3220: opioids

• - enkephalins
• - endorphins

closed gates, kappa receptors

decrease pain conduction, mu receptors

•Exercise

•Eating

• •Breast
• feeding

• •Distraction,
• imagery, relaxation

• •Low
• dose antidepressants

• •TENS (transcutaneous electrical nerve
• stimulation)

• - angonist
• - antagonist
• - combined

• stimulate the mu and/or kappa receptors by fitting into sites on the receptors
• - they are direct stimulators of a specific site 
• - well known of these is morphine [most effective]

compete [with agonist] for and block mu or kappa receptor sites, stopping the stimulation

agonist to mu, antagonist to kappa or revered

• - morphine 
• - hydromorphone [dilaudid]
• - oxycodone
• - merperidine [demerol]
• - propoxyphene [darvon]
• - fentanyl [subblimaze]
• - levorphanol

• - nalbuphine [nubain]
• - butorphanol [stadol]
• - pentazocine [talwin]

Analgesia [person is still conscious but the pain component is taken away] – this means taking away pain

• - CNS depression
• - Suppression of cough reflex
• - Respiratory depression
• - Euphoria
• - Histamine release – itchy feeling
• - Alteration in CTZ – chemoreceptor trigger zone => makes people need vomit increase - Urinary retention, constipation
• - Miosis- constricted [pin point] pupils

• - no euphoria
• - OTC
• - non- addicting

- Codeine: used to be OTC but now need a prescription

- Dextromethorphan: can get without a prescription

•Spasm of sphincter of Oddi [muscle that controls the relsease of pancreatic enzymes] – worsens pancreatic pain

• •Respiratory depression in opioid-naïve (esp. very young, old, COPD, heart failure, asthma)
• higher risk for problems

• •Opioids mask miosis, vomiting, mental changes in head injury – do not recommended use of opioids in pt with a head injury b/c it can mask the fact that the person has been
• vomiting, pinpoint pupils and mental changes

Respiratory depression

Constipation

•MONITOR FOR RESPIRATORY DEPRESSION

• •Nausea/vomiting – the more the pt
• move around the more likely they are to throw up, so if you tell your pt
• to lie still and quiet, a lot of times they won’t have a serve problem with
• that. Can also give medications to counter act this affect.

• •Hypotension – esp. with dehydration, BP
• meds [anticipate that they could pass out if they stand up too fast]

•Constipation – move, diet, COLACE, Senna

• •Itching – cold, Nubian [also an opioid
• but blocks the receptors for stimulation of histamine] [usually starts at the
• nose]

• •CNS depression – timing, stimulation
• [sometimes pt
• use opioids at night and try to use more of the NSAIDs during the day]

• •Urinary retention – remind to void,
• catheter

• they can last more than 24 hours for respiratory depression – even though the patient doesn’t look sleepy, you still have to monitor them for respiratory depression even into the next day when its given by this specific route
• -

Need more of medication to get same effect over time – need to increase dose to keep pain relief overtime

There is no limit to how much you can take and the effect increases with an increase in dose. This is NOT true for NSAIDs, taking 2 Tylenol will have the same effect as taking 4.

• •Most opioids have no ceiling effect
• –Can increase dose

• • NSAIDs DO have ceiling effect –
• no matter how much you take, don’t give more relief

•Analgesia

•Euphoria

•Respiratory depression

•Constipation

•Urinary retention

•Miosis (pinpoint pupils)

• A person tolerant to one opioid or opiate
• will be tolerant to others
• e.g. heroin and morphine
• - If a person came in after using heroin on the streets and is having withdrawal symp, it is possible to give them morphine to
• counteract the effects

• •Side effects (unintended effects) are
• highest in new users of opioids – especially nausea.

• •Nausea comes from direct effect on the
• brain centers for vomiting, but is less if you are lying down and don’t move.

• •Over time, some effects decrease, making
• it possible to increase medication dosage.

respiratory depression

more than one week

•Yawning

•Rhinorrhea (runny nose)

•Sweating

•Piloerection (goose bumps)

•Anorexia

•Limb tremors

•Mydriasis  (dilated pupils

•Irritability, anxiety

• A physically dependent person will not
• undergo withdrawal if given another opioid or opiate. This is why we can
• substitute morphine for heroin etc.
• e.g. heroin and morphine
•  heroin and methadone

• Equianalgesic Charts
• -  This gives you a conversion from when your changing your patient from say taking morphine to oxycodone [what's the equivalent dosages?]

•IM morphine dose is 1/6 PO dose for opioid-naïve but 1/3 PO dose for opioid-tolerant [have to give a higher dose for orals meds then iv meds]

•Depends on route (oral, parenteral)

•Tables are based on single doses, not steady-state blood levels

• •Patient may have incomplete tolerance to second opioid – need 33-55%
• dose reduction from that listed in chart

•Methadone (T ½ = 15-30 h) lasts days after discontinuation

•“First pass” effect of oral medications

• •Need higher dose of oral than parenteral
• dose of a given med

• •Blood-brain barrier and lipid solubility
• or placement into epidural or intrathecal
• spaces [has much higher effect on a much lower dose and last for a longer time
• as well] –The more soluble it is to fat the
• better it can cross over

• •IM or SC use very unpredictable, and
• painful

Fever

• –Vulnerable people - opiate naïve,
• infants, elderly, respiratory problems, CNS problems

• –With other CNS depressants –
• alcohol, benzodiazepines, etc.

–Addicted persons

• 1. make sure their breathing
• 2. get narcan - it reverses resp depression

•Overdose treatment

•Maybe maintaining abstinence in addicts?

•WILL PRECIPITATE VIOLENT WITHDRAWAL IN OPIOID DEPENDENT PERSONS when given narcan! [have to balance the dosage]

• •Narcan (Naloxone) – antidote to the opiods
• [blocks access of the opoiod to the receptors that are causing
• the problems with the overdose]

•Short acting – need longer term

•Available when opioids are used, esp. parenteral

• •Most stimulate kappa receptors, but block
• mu receptors.

• •Same effects as agonists, but less
• euphoria, respiratory depression, abuse potential generally

•MOST IMPORTANT:  if you give mixed opioid to someone dependent on opioid agonist, you will precipitate sudden withdrawal syndrome!!

•Some examples: Nubain, Stadol, Talwin

•codeine – same effect as ASA or APAP, but together with NSAID, increased effects, due to two mechanisms for effect

•codeine – some people genetically metabolize to active metabolite faster, some lack enzyme so no pain relief

• •propoxyphene (Darvon)
• – cardiac toxic metabolite in renal impairment!
• – FDA removed 2011

fast pain relief

they get little to no pain relief

•MORPHINE [oldest medication]

• •Decreases cardiac work by decreased
• BP, so good for heart pain

• •Best yet!
• –Metabolizednby liver and kidney
• –Well known dosing
• –Given orally, SC, IM, IV, intrathecal

• - Decreases the cardiac work by vasodilation thus decreasing B/P and increases circulation
• in the heart
• - Used a lot in heart failure and pulmonary edema because it decrease the work of the
• heart

• •reduces afterload and venous
• return

•promotes vasodilation

• •respiratory depressant effect
• slows breathing, increases efficiency

•relieves anxiety

• –Can metabolize into normeperidine metabolite which causes seizures in
• renal impairment!

–Infrequently used now

• •Oxycodone – can be used in regular
• or long lasting format

• •Oxycodone ER (Oxycontin;  no acetaminophen)
• –if crushed, get dose dumping

• •Oxycodone + acetaminophen (Tylox,
• Percocet)

• - If your using a long acting formulation that had ER at they end it CANNOT be
• crushed!! Crushing it will cause dose dumping
• - Most are combined with Tylenol or acetaminophen so you also have too look at the
• total dose of acetaminophen for the day

VICODIN - HYDROCODONE

• - lollipops, PCA, transdermal patch or PCA (electrical)
• - Take care, very concentrated compared to morphine
• - Used for anesthesia
• - Similar to morphine

• - Spinal
• - Dermal patches 
• - Subcutaneous infusion
• - 2 types of Patient Controlled Analgesia (PCA) delivery systems

epidural or intrathecal <[deeper into the spinal fluid] – LONG DURATION 24 hours – watch for respiratory depression – they get good analgesia without knocked out and they can be up and walking around within the first 24 hours

• peak effect at 24 hr, replace at 72
• hr.  Avoids “first pass” effects.  Persistant
• effects after removal.  AVOID HEAT
• (Fever, heating pad, bath) – rapid absorption with heat

–Pumps – IV and intrathecal: best control of symptoms without having overdose complications

–Intradermal – by electricals stim of skin?

• •for escalating pain in palliative
• home care (CA)

•morphine

• •hydromorphone (Dilaudid) (greater potency, lower volume
• fluid infused)

• •can add on to transdermal
• fentanyl patch

• Hepatic metabolites:
• –morphine-6-glucuronide
• (M6G)
• •10-20 X potency of morphine
• •accumulates in renal impairment!

• –morphine-3-glucuronide
• (M3G)
• •inactive
• •antagonizes morphine and M6G
• •accumulates in renal impairment!

• [it’s affects on serotonin levels]
• –Low Dose Tricyclics (TCAs): neuropathic pain, lupus, fibromyalgia, migraine

–Selective serotonin and norepinephrine reuptake inhibitor (SSNRI): Duloxetine (Cymbalta) – peripheral neuropathy in diabetes

• neuropathic pain, nerve compression, chronic fatigue syndrome
• –gabapentin (Neurontin)
• –pregabalin (Lyrica)
• –carbamezepine (Tegretol)
• –valproic acid (Depakene, Depakote)

• reduce inflammation and edema
• near nerve tissue [that’s causing pain]
• –Pain from bone, liver, renal CA, nerve compression, increased intracranial pressure

• menthol, camphor, eucalyptus, capsaicin <[peper]
• –Stimulate large-diameter “A” nerve fibers that close gates

• EMLA cream, Lidoderm patch 5%) –
• neuropathic pain, chronic low back pain, osteoarth.
• –Topical anesthetic blocks Na+ channels, dampens peripheral nociceptor
• sensitization and CNS hyperexcitability
• –Analgesia without numbness

• •Tramadol (Ultram) – two mechanisms,
• opioid + SNRI

–Stimultaes the same recp as the opioids do plus serotonin and norepinephrine receptors….

- Clonidine (Duraclon [for pain >epidural],

- Catapres [for BP>oral med]) – alpha2 andrenergic agonist, BP effects, has to be given epidurally when using it to block pain

•others