Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

RBF > 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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 (metal) cardiac valves. In these examples, only a anticoagulant needs to be used.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is unfractionated Heparin and when is it used?

A
  • Linear mucopolysaccharide with a high molecular weight of 3000-40000.
  • It also carries a high negative charge and so is unable to cross mucosal membranes
  • therefore has to be given intravenously via constant infusion.

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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
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.
  • APTT must be performed due to this variability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is unfractionated heparin barely used?

A

It is…

  • Difficult.
  • Complicated.
  • Time Consuming.
  • Blood Tests are +ve for it.
  • Requires APTT control.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the adverse effects of heparin?

A

Bruising/Bleeding

  • Intracranial
  • Injection Sites
  • GI bleeding
  • Epistaxis

Thrombocytopenia (HIT - heparin induces thrombocytopenia)

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

Osteoporosis -(don’t use for more than 3/4 days now though)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are LMWHs?

A
  • Smaller chains of heparin generaqted by chemical or enzymatic depolymerisation, that bind to Anti-thrombin III.
  • 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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the advantages of LMWHs?

A
  1. They are better absorbed and have a higher bioavailability.
  2. They do not bind to plasma proteins and platelets and therefore have a longer half-life,
  3. Have a more predictable dose-response and don’t require any monitoring.
  4. Can also be given s.c., have lower risks of thrombocytopenia and bleeding and are safe to use during pregnancy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

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

A
  • Cannot be monitored by APTT (rarely can monitor Xa activity)
  • Not fully reversed by protamine.
  • Can accumulate with renal failure.
  • Are renally excreted, should not be used in cases eGFR <15
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is enoxaparin (an LMWH) administered?

A

Subcutaneous Administration

  • Prophylaxis: 20 - 40mg od sc
  • Treatment: 1mg/kg bd sc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
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.

17
Q

What is, and are the mechanisms of Warfarin action?

A

Warfarin is an oral anticoagulant that acts by antagonising Vitamin K

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

18
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 (CF: II, VII, IX and X)

19
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 (often post anterior MI). It is also used in the prevention of venous and arterial thromboembolism such as in individuals with mechanical heart valves or suffers of AF.

20
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. Your own enzymes break down the clot.

21
Q

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

A
  • Treatment is 3-6 months for transient risk factors causing DVT
  • 6 months for first idiopathic DVT or PE
  • Lifelong if >1 episode
  • Lifelong if the individual has AF/Mechanical Heart Valves
22
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.

23
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.

24
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.
25
Q

What is the INR?

A

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.

26
Q

What is the therapeutic range of the INR for warfarin?

A
  • Venous Thrombosis: 2 - 3
  • Mechanical Prosthetic Valves or recurrent thromboses: 3 - 4.5

Unfortunately as soon as we start to get above 5 we markedly increase the risk of intracranial haemorrhages

27
Q

What drugs potentiate Warfarin?

A

It is those that inhibit the effect of cytochrome P450

  • Alcohol
  • Amiodarone
  • Antibiotics - Erythromycin, metronidazole, ciprofloxacin, tetracycline.
  • Anticonvulsants - Sodium Valproate
  • Anti-Fungals
  • Antacids
  • Anti-Lipid Agents - Simvastatin
  • Analgesics - Paracetamol and NSAIDs
  • Allopurinol
28
Q

What drugs inhibit the effects of Warfarin?

A

These are drugs that induce the action of Cytochrome P450

  • Alcohol
  • Azathioprine
  • Barbiturates
  • Carbamazepine
  • Contraceptives
  • Griseofulvin
  • Rifampicin
29
Q

What are pentasaccharides?

A

These promote antithrombin and factor Xa complex. They are given to individuals with on heparin who develop heparin-induced thrombocytopenia (HIT)

30
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.

31
Q

What is dabigatran?

A

This is a prodrug given orally that acts as an anticoagulant that acts by irreversibly binding to - and competitively inhibiting - thrombin (IIa).

32
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.

Given with tartaric acid in capsule as acid helps absorption, can cause rather painful heartburn in some people

Reversible with idarucizumab (a monoclonal AB)

33
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 - not good in these situation like warfarin is

34
Q

What is Rivaroxaban?

A

A Factor Xa inhibitor that isn’t metabolised by CYP450 but is renally excreted so like dabigatran shouldn’t be used in those with renal impairment.

Has NO ANTIDOTE (other than in some countries they give FXa)

(also does not work for metal heart valves)

35
Q

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

A

RBF (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions