Download Drug Delivery Employed in Pain Pharmacotherapy

Drug Delivery Employed in Pain
Pharmacotherapy
Daniel Wermeling,
Pharm.D.
Professor
225 COP
Objectives
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Describe the technologic approaches used in
analgesic drug delivery routes of admin.
Describe the physiologic & pharmacokinetic
basis for routes of administration
Describe products using each of the
administration routes, their common clinical
use, risks and precautions
Why change the route or
method of administration?
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Different drug exposure (PK) profile
–
Examples
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To have a quicker onset
To have sustained blood levels
To change the formation of metabolites
To avoid the gastrointestinal tract
–
–
–
destruction in gut
hepatic first pass metabolism
gut not functioning
Why change the route or method of
administration?
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To send medication directly to the site of
action, Examples:
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To have efficient, non-invasive delivery
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Topical
Epidural or Intrathecal
Transmembrane approaches such as rectal,
buccal, nasal, transdermal
Patient factors:
–
Convenience, age, dexterity, support
Routes of Administration to be
Discussed
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Oral
Intravenous
Subcutaneous
Epidural
Intrathecal
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Rectal
Nasal
Buccal
Topical
Transdermal
Oral Opioid Products
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Immediate Release (IR) for acute pain &
breakthrough cancer pain
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Dosed every 2 to 6 hours
APAP now in lower dosages in some combo products
Extended or Controlled Release (ER) for chronic
pain – See FDA REMS – Risk of Deaths
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Patient should have already been receiving opioids and
developed some tolerance
Depending on product, dosed every 12 or 24 hours
continuously
Provides more stable blood level PK profile
Must closely follow use instructions
Large dose per unit is diversion and abuse prone
Oxycontin Concentration vs Time
Morphine Sulfate
MS Contin (CRM) vs Avinza (MSER)
Abuse Deterrent Formulations
Now Mainstay for ER/LA Products
Type of
Abuse
Physical
Barriers
Agonists
& Antag.
Aversion
Prodrug
Alternate
Routes
IV
+
+
+
+
+
Snorting
+
+
+
-
+
Chewing
+
+
+
-
+
Alcohol
+/Interaction
+/-
-
-
+
Intact
Abuse
-
-
+/-
+
-
Misuse
+/-
+/-
-
+
-
Remoxy and Oxytrex
Pain Therapeutics, Inc.
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Oxycodone ER tablets with abuse reduction
technology
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Remoxy is oxycodone within a polymer matrix
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No drug release if crushed and ingested
Forms a viscous gel if wetted, can not be injected
Releases less drug if attempts to dissolve in vodka
Oxytrex is oxycodone in standard erosion tablet combined
with low dose naltrexone
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Oral route provides pain relief due to low BA of naltrexone, a
mu receptor antagonist like naloxone
Dissolving and injecting will not result in euphoria and
hopefully prevent acute intoxication/death
Potential limitation of missmatch of PK/PD, delayed problem
CR vs IR Oxycodone Crushed in
Water and Ethanol
Commercial Oxycodone
Remoxy Oxycodone
Actiq
transmucosal/oral fentanyl
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Potent opiate within a
confection
Breakthrough Cancer
Pain indication
Buccal and oral
absorption
Adjunct to SR products
Follow directions
Don’t leave in mouth!!
Off-label use?
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Transmucosal Fentanyl Plasma Levels
Fentora - Fentanyl Effervescent Buccal
Tablets
Darwish 2005
Other transmucosal fentanyl
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Oral buccal spray
Nasal spray
Oral film
These products are not generally
interchangeable at same dose
Caution – high doses in certain unit sizes
can be lethal in non-tolerant individuals
Transdermal
Duragesic Fentanyl Patch
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Potent opiate solution
in a patch matrix
Drug diffuses into skin
and forms reservoir
passing drug to blood
stream – onset and
offset is delayed
Chronic delivery
72-hour release product
Patient should already
have received opiates
and developed
tolerance
Fentanyl Blood Levels Over Three
Days of Wearing Patch
Comparison of Patch to Orals
Morphine Equivalency Chart
Read J & J Letter to Doctors
Significant Warnings
Butrans® Buprenorphine
Transdermal System
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Partial mu-agonist
For moderatesevere chronic pain
requiring ATC
opioid analgesia for
extended period of
time
Many warnings
On-Q Delivery of Bupivicaine
Into Surgical Wound
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Post-surgical delivery of
local anesthetic to
wound
Continuous infiltration
for 2-3 days
Blocks pain without
systemic CNS
depressant medication
effects
Risks – CNS and CV
toxicity
EMLA Cream
2.5% Lidocaine and 2.5% Prilocaine
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Indicated for local analgesia for normal skin or
genital mucous membrane
Pretreatment for infiltration anesthesia or superficial
minor surgery
Great for kids
Sprix® Ketorolac Nasal Spray
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NSAID alternative to IM injection
For moderate to severe pain
May use in patients 18-65 years of age
Up to 5 days of use
Lazanda® Fentanyl Nasal Spray
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Powerful Rx for
Breakthrough pain
in patients tolerant
to opioids
Significant
prescriber, pt
selection, Rx Guide,
REMS, and other
factors
Patient Controlled IV Analgesia
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A device is given to patients allowing them to
self-administer small IV doses of opioids
Other routes are possible (intraspinal)
Device is programmed for dose, lockout time
and maximum per hour
Dosing history is reviewable
Typical Acute Pain Rx – morphine 1-2 mg
per IV injection with 8 min. lockout, 10 mg/hr
max
Typical IV PCA Prescription
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Morphine 1 mg/mL, 30 cc
Self-dose 1.5 mg per actuation
Lockout interval – 6 minutes
!!! Care if using basal infusion too!!!!
Rescue by nurse – 2 mg every 20 minutes by
RN
1 hour limit – 10 mg
Hold PCA for RR<10, SBP < 90
Naloxone 0.4 mg ampules at bedside
IV PCA & Opiate Dosing Guideline
Momeni, Drugs, 2006
Patient Controlled Analgesia for
Acute Pain
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Advantages over intermittent therapy
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Avoids fluctuations, decrease delays
Some patients prefer participation
Some side effects can be reduced
Better pain control speeds recovery
Establish daily opioid needs for oral conversions
Cautions
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Family controlled analgesia
Systems errors
Human errors
Adding background continuous infusion
Additional IV PCA Uses – More
Advanced Considerations
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Dose-finding for cancer pain
Dose-finding for Drug Abuse History Patients
Conversions from IV to Oral or Other
Patients with tolerance to opioids
IV Patient-Controlled Analgesia Device
PCA via Other Routes/Methods
PCA Flow Sheet – See Handout
Intraspinal Delivery
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Delivery of medication to the epidural or
subarachnoid (intrathecal) space
Block nerve transmission
Opioids, and local anesthestics or clonidine in
combination
Dosing via single bolus, intermittent, continuous or
PCA infusion
Physical-chemical properties of medication dictate
onset, duration of effect and some side effects
Intraspinal Delivery
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Must use sterile solutions with no
preservatives (neurotoxic)
Side effects are consistent with
pharmacology and on rare occasion can be
intense
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Common – pruritis, urinary retention, N/V
Less – sedation, dec. resp., autonomic
fluctuations
Acute and Chronic pain utility
Spinal Anatomy
Dermatomal Distribution and
Intraspinal Analgesia
Properties of Epidural Opioids
Drug
Part.
Coef.
Onset
(min)
Peak
(min)
Durat.
(hr)
Dose
(mg)
Morphine
1.4
25
60
12-20
5-10
Methadone
116
10-15
17
8
5
Fentanyl
813
5-10
20
6
0.1
Sufentanil
1778
10
15-20
3-4
0.05
Medtronic Implanted Pump
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Radio-controlled,
programmable device
Drug reservoir has 30 day
infusion supply
Surgery to implant pump &
catheter tunnel to IT or EPI
space
Chronic cancer or
neurpathic pain
Expensive, > $ 20K for
device, surgery, refills
Medtronic Implantable Pump
Medications Placed in IT Pumps
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Local Anesthetics
Opioids
Clonidine
Ziconotide
And Combinations of Above