Anticoagulant drug classes
warfarin unfactionated heparin low molecular weight heparin selective factor Xa inhibitors direction thrombin inhibitors
intrinsic and extrinsic pathway meet at
activation of factor X
Vitamin K is needed for synthesis of which coagulation factors
Factors II, VII, IX, X
Protein C and S (natural anticoag)
Warfarin mechanism of action
Vitamin K antagonist:
acts on the carboxylation pathway by inhibiting the regeneration of active vitamin K.
- epoxide reductase enzyme complex
warfarin uses
prevents further extension of formed clots
prevents secondary thromboembolic complications
- no direct effect on established thrombus
- no reversal of ischemic tissue damage
warfarin onset
24 hours
warfarin peak
72-96 hours
warfarin duration of single dose
2-5 days
Warfarin drug effects parallel half life of factors and proteins
Factor II: 60 hrs VII: 4-6 hours IX: 24 hours X: 48 hours Protein C: 8 hours Protein S: 30 hours
Warfarin pharmacokinetics
mixture of R- and S- enantiomers (mirror images)
S: 2-5x anticoag activity
- - metabolized by CYP2C9: dec. warfarin clearance
R: metabolized by CYP pathways: longer half-life
99% albumin bound (low albumin -> inc. free drug)
drugs that enhance warfarin’s anticoag effect
- chloral hydrate: displace warfarin from albumin
- amiodarone, clopidogrel, “-zole”: dec. warfarin metabolisms by inhibiting P450 enzymes
- broad- spectrum abx: dec. gut bacteria-> dec. availability of Vitamin K in GI tract
- anabolic steroids: inhibit synthesis and inc. degradation of coag factors.
Drugs that dec. warfarin’s anticoag effect
- cholestyramine: inhibits warfarin absorption in GI
- barbiturates, carbamazepine, phenytoin, rifampin: accelerate warfarin metabolism by inducing P450 enzymes
- vitamin K (reduced): bypasses warfarin’s inhibition of epoxide reductase
food interactions with warfarin
vitamin K-rich:
- green, leafy veggies
- beef or pork liver
- many fruits, veggies, legumes
Warfarin AE
bleeding
- severe hemorrhage: administer FFP which contains coag factors
- vit. K
Skin necrosis
- microvascular thrombosis via inhibition of C and S
- bridge with heparin
Purple toe syndrome
- breakage of small cholesterol deposits into feet
Osteoporosis
- dec. dietary intake of vit K. / inhibition of vit. K
Warfarin use
completion of anticoag initiated with heparin
prevention of thrombus
Warfarin monitoring
goal INR: 2-3.5
Narrow TI
drug interactions
toxicity risk
warfarin reversal agents
Vitamin K
prothrombin complex
recombinant factor VIIa
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module 1 pharmacodynamics and pharmacokinetics46
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Module 1 ADME20
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Module 1 ADME (ME)14
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module 1 pharmacokinetics24
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Module 1 special populations17
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module 1 synch16
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Module 17 preg categories, drug scheduling14
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module 17 drug regulation and monitoring18
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module 6 autonomics45
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module 6 adrenoreceptor antagonist13
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module 6 cholinergic agonists24
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week 2 synch7
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Module 7 hypertensives29
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module 7 beta blockers23
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module 7 adrenergic agonists14
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module 7 ACE inhibitors, angiotensin receptor blockers, renin inhibitors14
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module 7 calcium channel blockers12
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module 7 vasodilators and digoxin21
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synch session modules 7 and 1021
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module 10 lipid lowering meds30
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module 8 antiarrhythmics class 120
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module 8 antiarrhythmics class 2 and 322
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module 8 antiarrhythmic class 417
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module 9 antiplatelet meds23
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module 9 warfarin17
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module 9 anticoagulants24
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Module 9 thrombolytics and reversal agents10
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Module 2 immunology and eicosanoids25
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module 2 antihistamines18
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Module 2 anti-asthmatic drugs27
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module 2 anti-inflammatory asthma agents17
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module 2 management of asthma12
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Module 2 gout34
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Module 5 tobacco, alcohol, benzo34
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module 5 stimulant abuse11
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module 5 opiates and heroin27
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module 4 non-opioid alagesics21
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module 4 NSAIDS15
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module 4 opioid characteristics15
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module 4 opioid agents35
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module 4 opioid tolerance and dependence14
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module 4 adjuvant analgesics8
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module 4 anti-rheumatic drugs34
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modules 2,4,5 synch session15
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module 3 antidepressants and neurotransmitters15
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module 3 MAOI, SSRI, TCA19
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module 3 SNRI, atypical antiD, serotonin receptor agonist35
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Module 3 anti-migraine21
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module 3 antiemetics19
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module 3 seizure31
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module 3 anticonvulsants42
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Module 3 anti-parkinson24
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module 3 antipsychotics24
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module 3 atypical antipsychotic20
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module 3 sedatives and hypnotics27
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module 3 anti-alzheimer's drugs16
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Module 13 agents affecting GI motility25
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module 13 Upper GI tract, PUD, GERD14
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module 13 PUD and GERD meds26
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module 13 GERD meds 216
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module 16 DM overview33
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module 16 biguanides and TZD13
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module 16 non-insulin meds21
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module 16 non-insulin meds 217
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module 16 hyperglycemia management and CV impact16
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module 16 inhaled insulin5
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module 16 hyperthyroid meds15
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module 16 hypothyroid meds14
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module 16 weight management17
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module 16 wt management 219
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module 16 osteoporosis overview14
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module 16 antiresorptive agents, bone anabolic agents33
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module 16 phosphate binders, Ca, Vit. D27
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module 14 gonadal hormone inhibitors28
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module 14 uterotonics11
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module 14 birth control15
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module 14 HRT estrogen16
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module 14 HRT androgen and phosphodiesterase 5 inhibitors13
