Drug of the Day

Question 1

Common indications: aspirin

Answer 1

• Atrial fibrillation (AF) before considering anticoagulants
• Secondary prevention of stroke and TIA
• Secondary prevention of acute coronary syndromes (ACS)
• Post primary percutaneous coronary intervention (PCI) and stent to reduce ischaemic
complications
• Often co prescribed with other antiplatelet agents
• NSTEMI/STEMI - initial once only 300 mg loading dose – chewable is best!
acute ischaemic stroke initial 300 mg daily 2 weeks
• Gastric protection required for long term use in at risk patients (proton pump inhibitor)

Question 2

MOA: aspirin

Answer 2

When platelet-rich thrombus forms in
atheromatous arteries and occludes the circulation.

Aspirin irreversibly
inhibits cyclooxygenase (COX) to reduce production of the
pro-aggregatory factor thromboxane from arachidonic acid
= reducing platelet aggregation and the risk of arterial occlusion.

The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of a platelet (which does not have a nucleus to allow synthesis of new COX) and thus only wears off as new platelets are made.

Question 3

Important adverse effects

Answer 3

Gastrointestinal irritation, GI bleeding (peptic ulcer), haemorrhage (stroke)
hypersensitivity

Question 4

Contraindications: aspirin

Answer 4

Reye’s syndrome (life-threatening illness that principally affects liver and brain) – avoid <16 years

Hypersensitivity- had allergic symptoms

3rd trimester – premature closure of ductus arteriosus

Question 5

Important drug interactions: aspirin

Answer 5

other antiplatelet and anticoagulants (additive/synergistic action)
• COX-1 polymorphisms result in lack of efficacy in some

Question 6

Name three ADP receptor antagonists

Answer 6

clopidogrel
prasugrel
ticagrelor

Question 7

MOA: clopidogrel

Answer 7

Inhibit binding of ADP to P2Y12 receptor → inhibit activation of GPIIb/IIIa receptors
independent of COX pathway
Clopidogrel and prasugrel are irreversible inhibitors of P2Y12
Prodrugs – they have active hepatic metabolites
• Clopidogrel has slow onset of action without a loading dose –
some inter-individual variability in antiplatelet action

Question 8

How does MOA of ticagrelor differ from clopidogrel?

Answer 8

Ticagrelor and prasugrel have more rapid onset of action
• Ticagrelor acts reversibly at different site to clopidogrel
and has active metabolites

Question 9

Important adverse effects: clopidogrel

Answer 9

Bleeding! GI upset – dyspepsia and diarrhoea

rarely - thrombocytopenia

Question 10

Contraindications: clopidogrel

Answer 10

caution in high bleed risk patients with renal and hepatic impairment

Question 11

Important drug interactions: clopidogrel

Answer 11

clopidogrel requires CYPs for activation
CYP inhibitors – omeprazole, ciprofloxacin, erythromycin, some SSRIs
need to consider use of other PPIs with clopidogrel
ticagrelor can interact with CYP inhibitors and inducers
caution when co prescribed with other antiplatelet and anticoagulant agents or NSAIDs –
increased bleeding risk
• clopidogrel needs stopping ~ 7 days prior to surgery in most patients

Question 12

ADP receptor antagonist indications

Answer 12

• ADP receptor antagonists used for wide variety of presentations where antiplatelet needed
• Clopidogrel
mono therapy where aspirin is contraindicated
NSTEMI patients – 3 months
STEMI patients - up to 4 weeks
Ischaemic stroke and TIA long term secondary prevention
• Prasugrel and ticagrelor with aspirin in ACS patients (undergoing PCI) for up to 12 months
• Risk of cardiovascular events vs. bleeding risk and other antiplatelet drugs all need to be
considered when prescribing these and any other antiplatelet agents

Question 13

Drug class: dipyridamole

Answer 13

Phosphodiesterase inhibitors

Question 14

MOA: dipyridamole

Answer 14

dipyridamole inhibits cellular reuptake of adenosine → increased [adenosine] → inhibits platelet
aggregation via adenosine (A2) receptors
• Also acts as phosphodiesterase inhibitor which prevents cAMP degradation → inhibit expression
of GPIIb/IIIa

Question 15

Adverse effects: dipyridamole

Answer 15

V+D, dizziness

Question 16

Drug-drug interactions: dipyridamole

Answer 16

antiplatelets and anticoagulants, adenosine

Question 17

Indications: dipyridamole

Answer 17

Secondary prevention of ischaemic stroke and TIAs
• Adjunct for prophylaxis of
thromboembolism following valve replacement
Stroke – modified release

Question 18

Drug class: abciximab

Answer 18

Glycoprotein IIb/IIIa inhibitors

Question 19

MOA: abciximab

Answer 19

Blocks binding of fibrinogen and von Willebrand factor (vWF)

• Target final common pathway – more complete platelet aggregation
• Abciximab – antibody - blocks GPIIb/IIIa receptors
>80% reduction in aggregation – bleeding risk
• Administered i.v.

Question 20

Adverse effects: abciximab

Answer 20

Bleeding! dose adjustment for body weight

Question 21

Drug-drug interactions: abciximab

Answer 21

caution with other antiplatelet and anticoagulant agents

Question 22

Abciximab indications

Answer 22

Specialist use in high risk percutaneous transluminal coronary angioplasty
patients with other drugs

Question 23

Indications: fibrinolytic agents

Answer 23

Alteplase in acute ischaemic stroke <4.5 hours from symptoms
• Following STEMI diagnosis acutely vs. primary PCI (see next slide)
• Streptokinase can only be used once as antibodies develop

Question 24

Adverse effects: fibrinolytic agents

Answer 24

Bleeding

Question 25

Important drug-drug interactions: fibrinolytic agents

Answer 25

antiplatelets and anticoagulants

Question 26

Drug class: clopidogrel

Answer 26

ADP receptor antagonist

Question 27

Common indications: clopidogrel

Answer 27

Clopidogrel is generally prescribed with aspirin, although clopidogrel may be used alone where aspirin is contraindicated or not tolerated. For treatment of acute coronary syndrome (ACS), where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality. To prevent occlusion of coronary artery stents. For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease. 4 To reduce the risk of intracardiac thrombus and embolic stroke in atrial fibrillation where warfarin and novel oral anticoagulants are contraindicated.

Question 28

MOA clopidogrel

Answer 28

Clopidogrel is a pro-drug that requires metabolism by hepatic cytochrome P450 enzymes to its active form to have antiplatelet effect. Clopidogrel prevents platelet aggregation and reduces the risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12 subtype) on the surface of platelets. As this process is independent of the cyclooxygenase pathway, its actions are synergistic with those of aspirin.

Question 29

Adverse effects: clopidogrel

Answer 29

Bleeding - needs to slop 7 days prior to surgery in most patients Gastrointestinal upset, including dyspepsia, abdominal pain and diarrhoea, is also common Rarely - thromobocytopenia

Question 30

Drug-drug interactions: clopidogrel

Answer 30

Its efficacy may be reduced by cytochrome P450 inhibitors by inhibiting its activation. Relevant examples include omeprazole, ciprofloxacin, erythromycin, some antifungals and some SSRIs. Where gastroprotection with a proton pump inhibitor is required for patients taking clopidogrel, lansoprazole or pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation. Co-prescription of clopidogrel with other antiplatelet drugs (e.g. aspirin), anticoagulants (e.g. heparin) or NSAIDs increases the risk of bleeding.

Question 31

Drug class: amiodarone

Answer 31

Class III K channel blocker

Question 32

Common indications: amiodarone

Answer 32

``` In the management of a wide range of tachyarrhythmias, including atrial fibrillation (AF), atrial flutter, supraventricular tachycardia (SVT), ventricular tachycardia (VT) and refractory ventricular fibrillation (VF). It is generally used only when other therapeutic options (drugs or electrical cardioversion) are ineffective or inappropriate. ```

Question 33

MOA: amiodarone

Answer 33

blockade of sodium, calcium and potassium channels, and antagonism of !- and "-adrenergic receptors. These effects reduce spontaneous depolarisation (automaticity), slow conduction velocity, and increase resistance to depolarisation (refractoriness), including in the atrioventricular (AV) node. By interfering with AV node conduction, amiodarone reduces the ventricular rate in AF and atrial flutter. Through its other effects, it may also increase the chance of conversion to, and maintenance of, sinus rhythm. In SVT involving a self-perpetuating (‘re-entry’) circuit that includes the AV node, amiodarone may break the circuit and restore sinus rhythm. Amiodarone’s effects in suppressing spontaneous depolarisations make it an option for both treatment and prevention of VT. The same rationale underlies its use in refractory VF, although there is little evidence from clinical trials to support this.

Question 34

Adverse effects: amiodarone

Answer 34

When taken chronically, it has many side effects, a number of which are serious. These include effects on the lungs (pneumonitis), heart (bradycardia, AV block), liver (hepatitis) and skin (photosensitivity and grey discolouration). Due to its iodine content (amIODarone) and structural similarities to thyroid hormone, it may cause thyroid abnormalities, including hypo- and hyperthyroidism. Amiodarone has an extremely long half-life. After discontinuation, it may take months to be completely eliminated.

Question 35

Important drug- drug interactions amiodarone

Answer 35

it increases plasma concentrations of digoxin, diltiazem and verapamil. This may increase the risk of bradycardia, AV block and heart failure. The doses of these drugs should be halved if amiodarone is started.

Question 36

What class of drug is celecoxib?

Answer 36

Anti-inflammatory COX2 inhibitor CoX2 selectivity

Question 37

Common indications: celecoxib

Answer 37

Pain and inflammation - OA - RA - ankylosing spondylitis

Question 38

MOA of celecoxib

Answer 38

Selective for COX2

Question 39

ADR celecoxib

Answer 39

less GI ADRs, renal ADRs

Question 40

DDI celecoxib

Answer 40

increased risk of MI including in low risk patients

Question 41

Drug class: azathioprine

Answer 41

immunosuppressant

Question 42

Indications: azathioprine

Answer 42

SLE & vasculitis as maintenance therapy RA - very weak evidence Inflammatory bowel disease

Question 43

MOA: azathioprine

Answer 43

cleaved to 6-mercaptopurine (6-MP) | anti-metabolite decreases DNA and RNA synthesis

Question 44

ADR: azathioprine

Answer 44

Bone marrow suppression Increased risk of malignancy Increased risk of infection Hepatitis