Anticoags And Analgesics

Front 1

Addiction

Back 1

: behavior pattern of overwhelming involvement with obtaining and using a drug. Will occur in < 1% of patients receiving pain therapy with opioid analgesics.

Front 2

physical dependance

Back 2

withdrawal symptoms appear upon stopping drug

Front 3

tolerance

Back 3

when a particular dose loses its effectiveness

Front 4

Pain Assessment

Back 4

Acute vs Chronic
Tumors Vs Tx
Nociceptive vs Neuropathic

Front 5

Acute vs Chronic

Back 5

very important in a cancer patient bc must r/o oncologic emergency (i.e. spinal cord compression with back pain)

Front 6

Nociceptive vs Neuropathic

Back 6

Nociceptive – somatic & visceral structures

Somatic - sharp, localized, throbbing, pressure-like

Visceral - diffuse, irritating, cramping

Neuropathic – peripheral or central nervous system
Burning, sharp, shooting

Front 7

Mild Pain

Back 7

Defined as 1-2,3-4 on a 0-10 point VAS
Acetaminophen
Non steroidal anti-inflammatory drugs (NSAIDs)
Mild opioids combinations (Darvocet)

Front 8

Moderate Pain

Back 8

Defined as 5-6 on a 0-10 VAS
Small doses of morphine or oxycodone alone
Combination agents may work

Front 9

Severe Debilitating Pain

Back 9

Defined as 7-10 on 0-10 VAS
Morphine is drug of choice

Front 10

Pharmacologic options for pain

Back 10

non-opiods: APAP (tylenol), NSAIDS-ASAs cox's

opiods- moderate pain: codeine, hydrocodone, oxycodone
Sever:morphine, oxycodone, hydromorphone, fentanyl

Front 11

Non narcotic analgesics

Back 11

AcetaminophenDose dependentWatch in liverSalicylatesGI side effects & caution in childrenNSAIDsLess GI tox & watch in  renalNonacetylated salicylatesLess GI tox & better for sparing platelets

Front 12

Acetaminophen

Back 12

Step 1 analgesic, co-analgesicAnalgesic and antipyretic effectsMechanism: inhibits prostaglandins in CNS and peripherally blocks pain impulse generationOnset of action is 30 – 60 minutesDuration of action is 4 hoursMetabolized in liver, excreted in urineWell tolerated without common toxicities expected with NSAIDsAvailable in many different dosage formsMax daily dose is 4 grams

Front 13

NSAIDS

Back 13

Non Steroidal Anti-Inflammatory DrugsAnalgesic, antipyretic and anti-inflammatory effectsInhibits cyclo-oxygenase (COX)enzyme that releases PG known to sensitize or activate peripheral nociceptorsVary in COX-2 selectivityDose-response curve plateausAll the drugs in this class exhibit an analgesic ceiling effectParticularly helpful in bone pain

Front 14

Limitations of NSAIDS

Back 14

GastropathyAnti-platelet effectRenal toxicityDrug interactions

Front 15

Cox 2s

Back 15

Patients where an NSAID is indicated with:
History of GI ulcers
Elderly
Low platelet count < 50K
Receiving anticoagulation
Receiving corticosteroids
Coagulopathy
Prior intolerance to non-selective NSAID

Front 16

Celecoxib (Celebrex)

Back 16

Cox 2Used for acute and chronic painDose 100-200 mg PO daily max doseFamilial adenomatous polyposis (FAP)400 mg PO BIDMany drug interactions that should be watched (warfarin, CYP450)Caution in pts with sulfonamide allergy

Front 17

Tramadol (Ultram)

Back 17

Binds to the mu-opiate receptors but also binds to norepinephrine and serotonin50-100 mg PO every 4-6 hr (max 400 mg/day)Needs to be adjusted in renal dysfunction (CrCl < 30 ml/min)Limited by N/V, constipation, and dizziness; may lower seizure thresholdsimilar to opiod but no dependance risk, no fever block

Front 18

Opiods

Back 18

Major class of analgesics in the management of moderate to severe cancer pain

Well-established efficacy

Common toxicities are generally easily managed or prevented

Doses are easily titrated

Front 19

Morphine

Back 19

Gold standard for pain management
Multiple dosage forms
PO (IR and SR), IV, PR
Active metabolite
morphine-6-glucuronide
Well tolerated
Release of histamine
Adverse events: sedation, urinary retention, decreased respirations, CONSTIPATION
Initial dosing is based on severity of pain usually 1 mg IV q4h as needed
Inexpensive

pts generally become tolerant to the sedative effects but NOT the constipations

Front 20

Oxycodone

Back 20

Slightly more potent than morphine
Fewer dosage forms
PO (IR and SR)
Multiple combination products
Milder side effect profile relative to morphine
Street value must be considered

Front 21

Hydromorphone (Dilaudid)

Back 21

Approximately 6 times more potent than morphine
Usual starting dose is 0.2 mg IV q3h prn
Available as both IV and PO product
No PO SR dosage form
Useful alternative in liver/renal failure patients
No active metabolite
Less nausea/vomiting and pruritis relative to morphine

Front 22

Oxymorphone (opana)

Back 22

Available: IV, PO (IR & ER)
Changing from IV to PO
10 x IV dose divided in two doses
Changing between immediate release and extended release
2 times the IR dose

10x as potent as morphine

Front 23

Fentanyl

Back 23

100 times as potent as morphine; titrate slowly
1 mg IV morphine = 10 mcg fentanyl
Unique dosage forms
IV, transdermal, lozenge
Least likely to induce histamine release
It is not known whether the dose requires adjustment for renal or hepatic failure; Renally eliminated and hepatically metabolized

Front 24

Fentanyl topical

Back 24

Serum concentrations undetectable 2 hours after application, then  gradually over 12-24 hours and thereafter remain constant
Give supplemental doses during first 12-24 h
Use lowest dose initially (25 mcg/hr), and gradually  every 3 days. Use higher doses in opioid tolerant patients [very high doses have been used - 1600 mcg/hr]. Some may need every 48 hour dosing
Not recommended to  faster than every 72 hours - may result in very high serum concentrations
Watch administration with high fevers and do not use with heating pad or other direct heat sources

Front 25

Fentanyl transmucosal

Back 25

Do not use in opioid naive patients
Rapid onset of action
Dangerous around children

Front 26

meperedine

Back 26

NOT recommended for pain management unless no other options
Short duration of action
Toxic metabolite
Normeperidine
CNS toxic – seizures
Useful for post-anesthesia and amphotericin B related rigors

Front 27

methadone

Back 27

Cheap form of pain management

Dosing is complex because of longer half lives with administration

Should only be dosed with advisement of practitioner with experience (pain control or palliative care)

Opioid agonist & NMDA antagonist

Very large inter-patient variability in PK
80% oral bioavailability
t½ = 15-60 hours (up to 130 hours)

Opioid rotation or opioid resistance

Drug interactions – increased toxicity (sedation/resp depression) with CYP 3A4 inhibitors (i.e. fluvoxamine & other antidepressants)

Front 28

Major Adverse Effects of Narcotics

Back 28

CNS
Respiratory System
Urinary Effects
CV Effects
CONSTIPATION!!!!
Must give bowel stimulant not just stool softener
Sennakot with docusate 2 tablets at bedtime or
Miralax at bedtime

Front 29

Adjuvant therapy (FYI)

Back 29

Tricyclic Antidepressants
Potentiates opiates
Used for neuropathic pain
Amitriptyline

Anticonvulsants
Used for neuropathic pain
Carbamazepine/Gabapentin

Corticosteroids
Pain from infiltration of nerves/bone pain/compression
Dexamethasone

Front 30

Heparin

Back 30

MOA: complexes with Antithrombin III accelerating its ability to inactivate factors IIa, Xa, and IXa

Front 31

Unfractionated heparin

Back 31

Dosing: weight based given by continuous infusion
Load: 80 units/kg or Maintenance: 18 units/kg/hr
Load : 5000 units or Maintenance : 1300 units/hr

Monitoring:
check aPTT (activated partial prothrombin time) at 6 hours and adjust dose to keep aPTT within the therapeutic range

Recheck aPTT every 6 hours for 1st 24 hours then every morning unless outside therapeutic range

Front 32

low molecular weight heparins

Back 32

Improved bioavailability and more predictable pharmacokinetics
Do not have to monitor aPTT
Longer half life
Good for treatment of home DVT or uncomplicated PE
Use in caution in obese patients and those with renal insufficiency

Enoxaparin (Lovenox)
Dalteparin (Fragmin)
Fondaparinux (Arixtra)

Front 33

Enoxaparin ( lovenox)

Back 33

Indicated in the treatment and prophylaxis of venous thromboembolism (VTE)
Treatment: 1 mg/kg SQ q12h or 1.5 mg/kg daily
Prophylaxis: 30 mg SQ q12h or 40 mg SQ daily

Front 34

Dalteparin (Fragmin)

Back 34

Prevention of VTE (approved)
Low risk 2500 units SQ daily
High risk 5000 units SQ daily
Treatment of VTE (unapproved)
200 unit/kg SQ daily

Front 35

Fondaparinux (Arixtra)

Back 35

Factor Xa inhibitor
Good option for heparin-induced thrombocytopenia (HIT)
VTE Treatment
< 50 kg 5 mg SQ daily
50-100 kg 7.5 mg SQ daily
> 100 kg 10 mg SQ daily
VTE Prophylaxis
All weights 2.5 mg SQ daily
Use in caution in renal insufficiency

Front 36

Warfarin

Back 36

MOA: inhibits the production of vitamin K dependent clotting factors (II, VII, IX, X)
It will take at least 5-7 days to reach steady state
Most bridge therapy with heparin product when treating
If load patients with warfarin – protein C and protein S will be gone (natural anti-coagulants)  could produce hypercoagulable state
Skin necrosis – bruising on buttocks, thighs, penis, breasts
Adverse events: bleeding

Front 37

Monitoring of Warfarin

Back 37

Check international normalized ratio (INR)
The goal INR depends on the indication
A fib goal 2-3
Mechanical Heart valves
aortic position  2.0—3.0
mitral position  2.5 – 3.5 or 2.0—3.0 + ASA 80-100 mg
additional RFs, or systemic embolism despite adequate anticoagulation  2.5-3.5 + ASA 80-100mg
Bioprosthetic heart valves
Aortic or mitral position  2.0—3.0 for 3 months followed by ASA 162 mg daily
History of systemic embolism  2.0—3.0 for 3-12 months followed by ASA 162 mg daily

Front 38

drug Interactions with warfarin

Back 38

Highly protein bound
H2 blockers/PPIs
Antibiotics
Antiepileptic Agents
Barbiturates
Carbamazepine
Phenytoin
Lipid lowering agents
Antifungal agents
Leukotriene Inhibitors
Antidepressants

Front 39

warfarin dosing

Back 39

INR < 2
small increase (i.e., INR 1.7)   weekly dose by 5-10%
large increase (i.e., INR 1.4)   weekly dose by 10-20%
INR > 3
small decrease (i.e. INR 3.3)   weekly dose by 5-10%
large decrease (i.e. INR 4.2)  hold 1 dose,  weekly dose by 10-20%

Front 40

Food interactions with Warfarin

Back 40

Foods that are rich in vitamin K
Dark green leafy vegetables
Broccoli
Collards, etc
Green tea

Front 41

Vitamin K Supplentation

Back 41

ADEK vitamin not used any more because now has 700 mg vitamin K
Viactiv chews (vitamin D and K)
Contains 80 mg vitamin K
Two chews daily to minimize interactions with food and drugs

Front 42

Vitamin k administration

Back 42

INR 5-9 & not bleeding
Vit K 2.5-5 mg PO
recheck INR is 24-48 hours or hold dose until therapeutic

INR > 9 & not bleeding
vitamin K 5 mg po
recheck INR in 24 hours

INR > 20 or rapid reversal
vitamin K 10 mg slow IV and plasma transfusion or prothrombin complex concentrate depending on the urgency of the situation
Recheck INR every 6 hours

Front 43

Aspirin

Back 43

MOA: inhibits cyclooxygenase which inhibits formation of
Thromboxane-TXA2 (vasoconstrictor; **irreversible) inhibits platelet aggregation and activation
Increases risk for bleeding
prostacyclin (PC; vasodilator; reversible)
Major Adverse effects: GI Bleed, renal insufficiency
Doses: 81-325 mg PO daily
Used for post-heart attack and stroke

Front 44

Ticlopidine (Ticlid)

Back 44

MOA: inhibits platelet activation and aggregation but mechanism is different from any other antiplatelet drug
Onset of action is 24-48 hours
Side effects: diarrhea, rash, reversible neutropenia (2%)
Drug interactions: Substrate of CYP3A4 inhibits CYP2C19 strong
Dose: 250 mg twice daily with food
Monitoring: CBC with diff q 2 weeks for 1st 3 months

Front 45

Clopidogrel (plavix)

Back 45

MOA: blocks ADP receptors  inhibits platelet activation and aggregation
Prevents activation of GPIIb/IIIa
Platelets that are affected last the rest of the platelet life

Steady state: 3-7 days

Drug interactions: minor CYP3A4

Dose: load 300 mg and then 75 mg daily with or without food

MP: routine CBC monitoring not necessary