You were a pharmacist working in an acute hospital. A 72-year-old man was admitted for suspected stroke symptoms with right-sided weakness and speech problems. He arrived at the emergency department 83 minutes after symptom onset. He had a past medical history of paroxysmal atrial fibrillation, hypertension, hyperlipidaemia, chronic kidney disease (Stage 3B, Glomerular Filtration Rate (“GFR”) 44 mL/min) and coronary artery disease. His blood pressure and pulse rates were 170/96 inmHg and 110 bpm respectively. He had been on dabigatran 150 mg twice daily for the prevention of stroke. The neurologist and stroke nurse decided to commence intravenous thrombolytic therapy in the emergency department. Initial investigation results were as follows:

• Computerised Tomography (“CT”) scan of the brain showed no evidence of intracranial haemorrhage
• Activated partial thromboplastin time (“APTT”) was 41s (reference range = 27.4 - 37.4s)
• Serum creatinine level was 126 µmol/L (reference range - 65 - 109 µmol/L)

a) Suggest the drug of choice for intravenous thrombolytic therapy.                 (1 mark)

b) What is the recommended dosage of the thrombolytic drug?                     (1 mark)

c) What is the maximum therapeutic time window for intravenous thrombolytic therapy? (1 mark)

d) List THREE contraindications for intravenous thrombolytic therapy.  (3 marks)

e) The neurologist is concerned of increased bleeding risk with thrombolytic therapy while the patient is taking dabigatran. Suggest the drug of choice to reverse the anticoagulation effects of dabigatran and its dosage. List TWO approved indications of this reversal agent.  (4 marks)

f) The clinician started with dronedarone for the treatment of persistent palpitations secondary to paroxysmal atrial fibrillation. Discuss the potential drug-drug interactions and recommendations on pharmacotherapy for dronedarone and the four direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) in this patient with moderate chronic kidney disease. (8 marks)

g) The patient developed dysphagia after stroke. Nasogastric enteral tube was inserted for feeding. The clinician determined that the patient should continue oral anticoagulation therapy. Which direct oral anticoagulant(s) are suitable for administration through enteral feeding tube? (2 marks)