Pain (R) Flashcards
cyclooxygenase enzymes
cox-1 and cox-2
COX-1: MOA & s/e
catalyzes synthesis of PGs used in normal body functions (eg. gastric cytoprotection)
“housekeeping” enzymes
blocking causes unwanted GI s/e
COX-2: example
acutely expressed as a part of the inflammatory response to cell damage
celecoxib(Celebrax)
NSAIDs are used for & MOA
-pain
-fever
-inflammation
-cardio-protection (ASA only)
block the synthesis of inflammatory prostaglandins by inhibiting cox enzyme from eliciting their actions
ASA: MOA
irreversible inhibitor (permanent) of COX-1 & COX-2
indomethacin
reversible inhibitor w/ greater affinity for COX-1
high risk for upper GI bleed/perf
coxibs: MOA & rx’ed for?
aka cox-2 inbibitors
selectively blocks COX-2 enzyme
spare the inhibition of COX-1
-pain
-fever
-inflammation
3 clinical efficacies of NSAIDs
-equal(analgesia & anti-inflammatory effects)
-therapeutic efficacy is based on pt’s response (associated with w/dose-dependent renal toxicity)
display “ceiling” effect
ceiling effect
higher doses do not provide any additional pain relief
-may inc the likelihood of s/e
non-selective NSAIDs
associated w/ GI toxicity if a pre-existing ulcer or dyspepsia, H. pylori infection & older age
managing GI s/e
-take w/ food or milk
-switch to diff NSAID w/ better safety profile
-COX-2 selective agent (celecoxin)
-gastroprotection (H2RA, PPI, misoprostol)
pts w/ increased risk of GI bleeding/ulcer that req a NSAID…rx
celecoxib (Celebrex)
if pt has a high risk of GI complications (hx of NSAID-related GI bleeding) additional drug class s/b Rx
PPI
risk of upper GI bleed: low
- ibuprofen (lower than ALL tNSAIDs)
- celecoxib (Celebrex)
risk of upper GI bleed: medium
-diclofenac
-etodolac
-meloxicam
-ketoptofen
-nabumetone
-naproxen
risk of upper GI bleed: high
-indomethacin, sulindac
-ketorolac (Toradol)
-piroxicam
preventative/therapeutic measures for: dyspepsia, abd pain, GI discomfort
combine NSAID w/ PPI or H2 blockers
preventative/therapeutic measures for: GI bleeding
-avoid NSAIDs w/ h/o NSAID-associated UGI bleeding
-add PPI/misoprostol
-celecoxib +/- PPI/misoprostol
NSAID black box warning (GI)
-inc risk: GI a/e including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
-can occur at any time during use & w/o warning sxs
elderly at greater risk
preventative/therapeutic measures for: impaired renal fn
avoid?
BP meds?
-avoid NSAIDs
-use NSAIDs w/ caution when combined w/ meds that potential decease renal function (ACE inhibitors, beta-blockers)
preventative/therapeutic measures for: respiratory (aspirin-exacerbated resp disease)
use NSAIDs & ASA w/ caution in pts w/ asthma, esp w/ nasal polyps or recurrent sinusitis
NSAIDs & COXibs are associated w/
increased CV risk & bleeding risk
-fluid retention, HTN, edema
-rarely MI, stroke, CHR
cardiovascular: low risk from NSAIDs & COX
ibuprofen
naproxen
cardiovascular: high risk from NSAIDs & COX (name med)
diclofenac
preventative/therapeutic measures for: cardiovascular complications (worsening HTN, MI)
think:
type of NSAID
which conditions
-avoid COX-2 inhibitors/non-selective NSAIDs in pts at risk of CV events
-avoid NSAIDs in pts w/ CHF
-use NSAIDs w/ caution in pts w/ HTN [mean BP increase is 5mmHg]
preventative/therapeutic measures for: hepatic complications
avoid NSAIDs in pts w/ cirrhosis due to potential hematologic and renal complications
black box warning: cardiovascular for NSAIDs
inc risk of:
CV thrombotic events
myocardial infarction
stroke
(can be fatal)
preventative/therapeutic measures for: clotting problems contributing to significant bleeding
-avoid NSAIDs in pts w/ platelet defects or thrombocytopenia
-avoid combining NSAIDs w/ anticoagulants [risk of GI bleed increases 3-6x]
-if NSAIDs are nec in pts w/ an anticoagulant, expect an increase in INR [INR inc up to 15%]
-avoid daily low-dose ASA if CV risk is low (<3% annual risk)
preventative/therapeutic measures for: prolonged pregnancy or labor
avoid NSAIDs toward the end of pregnancy (6-8wk before term)
STEPS
simplicity
tolerability
evidence
price
safety
if a pt fails therapy w/ an agent from one class of NSAIDs then
use of an agent from another class is reasonable
cox-2 selective agents have ideal indication for
-high risk GI bleed
-high intolerance of non-selective NSAIDs
-tx failure w/ non-selective agents
NSAIDs efficacy for neuropathic pain
minimal value
acetaminophen
-blocks PG synthesis in CNS
-inhibits peripheral pain impulses
does not interfere w/ COX-1 or COX-2 (no anti-inflammatory benefit)
initial therapy for mild-moderate pain
McNeil Consumer Healthcare reduced acetaminophen dose to
max 3,000mg daily and increased the dosing interval to q6
American Geriatric Society (AGS) Panel on Pharmacological Management of Persistent Pain in Older Persons recommend - how much acetaminophen?
less than 2g :
-frail patients
-80+ yo
-consume alcohol
what’s the dose for APAP when used for longer term duration (>7d) ?
3g/day w/ normal liver fn
what increases the risk of hepatotoxicity?
-heavy alcohol use
-malnutrition
-fasting
-low body wt
-advanced age
-febrile illness
-select liver disease
-use of drugs w/ APAP
dose: 2g/day or avoidance
adjuvant analgesics
medications possessing analgesic properties but developed for purposes other than pain relief
-anticonvulsants
-antidepressants
-lidocaine patches
-corticosteroids
-muscle relaxants
gabapentin or lidocaine patch
for post-herpetic neuralgia
1st line of therapy for diabetic peripheral neuropathy (DPN)
-amitriptyline avoid in elderly
-duloxetine (SNRI; coexisting depression)
-pregabalin (severe pain/insomnia)
TCAs
for trigeminal neuralgia
(a condition that causes painful sensations similar to an electric shock on one side of the face)
opioids
most drugs are selective for mu receptor type
mu-1: produces effects of analgesia
mu-2: linked to sedation, reduced BP, itching, N, euphoria, dec resp, miosis (constricted pupils), dec bowel motility aka constipation
opioids are safe for
-acute, severe pain
-mod-severe cancer pain
-mod-severe chronic non-malignant & severe neuropathic [3rd/4th line)
-mod-severe headaches [last resort: contraindication w/ triptans]
do opioids have a ceiling effect?
No
opioid treatment: intermittent pain
begin w/ short-acting
morphine, oxycodone, hydrocodone
-try one at a time
-q4-6hr
opioid treatment: continuous pain
long-acting agents:
-CR (controlled release) morphine
-methadone
-use short-acting agents to determine starting point
-short-acting agents may be necessary for BTP
when does tolerance to most side effects occurs?
within first wk
recommendations for ongoing s/e sedation
-reduce dose by 25% & inc interval
CNS stimulants:
-caffeine 100-200mg POq6h
-methylphenidate 5-10mg PO 1-3x/day
-dextroamphetamine 5-10mg PO 1-3x/day
-modafinil100-200mg PO daily
highest risk for respiratory depression
opioid naive
risk is minimized in chronic users bc pts rapidly develop tolerance to this effect
for mild respiratory depression
decrease dose by 25%
for severe respiratory depression
naltrexone
antiemetic / prevention
hydroxyzine
diphenhydramine
ondansetrol
dose for hydroxyzine (1st generation histamine H1 antagonist)
25-100mg PO/IM q4-6 PRN
dose for diphenhydramine (Benadryl) antihistamine
25-50mg PO/IM q6 PRN
dose for ondansetron
4-8mg PO TID
antiemetic / treatment
prochlorperazine
haloperidol
metoclopramide
granisetron
ondansetron
palonosetron
if PRN unsuccessful may administer around-the-clock
CNS irritability: define & tx
usually abates soon after initiation of therapy
-if confusion or delirium persists for more than 2wks:
dicn’t/alternate opioid
dose reduction
treat w/ BZD
haloperidol
pruritis
more common w/ parenteral than oral opioids
-do not confuse w/ true allergy
tx:
diphenhydramine (Benadryl)
promethazine
constipation
-tolerance does not develop to this s/e
-goal: 1 non-forced BM q1-2d
stimulant laxative
promote motility/peristalsis
-senna
-bisacodyl (Dulcolax) 17.2mg/day
stool softener
counteract drying & hardening effects of increased transit time
docusate 100mg/day
peripheral opioids antagonists
does not affect analgesic response or promote withdrawal because it does not cross the BBB
allergenicity
true allergy to codeine (or related compound), the risk of cross-reactivity w/ another opioid can be reduced if an analgesic from a different chemical class is used
for severe, life-threatening reactions consider using
non-narcotic analgesics, such as NSAID agents or acetaminophen
cross allegenicity
pick drugs from another class
3 classes of opioids
-phenanthrenes
-phenylpiperidines
-phenylheptanones
phenanthrenes
morphine
hydromorphone
oxymorphone
levorphanol
codeine
hydrocodone
oxycodone
phenylpiperidine
meperidine
fentanyl
sufentanil
alfentanil
phenylheptanones
(diphenylheptanes)
methadone
levomethadyl
FDA definition of opioid tolerance
for at least 1 wk s/he has been receiving oral
-morphine 60mg/d
-transdermal fentanyl 25mcg/hr
-oxycodone 30mg/d
-hydromorphone 8mg/d
-oxymorphone 25mg/d
aberrant drug-related behavior
a behavior outside outside the boundaries of the agreed on treatment plan, est as early as possible in the doc-pt relationship
2 opioid antagonists
naloxone
naltrexone
naloxone
(Narcan)
tx of opioid agonist-induced respiratory depression and known/suspected overdose of opioid
reverses both toxic and clinical effects of opioids
naltrexone
the adjuvant tx of alcoholism and nicotine dependence
-used off-label for opiate agonist dependence and withdrawal
-wt loss
