24 - Warfarin Flashcards
Warfarin
LAB MONITORING
Baseline:
- *INR / risks of beeding**
- *BMP** (renal fxn)
- *CBC**
LFT @ baseline & every 12 months
Warfarin Drug-Disease State Interactions:
TUBE FEEDINGS
TUBE FEEDINGS
changes in absorption or vit K content
↓Warfarin sensitivity
Frequency of INR Monitoring for:
Dose held today in patient with significant supratherapeutic INR
Check INR within:
1 - 2 Days
Warfarin Dose Adjustment
Reading after >7 days of continuous dosing
INR 4.1 - 5
4.1 - 5
HOLD up to 2 Daily Doses
&
↓Weekly dose by 10-20%
Warfarin Dose Adjustment
Reading after >7 days of continuous dosing
INR 3.1 - 4
3.1 - 4
HOLD 1 daily dose
&
↓Weekly dose by 5-20%
MANAGEMENT OF HIGH INRS & BLEEDING
INR 4.5 - 10
w/o bleeding
Monitor INR / CBC / Bleeding
no Vit K treatment
Warfarin Contrainidcations
Pregnancy
first 3 months
Active major Bleeding
Unsupervised patients with:
Senility / Alcoholism / Psychosis / lack of cooperation
Malignant Hypertension
Lumbar Block Anesthesia
Frequency of INR Monitoring for:
Routine follow-up of medically for stable patients
Check INR within:
4 - 6 Weeks
Warfarin Drug-Disease State Interactions:
RENAL DISEASE
RENAL DISEASE
↓CYP2C9 Activity
↓Warfarin Dose Requirement
Warfarin Drug-Disease State Interactions
- *Conditions that**
- *↓warfarin sensitivity** –> require ↑Warfarin Dose
- *↓INR**
- *Chronic Alcoholism**
- *↑**warfarin metabolism –> ↑warfarin dose
- *Tube Feedings**
- *↓**warfarin sensitivity, changes in absorption / vit K content
- *HypoThyroidism**
- *↓catabolism of clotting factors –> ↑warfarin dose**
Smoking & Chewing Tobacco
induce CYP1A2 –> ↑warfarin dose
Warfarin Drug-Disease State Interactions:
LIVER DISEASE
LIVER DISEASE
↓clotting factors & ↓warfarin clearance
↑INR
Frequency of INR Monitoring for:
Routine follow-up of medically unstable or unreliable patients
Check INR within:
1 -2 Weeks
Warfarin Drug-Disease State Interactions:
HYPERThyroidism
HYPERThyroidism
↑catabolism of clotting factors
↑Warfarin Sensitivity
Warfarin Drug-Disease State Interactions:
HEART FAILURE
HEART FAILURE
hepatic congestion -> ↓warfarin metabolism
Warfarin Dose Adjustment
Reading after >7 days of continuous dosing
INR 1.5-1.9
1.5 - 1.9
may give extra daily dose
&
↑Weekly dose by 5-15%
Warfarin Drug-Disease State Interactions:
ACUTE ALCOHOL INGESTION
ACUTE ALCOHOL INGESTION
inhibits warfarin metabolism
↑INR
Warfarin
Side Effects
- *Fetal Hemorrhage_ & _Teratogenesis**
- do NOT use in pregnant,* can be used postpartum okay lactation
WARFARIN INDUCED SKIN NECROSIS
Protein C & Protein S deficiency
within 1-10 days of start
Purple Toe Syndrome
develops 3-8 weeks after start
Warfarin Dose Adjustment
Reading after >7 days of continuous dosing
INR <1.5
<1.5
Give extra daily dose times 1
&
↑Weekly dose by 10-20%
When to use a
SMALLER INITIAL DOSE(<5mg)
for Warfarin
Increased Sensitivity to Warfarin
Older Adult / ↓Body Weight
CHF / Liver Disease / ESRD
Surgery / Diarrhea / Albumin <3
Malnourish / NPO
↑INR Meds
CYP2C9 or VKORC1 Varients
Frequency of INR Monitoring for:
STABLE w/ current dose for 2 weeks ago
Check INR within:
2 - 4 Weeks
Frequency of INR Monitoring for:
Dose Change Today
Check INR within:
1 - 2 Weeks
Dose change today
MAJOR DRUG INTERACTIONS of WARFARIN:
↑ risk of bleeding = ↑ INR
BACTRIM** & **AMIODARONE
↓ warfarin dose by 50% & ↓ warfarin dose by 35-65%
Commonly Antibiotics = inhibit warfarin clearance = ↑ INR
Metronidazole** / **Quinolones** / **Antifungals** / **Erythromycin
STATINS** / **STEROIDS
Cimetidine / Omeprazole
Aspirin / NSAIDs
3G DIETARY SUPPLEMENTS
Garlic / Ginseng / Ginger
Warfarin Drug-Disease State Interactions
Conditions that
↑warfarin sensitivity –> require ↓Warfarin Dose
↑INR
- *Advanced Age**
- *↓**vitamin K stores or ↓vit K clotting factors
- *ACUTE Alcoholism**
- inhibits warfarin metabolism* –> ↑INR
- *Liver Disease**
- *↓vit K clotting factors & ↓warfarin clearance –> ↑INR**
- *Renal Disease**
- *↓CYP2C9** activity
Heart Failure
hepatic congestion –> ↓warfarin metabolism
Cardiac Valve Replacement
↑warfarin sensitivity
HYPERthyroidism
↑catabolism of clotting factors –> ↑warfarin sensitivity
FEVER / DIARRHEA / ACUTE INFECTION / MALIGNANCY
Warfarin Drug-Disease State Interactions:
HypoThyroidism
HypoThyroidism
↓catabolism of clotting factors
↑Warfarin Dose
Warfarin Drug-Disease State Interactions:
SMOKING & TOBACCO
SMOKING & TOBACCO
Smoking : ↑CYP1A2
Chewing tobacco: Contains VIT K
↑Warfarin Requirements
MANAGEMENT OF HIGH INRS & BLEEDING
INR >10
w/o bleeding
Give ORAL Vit K
MANAGEMENT OF HIGH INRS & BLEEDING
Any INR
MAJOR BLEEDING
Rapid Reversal of AC w/ 4-factor Prothrombin
AND
Vitamin K** **5-10mg
slow IV injection
Warfarin Drug-Disease State Interactions:
CHRONIC ALCOHOLISM
CHRONIC ALCOHOLISM
↑Warfarin Metabolism
↑Warfarin DOSE
Target INR
Almost Always:
2-3
Except for:
Mitral / Aortic Valve Replacement
- *2.5-3.5
(3) **
Warfarin Drug-Disease State Interactions:
FEVER** or **DIARRHEA
FEVER** or **DIARRHEA
↑INR
Diarrhea = reduction in VITK secretion by GUT flora
Fever = Increased catabolism of clotting factors
Warfarin
PK
Peak effect = 3-5 Days
depends on half life & time to deplete clotting factors
Factor 2 = longest half life
- *S**(trong) Enantiomer = 2.7-3.8x more potent
- *CYP2C9** > 3A4
- 2C9 has a HIGHER impact on INR due to S being more potent*
- *R-Enantiomer**
- *1A2 > 3A4 > 2C19**
Warfarin Drug-Disease State Interactions:
Acute Infection** or **Malignancy
Acute Infection** or **Malignancy
↑Warfarin Sensitivity
Warfarin Drug-Disease State Interactions:
CARDIAC VALVE REPLACEMENT
CARDIAC VALVE REPLACEMENT
↑Warfarin Sensitivity
due to
HypoAlbuminemia & reduced oral intake
Warfarin
MoA
SNOT - C+S
Interferes with conversion of:
Vitamin K Epoxide
Inhibits activation of:
Seven Nine 1O Two
Inhibits:
- *Protein C** + S
- natural inhibitors of coagulation cascade*
MAJOR DRUG INTERACTIONS of WARFARIN:
↓ anticoagulant effectiveness = ↓ INR
- *RIFAMPIN**
- may require a HIGER dose of warfarin*
Barbiturates
Cholestyramine
Carbamazepine
ST. JOHNS WORT = CYP450 inducer
↑ warfarin metabolism –> ↓ anticoagulant effectiveness = ↓ INR