125mcg daily

Doses 80-160mg PO or 50-100mg IV over 20mins