Drugs in the bloodstream Flashcards
What enzyme does warfarin inhibit
Vitamin K epoxide reductase
Warfarin Pharmacokinetic
99%plasma prtein bound
almost entirely metabolised by he liver, metabolites excreted in urine + faeces
Elimiation t1/2 35 to 45 hours
Significant drug interactions- either from being displaced from plasma proteins or liver indction/inhibition
What drugs cause inhibition of warfarin metabolism (and so potentiate effects)/
Cimetidine
ALcohol
Allopurinol
Erythromycin
Ciprofloxacin
Metronidazole
What can displace warfarin from plasma proteins?
NSAIDS
WHat drugs induce enzymes and thus inhibit warfarin action?
Barbituates
rifampacin
CArbamazepine
What does cholestyramine do with warfarin?
INhibits effect as decreased fat soluble lipid absorption
What is INR
the ratio of a patients prothrombin time to a normal control sample
How do you treat high INRs? (INR >8 and RF)
Stop warfarin
Can give FFP (15ml/kg) but does not fully revers
Administer Vit K 5mg- will work within 12 hours and 10mg will saturate stores, preventing re-warfarinisation
Prothrombin complex can be used for complete reversal
Risks of warfarin in pregnancy?
- Crosses the placenta and may cause fetal haemorrhage
- Spont. abortion
- Stillbirth
- Neonatal death
-Teratogenicity (5% incidence of birth defects)
In later pregnancy central nervous system disorders are more prevalent
What is heparin?
Heparin is a glycosaminoglycan, mucopolysaccharide
Organic acid and occurs naturally in the liver and mast cells,
mainly made from porcine intestinal mucosa
molecula weight is 12-15kDa
What is the MOA of heparin
Binds reversibly and potentiates antithrombin 3- plasma serine protease inhibitor.
What does ATIII inhibit
Mainly coag factors 2, 9 and 10 but can also inhibi 12, 11 and plasmin.
Antiplatelet effects also occur through effects on fibrin
Pharmacokinetics of UFH?
Only given SC or IV- negative charge stops oral absorption
Highly plasma protein boung, individual variation leading to differences in efficacy
Low lipid solubility- does not cross BBB or placenta
t1/2 is 30-60 mins
Metabolised by hepatic heparinase
Excreted in the urine
What are lmwh?
Short chain polysaccharides with a predictable anticoag action
Avg weight is <8000kDa
What does LMWH act on
Full anti xa action but less anti 2a action due to shorte chain lengths
Half life of LMWH and why
2-3x longer than unfractionated due to a lower affinity for heparin binding proteins
How can you monitor effect of LMWH
Xa assays
Advantages of LMWH?
ONce daily dosing
no need to monitor aptt
smaller risk of bleeding- less plt interaction
Smaller risk of osteoporosis
Smaller risck of HIT
LEss effect on thrombin
Commonest adverse reactions to heparin ?
Haemorrhage, hyperkalaemia and hypotension if admin. quickly
WHat is HIT
An immune mediated thromboctopenia where heparin is recognised as foreign.
Heparin binds to plt factor 4 stimulating IgG ab formation and predisposition to thrombosis.
Most are asymptomatic.
WHen does the platelet count normally fall in HIT
5-14 days after heparin is started, or quicker if pt has received heparin in the last 3 months
What is danaparoid?
Factor Xa inhibitor, heparinoid. Can be used in HIT. Mixture of heparan, dermatan and condroitin suphatea
Advers effects of danaparoid?
Low platelets due to some structural similarities with heparin, exacerbations of asthma
