24 - Warfarin Flashcards by Karlo Sison

Warfarin
LAB MONITORING

Baseline:

*INR / risks of beeding**
*BMP** (renal fxn)
*CBC**

LFT @ baseline & every 12 months

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Warfarin Drug-Disease State Interactions:

TUBE FEEDINGS

changes in absorption or vit K content

↓Warfarin sensitivity

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Frequency of INR Monitoring for:

Dose held today in patient with significant supratherapeutic INR

Check INR within:

1 - 2 Days

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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%

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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%

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MANAGEMENT OF HIGH INRS & BLEEDING

INR 4.5 - 10

w/o bleeding

Monitor INR / CBC / Bleeding

no Vit K treatment

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Warfarin Contrainidcations

Pregnancy
first 3 months

Active major Bleeding

Unsupervised patients with:
Senility / Alcoholism / Psychosis / lack of cooperation

Malignant Hypertension

Lumbar Block Anesthesia

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Frequency of INR Monitoring for:

Routine follow-up of medically for stable patients

Check INR within:

4 - 6 Weeks

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Warfarin Drug-Disease State Interactions:

RENAL DISEASE

↓CYP2C9 Activity

↓Warfarin Dose Requirement

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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

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Warfarin Drug-Disease State Interactions:

LIVER DISEASE

↓clotting factors & ↓warfarin clearance

↑INR

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Frequency of INR Monitoring for:

Routine follow-up of medically unstable or unreliable patients

Check INR within:

1 -2 Weeks

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Warfarin Drug-Disease State Interactions:

HYPERThyroidism

↑catabolism of clotting factors

↑Warfarin Sensitivity

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Warfarin Drug-Disease State Interactions:

HEART FAILURE

hepatic congestion -> ↓warfarin metabolism

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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%

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Warfarin Drug-Disease State Interactions:

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

↓catabolism of clotting factors

↑Warfarin Dose

**Warfarin Drug-Disease State Interactions**: ## Footnote **_SMOKING & TOBACCO_**

**_SMOKING & TOBACCO_** Smoking : **↑****CYP1A2** Chewing tobacco: **Contains VIT K** ↑**_Warfarin Requirements_**

MANAGEMENT OF HIGH INRS & BLEEDING ## Footnote **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: **S**even **N**ine 1**O** **T**wo 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**