Sample SAQs

Question 1

with reference to AF, explain the molecular mechanism of action of flecanide

Answer 1

1. AF is a re-entrant rhythm that is due to changes in conduction velocity and refractory period of areas of atrial muscle cells
2. disruption to either the refractory period or conduction velocity can return the patient to sinus rhythm
3. flecainide provides a marked block of the voltage gated Na+ channels in atrial muscle cells
4. This block is use-dependent and leads to a slowing of conduction velocity in areas of high activity
5. slowing conduction velocity can disrupt a re-entrant rhythm enabling the heart to return to a normal sinus rhythm

Question 2

Explain, from a clinical perspective, what signs and symptoms would alert you to the possibility that your patient has digoxin toxicity

Answer 2

1. signs- bradycardia or tachycardia
2. symptoms- GI symptoms: nausea, vomiting and abdominal pain
   - visual disturbances: blurred or yellow vision
   - CNS disturbances: confusion
   - cardiovascular disturbances: fatigue or palpitations

Question 3

What would you look for in patient notes as factors that might have contributed to digoxin toxicity and why

Answer 3

1. look for drug-drug interactions (eg. amiodarone)
   - amiodarone inhibits PgP that clears digoxin from the body
2. look for electrolyte disturbances such as hypokalaemia
   - hypokalaemia potentiates the effects of digoxin at the Na+/K+ ATPase
3. look for renal impairment
   - renal impairment will inhibit the removal of digoxin from the body

Question 4

discuss from a pharmaceutical science perspective, how would you monitor digoxin levels in the blood and what factors might influence the efficacy of the assay and why

Answer 4

1. most appropriate approach is to use ELISA of blood sample taken 6 hours after dosing, however other alternative methods such as HPLC is valid
2. description of how ELISA works
3. limitations within the assay- assay precision, interferences from other compounds and cross reactivity against metabolites

Question 5

from a pharmacological perspective, explain the mechanisms behind the ability of digoxin to have different effects on the heart rate depending on the plasma concentration of the drug

Answer 5

1. bradycardia due to digoxin stimulating the release of Ach from the AV node and slowing conduction velocity through the AV node, increasing its refractory period and so reducing ventricular beats
2. also inhibits Na+/k+ ATPase, which increases intracellular Na+ ions and inhibits the Na+/Ca2+ exchanger and increases intracellular Ca2+
3. This increase in Ca2+ prolongs phase 0 and phase 4 of the cardiac action potential slowing rate
4. normal functioning of the Na/Ca2+ exchanger depolarises the cell, but increasing intracellular Na+ will reduce this depolarisation so lows automaticity
5. tachycardia due to the formation of delayed afterdepolarisations
6. these are caused by Ca2+ overload which is a condition caused by digoxin and Ca2+ release from the sarcoplasmic reticulum
7. this increased Ca2+ can drive the Na+/Ca2+ exchanger which would depolarise the cell or the Ca2+ could activate Cl- currents to dgpolise the cell causing a ventricular tachycardia