– Also called cardiac glycosides
– Digitalis are in fact only small positive inotropic with some peripheral vascular effects.
– At the level of myocardial cell, digitalis bind to membrane receptors and inhibit Na + / K + ATPase membrane.
This blocks the outlet of extracellular Na + => [Ca2 +] int high (Na + exchanger / Ca2 +) => increasing the contractile force of the myocardial cell.
– Digitalis also have an indirect effect by enhancing vagal tone -> negative chronotropic effect
– Action on baroréceptices activating cells of the aortic arch, carotid sinus
A- Pharmacological actions:
1- Cardiac effects:
– Increase the contractile force: positive inotropic
– Increase the excitability of the myocardium: Positive effect bathmotropic
– Decrease in heart rate: negative chronotropic effect
– Decrease the conduction of electrical influence: negative dromotropic
2- extracardiac effects:
– Rein: improves renal perfusion; anti-aldosterone effect, so an indirect diuretic effect
– Vessels: arteriolar vasoconstriction; increase venous tone (preload)
– CNS: stimulation of vagal centers and vomiting
– Autonomic Nervous System: activation of vagal tone (at all levels) that inhibits condairement-friendly effect.
– Digitalis sensitize the heart to action inotropic catecholamine
– Oxygen consumption decreases on insufficient heart
– Effect negative dromotropic: at the node of Aschoff and Tawara-His bundle refractory periods are elongated and conduction velocity is slowed down.
– The negative effect explains bathmotropic property to trigger an intrinsic pacemaker in the atria and ventricles, causing the arrhythmia, net in case of digitalis intoxication.
– At the level of the CNS: the digitalis to toxic doses cause a cortical excitation (occipital) causing hallucinations and visual disturbances.
– A toxic level at the SNV sympathetic activation with increased release of catecholamines; the consequences of which remain unclear.
– At the heart insufficient improvement in cardiac output induced vasodilation
– Sinus bradycardia or AV block 1st degree (moderately high PR)
– Flattening of the T wave; negativity but asymmetric
– Shortening of QT
– Base Offset cupuliforme concave upward ST
– Appearance of a wave U
B- Digitalis Intoxication:
* Aggravating factors at the cellular level:
– Overload intracellular calcicosodique
– Drop extracellular potassium (hypokalemia)
– High level of sympathetic tone
* The toxic concentrations:
– ≥ 3 ng / ml for digoxin
– ≥ 45 ng / ml for digitoxin
* Medicines that increase digitalis toxicity: amiodarone (but possible association); quinidine (with digoxin); verapamil (digoxin); erythromycin; ibuprofen; indomethacin; antacids; coal; … cholestyramine. (Sulfasalazine-induced against a sharp decrease in digoxin).
* Note: severe intoxication often result in hyperkalemia
1- extracardiac Events:
– Digestive: vomiting; transit disorders
– Eyepieces: dyschromatopsia yellow, green, scotoma, colorful halo
– Neurological: headache, insomnia, neuralgia V, convulsion, depression
– More rarely: rash; gynecomastia; diffuse arterial spasm
2- Cardiac Events:
– Av conduction disorders (BAV …) and atrial rhythm disorders, ventricular
– Tachysystole atrial always evocative; flutter or atrial fibrillation rarer
– Junctional tachycardia
– ESV, ESA, TV, FV
– Bidirectional Ventricular tachycardia (several automation households)
– At a late stage, intraventricular conduction disorders and inexcitability
– Stop all administration of digitalis and serum sample
– Gastric lavage drug if taken before 3:00.
– Serum 5% glucose infusion
– Systematic potassium intake unless initial hyperkalemia, renal insufficiency, conduction disorders of degree.
– Driving up a pacing probe if CCHB with slow escape rhythm
– Atropine so minor conduction defects (sinus bradycardia, BSA, minor BAV)
– Immunotherapy in case of mass poisoning with signs of severity (Anti-Fab)
– Dihydantoïne in case of symptoms of ventricular rhythm or lidocaine (amiodarone, propranolol may also be used)
C- Indications and cons-indications:
* Congestive heart failure: more effective when the heart is dilated, there is an ACFA, the patient is not in hypovolemia, the IC is not terminal.
* Supraventricular rhythm disorders
This is the preferred indication of digitalis: FA, flutter
– BAV degree unaided
– Atrial rhythm disease and sinus dysfunction
– Ventricular tachycardias
– Repetitive ESV, polymorphic
– Wolff-Parkinson-White syndrome
– Ionic disorders: hypokalemia, hypercalcemia
– Obstructive or restrictive heart disease
– Aortic stenosis.
3- pharmacokinetic properties:
Fat largest => almost complete digestive resorption; almost completely metabolized by the liver; biliary and urinary elimination; high plasma protein binding (90%) => greater plasma half-life (4-6 days)
Water solubility greater => lower digestive resorption (<80%); low protein binding (20%); minimal hepatic metabolism (10%); higher renal elimination. ½ life = 36 hours
– Competition between potassium and digitalis at the myocardial cell: decrease the local concentration of K + ions leads to increased fixation of digitalis
– The other positive inotropic: sympathetic and related amines, glucagon, phosphodiesterase inhibitors, sodium channel agonist