Cardio pharmacology (II): Rate And Rhythm Control Flashcards
Digoxin indication
Atrial fibrillation or flutter.
Heart failure
Emergency loading dose for atrial fibrillation or flutter.
Digoxin Therapeutic Range
0.7 to 2 nanogram/mL (wide inter-individual variations).
How do you start digoxin (dose)
Loading dose of 250 micrograms to 750 micrograms for 7 days followed by maintenance dose 125 micrograms-250 micrograms adjusted according to renal function and heart rate response.
What is max maintenance dose of digoxin.
(a) 250 micrograms
(b) 125 micrograms
(c) 300 micrograms
(d) 150 micrograms
(a) 250 micrograms daily
When would you suspect DigToxicity.
(a) 0.5 nanogram/mL
(b) 3.0 nanograms/mL
(c) 3.0 nanograms/L
(d)1.5 nanogram/mL in presence of hypokalemia
(e) 0.8 nanograms.
(f) 1.8 nanograms/L nanograms
(b) 3.0 nanograms/mL + (d) 1.5 nanogram/mL in presence of hypokalemia because dig toxicity is more pronounced in hypokalemia due to less competition to bind to sodium potassium pump.
What are the symptoms of DigToxicity.
Confusion, nausea, anorexia, visual colour disturbances.
What is the antidote for DigToxicity
DigiFab antibody
Monitoring for Digoxin
(a) Routine monitoring
(b) Monitoring when patient presents with confusion and visual colour disturbances
(c) Monitoring when patient is on amiodarone or diltiazem
(d) Monitoring when patient comes in for regular blood pressure and heat rate monitoring.
(b) and (c)
What is being monitored for digoxin and why.
Serum electrolytes (K+, Mg2+ and Ca2+) as electrolyte imbalances (hypokalaemia, hypo magnesia, and hypercalcaemia) can potentiate toxicity, renal function and heart rate ( HR greater than 60 bpm).
What HR do you want patients to be at whilst on digoxin.
> 60 bpm.
Mechanism of Digoxin and its effects on cardiac tissue.
Digoxin inhibits sodium-potassium ATPase pump increasing the contractility of the heart by increase sodium and in turn calcium forming more cross-bridges to allow for powerful contractions.
Mechanism of Digoxin nodal cells.
Reduces AV node conduction via the vagus nerve.
Does digoxin affect preload/afterload/stroke volume and is it an increase or decrease or no effect.
Digoxin increases stroke volume.
Digoxin have no effect on preload.
Digoxin has no effect on after load.
Is digoxin a negative chronotrope or inotrope.
Chronotrope.
Is digoxin a positive chronotrope or inotrope.
Inotrope.
Digoxin adverse effects
Arrhythmias, possible AV block.
Digoxin: Caution and Contraindication
Heart Block.
Renal Failure.
Electrolyte imbalance
HF: patient on selective calcium channel blocker-> cardio-suppressant effects.
Pharmacokinetics of digoxin: a. Half-life? b. Excreted by which organ. c. When is steady state concentration achieved?
a. 30-40 h.
b. Kidney
c. 5-7 days
Pharmacokinetics Digoxin: a. Metabolism.
a. CYP3A4 enzymes
How is digoxin renally cleared and the clinical significance with diuretics.
Digoxin is excreted by the nephrons through tubular secretion and drugs that inhibit tubular secretion such as spironolactone and amiodarone can cause a build up of digoxin. Also renal impairment slows down elimination leading digoxin toxicity.
What drugs can impair renal function and effect digoxin excretion.
ACE-inhibitor and NSAIDs.
What drug when used concomitantly with digoxin will increase the risk of pro-arrhythmia.
Tricyclic antidepressant: block noradrenaline and adrenaline uptake increasing risk of SNS activation.
Which serotonergic receptor is implicated in pro-arrthymia.
Serotonin acts solely via 5-HT4-receptors to control human cardiac contractile … It may be assumed that 5-HT can exert a proarrhythmic effect
What drug when used concomitantly with digoxin will increase digoxin levels.
Diuretics
Proton pump inhibitor
What herbal remedy when used concomitantly with digoxin will reduce digoxin level.
St. John’s Wort.
Is amiodarone a positive or negative chronotrope.
Negative
Is amiodarone a positive or negative inotrope
(Very little effect) Negative.
Amiodarone effect on after load/Preload/cardiac conduction/cardiac output- increase decrease or no effect.
Amiodarone decreases peripheral resistance (after load) due to vasodilation of vessels by beta and alpha antagonism.
Preload: no effect
Cardiac output: marginal increase.
Cardiac conduction: decreased.
Amiodarone mechanism of action.
Blockade of sodium, calcium and potassium channels and antagonism of the alpha and beta-adrenergic receptors.
Amiodarone pharmacodynamic effects.
Reduces spontaneous depolarisation (automaticity).
Slows conduction velocity and increases resistance to depolarisation (refractoriness).
Prevents self-perpetuating re-entry circuit, including AV node, thus restoring sinus rhythm.
Adverse effect of Amiodarone. (Think 79-year-old woman case study)
Nausea, vomiting and taste disturbance associated with loading dose.
Pulmonary toxicity (pneumonitis and fibrosis) which can occur during the therapy (79 yr old woman).
Thyroid dysfunction: hypo/hyperthyroidism due to its resemblance to iodine.
Cardiac toxicity: bradycardia and conduction disturbances associated with increasing dose.
Visual disturbance: corneal micro deposits.
Photosensitivity reaction: common and persist several months after stopping amiodarone treatment. Blue discolouration.
What is the baseline test that need to be carried out before initiating amiodarone.
Liver function test, urea & electrolytes, thyroid function test, chest X-ray and electrocardiography.
What is the half life of amiodarone.
a. 60 days
b. 12 days
c. 80 days
d. 50 days
(d) 50 days.
Caution and contraindication Amiodarone
Heart block
Liver failure.
Elderly.
Hypotension.
What enzymes does Amiodarone inhibit or induce.
Inhibitor of CYP3A4, CY2C9.
Does Amiodarone increase or decrease the concentration of Simvastatin.
Increase. CYP3A4 inhibitor.
Which drug-drug interaction causes rhabdomyolysis.
a. Amiodarone +simvastatin.
b. Amiodarone + warfarin.
c. Warfarin +Simvastatin.
d. Simvastatin + Carbamazepine.
e. Grapefruit +simvastatin.
(a) amiodarone and simvastatin.
Mechanism of flecainide
Sodium channel blocker.
CYP enzyme flecainide inhibits or induce
CYP2D6 inhibitor
Which interaction increases the concentration of dexamethasone
a. dexamethasone + warfarin
b. dexamethasone + carbamazepine
c. dexamethasone + amiodarone
d. Dexamethasone + flecainide
(d) Flecainide
