Pulmonary embolism Flashcards
1
Q
Fibrinolytic drugs
Common indications
A
- Acute ischaemic stroke- alteplase increases the chance of living independently if it is given within 4.5hrs of the onset of stroke
- Acute ST-elevation MI- alteplase and streptokinase can reduce mortality when they are given within 12hrs of the onset of symptoms in combination with antiplatelet agents and anti-coagulants. However, primary PCI (where available) has largely superseded fibrinolytic in the context
- For massive pulmonary embolism with haemodynamic instability fibrinolytic drugs reduce clot size and pulmonary artery pressures, but there is no clear evidence that they improve mortality
2
Q
Fibrinolytic drugs
MOA
A
- Fibrinolytic drugs, also known as thrombolytic drugs, catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots and re-canalise occluded vessels
- This allows reperfusion of affected tissue, preventing or limiting tissue infarction and cell death and improving patient outcomes
3
Q
Fibrinolytic drugs
Adverse effects
A
- Common adverse effects include nausea and vomiting, bruising around the injection site and hypotension.
- Adverse effects that require treatment to be stopped include serious bleeding, allergic reaction, cardiogenic shock and cardiac arrest.
- Serious bleeding may require treatment with coagulation factors and antifibrinolytic drugs, e.g. tranexamic acid, but this is usually avoidable as fibrinolytic agents have a very short half-life.
- Reperfusion of infarcted brain or heart tissue can lead to cerebral oedema and arrhythmias, respectively.
4
Q
Fibrinolytic drugs
Warnings
A
- There are many contraindications to thrombolysis, which are mostly factors that predispose to bleeding including recent haemorrhage; recent trauma or surgery; bleeding disorders; severe hypertension; and peptic ulcers.
- In acute stroke, intracranial haemorrhage must be excluded with a CT scan before treatment.
- Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytic can be used), as the development of anti-streptokinase antibodies can block its effect.
5
Q
Fibrinolytic drugs
Interactions
A
- The risk of haemorrhage is increased in patients taking anticoagulants and platelet agents
- ACEI appear to increase the risk of anaphylactoid reactions
6
Q
Heparins and fondaparinux
Common indications
A
- VTE - LMWH is the first choice agent for pharmacological VTE prophylaxis in hospital inpatients, and for initial treatment of DVT and PE
- ACS- LMWH and fondaparinux are part of first-line therapy to improve revascularization and prevent intracoronary thrombus progression
7
Q
Heparins and fondaparinux
MOA
A
- Thrombin and Factor Xa are components of final common coagulation pathway that leads to the formation of a fibrin clot
- By inhibiting their function, heparins and fondaparinux prevent the formation and propagation of blood clots
- Unfractionated heparin (UFH) activates antithrombin that, in turn, inactivates clotting factor Xa and thrombin
- LMWH have similar MOA but preferentially inhibit factor Xa
- Fondaparinux is similar to heparin but only inhibits Xa
8
Q
Heparins and fondaparinux
Adverse effects
A
- The main adverse effect of heparins and fondaparinux is bleeding. This risk may be lower with fondaparinux than with LMWH or UFH.
- As with many injectables, these drugs may cause injection site reactions.
- Rarely, heparins may cause a dangerous syndrome characterised by low platelet count and thrombosis (heparin-induced thrombocytopenia).
- This immune reaction is less likely with LMWH and fondaparinux than UFH.
9
Q
Heparin and fondaparinux
Warnings
A
- Anticoagulants should be used with caution in patients at increased risk of bleeding, including those with clotting disorders, severe uncontrolled hypertension, or recent surgery or trauma.
- Heparins should be avoided around the time of invasive procedures, particularly lumbar puncture and spinal anaesthesia.
- In patients with renal impairment, LMWH and fondaparinux may accumulate and should be used at a lower dose, or unfractionated heparin used instead.
10
Q
Heparin and fondaparinux
Interactions
A
- Combining antithrombotic drugs increases the risk of bleeding.
- This should usually be avoided unless there is a special reason for combined therapy, such as in the use of LMWH while initiating warfarin, or the use of antiplatelet drugs (e.g. aspirin, clopidogrel) with fondaparinux/LMWH in ACS.
- In major bleeding associated with heparin therapy, protamine can be given to reverse anticoagulation.
- This is effective for UFH but much less so for LMWH. It is ineffective against fondaparinux.
11
Q
Warfarin
Common indications
A
- DVT and PE
- Embolic complications in AF
- Embolic complications after heart valve replacement
12
Q
Warfarin
MOA
A
- Warfarin inhibits hepatic production of vitamin K dependent coagulation factors and co-factors
- Vitamin K must be in its reduced form for the synthesis of coagulation factors
- It is then oxidised during the synthetic process
- An enzyme called it K epoxide reductase reactivates oxidised vit K
- Warfarin inhibits vit K epoxide reductase, preventing reactivation of it K and coagulation factor synthesis
13
Q
Warfarin
Adverse effects
A
- The main effect of warfarin is bleeding
- A slight excess of warfarin increases the risk of bleeding from existing abnormalities such as peptic ulcers or following minor trauma
- A large excess of warfarin can trigger spontaneous haemorrhage such as epistaxis (Nose bleed) or retroperitoneal haemorrhage
14
Q
Warfarin
Adverse effects
A
- As there is a fine line between thrombosis and haemorrhage in patients taking warfarin, potential risks and benefits must be carefully balanced.
- Warfarin is contraindicated in patients at immediate risk of haemorrhage, including after trauma and in patients requiring surgery.
- Patients with liver disease who are less able to metabolise the drug are at risk of over-anticoagulation/bleeding. In pregnancy, warfarin should not be used in the first trimester as it causes fetal malformations, including cardiac and cranial abnormalities.
- It should not be used towards term, when it may cause maternal haemorrhage at delivery.
15
Q
Warfarin
Interactions
A
- The plasma concentration of warfarin required to prevent clotting is very close to the concentration that causes bleeding (low therapeutic index).
- Small changes in hepatic warfarin metabolism by cytochrome P450 enzymes can cause clinically significant changes in anticoagulation.
- Cytochrome P450 inhibitors (e.g. fluconazole, macrolides, protease inhibitors) decrease warfarin metabolism and increase bleeding risk.
- Cytochrome P450 inducers (e.g. phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots.
- Many antibiotics can increase anticoagulation in patients on warfarin by killing gut flora which synthesises vitamin K.
