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arebef > Dawes: Anticoagulant Drugs > Flashcards

Dawes: Anticoagulant Drugs Flashcards

1
Q

What are the two anticoagulants used most in clinical practice?

A
  1. Warfarin
  2. Heparin - Fractionated and Unfractionated
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2
Q

What are the indications that an anticoagulant should be used?

A

Patient has an arterial disease such as coronary artery disease, cerebrovascular disease or peripheral vascular disease. In these examples, the anticoagulant should be coupled in its usage with an anti-platelet drug.

Patients with a thrombo-embolic disease such as atrial fibrillation, venous thrombo-embolism and prosthetic cardiac valves. In these examples, on a anticoagulant needs to be used.

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3
Q

What is Virchows Triad?

A

This consists of three components that act together to increase an individuals risk of thrombosis. The components that makeup Virchow’s triad include…

  1. Hypercoagulability
  2. Endothelial Damage
  3. Stasis
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4
Q

When is Heparin used?

A

Heparin is used in the treatment of acute coronary syndromes, the treatment and prophylactically in thromboembolism (DVT, PE and AF) and as a temporary warfarin replacement for pregnant patients.

  • Its main uses are acute.
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5
Q

Describe the properties of unfractionated heparin and how they affect how it is used…

A

Heparin is a linear mucopolysaccharide with a high molecular weight of 3000 - 40000. It also carries a high negative charge. Because of its ionic nature, it is unable to cross mucosal membranes and therefore has to be given intravenously via constant infusion.

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6
Q

What is the mechanism of action for Unfractionated Heparin?

A

It binds to - and increases the activity of - anti-thrombin. As a result, thrombin (IIa) and factor Xa.

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7
Q

What is the pharmacokinetics of unfractionated heparin?

A
  • Must be given parentally (iv, sc) as its negative charge does not allow for GI absorption.
  • Rapid Onset and Offset of Action due to its short half-life (<60min) and reticulo-endothelial uptake.
  • Has variable bio-availability due to its unpredictable binding to cells and plasma proteins - Such as platelets and albumin.
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8
Q

Why is an APTT performed on patients receiving unfractionated heparin? What is the therapeutic range?

A

An APTT test needs to be performed because heparin has variable bio-avaliablity as it binds to platelets and albumin. The therapeutic range is between 50 - 80 seconds which is twice that of the normal adult reference range of 25 - 37 seconds.

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9
Q

Describe heparin infusion…

A

The loading dose is given as an IV bolus at 60units/kg - with a maximum loading dose of 500 units. This loading dose is given over the space of five minutes.

The maintenance dose is given at 12 units/kg/hour - with a maximum of 1000 units per hour.

Need to titrate heparin dose using APTT testing six hours after starting the infusion.

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10
Q

Heparin Infusion Guide…

A
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11
Q

Why is unfractionated heparin barely used?

A

It is…

  • Difficult.
  • Complicated.
  • Time Consuming.
  • Blood Tests are +ve for it.
  • Requires APTT control.
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12
Q

What are the adverse effects of heparin?

A

Bruising/Bleeding

  • Intracranial
  • Injection Sites
  • GI bleeding
  • Epistaxis

Thrombocytopenia

  • Check platelets every 2 days
  • Autoimmune Phenomenon
  • Serious Thrombosis

Osteoporosis

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13
Q

How do you reverse the effects of heparin?

A
  1. Stop Heparin.
  2. If actively bleeding, give Protamine.
  3. Monitor APTT if UF Heparin
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14
Q

How does protamine sulphate work?

A

It acts by dissociating heparin from anti-thrombin III. This binding is irreversible but has little effect on LMWH.

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15
Q

What are LMWHs?

A

Smaller chains of heparin that bind to Anti-thrombin III. It does not inactivate thrombin (IIa) but instead is specific to inhibition of Xa. Unlike UF Heparin, LMWHs have a reliable dose-effect relationship and therefore no monitoring is required.

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16
Q

What are the advantages of LMWHs?

A

They are better absorbed and have a higher bioavailability. They do not bind to plasma proteins and platelets and therefore have a longer half-life, have a more predictable dose-response and don’t require any monitoring.

Can also be given s.c., have lower risks of thrombocytopenia and bleeding and are safe to use during pregnancy.

17
Q

What are the “pro’s” of using LMWHs instead of UF Heparin?

A
  • Improved PK, especially if given via the sc route.
  • Does not require monitoring.
  • Less thrombocytopenia.
  • Less osteoporosis.
18
Q

What are the “con’s” of using LMWHs instead of UF Heparin?

A
  • Cannot be monitored by APTT.
  • Not fully reversed by protamine.
  • Can accumulate with renal failure.
19
Q

How is enoxaparin (an LMWH) administered?

A

Subcutaneous Administration

  • Prophylaxis: 20 - 40mg od sc
  • Treatment: 1mg/kg bd sc
20
Q

How is a PE/DVT treated?

A
  1. Initially LMWH - Subcutaneous Injection
  2. Give Warfarin
  3. Continue LMWH for 5 - 7 days until INR is therapeutic

Oral LMWH can be used for doses that do not need to be immediate e.g. maintenance doses.

21
Q

What are the mechanisms of Warfarin action?

A

Warfarin acts by antagonising Vitamin K. As vitamin K is required to for clotting factors VII, IX, X and II warfarin inhibits their synthesis.

22
Q

Why does warfarin have a slow onset?

A

Slow onset as clotting factors lasts for seven days in the bodies circulation. As a result, need to wait for the already formed clotting factors to degrade before a response is witnessed.

23
Q

What are the uses of warfarin?

A

Warfarin is used in the treatment of venous and arterial thrombosis such as DVT/PE and Mural Thrombus. It is also used in the prevention of venous and arterial thromboembolism such as in individuals with mechanical heart valves or suffers of AF.

24
Q

Does warfarin break down clots?

A

No it does not. It instead acts by preventing the worsening of blood clot and allows endogenous proteases to break down the clot.

25
Q

How long does someone need to be put on warfarin for?

A
  • Treatment is 3-6 months for DVT and 6 months for PE.
  • Lifelong if >1 episode.
  • Lifelong if the individual has AF/Mechanical Heart Valves.
26
Q

Can warfarin be used in cancer sufferers?

A

Cancers are thrombogenic and therefore resistant to warfarin. As a result, the individual must be put on LMWHs.

27
Q

How is warfarin metabolised?

A

It is administered orally and about 99% is bound to plasma proteins. It is able to cross the placenta and therefore is bad in pregnant women.

Once absorbed, it is metabolised in the liver by cytochrome P450. This metabolisation occurs via oxidation, glucuronidation and enterohepatic cycling. These combine to give it a half-life of 36 hours and are the reason for its large number of drug interactions.

28
Q

What are the unwanted effects of warfarin?

A
  • Intracranial or Haemorrhage - Usually in patients who are elderly, have a high INR target, have cerebrovascular disease, have previous GI ulcers, have liver/renal disease or have raised BP or malignancy.
  • Teratogenic - First trimester leads to bone and CNS problems, osteodysplasia, optic atrophy or microcephaly. Last 4 weeks cause to intracranial haemorrhage.
29
Q

What is the INR?

A

This is the patients PT/ the mean normal PT

Titrate the warfarin dose to this INR and make sure to measure it 2-3 times weekly initially. Those on long-term warfarin can have an INR measurement every week-fortnight-month.

30
Q

What is the therapeutic range of the INR for warfarin?

A
  • Venous Thrombosis: 2 - 3
  • Mechanical Prosthetic Valves: 3 - 4.5
31
Q

What drugs potentiate Warfarin?

A
  • Alcohol
  • Amiodarone
  • Antibiotics - Erythromycin, metronidazole, ciprofloxacin, tetracycline.
  • Anticonvulsants - Sodium Valproate
  • Anti-Fungals
  • Antacids
  • Anti-Lipid Agents - Simvastatin
  • Analgesics - Paracetamol and NSAIDs
  • Allopurinol
32
Q

What are the risks of intracranial haemorrhage when using warfarin?

A
33
Q

What drugs inhibit the effects of Warfarin?

A
  • Alcohol
  • Azathioprine
  • Barbiturates
  • Carbamazepine
  • Contraceptives
  • Griseofulvin
  • Rifampicin
34
Q

How is an increased INR managed?

A

Life-Threatening Bleeding

  1. Stop Warfarin, give FFP and blood.
  2. IV Vitamin K = i - 10 mg
  3. Oral Vitamin K
  4. IV Beriplex - Pro-thrombin complex concentrate containing factors II, IX, X and VII.

Non-Life-Threatening Bleeding

Withold Warfarin, recheck INR and lower dosage.

35
Q

What are pentasaccharides?

A

These promote antithrombin and factor Xa complex. They are given to individuals with heparin-induced thrombocytopenia.

36
Q

What is dabigatran?

A

This is an anticoagulant that acts by irreversibly binding to - and competitively inhibiting - thrombin (IIa).

37
Q

What are some of the specifics of the dabigatran drug?

A

It is not cytochrome p450 dependent and has a half-life of 12 - 14 hours after multiples doses. This half-life increases in individuals with renal failure (eGFR < 30 ml/hour) and therefore should be avoided in renal failure patients.

38
Q

What is dabigatran used for in NZ?

A
  • Atrial Fibrillation at 150 mg bd
  • VTE (prevention and treatment)

Do not use dabigatran for mechanical valves.

39
Q

How do you manage the bleeding of an individual on dabigatran?

A

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