Hematological Flashcards
Anticoagulants
Warfarin (Coumadin)
Indications & Pharmacodynamics
- Indication
- prevention and treatment of venous thrombosis, systemic embolism, pulmonary embolism, prevention of embolic stroke and atrial fibrillation
- Prosthetic heart valves need warfarin to stay patent
- Pharmacodynamics: competitively inhibits VKORC1 complex, depleting functional vitamin K reserves and reducing hepatic synthesis of several clotting factors
- Inhibits synthesis of Vitamin- K - dependent clotting factors X, IX, VII, and II
- Well absorbed when taken orally
Anticoagulants
Warfarin (Coumadin)
Caution/contraindications: Avoid, caution, contraindication, black box warning, pregnancy
When might the prescriber need to consider a lower dose?
How long is the half-life?
What nutrient considerations need to be made?
What is the antidote?
- Caution/contraindications
- Avoid: hypermetabolic state
- Caution: hepatic impairment, fall risk, dementia or uncontrolled HTN
- Contraindicated: actively bleeding, hemophilia, thrombocytopenia, severe hypertension, hemorrhage, infective endocarditis
- Black box warning: may cause fatal bleeding
- Pregnancy - avoid; lactation - safe
- Long half-life: 3-4 days
- Consider lower dose if
- Older than 75 years old
- Multiple comorbid conditions
- Elevated liver enzymes
- Changing thyroid status
- Maintain stable intake of foods high in vitamin K
- Antidote is vitamin K
Anticoagulants
Warfarin (Coumadin)
Therapeutic index monitoring: how is this monitored? What are the ranges?
- Narrow therapeutic index, regular lab monitoring required (INR)
- Prosthetic valve: 2.5-3.5
- Standard: 2-3
- Monitor daily until in therapeutic range for 2 consecutive days, then 2-3 times per week for 1-2 weeks; then less frequently but at least every 6 weeks
Anticoagulants
Warfarin (Coumadin)
Examples of drug/food interactions that decrease the fx of warfarin (5)
There are two major enzymes of the CYP450 system that have an effect on warfarin - what are they and what effect do inducers vs. inhibitors of these enzymes have on Warfarin?
- Drugs/food that decrease the fx of Warfarin
- St. Johns Wort
- Co-enzyme 10
- Oral contraceptives
- carbamazepine
- Vitamin K foods
- inhibitors of the CYP1A2 and 2C9 increase effects of Warfarin
- inducers of CYP1A2 and 2C9 decrease the effects of Warfarin
Anticoagulants
Warfarin (Coumadin)
Adverse fx (2)
hemorrhagic skin necrosis and cyanotic toes, rare allergic reactions with maculopapular rash eruption
Anticoagulants
Heparin
Indications & Pharmacodynamics
- Indications: prevention of post-operative embolism; given 2 hours pre-operatively, then maintenance 8-12 hours for 7 days after surgery
- Pharmacodynamics: potentiates the action of antithrombin III and inactivates thrombin as well as other anticoagulation factors (factor Xa, IXa, XIIa, XIII) and prevents the conversion of fibrinogen to fibrin
- Given IV or SC
- Extensively protein bound
- Metabolized by liver and renally eliminated
Anticoagulants
Heparin
Caution/contraindications: avoid, caution, pregnancy, antidote, drug interactions
What lab test is used for monitoring while on heparin therapy?
- Avoid: advanced hepatic or renal impairment, bleeding disorders or active bleeding
- Caution: conditions that may predispose to hyperkalemia
- Pregnancy - avoid; lactation - compatible
- Antidote: protamine sulfate
- Drug interactions: cephalosporins, penicillin, warfarin, antiplatelets thrombolytics, valproic acid
- Monitoring: aPTT
Anticoagulants
Heparin
Adverse fx (3)
thrombocytopenia, anemia, hyperkalemia
Anticoagulants
Low molecular weight heparin
Indications & Pharmacodynamics
- Indications: DVT, PE, prophylaxis; given two hours before surgery
- Pharmacodynamics: potentiates activity of antithrombin III and inactivates factors Xa
Anticoagulants
Low molecular weight heparin
Caution/contraindications: avoid, caution, pregnancy & adverse fx (3)
What monitoring is needed?
- Avoid: allergies to pork, sulfites or benzyl alcohol
- Caution: renal impairment, untreated HTN, retinopathy, severe liver disease
- Compatible with pregnancy and lactation - this is the preferred medication for pregnancy
- Monitoring: platelet and Hct
- Adverse fx: anemia, hemorrhage, peripheral edema
Anticoagulants
Dabigatran (Pradaxa)
Indications & Pharmacodynamics
- Indications: reduces risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
- Pharmacodynamics: direct thrombin inhibitor (thrombin is required for the conversion of fibrinogen to fibrin in the clotting cascade; fibrin directly precedes clot formation)
Anticoagulants
Dabigatran (Pradaxa)
Caution/contraindications: black box warnings, pregnancy, antidote & adverse fx (3)
- Black box warnings: discontinuation and increase of thrombotic events; epidural or spinal hematomas with spinal interventions
- Pregnancy/lactation: avoid
- Antidote: idarucizumab (praxbind)
- Adverse fx: dyspepsia, gastritis, hemorrhage
Anticoagulants
Factor Xa oral anticoagulants: Rivaroxaban, apixaban, edoxaban, betrixaban
Indications & Pharmacodynamics
- Indications: treatment of DVT and/or PE and reduction of stroke and systemic embolism in nonvalvular atrial fibrillation; prophylaxis of DVT following knee replacement surgery
- Pharmacodynamics: direct factor Xa inhibitors
Anticoagulants
Factor Xa oral anticoagulants: Rivaroxaban, apixaban, edoxaban, betrixaban
Caution/contraindications
2 general, specific to rivaroxaban, apixaban, edoxaban
What is the antidote?
- Black box warning: discontinuation and increase of thrombotic events; epidural or spinal hematomas with spinal interventions
- Pregnancy/lactation: avoid
- Rivaroxaban: not used in patients with moderate to severe liver impairment and when CrCl is less than 30
- Apixaban: used with caution in moderate liver impairment, contraindicated in severe, avoid use in severe renal impairment
- Edoxaban: used with caution in moderate liver impairment, contraindicated in severe and when CrCl is less than 15
- Antidote: andexanet alfa (andexxa)
Anticoagulants
Factor Xa oral anticoagulants: Rivaroxaban, apixaban, edoxaban, betrixaban
Adverse fx (10)
1 general
3 for rivaroxaban
1 for apixaban
4 for edoxaban
- General: hemorrhage
- Rivaroxaban: back pain, abdominal pain, dyspepsia
- Apixaban: nausea
- Edoxaban: skin rash, GI bleeding, vaginal bleeding, dermal bleeding
Antiplatelets
Aspirin
Indications & Pharmacodynamics
- Indications: MI and stroke prevention and acute coronary syndrome; Low-dose used to prevent preeclampsia in pregnancy
- Pharmacodynamics: irreversibly antagonizes cyclooxygenase pathway, interfering with platelet aggregation
Antiplatelets
Aspirin
Caution/contraindications: avoid, caution, pregnancy, interactions & Adverse fx (5)
- Avoid: pediatrics with flu or chicken pox; severe liver disease
- Caution: CrCl less than 10
- Pregnancy/lactation: low-dose safe
- Interactions: herbals, NSAIDS
- Adverse fx: bleeding, GI ulcer/bleeding, angioedema, Steven Johnson syndrome, tinnitus (ototoxicity)
Antiplatelets
Clopidogrel (Plavix)
Indications & Pharmacodynamics
- Indications: unstable angina, recent MI, ACS; alternative to aspirin if it is contraindicated
- Pharmacodynamics
- Prodrug: metabolized into active metabolite
- Reduces platelet aggregation by inhibiting the ADP pathway of platelets
- No effect on prostaglandins
Antiplatelets
Clopidogrel (Plavix)
Caution/contraindications: avoid, pregnancy & Adverse fx (2)
- Avoid: severe hepatic disease and patients with GI ulcers
- Pregnancy/lactation: ok IF indicated
- Adverse fx: bleeding, Steven Johnson syndrome
What are some causes of iron deficiency anemia? (5)
- inadequate intake
- acute or chronic blood loss
- menstruation
- pregnancy
- periods of accelerated growth in children
Dosing of iron for adults, premature infants and infants/young children
- Adults 150-300mg elemental iron daily
- Premature infants: 2-4mg/kg/day
- Infants and young children: 4-6 mg/kg/day
What are some patient education topics when prescribing iron? (3)
- Increase fluids and fiber
- Take on an empty stomach or with vitamin C to help with absorption
- It can take 4-6 weeks to see improvement of symptoms
Iron: Caution/contraindications (pregnancy, contraindications, drug reactions, monitoring) & adverse fx (3)
- Pregnant women usually take during 2-3 trimester and while lactating
- Contraindications: hemochromatosis, hemolytic anemia
- Drug reactions: chelation
- Monitoring: reticulocyte count 7-10 days after starting therapy, Hgb at 2 weeks then based on individual risk
- Adverse fx: constipation, GI upset, acute toxicity possible
Folic acid: When is it taken for prevention vs. treatment?
What is the difference in dosing between prevention vs. treatment?
- Prevention: pregnancy, methotrexate therapy
- Treatment: Deficiency related to absorption issues, phenytoin, result of increased demand during pregnancy, alcoholism, hypothyroidism, hemolytic anemia or malignancy
- Dosing is higher for treatment than prevention
Folic acid: pharmacokinetics
- Oral, IM or SC well absorbed
- Metabolized by liver
- Excreted in urine and feces
Indication and dosing for Vitamin B12
- Indications: pernicious anemia
- Dosing: 1000 mcg oral cobalamin daily for 6-12 weeks
- Pernicious anemia dosing
- 1000mcg/day IM or SC for 7 days then 100 to 1000mcg IM per week for a month
- Maintenance 1000mcg IM monthly; 500mcg intranasal cyanocobalamin weekly, 1000mcg daily
- Pernicious anemia dosing
How is Vit B12 administered? What needs to be monitored at the start of therapy? How is effectiveness of the therapy determined?
- injections, intranasal, oral
- Monitor serum potassium
- Effectiveness determined by relief of symptoms
Vit B12: Adverse fx (7)
- hypokalemia
- headache
- pain at injection site
- transient diarrhea
- urticaria
- pruritis
- anaphylactic shock (patients sensitive to cobalamins)
What syndrome can occur in pediatrics taking aspirin?
Reye’s syndrome
