what are the natural pain controls our bodies produce?
- - enkephalins
- - endorphins
closed gates, kappa receptors
decrease pain conduction, mu receptors
When do we make our own opioids?
- imagery, relaxation
- •TENS (transcutaneous electrical nerve
3 types of opioid meds
- - 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
Mu-receptor agonist drugs
- - morphine
- - hydromorphone [dilaudid]
- - oxycodone
- - merperidine [demerol]
- - propoxyphene [darvon]
- - fentanyl [subblimaze]
- - levorphanol
kappa - receptors agonist
- - nalbuphine [nubain]
- - butorphanol [stadol]
- - pentazocine [talwin]
What happens when you stimulate mu or kappa receptors?
Analgesia [person is still conscious but the pain component is taken away] – this means taking away pain
Effects of agonist stimulation of mu and kappa receptors
- - 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
Some side effects & adverse reactions of opiods
•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
What is the most dangerous side effect of opioids?
Which effect from opioids is most persistent over time?
Dealing with side effects of opioids
•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]
– move, diet, COLACE, Senna
- •Itching – cold, Nubian [also an opioid
- but blocks the receptors for stimulation of histamine] [usually starts at the
- •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,
when giving opioids into the spinal cord, what should your remember
- 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
Is there a limit to how much you can increase the dose [opioids], and still get the effect?
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
Tolerance to opioids develops to....?
No changes in tolerance to what when taking opioids
•Miosis (pinpoint pupils)
what is opiod Cross-tolerance
- 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.
OPIOID NAÏVE PATIENTS ARE THE MOST LIKELY TO SUFFER __?__ __?__ FROM MORPHINE!
How long does it take to develop physical dependence on morphine?
more than one week
SYMPTOMS OF OPIOID WITHDRAWAL(Opioid Abstinence Syndrome)
•Rhinorrhea (runny nose)
•Piloerection (goose bumps)
•Mydriasis (dilated pupils
Cross dependence [opioids]
- 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
How do you know how much to give of various opioids?
- Equianalgesic Charts
- - This gives you a conversion from when your changing your patient from say taking morphine to oxycodone [what's the equivalent dosages?]
Limitations of Equianalgesic Charts
•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
Effect of route on dose [opioid]
•“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
Which is NOT a sign of opioid overdose?
when do opiod overdoses occur?
- –Vulnerable people - opiate naïve,
- infants, elderly, respiratory problems, CNS problems
- –With other CNS depressants –
- alcohol, benzodiazepines, etc.
what steps should your take with an opioid overdose
- 1. make sure their breathing
- 2. get narcan - it reverses resp depression
Use of opioid antagonists
•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
Opioids with mixed agonist/antagonist effects
- •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
Common opioid agonists:mild to moderate pain
– same effect as ASA or APAP, but together with NSAID, increased effects, due to two mechanisms for effect
– 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
People who metabolizes codeine fast get what type of pain relief
fast pain relief
people who metabolizes codeine slow or lack the enzyme get what type of pain relief?
they get little to no pain relief
Common opioid agonists for moderate to severe pain: morphine
•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
In Heart Failure, Pulmonary Edema Morphine
- •reduces afterload and venous
- •respiratory depressant effect
- slows breathing, increases efficiency
Moderate to severe pain: meperindine (demerol)
- –Can metabolize into normeperidine metabolite which causes seizures in
- renal impairment!
–Infrequently used now
Moderate to severe pain, oxyconde
- •Oxycodone – can be used in regular
- or long lasting format
- •Oxycodone ER (Oxycontin; no acetaminophen)
- –if crushed, get dose dumping
- •Oxycodone + acetaminophen (Tylox,
- - 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
THE MOST COMMONLY PRESCRIBED DRUG IN THE USA is?
VICODIN - HYDROCODONE
Moderate to severe pain: fentanyl (Sublimaze)
- - lollipops, PCA, transdermal patch or PCA (electrical)
- - Take care, very concentrated compared to morphine
- - Used for anesthesia
- - Similar to morphine
Alternate routes for opioids
- - Spinal
- - Dermal patches
- - Subcutaneous infusion
- - 2 types of Patient Controlled Analgesia (PCA) delivery systems
[opioid] spinal route
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
[opioid] Dermal patches
- 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
2 types of Patient Controlled Analgesia (PCA) delivery systems [opioids]
–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)
- •hydromorphone (Dilaudid) (greater potency, lower volume
- fluid infused)
- •can add on to transdermal
- fentanyl patch
Renal Impairment and Opioids
- Hepatic metabolites:
- •10-20 X potency of morphine
- •accumulates in renal impairment!
- •antagonizes morphine and M6G
- •accumulates in renal impairment!
Adjuvant pain meds: Antidepressants
- [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
Adjuvant pain meds: Antiepileptic Drugs (AEDs)
- neuropathic pain, nerve compression, chronic fatigue syndrome
- –gabapentin (Neurontin)
- –pregabalin (Lyrica)
- –carbamezepine (Tegretol)
- –valproic acid (Depakene, Depakote)
Adjuvant pain meds: Corticosteroids
- reduce inflammation and edema
- near nerve tissue [that’s causing pain]
- –Pain from bone, liver, renal CA, nerve compression, increased intracranial pressure
TOPICAL AGENTS TO TREAT PAIN: Counter-irritants
- menthol, camphor, eucalyptus, capsaicin <[peper]
- –Stimulate large-diameter “A” nerve fibers that close gates
TOPICAL AGENTS TO TREAT PAIN: Lidocaine patch
- 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
Centrally acting analgesics
- •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