Anticoagulant drugs Flashcards Preview

Regulation of Body Function > Anticoagulant drugs > Flashcards

Flashcards in Anticoagulant drugs Deck (33):
1

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

Coronary artery disease
Cerebrovascular disease
Peripheral vascular disease

2

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

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

3

What is virchows triad?

hyper coagulability, endothelial damage, stasis

4

Heparin, uses

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

5

Heparin molecules - describe

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

6

Unfractionated heparin
- what
- MoA
- Monitoring?

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)

7

UH - pharmacokinetics

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

8

Unfractionated heparin, what is the therapeutic range measured on APTT

Adult reference range 25-37sec
Therapeutic range 50-80sec

9

Unfractionated heparin
- loading dose
- maintenance infusion

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

10

Disadvantages of unfractionated heparin therapy

difficult
complicated
time consuming
blood tests
variable APTT control

11

Adverse effects of unfactionated heparin use

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

12

Reversal of UF heparin therapy

- Stop heparin
- If actively bleeding give protamine
- Monitor APTT if unfractionated heparin

13

Protamine sulphate?

- dissociates heparin from antithrombin III
- Irreversible binding to heparin
- Little effect on LMWH

14

About LMWH

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

15

LMWH - advantages

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

16

LMWH vs unfracitonated heparin
pros and cons

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

LMWH admin

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

18

treatment for PE/DVT

- initially LMWH
- Give warfarin
- Continue LMWH for 5-7 days until INR therapeutic

19

Warfarin MoA

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

Uses of warfarin

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

Risk stratification for warfarin treatment

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

22

Warfarin admin and metabolism

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

Warfarin GI absorption

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

Warfarin unwarranted effects

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

25

Relative contraindications to warfarin therapy

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

INR?

Patients PT in secs / Mean normal PT in secs

27

Individual variation in warfarin metabolism caused by

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

28

Examples of drugs potentiating warfarin

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

29

Drugs inhibiting warfarin

Azathioprine
Barbiturates
Carbamezapine

30

Management of Increased INR

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

Hirudin

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

32

Dabigatran

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

33

Idracuzimab

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