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

inhibits adrenergic stimulation (alpha- and beta-blocking properties), affects sodium, potassium, and calcium channels, prolongs the action potential and refractory period in myocardial tissue; decreases AV conduction and sinus node function

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

- Sinus rhythm slowed by 15% secondary to slowed diastolic depolarization of nodal cells
- AV nodal automaticity is decreased and AV nodal conduction speed is slowed 25%
- After IV administration decreased SVR and LV contractility
- Coronary artery vasodilation with increased coronary blood flow
- QT prolongation

IV, PO BA 60-80%

poorly absorbed, BA 40-70%

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

96%

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

66L/kg

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

complex metabolism, hepatic via de-ethylation catalysed by CYP 2C8 and 3A4. active metabolite N-desethylamiodarone

Urine (50% to 70% unchanged)

via skin, faeces, urine, lachrymal glands

36-48 hours

~40-55 days

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)

CVS - not arrhythmogenic despite QT prolongation (likely because of its multiple actions), bradycardia and hypotension
Resp- pneumonitis, fibrosis or pleuritis.
Endo - it may cause hypothyroidism (6%) or hyperth (1%).
Hepa - cirrhosis, hepatitis, jaundice. LFT monitoring.
Corneal microdeposits common- resolve on cessation.

structurally resembles thyroxine.

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

critical care for treating many arrythmias
- SV arrhythmias: preferred antiarrhythmic in patients with structural heart disease
- Ventricular arrhythmias: Cardiac arrest due to VT / unstable VT, stable sustained or nonsustained VT, Prevention of IVD shocks, Primary and secondary prevention of SCD due to VT, symptomatic ventricular premature beats

glycoside derived from the dried leaves of the foxglove

Block Na-K-ATPase pump

benzofuran derivative - 37% iodine by weight

class III antiarrhythmic displays actions of all four classes.

Level 1

Level 1

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

onset / duration 2 days to 3 wks / 1 wk to 5 mon

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

tablets – 100/ 200mg. clear colourless solution 50mg/ml for inf. Therapeutic range (1-2.5mg/L) but monitoring rarely necessary

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

doses PO 200mg TDS 1/52, BD 1/52, then OD
IV 5mg/kg (max 150+150mg) over 1hr → 15mg/kg (max 900mg) over 24 hrs IV

Mainly due to its effects on CYP450 enzymes (CYP3A4, CYP2C9, CYP2D6) and P-glycoprotein (P-gp)

Increased Drug Levels:
- Inc Bleeding risk (Warfarin, DOACs)
- Inc Toxicity risk (Digoxin, Phenytoin, Cyclosporine, Tacrolimus)
- Myopathy risk (Statins)

Additive Effects:
- Beta-blockers, Verapamil/Diltiazem: Bradycardia and hypotension.
- QT-prolonging drugs: Risk of torsades de pointes.

Reduced Effectiveness:
- Alters thyroid metabolism (causing hypo-/hyperthyroidism).
- May affect oral antidiabetics' efficacy.