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RBF: 1) Drugs > Lecture 7 - Anticoagulant drugs > Flashcards

Lecture 7 - Anticoagulant drugs Flashcards

1
Q

List anti-coagulant drugs?

A
  1. Un-Fractionated Heparin (UH).
  2. Low-Molecular-Weight Heparin (LMW).
  3. Warfarin.
  4. Dabigatran.
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2
Q

List anti-platelet drugs?

A
  1. Aspirin.
  2. Clopidogrel.
  3. Dipyridamole.
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3
Q

List the arterial diseases that anti-coagulants are used for?

A
  1. Coronary artery disease.
  2. Cerebrovascular disease.
  3. Vascular disease.

P.S. Use anti-platelets as well.

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4
Q

List the thrombo-embolic diseases that anti-coagulants are used for?

A
  1. Atrial fibrillation.
  2. Venous thrombo-embolism (DVT, PE).
  3. Prosthetic cardiac valves.
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5
Q

What is the mechanism of action for UH?

A

It binds to anti-thrombin III (3) and increases its activity - AT III inactivates thrombin and factor Xa (as well as IXa, XIa and XIIa).

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6
Q

How do you give UH?

A

Intravenously as a bolus. Because it is long chained it can’t be given orally as it cannot be absorbed (won’t pass through mucosal membranes).

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7
Q

Is UH short chained or long chained?

A

UH is long chained, whereas LMWH is short chained.

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8
Q

What type of monitoring does UH require?

A

UH requries APTT (activated partial thrombin testing time) monitoring - so a person on UH needs to have their blood tests done regularly.

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9
Q

What is the UH therapeutic range (APTT)?

A

APTT = 50-80 seconds.

APTT increases with UH.

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10
Q

What is the loading dose formula for UH?

A

60 units per kg (max is 5000 units).

e.g 60 units x 70 kg = 4200 units loading dose given intravenously.

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11
Q

What is the maintenance infusion for UH?

A

12 units per kg per hour (max 1000units per hour).
It is in a heparin solution of 100 units/ml (e.g. 25000 units in 250ml saline).

e.g. 12 units x 70 kg x 1 hour = 840 units per hour.
840 units/ml = 8.4ml per hour.

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12
Q

What do you have to do after 4 hours of infusing UH?

A

You need to measure the patients APTT.

APTT needs to be at the therapeutic range - 50-80seconds.

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13
Q

What happens if after 4 hours of UH, patients APTT is <50seconds?

A

Essentially the coagulation cascade is over working and a person is producing too many clotting factors (so the drug - UH - is not working properly). You need to increase the rate at which UH is given (e.g. increase ml per hour) and increase the dose of UH.

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14
Q

What happens if after 4 hours of UH, patients APTT is >80 seconds?

A

Essentially the coagulation cascade is under working and a person is bleeding out (the drug - UH - is over anti-coagulating/working too well/much) . You need to decrease the rate at which UH is given and decrease the dose.

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15
Q

What is special about UH?

A

Because it has fast onset it can be used in emergency situations, also because it can be terminated rapidly it can be used for those who are at high risk of bleeding.
UH can also be given to pregnant women who are at risk of clotting.

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16
Q

What is UH used for?

A
  1. Acute coronary syndromes.

2. Initial treatment of DVT and PE.

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17
Q

Why should a patient not take UH?

A

A patient shouldn’t take UH if they have the following:

  1. Haemophilia.
  2. Thrombocytopenia (as there is a decrease in platelets).
  3. Recent cerebral haemorrhage.
  4. Hypertension.
  5. Peptic ulcer.
  6. Acute endocarditis.
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18
Q

What are the adverse effects of UH?

A
  1. Haemorrhage.
  2. Thrombocytopenia - especially HIT.
  3. Hyperkalaemia.
  4. Osteoporosis.
  5. Skin necrosis.
  6. Injection site reactions.
  7. Hypersensitivity reactions.
  8. Bruising/bleeding.
  9. Nose bleeds.
  10. GI blood loss.
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19
Q

What do you do if a patient (who takes UH) gets thrombocytopenia?

A

You need to check their platelets every 2 days, lab assay for the antibodies and stop heparin.

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20
Q

How do you reverse UH therapy?

A
  1. Stop heparin.
  2. If the pt is actively bleeding, give them protamine (it dissociates heparin from ATIII).
  3. Monitor APTT (should see a decrease in APTT).
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21
Q

What is the mechanism of action for low molecular weight heparin (LMWH)?

A

It inhibits factor Xa.

22
Q

How do you give LMWH?

A

You give it subcutaneously.

23
Q

Why is LMWH preferred over UH?

A

It is preferred because of the following:

  1. Does not bind to plasma proteins, macrophages, or endothelial cells.
  2. No monitoring is required.
  3. Patient can give it to themselves at home, no hospital required.
  4. Lower risks of thrombocytopenia and bleeding.
  5. Better absorbed.
24
Q

Is LMWH short chained or long chained?

A

Short chained.

25
Q

What is the dosage of LMWH?

A

1mg per kg x 2 (twice daily)

e.g. 1mg x 70kg = 70mg twice daily.

26
Q

What is LMWH used for?

A
  1. Prophylaxis of DVT.
  2. Treatment of DVT.
  3. Treatment of PE.
  4. Unstable angina.
  5. NSTEMI.
  6. STEMI.
  7. AF.
27
Q

Why should a patient not take LMWH?

A

A patient shouldn’t take LMWH if they have the following:

  1. Haemophilia.
  2. Thrombocytopenia.
  3. Cerebral haemorrhage.
  4. Hypertension.
  5. Peptic ulcer.
  6. Bacterial endocarditis.
  7. Elderly.
  8. Low body weight (caution).
  9. Renal impairment (GFR < 30).
28
Q

What are the adverse effects of LMWH?

A
  1. Haemorrhage.
  2. Thrombocytopenia.
  3. Hyperkalaemia (this is due to LMWH inhibiting aldosterone secretion).
  4. Osteoporosis (not as much as UH).
  5. Skin necrosis.
  6. Injection site reactions.
  7. Hypersensitivity reactions.
29
Q

What are the LMWH drugs?

A
  1. Enoxaparin.
  2. Tinzaparin.
  3. Dalteparin.
30
Q

What is the mechanism of action of warfarin?

A

It is a vitamin k antagonist that stops the recarboxylation of factors VII, IX, X, thrombin, protein C and protein S.

31
Q

What do you use warfarin for?

A
  1. Prevention and treatment of VT and PE.
  2. Prevention of stroke following MI and AF.
  3. Mechanical heart valve.
32
Q

How long do you give warfarin for?

A

It all depends on what the patient has:

  1. DVT = 3-6 months of treatment.
  2. PE = 6 months of treatment.
  3. More than one episode of DVT/PE = lifelong.
  4. Mechanical valves/AF = lifelong.
33
Q

Why should a patient not take warfarin?

A
  1. Hemorrhagic stroke.
  2. Bleeding risk.
  3. Pregnant.
34
Q

Why do you not give pregnant women warfarin?

A

Warfarin crosses the placenta and can be thrombogenic for the fetus - it can increase bleeding in the fetus.

It can cause the following in the fetus in the first trimester:

  1. Bone/CNS problems.
  2. Osteodyplasia.
  3. Optic atropy.
  4. Microcephaly.

It can cause the following in the fetus in the last 4 weeks in pregnancy:
1. Intracerebral haemorrhage.

35
Q

How do you give warfarin?

A

Orally.

36
Q

How do you monitor warfarin?

A

INR = international normalised ration.

INR is done via blood tests.

37
Q

How often do patients on warfarin need monitoring?

A

When a patient is first started on warfarin they require monitoring every single day. Once they’ve been on it for a few weeks, they only need a check once a week. Gradually they become once every month.

38
Q

What is the therapeutic range of INR for a patient on warfarin?

A

INR of 2.0-3.0 = VT/PE treatment.

INR of 3.0-4.5 = Mechanical/prosthetic valve.

39
Q

What are the adverse effects of warfarin?

A
  1. Haemorrhage.
  2. Nausea.
  3. Vomiting.
  4. Diarrhoea.
  5. Jaundice.
  6. Hepatic dysfunction.
  7. Pancreatitis.
  8. Pyrexia (fever).
  9. Skin necrosis.
40
Q

What happens if INR is at 4-6?

A

This means that the patient is at a risk of intracranial haemorrhaging. This means that warfarin is over working.

41
Q

What happens if INR is below 2?

A

This means that the patient is at risk of clotting more so than normal. This means that warfarin is not working.

42
Q

What drugs will increase the anticoagulant effect of warfarin when interacted with it (when you take warfarin and these drugs)?

A

The following drugs are Cytochrome P450 inhibitors, and will increase the INR (>3) and increase the risk of bleeding:

  1. Alcohol.
  2. Amiodarone - anti-anginal and arrhythmic drug.
  3. Anti-biotics e.g. erythromycin, metronidazole, ciprofloxacin, tetracycline.
  4. Anti-fungals e.g fluconazole.
  5. Antacids e.g. cimetidine, omeprazole.
  6. Anti-lipids e.g. simvastatin, fibrates.
  7. Analgesics e.g. NSAIDs, paracetamol.
  8. Allopurinol - used to treat high uric acid.
43
Q

What drugs will decrease the anticoagulant effect of warfarin when interacted with it?

A

The following drugs are Cytochrome P450 inducers, and will decrease the INR (<2) and increase the risk of clotting:

  1. Alcohol.
  2. Azathioprine - immunosuppressive drug.
  3. Barbiturates.
  4. Carbmazepine/phenytoin - drug for epilepsy.
  5. Contraceptives.
  6. Griscofulvin - anti-fungal.
  7. Rifampicin - anti-biotic.
44
Q

How do you treat an increased INR?

A

This patient with an increased INR is at risk of bleeding. This all depends on the severity of the bleeding.

  1. Give the pt IV Vitamin K (1-10mg) - vitamin k has a long action on reducing warfarin effect but slow onset.
  2. IV Prothrombinex - this is a pro-thrombin complex concentrate the contains factor II, VII, IX, X and protein C. It is used for immediate warfarin reversal (minutes).
  3. With less life threatening cases, stop warfarin and recheck INR daily.
45
Q

What is the mechanism of action of dabigatran?

A

It directly inhibits thrombin with a rapid onset of action (pro-drug).

46
Q

How is dabigratan given?

A

Orally.

47
Q

What is dabigatran used for?

A
  1. Prevention of stroke and systemic embolism in AF.
  2. Transient ischaemic attack.
  3. Systemic embolism.
  4. Left ventricular ejection fraction <40% (systolic heart failure).
  5. Heart failure.
  6. Hypertension.
  7. Diabetes.
  8. DVT/PE treatment.
48
Q

Why should a patient not take dabigatran?

A
  1. Active bleeding.
  2. Significant risk of major bleeding.
  3. Severe diarrhoea.
  4. Renal impairment.
  5. Pregnant.
49
Q

What are the adverse risks of dabigatran?

A
  1. Nausea.
  2. Dyspepsia (aka indigestion).
  3. Diarrhoea.
  4. Abdominal pain.
  5. Anaemia.
  6. Haemorrhage.
50
Q

What can you give if someone is bleeding on dabigatran?

A

Idarucizumab - IV bolus.

RBF: 1) Drugs (8 decks)

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