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Regulation of Body Function > Anticoagulant drugs > Flashcards

Anticoagulant drugs Flashcards

1
Q

What are the types of disease that you’d use anti-platelets and anticoagulants for?

A

Coronary artery disease
Cerebrovascular disease
Peripheral vascular disease

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2
Q

What are the types of thromboembolic diseases that you’d just use anticoagulants for?

A

Atrial fibrillation
Venous thrombi-embolism (DVT, PE)
Prosthetic cardiac valves (metal)

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3
Q

What is virchows triad?

A

hyper coagulability, endothelial damage, stasis

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4
Q

Heparin, uses

A 
Acute coronary syndromes 
Thromboembolism (prophylaxis and treatment) 
Venous: DVT and PE 
Arterial AF 
Warfarin replacement - pregnancy
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5
Q

Heparin molecules - describe

A 
linear mucopolysaccharide chains 
MW very variable: 3000 - 40000 
Unfracitionated heparin (IV, continuous infusion)
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6
Q

Unfractionated heparin

  • what
  • MoA
  • Monitoring?
A 
Mix of variable length heparin chains 
- pig intestine mucosa and bovine lung 
MoA 
- binds to and increases activity of anti thrombin III 
antithrombin III inactivates 
- thrombin (IIa) and factor Xa 
- and also IXa, XIa, XIIa 
requires APTT monitoring (blood test)
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7
Q

UH - pharmacokinetics

A 
Must be given parentally (IV, SC) 
- negative charge, no GI absorption 
Rapid onset and offset of action 
- Short half life (<60min)
- Reticuloendothelial uptake 
Variable bioavailability due to unpredictable binding to cells and plasma proteins 
- platelets (heparin neutralising protein); endothelial cells 
- Albumin 
- Needs monitoring with APTT
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8
Q

Unfractionated heparin, what is the therapeutic range measured on APTT

A

Adult reference range 25-37sec

Therapeutic range 50-80sec

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9
Q

Unfractionated heparin

  • loading dose
  • maintenance infusion
A 
LD: 
- 60 units/kg (max 5000units) 
- give bolus dose iV 
- over 5 mins 
MD 
- Heparin solution 100units/ml, 25000units in 250ml saline k

commence at 12 units / kg/ hr max
titrate heparin dose appropriately vs APTT

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10
Q

Disadvantages of unfractionated heparin therapy

A 
difficult 
complicated 
time consuming 
blood tests 
variable APTT control
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11
Q

Adverse effects of unfactionated heparin use

A

brusing/ bleeding

  • intracranial
  • Injection site
  • GI loss
  • Epistaxis

Thrombocytopenia (HIT)

  • check platelets every 2 days
  • Autoimmune phenomenon (usually 1-2 weeks of Rx)
  • May bleed or get serious thromboses
  • Lab assay for these antibodies
  • Stop heparin

Osteoporosis with long term use

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12
Q

Reversal of UF heparin therapy

A
  • Stop heparin
  • If actively bleeding give protamine
  • Monitor APTT if unfractionated heparin
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13
Q

Protamine sulphate?

A
  • dissociates heparin from antithrombin III
  • Irreversible binding to heparin
  • Little effect on LMWH
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14
Q

About LMWH

A

Much more predictable in MOA and bioavailability
Smaller chains usually 4-5 Kdaltons
- generated by chemical or enzymatic depolymerisation of unfractionated heparin
Like UH have unique sequence to bind to antithrombin III
- Doesn’t inactivate thrombin IIa
- Affects factor Xa specifically
Reliable dose effect relationship
No monitoring required can measure factor Xa activity

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15
Q

LMWH - advantages

A

Better absorbed - higher bioavailability
Doesn’t bind to plasma proteins, macrophages or endothelial cells
- Loger biological half life
- More predictable dose response
- No monitoring required
Can be given Sc in an outpatient setting (teach patient how to give the dose themselves)
Lower risk of thrombocytopenia and bleeding
Safety and use during pregnancy not evaluated

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16
Q

LMWH vs unfracitonated heparin

pros and cons

A 
pros 
- improved Pk especially SC route 
- monitoring not usually required 
- less thrombocytopenia 
- less osteoporosis 
Cons 
- Cannot be monitored by APTT 
- not fully reversed by protamine 
- care in renal failure (UF was cleared by the reticular endothelial system, LMWH cleared by the kidneys)
17
Q

LMWH admin

A

Subcutaneous admin (OD/BD)
- Enoxiparin
Prophylaxis: 20-40mg od sc
Treatment 1mg/kg bd sc (reduce of low GFR)

18
Q

treatment for PE/DVT

A
  • initially LMWH
  • Give warfarin
  • Continue LMWH for 5-7 days until INR therapeutic
19
Q

Warfarin MoA

A

Vit K required by the liver to synthesise various clotting factors
slow onset of anticoagulant action, as half life of coat factors: VII, IX, X and II is a few days, therefore cant be used for immediate DVT/ PE treatment
Specifically prevents the osculation between oxidised and reduced vitamin K

20
Q

Uses of warfarin

A

Treatment of venous or arterial thrombosis
- DVT/PE
- Mural thrombus (post anterior MI) reduce risk of embolisation
Prevention of venous or arterial thromboembolisaiton
- mechanical heart valves
- AF (risk of systemic emboli)

21
Q

Risk stratification for warfarin treatment

A

Treatment is 3-6 months for DVT, 6 months for PE
Lifelong if > 1 episode
lifelong - mechanical valves/ AF

22
Q

Warfarin admin and metabolism

A

oral admin, OD, 99% bound to plasma protein
Completely absorbed - crosses placenta
Metabolised by the liver cytochrome P450, so lots of drug interactions
- oxidation
- Glucuronidaiton
- Enteroheptic cycling
t1/2 = 36 hours

23
Q

Warfarin GI absorption

A 
Oral preparation 
High bio availability taken orally 
Rapid absorption 
Pharmacological activity takes days 
- Long effective half life 
- Awaiting degradation of active factors 
Factor II t1/2 = 60 hours
24
Q

Warfarin unwarranted effects

A 
Haemorrhage (e.g. in older age groups, people with cerebrovascular disease) 
- intracranial 
- GI 
Teratogenic 
- First trimester (very bad for babe)
25
Q

Relative contraindications to warfarin therapy

A 
Pregnancy 
Situations where the risk of haemorrhage is greater than the potential clinical benefits of therapy 
- Uncontrolled alcohol/ drug abuse 
- Unsupervised dementia / psychosis 
- Falls 
- poor concordance / insight
26
Q

INR?

A

Patients PT in secs / Mean normal PT in secs

27
Q

Individual variation in warfarin metabolism caused by

A 
Absorption: 
- Diarrhea / vomiting 
metabolism 
- Liver disease 
Nutrition / dietary (vit K) 
Co exisiting illness
28
Q

Examples of drugs potentiating warfarin

A

Amiodarone
Antibiotics e.g. erythromycin
Anti- fungals e.g. fluconazole

29
Q

Drugs inhibiting warfarin

A

Azathioprine
Barbiturates
Carbamezapine

30
Q

Management of Increased INR

A

life threatening bleeding: stop warfarin, give FFP and blood
IV and vit K 1-10mg, vit K has long action on reducing warfarin effect but slow onset
Oral vit K
IV beriplex
- prothrombin complex concentrate
- Contains factor II, VII, IX, X protein C

For less lie threatening cases, withhold warfarin re check INR, lower dosage

31
Q

Hirudin

A

Derived from leech
Thrombin inhibitor
Antithrombin II indépendant
Little effect on platelets

32
Q

Dabigatran

A 
(dabigatran etexilate) 
- prodrug 
- capsule with tartaric acid 
- Gut, plasma, liver esterases 
Competitive reversible inhibitor
33
Q

Idracuzimab

A

intravenous monoclonal antibody
for atrial fibrillation
VTE prevention and treatment
cant use for mechanical valves

Regulation of Body Function (31 decks)

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