Drug of the Day Flashcards
Common indications: aspirin
• 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)
MOA: aspirin
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.
Important adverse effects
Gastrointestinal irritation, GI bleeding (peptic ulcer), haemorrhage (stroke)
hypersensitivity
Contraindications: aspirin
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
Important drug interactions: aspirin
other antiplatelet and anticoagulants (additive/synergistic action)
• COX-1 polymorphisms result in lack of efficacy in some
Name three ADP receptor antagonists
clopidogrel
prasugrel
ticagrelor
MOA: clopidogrel
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
How does MOA of ticagrelor differ from clopidogrel?
Ticagrelor and prasugrel have more rapid onset of action
• Ticagrelor acts reversibly at different site to clopidogrel
and has active metabolites
Important adverse effects: clopidogrel
Bleeding! GI upset – dyspepsia and diarrhoea
rarely - thrombocytopenia
Contraindications: clopidogrel
caution in high bleed risk patients with renal and hepatic impairment
Important drug interactions: clopidogrel
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
ADP receptor antagonist indications
• 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
Drug class: dipyridamole
Phosphodiesterase inhibitors
MOA: dipyridamole
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
Adverse effects: dipyridamole
V+D, dizziness
Drug-drug interactions: dipyridamole
antiplatelets and anticoagulants, adenosine
Indications: dipyridamole
Secondary prevention of ischaemic stroke and TIAs
• Adjunct for prophylaxis of
thromboembolism following valve replacement
Stroke – modified release
Drug class: abciximab
Glycoprotein IIb/IIIa inhibitors
MOA: abciximab
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.
Adverse effects: abciximab
Bleeding! dose adjustment for body weight
Drug-drug interactions: abciximab
caution with other antiplatelet and anticoagulant agents
Abciximab indications
Specialist use in high risk percutaneous transluminal coronary angioplasty
patients with other drugs
Indications: fibrinolytic agents
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
Adverse effects: fibrinolytic agents
Bleeding
Important drug-drug interactions: fibrinolytic agents
antiplatelets and anticoagulants
Drug class: clopidogrel
ADP receptor antagonist
Common indications: clopidogrel
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.
MOA clopidogrel
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.
Adverse effects: clopidogrel
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
Drug-drug interactions: clopidogrel
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.
Drug class: amiodarone
Class III K channel blocker
Common indications: amiodarone
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.
MOA: amiodarone
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.
Adverse effects: amiodarone
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.
Important drug- drug interactions amiodarone
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.
What class of drug is celecoxib?
Anti-inflammatory
COX2 inhibitor
CoX2 selectivity
Common indications: celecoxib
Pain and inflammation
- OA
- RA
- ankylosing spondylitis
MOA of celecoxib
Selective for COX2
ADR celecoxib
less GI ADRs, renal ADRs
DDI celecoxib
increased risk of MI including in low risk patients
Drug class: azathioprine
immunosuppressant
Indications: azathioprine
SLE & vasculitis as maintenance therapy
RA - very weak evidence
Inflammatory bowel disease
MOA: azathioprine
cleaved to 6-mercaptopurine (6-MP)
anti-metabolite decreases DNA and RNA synthesis
ADR: azathioprine
Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
Hepatitis
