psych/neuro pain

what is somatic pain

injury to bones, joints, muscle, skin, CT; described as dull, throbbing, aching, localized

what is visceral pain

injury to internal organs such as GI tract, liver, stomach, pancreas; described as deep, cramping, sharp, stabbing, usually diffuse

what is neuropathic pain

damage to peripheral or central nerves; described as burning or tingling

taking APAP will increase of what

hepatotoxicity

does tylenol increase the risk of bleeding or GI irritation/ulcers

no

what are the therapeutic effects of NSAIDs

analgesia, anti-pyretic, anti-platelet, anti-inflammatory (at higher doses)

NSAIDs ______ inhibit COX-1/COX-2

reversibly

what are the major NSAID adverse events and warnings

(1) GI risk (black box warning)

⚫️increase of risk of bleeding

⚫️increase of ulceration

(2) renal/nephtrotoxicity

⚫️direct damage to kidneys

(3) cardiovascular risk

(4) increased general bleeding

what are the risk factors for GI risk for NSAIDs

prior history peptic ulcer disease

selective COX-2 inhibitors have a _____ risk with GI risk compared to non-selective

decrease

what are the risk factors for renal/nephrotoxocity for NSAIDs

preexisting kidney or liver disease

what are the NSAID DDIs

(1) anticoagulants = risk of bleeding

(2) aspirin + non-selective NSAID use = more ADRs including increase risk of bleeding + efficacy of aspirin

(3) SSRIs = increased risk of bleeding

(4) glucocorticoids =increased risk of ulcers/bleeding

t/f selective COX-2 inhibitors have the same therapeutic effect as non-selective NSAID

true

what are the different side effects between non-selective and selective COX inhibitors

COX-2 has less GI toxicity but increased CV risk

what is aspirin associated with

major bleeding, so should never be used for pain management

what is aspirin for in baby doses

reduce CV risks

what is the physiological response to opioids

(1) analgesia

(2) respiratory

(3) CNS

(4) GI

(5) dermatologic

(6) urinary

what is the most dangerous side effect of opioids and what should you monitor

respiratory depression; monitor O2 saturation and RR

what are the side effects of opioids in the CNS

(1) sedation

(2) confusion

(3) N/V

(4) physiologic dependence

(5) miosis (pupil constriction)

(6) cough suppression

what GI side effect are opioids related to

constipation

what dermatologic side effects are related to opioids

rash, (not a sign of true opioid allergy)

what are the different formulation of morphine

(1) IR

(2) ER

(3) IV

what are the "outpatient" opioids?

*Please note -- This is just a way to group them --- they are commonly used outpatient because they are PO (can also be used inpatient)

(1) Codeine

(2) Hydrocodone (+ acetaminopen)

(3) Oxycodone (+/- acetaminophen)

(4) Morphine

(5) Tramadol

-"CHOMT"

what are the main cons of morphine

= "outpatient" opioid

(1) increased risk of overdose in renal impairment (accumulation of morphine-6-glucuronide metabolite)

(2) increased risk of CNS side effects in renal impairment (accumulation of morphine-3-glucuronide metabolite)

- more histamine release

what schedule is morphine?

CII

Tramadol (CIV)

(1) Indication:

(2) Potency:

(3) Metabolite:

(4) Administration:

(5) Pros:

(6) Cons:

Tramadol (CIV) = "outpatient" opioid

(1) Indication: moderate to severe pain

(2) Potency: less potent

(3) Metabolite: prodrug converted by CYP2D6 to active metabolite

(4) Administration: PO only

(5) Pros: low risk for:

⚫️ sedation

⚫️ respiratory depression

(6) Cons:

⚫️ weak analgesic, ceiling effect

⚫️ increased seizure risk (avoid if sx history)

⚫️ caution in (unrecognized) ultra-rapid

⚫️ CYP2D6 metabolizers (avoid in children <12)

⚫️ risk of serotonin syndrome

⚫️ PO only

is tramadol a synthetic opioid

yes

what is the main moa of tramadol

weak mu-receptor agonist, inhibits reuptake of serotonin and norepinephrine

t/f tramadol is a prodrug

true

tramadol is a ________ converted by ________ to active metabolite

prodrug; CYP2D6

what is the indication for tramadol

moderate-severe pain

what formulation is tramadol available as

PO only

what are the pros for tramadol

low risk for sedation, respiratory depression, GI effects

what are the cons of tramadol

weak analgesic, seling effect

increased seizure risk - avoid if sx history

caution in (unrecognized) ultra-rapid CYP2D6 metabolizers

risk of serotonin syndrome with SSRIs, MAOIs, or triptans

PO only

what age group should avoid tramadol

children < 12 y/o

codeine is a _____ converted to ______ via _______

prodrug; morphine; CYP2D6

Codeine

(1) Prodrug:

(2) Indication:

(3) Schedule:

(4) Combo:

(5) Pros:

(6) Cons:

Codeine = "outpatient" opioid

(1) Prodrug: pro-drug converted to morphine via CYP

(2) Indication: moderate to severe pain

⚫️ short-term symptomatic relief of cough (adults only)

(3) Schedule: CII

(4) Combo: available as combo with APAP

(5) Pros: good antitussive (cough)

(6) Cons:

⚫️ weak analgesic w/ ceiling effect

⚫️ cautions in (unrecognized) ultra-rapid CYP2D6 metabolizers

-- avoid in children < 18y/o due to increased risk of respiratory

-- avoid in breastfeeding

⚫️ PO only

what is the indication for codeine

moderate-severe pain

short-term symptomatic relief of cough (adults only)

what schedule is codeine, codeine/APAP, and liquid

CII, CIII, CV

what is codeine as available as a combo with

APAP

what are the pros of codiene

less potent so less respiratory depression than morphine

good antitussive (cough)

what are the cons of codeine

weak analgesic w/ ceiling effect

caution in ultra-rapid CYP2D6 metabolizers

who should you avoid codeine in

breastfeeding

children <18 y/o due to increased risk of respiratory depression/death and abuse

codeine is only available as

PO

Hydrocodone

(0) Schedule:

(1) Indication:

(2) Potency:

(3) Administration:

(4) Pros:

(5) Cons:

Hydrocodone = "outpatient" opioid

(0) Schedule: CII

(1) Indication: moderate to severe pain

(2) Potency: equal potency to morphine

(3) Administration: ⚫️PO only

⚫️IR as combo only

⚫️Hydrocodone by itself is only available as ER

(4) Pros:

⚫️ moderate potency (relative to high potency opioids)

⚫️ multiple oral formulations = commonly prescribed

(5) Cons:

⚫️ mainly in combo products so APAP and ibuprofen dose is limiting factor

⚫️ PO only

hydrocodone has equal potency to

morphine

what are the formulations for hydrocodone

PO

IR as combo only

what is the brand name for hydrocodone/APAP

Vicodin, Lortab, Norco

what is the brand name of hydrocodone/ibuprofen

Vicoprofen

is hydrocodone available by itself

only available as ER

what are the pros of hydrocodone

commonly prescribed

less side effects than morphine

what are the cons of hydrocodone

mainly in combo products so APA and ibuprofen dose is limiting factor

PO only

alcohol increases blood levels of hydrocodone ER; do NOT administer together

Oxycodone

(0) Potency

(1) Schedule

(2) Indication

(3) Administration

(4) Pros

(5) Cons

Oxycodone = "outpatient" opioid

(0) Potency: slightly more potent than morphine

(1) Schedule: CII

(2) Indication: moderate to severe pain

(3) Administration: PO Only

⚫️ both by itself and in combo

(4) Pros:

⚫️ preferred in renal impairment

⚫️ less side effects than morphine

(5) Cons:

⚫️ PO only

⚫️ APAP dose limiting in combo products

which is more potent: oxycodone or morphine

oxycodone

is oxycodone available by itself or a combo

both

what are the pros of oxycodone

preferred in renal impairment

less side effects than morphine

what are the cons of oxycodone

PO only, APAP dose limiting in combo products

what are the "inpatient" opioids?

*Please note, I am labeling these ”inpatient opioids” as a way for you to group them and remember them. They are used inpatient because they are available IV and PO and the majority are on the more potent side (except for meperidine). However, they may also be used outpatient, especially in cancer patients who have a lot of pain.

(1) Merperidine

(2) Morphine

(3) Hydromorphone

(4) Fentanyl

-"MMHF"

-musty maids hate farts

Merperidine (CII)

(1) Potency

(2) Indication

(3) Side Effects

(4) Administration

(5) Pro

(6) Cons

Merperidine (CII) = "inpatient" opioid

(1) Potency: less potent than morphine

(2) Indication: not used as first line for pain due to side effects

(3) Side Effects:

⚫️Neurotoxicity

⚫️Seizures

(3) Administration:

⚫️ PO

⚫️ IV

(4) Pro: available IV

(5) Cons:

⚫️ increase metabolite accumulation in renal impairment

-- active metabolite is neurotoxic ==> seizure

-- now rarely used for acute pain

⚫️ CI with MAOIs

⚫️ Risk of serotonin syndrome

which is less potent: meperidine or morphine

meperidine

what is the indication for meperidine

not used as 1st line for pain due to side effects (neurotoxicity, seizures)

what are the cons of meperidine

increased metabolite accumulation in renal impairment -> active metabolite is neurotoxic -> might lead to seizures

is meperidine still used today

now rarely used for acute pain

Hydromorphone (CII)

(1) Potency

(2) Indication

(3) Administration

(4) Pros

(5) Cons

Hydromorphone (CII) = "inpatient" opioid

(1) Potency: much more potent than morphine

(2) Indication: severe pain

(3) Administration:

⚫️ IR

⚫️ Parenteral: IV, IM, SQ

⚫️ ER

(4) Pros: preferred in renal impairment (i.e. versus morphine) especially when we need a more potent agent or an IV agent

(5) Cons: easier to overdose

which is more potent: hydromorphone or morphine

hydromorphone

what is the indication of hydromorphone

severe pain

what is hydromorphone available as

IR, parenteral (IV, IM, subQ), ER

what are the pros of hydromorphone

preferred in renal impairment (vs. morphine) especially when we need a more potent agent or an IV agent

what are the cons of hydromorphone

easier to overdose

Fentanyl (CII)

(1) Potency

(2) Indication

(3) Administration

(4) Pros

(5) Cons

Fentanyl (CII) = "inpatient" opioid

(1) Potency: most potent

(2) Indication:

⚫️ Severe acute and chronic pain (opioid-tolerant pts ONLY)

⚫️ Used for analgesia/sedation in critically ill intubated patients

(3) Administration: IV, patch, lozenge, sublingual, tablet...

(4) Pros:

⚫️ Very fast acting, good for acute scenarios, used in ER, OR and ICU due to fast action, short duration

⚫️ Does not require renal/hepatic dose adjustment

⚫️ For severe chronic pain patch formulation used

(5) Cons:

⚫️ High risk of overdose

⚫️ Not for opioid naive pts for chronic pain

what is the most potent opioid

fentanyl

what is the indication for fentanyl

opioid-tolerant pts only, intubated pts

what are the pros of fentanyl

very fast acting, good for acute scenarios, used in ER, OR, and ICU due to fast action, short duration

doesn't require renal/hepatic dose adjustment

for severe chronic pain patch formulation used

what are the cons for fentanyl

high risk of overdose

not for opioid naive pts for chronic pain

what does it mean to be opioid tolerant (not-naive)

taking the following equal doses for at least one week:

oral morphine 60mg/day

what are examples of CYP2D6 and 3A4 substrates

(1) codeine

(2) meperidine (-> active metabolite (normeperidine); increase seizure risk in renal impairment)

(3) tramadol (-> active metabolite via 2D6; increase resp depression)

give examples of non-CYP metabolism

morphine (-> metabolite M3G (decrease seizure threshold in renal impairment); metabolite M6G (increase potency, increase resp depression in renal impairment)

how do you manage constipation in opioid-related side effects

all pts on opioids should get:

⚫️ stool softener (docusate) and mild laxative (senna, polyethylene glycol) if duration of opioid use is more than a few days

can a pt develop tolerance to constipation

no

how do you manage n/v for opioid-related side effects

give lower dose or a different opioid

how do you manage respiratory depression in opioid-related side effects

overdose reversal: give naloxone

what are the risk factors for opioid-related respiratory depression

concurrent use of benzodiazepine or other CNS depressants

how do you manage CNS side effects for opioids

(1) give lower dose; use a different opioid

(2) caution with other CNS depressants and when driving or operating heavy machinery

how do you manage dermatologic side effects in opioids

give an antihistamine or lowering dose

what are the different routes for naloxone

IV, intranasal, IM, subQ

what is nalaxone

pure opioid antagonist that competes and displaces opioids @ opioid receptor site

what are the steps if you suspect someone to be overdosing

1) suspect overdose: unarousable, recent drug use, shallow breathing, pinpoint pupils

2) administer naloxone intranasal: 4-8mg/spray in a single nostril (may repeat 3-5 if no response)

3) call 911

why must you use nalaxone with caution

precipitating acute opioid withdrawal in opioid dependent pts or on long acting opioids

what are DDIs for opioids

(1) CNS depressant

(2) MAO-I

(3) CYP2D6-I (decreased opioid efficacy)

⚫️ codeine

⚫️ tramadol

(4) SSRI, SNRI, TCAs, triptans, MAOIs (increased risk of serotonin syndrome)

⚫️ tramadol

⚫️ meperidine

(5) opioid antagonists

dosages at ______ MME/day increases risk of overdose

50

how do you start opioid therapy

(1) optimize

⚫️ non-pharmacologic and non-opioid therapies first

(2) avoid

⚫️ avoid opioids as first line for therapy except in:

-- end of life/palliative care, severe conditions

(3) prefer opioids in:

⚫️ severe trauma

⚫️ invaseive surgeries w/ moderate/severe pain

⚫️ when NSAIDs likely ineffective

when selecting an opioid for us, you should: (5 steps)

1) consider potency - less potent agent for minor injury;

2) consider opioid tolerance/naiveness - start with less potent agent and/or lower dose

3) consider formulation needed

4) consider PK - does pt have renal problems

5) consider adverse effects - does agent lower seizure threshold

for initial opioid therapy, use ______ formulations

IR

when should you use ER/LA opioid formulations

severe chronic pain:

- requiring around the clock opioids for at least one week

- receiving opioid tolerant doses

avoid _______ of chronic opioid use

abrupt discontinuation

what is the opioid pt education

- use enough to treat pain

- short tem use may lead to unintended long-term use

- limit max APAP intake (3-4gram/day)

- side effects: n/v, constipation, and sedation. side effects will improve over time except for constipation

- caution when driving/operation machinery

- limit alcohol

- do not abruptly stop opioid if taking chronically

- abstinence lowers tolerance; take less if restarting

- provide naloxone to high risk pts

what is physiologic opioid tolerance

reduced therapeutic effect of the same amount of an opioid used

when does opioid tolerance occur

analgesia, nausea, sedation, and respiratory depression

is physiological dependence the same as addiction

no

what is dependence

withdrawal sxs occurs when a drug is rapid d/c or reduction in dose