Pain meds

neuropathic pain

1.chronic pain caused by injury to, or disease of, the central and peripheral nervous systems, occurring as a result of a cascade of neurobiological processes, which lead to hyper-excitability in conducting pathways of somatosensory neurons.

Hyper-excitability is also hallmark of epileptic activity

hyperalgesia

hyperalgesia (exacerbated responses to painful stimuli) and allodynia (pain produced by otherwise non-painful stimuli) develop as a result of the pathological plasticity of sodium and calcium channels in several areas in the peripheral and spinal cord afferent pain pathways

neuropathic pain site

nerve

neuropathic pain quality

stinging

numbing

burning

radiating

neuropathic pain example

• neuropathy

• postherpetic neuralgia

• post stroke pain

neuropathic pain medications

• TCA

• gabapentin

• lyrica

somatic pain site

musculoskeletal

somatic pain quality

localized, dull, aching, sharp, throbbing, gnawing

somatic pain example

• sports injury

• postop nerve pain

• bone metastases

somatic pain medications

• opioids

• NSAIDs

• corticosteroids

• muscle relaxants

visceral pain site

involuntary muscle internal organs

visceral pain quality

poorly localized, deep, squeezing, pressure, radiating

visceral pain example

IBS, MI

visceral pain medications

• opioids

• corticosteroids

• NSAIDs

inflammatory pain site

noxious stimuli

inflammatory pain quality

warmth, redness, swelling

inflammatory pain example

• infections

• antibody formation

• physical injury

inflammatory pain medications

• NSAID

• corticosteroid

acute pain

•pain lasting <3-6 months

•Associated with tissue damage

•Self-limiting

•Treatment goal= rapid relief and cure

chronic non cancer pain

•Persisting beyond tissue healing- > 3-6 months

•Cause often unknown

•Treatment goal= some symptomatic relief but mostly improvement in daily function

factors affecting pain

depression, fatigue, insomnia, stress, anxiety, social and family issues, anger

pain meds

• opioids

• NSAIDs

• muscle relaxers

• antidepressants

• anti epileptic drugs

• OTC analgesics

opioid common adverse effects

Opioid Induced Constipation

Dry mouth

Nausea

Vomiting

mental confusion

Histamine-release reactions

Respiratory Depression!

opioid BBW

abuse, misuse, addiction potential, potential for fatal respiratory depression

opioid warnings: all opioids

additive sedation

caution in:

• elderly

• debilitated

• cachectic

• chronic pulmonary disease (hypoxia)

• TBI (intracranial pressure)

hypotension

dizziness/drowsiness

no alcohol

taper long term use

opioid allergy

opioid true allergy symptoms

difficulty breathing, severe hypotension, serious rash, swelling of lips, throat

morphine MOA

natural plant alkaloid opioid full agonist

morphine onset and duration

•Onset: IR (oral) = 30-60 min, IV = 5-10 min

•Duration: IR (oral) = 4 hr, ER (oral) = 8-24 hr

morphine dosing

IR = q4h

ER = q8-24h

morphine renal or hepatic

renal adjustments

morphine adverse effects and BBW

Caution in renal insufficiency

Hypotension and itchiness

Black Box: med errors with the oral solution

REMS for ER/CR formulation

codeine onset and duration (dosing)

•Onset: 30-60 min

•Duration: 4 – 6 hr

codeine adverse events

Caution in CYP2D6 altered metabolism

Caution in elderly

Hypotension and itchiness

hydrocodone MOA

semi-synthetic opioid full agonist

hydrocodone onset and duration

•Onset: 30-60 min

•Duration: 4-6 hr

hydrocodone renal or hepatic

CYP2D2 substrate

maybe both hepatic and renal

hydrocodone

•Metabolism: Hepatic CYP3A4 to active (hydromorphone) and inactive metabolites

•Almost always as a combination product, but can be standalone

•Little to no histamine involvement

hydrocodone concerns

Total daily dose of APAP

CYP2D6 poor metabolizer

Zohydro- EtOH accelerates absorption

hydromorphone MOA

Semi-synthetic opioid full agonist

hydromorphone onset and duration

•Onset:

Oral IR= 15-30 min

Oral ER= 6 hours

IV= 5 minutes

•Duration:

Oral, IV IR= 3-4 hours

Oral ER= 13 hours

hydromorphone

•Often used in PCAs and can be used intrathecally due to high potency

•Associated with minimal histamine release

•Metabolism: hepatic, no active metabolites

hydromorphone renal or hepatic

Renal and hepatic adjustments

hydromorphone adverse effects

dosing changes in renal/hepatic adjustments

oxycodone MOA

Semi-synthetic opioid full agonist

oxycodone onset and duration

•Onset: Oral IR= 10-15 min, Oral ER= 60 min

•Duration:

Oral  IR= 3-6 hr

Oral ER= < 12 hr

oxycodone metabolism

•hepatic CYP2D6 to active (oxymorphone) and weakly active metabolites

oxycodone renal or hepatic

renal adjustments

oxycodone adverse events

constipation

respiratory depression

meperidine onset duration

•Onset:

Oral= 10-15 min

IV= 10-20 min

•Duration: Oral= 2-4 hr

meperidine indications

•Not used in chronic pain management

•Can be useful in obstetric analgesia

meperidine adverse effects

Respiratory insufficiency and death when given within 14 days of an MAOI

Repeated doses can lead to nomeperidine accumulation. 24-48 hour use only

•Irritability, tremors, siezures

Can cause serotonin syndrome when combined with other serotonergic drugs

Renal adjustments in CrCl <50ml/min

fentanyl MOA

Synthetic opioid full agonist

fentanyl onset and duration

•Onset

Transmucosal= 5-15 min

Transdermal= 6hr

IV= <1 min

•Duration

Transmucosal= variable

Transdermal= 72-96 hr

IV= 30-60 min

fenanyl metabolism

•Metabolism: hepatic, primarily CYP3A4 to inactive metabolites

fentanyl

•Can accumulate in the fat cells

•Very potent- dosed in micrograms

•Preferred anesthesia analgesic

fentanyl cautions

NOT for opioid naïve patient in outpatient settings

NOT for acute pain in outpatient settings

NOT what is being abused- Illicitly manufactured fentanyl (IMF)

methadone onset and duration

•Onset

Oral= 30-60 min

IV= 10-20 min

•Duration

Oral= 4-8 hr

Tissue accumulation with repeated doses can extend this duration to 22-48 hr 

methadone metabolism

•hepatic CYP3A4, 2B6, 2C19 to inactive metabolites 

methadone cautions

Not for PRN use/ acute pain

Challenging PK- titrate every 3-5 days (longer in elderly)

Dose related QT prolongation

buprenorphine

•Partial agonist

Analgesic affects plateau at higher doses, then it behaves more like an antagonist

• Metabolism

Hepatic CYP3A4 to active metabolite

Extensive first pass effect

•Cautions

Ingestion of liquids decreases systemic exposure to buprenorphine from buccal film by 23%-37%

tramadol MOA

synthetic opioid weak agonist

tramadol onset and duration

•Onset: 1 hr

Duration: 9 hr

tramadol renal or hepatic

renal

tramadol caution

Max dose 400mg/day

Concomitant use of MAOI, risk of serotonin syndrome with other serotonergic agents

Mechanism is mostly working as an opioid on the mu opioid receptors, but also has some SNRI activity

Consider efficacy with hepatic impairment

Dose adjustments with renal insufficiency

tramadol max dose

400 mg/day