Pharm exam 1: section 3 Flashcards
Anticoagulation
Indications
Venous thromboembolism: prevention and tx Stroke prevention in setting of afib Ischemic stroke Prosthetic cardiac valve Coronary and PVD Hypercoagulable disease
Prophylaxis for clotting events in high risk pt that might have high risk procedure
Warfarin
Vitamin K antagonist
Inhibits synthesis of Vitamin K dependent clotting factors: X IX VII (half life = 6 hrs) II (prothrombin) (half like 60 hours) Coagulation inhibitor proteins C, Z, S Average half life 36-42 hrs (3-4 days) Onset: depends on time needed to deplete factors
Warfarin
Pharmacokinetics
Well absorbed PO
Metabolized by enzymes CYP1A2 & CYP2CP
Precautions and C/I
- Pregnancy category X
- Cautious use in pt w/ fall risk, dementia, or uncontrolled HTN
- avoid: recent hemorrhagic stroke, active bleeding, recent trauma/surgery, presence of spinal catheter, aneurysm, CNS tumor
Warfarin
Adverse reactions
Bleeding
-antidote is vitamin K
Allergic reactions
Drug interactions
- simvastatin, fish oil, garlic, prednisone may increase INR
- Phenytoin and phenobarbital may decrease INR
- decreased by foods w/ vitamin K
Warfarin
* never initiated at mono therapy bc takes a long time for warfarin to reach full therapeutic effect
Clinical Dosing Start @ 5mg/day (7.5mg/day if weight > 80 kg) Consider lower dose if: > 75 yo Multiple cormorbidities Elevated liver enzymes Changing thyroid status
INR hows prolongation w/in 3 days after starting d/t rapid depletion of factor VII
Full anticoagulation after depletion of factor II depleted (2-14 days)
Check daily until in range on 2 consecutive days
Check 2x weekly for 1-2 weeks
Then less frequently (@ least every 6 weeks)
Warfarin
Target INR
INR 2-3 VTE DVT stroke prevention in afib valves hypercoagulable condition
INR 2.5- 3.5
Heart valvle
hypercoagulable condition
Direct acting Oral anticoagulants
Dabigatran (Pradaxa)
Direct thrombin inhibitor
Poor bioavailability
formulated as prodrug
Few drug interactions
Renal clearance
Half life: 14-17hrs
Avoid in pt w/:
CrCl <15 ml/min
dialysis
prosthetic heart valve
Adverse reactions
bleeding (administer fresh frozen plasma)
GI vs intracranial bleeding
GI effects
Drug -drug interactions
- quinidine: increase levels by 100%
- amiodarone: increase levels by 50%
- rifampin: may decrease effects
- PPIs and antacids - separate doses by 2 hrs
Dosing: reduce risk of CVA in pt w/ afib
150mg BID - normal renal function
75mg BID - decreased renal function
Check hepatic function at baseline and periodically if concern
Cannot crush
Cannot be put in pill box bc its packaged in moisture proof container
Direct acting oral anticoagulants
Rivaroxaban (Xarelto)
PE tx
DVT prevention
Direct thrombin inhibitor
Poor bioavailability
formulated as prodrug
Few drug interactions
Renal clearance
Half life: 14-17hrs
Avoid in pts w/ heart valve
Avoid in CrCl < 30ml/min
must be taken with food to improve bioavailability
Direct acting oral anticoagulants
Apixaban (Eliquis)
Direct thrombin inhibitor
Poor bioavailability
formulated as prodrug
Few drug interactions
Renal clearance
Half life: 14-17hrs
Least dependence on CrCl
good for pts w/ kidney function issues
Direct acting oral anticoagulants
Edoxaban( Savaysa)
Less drug-drug interactions
Cannot use in CrCl: >95ml/min -> cause stroke
Direct acting Oral anticoagulants
Indications
DVT and PE treatment
DVT prevention
stroke
Bind to factor Xa: Block thrombin
faster onset than warfarin; injectable bridge therapy not necessary as with warfarin
no dietary interactions
dosing adjustment not necessary
Direct acting oral anticoagulants
Transitioning
From warfarin:
start when INR at lower end of therapeutic range
From unfractionated heparin:
start when heparin is discontinued
From low molecular weight heparin (LMWH):
start when LMWH due next (usually 12 hrs from last dose)
Heparin
Binds w/ antithrombin III
inactivates factors IXa, Xa,XIIa, XIII
Given: IV or subQ (immediate action - emergency situations)
Not absorbed in GI
Extensively protein bound
Metabolized by liver / renal excretion
Caution in Pregnancy; category C
Avoid in advanced hepatic or renal disease
Avoid in bleeding disorder or active bleeding
Heparin
Adverse reactions
HIT (immune response to heparin)
Life threatening bleeding
Pain at injection site, bruising: subQ
Antidote: protamine sulfate
Drug interactions
Cephalosporins and PCNs
warfarin, antiplatelets, thrombolytics
Valproic acid
Heparin
Dosing
Indications
Given 12 hrs pre-op
Maintenance q 8-12 hrs for 7 days post op
Monitor:
aptt
platelet and hematocrit q 2-3 days initially
Indications
acute thromboembolism
VTE prophylaxis
LMWH
Fragments of unfrationated heparin
Inactivates thrombin and factor Xa
No lab monitoring
Fixed dosing at prophylaxis: aptt may not be significantly prolonged at prophylaxis doses
Weight based with therapeutic dosing: At therapeutic doses aptt prolongation not used to measure therapeutic effect
Half life: 108-252 minute
LMWH
Enoxaparin
DVT or PE
Pre-op given 12 hrs before surgey
Still at risk for HIIT
LMWH
Fondaparinux
DVT
Hip fracture surgery or knee replacement
Risk for HIIT is subsequently lower
Education considerations
Warfarin
Dosing may vary from day to
Pills are different size and color for dose
Must explicitly state each day pt takes a certain dose to avoid miscommunication
Educate about INR checks
Warn of bleeding complication
Educate about food (leafy greens, asparagus, onion, garlic)
Education consideration
LMWH
Subq administered at home
Show how to administer
Rotate sites
Bleeding
Antiplatelet drugs
Aspirin
Must inform provider taking med
Inhibits cyclooxyrgenase (COX) Interferes w/ platelet aggregation
Well absorbed PO; take with food to be prevent GI distress)
Metabolized in liver
Renally excreted (pH affects excretion)
Contraindications Hypersensitivity cross sensitivity w/ NSAIDS Pregnancy category C (D in 3rd trimester) Reye's syndrome in children
Adverse reactions
bleeding
GI upset and bleeding
salicylism (tinnitus)
Interactions
other anti platelet, anticoagulant, fibrinolytic
Herbals (ginko, garlic, ginseng)
NSAIDS
Dosing
MI prevention: 75-162mg daily
afib: 75-325mg
CVA or TIA: 50-100mg daily
Education
take with a full glass of water
ASA must be stopped 7 days before surgery
Adverse: ASA toxicity: tinnitus, dizziness cerebral edema seizure bleeding or bruising
Antiplatelet drug
Aggrenox
Combination product (25mg ASA/ 200mg ER dipyridamole)
Dipyridamole inhibits platelet adhesion but MOA unknown
Antiplatelet drugs
Ticlodipine and clopidogrel
Reduce platelet aggregation by inhibiting adenosine diphosphate (promoter of platelet receptor binding)
Contranindication
avoid in pt w/ liver dysfunction
rapidly absorbed after PO admin
metabolized in liver
half life lengthens w/ repeated dosing
decreased renal clearance w/ age
Adverse reactions
neutropenia
Interactions
antacids
digoxin
cimetidine
Dosing
Stroke prevention in ASA intolerant pts: 250mg BID
clopidogrel
Reduce platelet aggregation by inhibiting adenosine diphosphate (promoter of platelet receptor binding)
Contranindication
avoid in pt w/ liver dysfunction
prodrug
excreted in urine and feces
Adverse reaction
bleeding
Interactions
proton pump inhibitors
CYP2C 19 inhibotors
Dosing
MI prevention: 75 mg daily
ST elevation ACS: 300mg daily < 75ys
75mg daily > 75yrs
Secondary CVA prevention 75mg
Education
Separate doses of clopidogrel and PPIs
Hematopoetic Growth Factors
Treat anemia
Epoetin alfa (Epogen, EPO, Procrit) and darbepoetin alfa (Aranesp)
-Stimulate erythropoiesis
-Used for treatment of anemia due to end stage renal
disease, AIDS or chemotherapy
-Preoperatively to prepare for allogeneic transfusions
Granulocyte colony stimulating factor filgrastim [Neuopgen] pegfilgrastim [Neulasta] tbo-filgrastim [Granix]) Stimulates granulocyte formation
Use
Neutropenia due to bone cancer and chemotherapy
Hematopoetic Growth Factors
Pharmacokinetics
Well absorbed SubQ
Metabolism and excretion not well understood
Precautions and contraindications Epoetin alfa & darbepoetin alfa HTN is only contraindication Increased risk of tumor growth Pregnancy Category C
Filgrastim & pegfilgrastim
Hypersensitivity to E. coli
Pregnancy Category C
Hematopoetic Growth Factors
Adverse Drug Reactions
All can produce bone pain (large bones - Sternum -> feels like MI pain; femur and pelvis)
Epoetin alfa & darbepoetin
Seizures / HTN (don’t give to HTN pts)
Decreased overall survival rate and/or tumor growth in patients with certain cancers
Filgrastim & pegfilgrastim
Hypersensitivity
Drug Interactions
Hematopoetic Growth Factors
Goal: prevent transfusion
Renal pts that are transplant candidates
Antibody exposure -> effects tissue typing that occurs
Hgn 11-12 range
Clinical Use and Dosing
Epoetin alfa to treat anemia, CKD, chemo, HIV
50-150 mcg/kg 3 times a week
Dose dependent on diagnosis
For allogeneic transfusion: 300 mcg/kg/d given 10 days prior to surgery, day of surgery and for 4 days after surgery
Darbepoetin: CKD and chemo
0.45-2.25 mcg/kg once weekly
Hematopoetic Growth Factors
Monitoring
Darbepoetin alfa: Hgb weekly, ferritin periodically
Epoetin alfa: Hct weekly, ferritin periodically, monitor BP
cannot receive if BP is high
Patient education
Administration
Self administration of SubQ medication
Use of iron supplements
Adverse drug reactions
HTN and allergic reactions
Anemia Pathophysiology
Iron deficiency anemia
Decreased iron carrying capacity of the blood
Inadequate intake or blood loss (acute or chronic)
Gastric bypass pt: cannot absorb enough iron
Treated with iron replacement
Folic Acid Deficiency Anemia
Seen in alcoholics, chronic malnutrition, fad diets, and diets low in vegetables
Drugs: Dilantin, sulfamethoxazole/trimethoprim, and oral contraceptives, methotrexate
Pernicious anemia
Vitamin B12 deficiency leads to macrocytic-normochromic anemia (large cells, normal in color)
Vegetarians, vegans, genetic predisposition, autoimmune disease
Iron deficiency Anemia
Prevention
Adequate intake via iron-rich diet (difficult w/ gastric bypass pts)
Monitor in periods of rapid growth (infancy, adolescence, pregnancy): increased risk bc needs are higher
Replacement in infants 1 mg/kg/day starting at 4 months (2 mg/kg/d in preterm infants)
Treatment
Oral vs. intravenous
Oral - once daily dosing or even once every other day dosing
Better GI tolerance every other day and equally efficacious
Iron deficiency Anemia
Monitoring
- Reticulocyte count 5-10 days after starting therapy
- Hgb, Hct, ferritin at 4 weeks and then at 3 months and annually
Outcome evaluation
Return to normal Hgb, Hct and ferritin levels
If Hgb, Hct and ferritin do not return to normal levels the patient should be evaluated for a source of blood loss or other pathology
- CANNOT be iron deficient if ferritin is normal and iron is low
Iron deficiency Anemia
Patient Education
Importance of prevention with adequate iron intake in diet
Administration
Empty stomach if tolerated with ½ glass of orange juice
Daily or every other day is best
Constipation (may need a stool softener)
Avoid calcium-rich foods/supplements when taking iron
Iron preparations
Iron preparations build serum iron and iron storage in the body
Enhanced absorption if iron stores low
Ferrous form is absorbed more readily
Food affects absorption - take on empty stomach
Eliminated via shedding of GI mucosal cells or via bleeding
Iron Contraindications
Adverse reactions
Precautions and Contraindications
Hemochromatosis and hemolytic anemia
Adverse Drug Reactions
GI symptoms (constipation, GI upset)
Acute toxicity possible especially in children
Drug interactions
Chelation (abx)
Decreased absorption decreased w/ aluminum, magnesium, calcium
Acid: ascorbic acid enhances absorption
Iron Dosing
Clinical use and dosing Iron deficiency anemia Adults 150-300 mg elemental iron daily Treat for 3 to 4 months after Hgb/Hct return to normal Premature infants 2-4 mg/kg/day Infants and young children 4-6 mg/kg/day
Monitoring
Reticulocyte count 7-10 days after starting therapy
Hgb at 2 weeks, then based on individual risk
Iron
Pt education
Patient Education
Prevention
Adequate intake of iron in diet
Administration
Take on empty stomach if tolerated (w/ orange juice)
Take with Vitamin C to enhance absorption
Avoid taking with dairy products, calcium, antacids
Adverse Reaction
Constipation (stool softener, laxative)
Acute iron toxicity if overdose, keep away from children
Folic acid deficiency anemia
Risk groups
Infants fed goat’s milk or powdered milk formula
Vegetarians and vegans
Pregnancy increases daily requirement need
Patients with Celiac disease, Crohn’s disease
giardial infections
short bowel syndrome
Drugs that affect folic acid absorption
Prevention
Adequate dietary intake
Folic acid supplementation in pregnancy
Folic acid deficiency anemia
Drug therapy for deficiency
Oral folic acid 1mg/day for 4 to 5 weeks
Hgb levels start to rise in a week
Women of childbearing age and pregnant women should consume 0.4-0.8 mg/day even if not deficient
Monitoring
Follow Hgb/Hct in 4 weeks and then regularly
Education
Length of need for folic acid
Indefinite folic acid tx for malnutrition
Side effects: skin rash irritability impaired judgement altered sleep pattern abd distention nausea
Serum folic level - 1mg
Pernicious Anemia
Pernicious anemia is caused by deficiency in Vitamin B12
Defective secretion of gastric intrinsic factor, which is necessary for vitamin B12 absorption
Vitamin B12 malabsorption occurs in 10-30% of adults > age 50 due to reduced pepsin activity and gastric acid secretion
Prevention
Eat foods high vitamin B12, such as mollusks (e.g., clams), fortified breakfast cereals, liver, trout, salmon, milk, and eggs
Diet cannot fix pernicious anemia
Pernicious anemia
Drug therapy
Oral, IM, SC and intranasal Vitamin B12 replacement
Nutritional deficit: 1000 mcg/day of cyanocobalamin is given until B12 normalizes
Pernicious anemia: Vitamin B12 therapy 1,000 mcg IM daily for 1 week followed by 100 to 1,000 mcg IM weekly for a month
Parenteral, nasal, or oral therapy may be used once a patient’s B12 levels return to normal.
Parenteral: 1,000 mcg cyanocobalamin IM monthly
Nasal: 500 mcg of cyanocobalamin weekly
Oral: 1,000 mcg daily (least expensive), easiest
Pernicious anemia
Monitoring: Reticulocyte counts Hgb and Hct iron folic acid vitamin B12 serum levels prior to treatment, at 5 to 7 days of therapy, then frequently until the Hgb and Hct are normal
Monitor potassium levels
Liver function tests every 2 to 4 weeks to monitor for hepatotoxicity
Pernicious anemia
Patient Education
Disease process and need for life long therapy
Vitamin B12 therapy regimen
Monitoring
Anemia of chronic disease
Occurs due to a inflammatory disease process
Older adults predisposed
Patients with osteomyelitis tuberculosis rheumatoid diseases hepatitis, carcinoma myeloma lymphoma leukemia at risk
Much less likely to respond to epoetin
Treat underlying disease
Patients with chronic kidney disease will respond to erythropoietin agents
Anemia of chronic disease
Treatment
If associated with chronic renal failure or zidovudine-treated HIV :
epoetin alfa 50-100 units/kg in adults
50 units/kg in children dosed three times a week
Epoetin alpha dose is titrated to keep Hgb level between 9 – 10.5g/dL
Dosage is increased by 25 percent if Hgb <9 g/dL
Epoetin alpha dose is decreased by 25 percent if hemoglobin approaches 12 g/dL or Hgb increases more than 1 g/dL in any 2-week period
