Pre-reading about Opioid Analgesia for Children Royal Children’s Hospital Melbourne Australia

Pre-reading about Opioid Analgesia for Children

Royal Children’s Hospital

Melbourne Australia

The use of opium

• Opium was first discovered in pre-biblical times; derived from the opium poppy

• Opium was widely used from the middle ages in a medicine known as “tincture of opium” or Laudanum

Children's Pain Management Service, RCH, Melbourne

What are opioids?

• All drugs with morphine-like actions are described as opioids

• Opioids were originally derived from the opium poppy (papaver somniferum) which has 25 alkaloids

• Only two of these alkaloids have any analgesic action: morphine and codeine


GlaxoSmithKline supplies ~25% of the world's medicinal opiate needs from opium poppies grown by farmers in Tasmania


Opioid or Narcotic?

Opioid: natural, semi-synthetic and synthetic drugs that relieve pain by binding to opioid receptors in the nervous system

Narcotic: obsolete term for opioid, because governments and media use the term loosely to refer to a variety of substances of potential abuse including opioids, cocaine and other substances


Opiate or Opioid?Opiate:

term used to refer to drugs derived from the opium poppy, for example, morphine (thus excluding synthetic opioids such as fentanyl)

Opioid:refers to any substance with morphine-like activity including natural, semi-synthetic and synthetic opioids


How morphine was named

• In 1805, a German pharmacist (Serturner) isolated an opium alkaloid

• He named it morphine (after Morpheus, the Greek god of sleep)


How do opioids work?

• All opioids bind to opioid receptors • Opioid receptors are located in the:• peripheral nervous system• spinal cord• brain

• When opioids bind to these receptors they affect the transmission of pain signals to the brain


Opioid receptors

There are three main types of opioid receptors:

• mu ()• delta ()• kappa ()

These receptors have multiple actions


Mu() opioid receptors

• The mu receptors are associated with:• analgesia• side effects

• Mu receptors are subtyped: mu-1 & mu-2


Action at the mu() receptor

• Mu-1 receptor is responsible for analgesia

• Mu-2 receptor is responsible for the opioid side-effects:• respiratory depression• cardiovascular depression• decreased gastrointestinal motility • sedation• euphoria• urinary retention


Mu-1 specific opioids do not exist• The opioid action of all known

natural and synthetic opioids at mu receptors is non-specific

• No opioid has yet been found or developed that acts only on the mu-1 receptor


Opioid receptor antagonist• Naloxone (NarcanTM) is a pure opioid

receptor antagonist• Naloxone displaces opioids bound to

opioid receptors• The duration of action of naloxone

is 30-60 minutes• Thus naloxone may wear off before

a longer acting opioid and symptoms of opioid toxicity may reappear


Indications for opioids

• Pain

• Intractable diarrhoea• Cough• Air hunger (end-stage respiratory

failure)


Contraindications to opioids

The following are not absolute contraindications,

as opioids may be used in small titrated doses:

• depressed conscious state (relative)

• head injury (relative)• respiratory insufficiency (relative)


Precautions

Neonates:• lower doses may be required• decreased clearance of opioids and

opioid metabolites


Side effects of opioids

• Opioid side effects occur regardless of which opioid is used

• Side effects are usually dose-related


Side effects of opioids

• respiratory depression

• sedation• euphoria • pinpoint pupils• itch • muscle rigidity

• bradycardia (with high doses)

• vasodilation • hypotension • urinary retention• nausea & vomiting• delayed gastric

emptying• constipation


Respiratory depression

• Respiratory depression from opioids is due to the combination of sedation, decreased tidal volume, reduced respiratory rate and a drop in oxygen saturation

• This results in hypoxia and raised carbon dioxide levels, which leads to further sedation and further respiratory depression


Different opioid drugsMorphine:

• pure opioid• powerful mu agonist• varied formulations (oral, IV/IM/SC)

• oral immediate release eg Morphine mixture/tabs, KapanolTM

• oral sustained release eg MS ContinTM

• the metabolites are M3G and M6G• morphine 3 glucuronide & morphine 6 glucuronide


Different opioid drugs

Codeine:• pure opioid• mu agonist• prodrug (converts to another form) • converts to morphine• 7-10% of some population groups are

unable to convert codeine to morphine, thus get no analgesia effect while others are rapid converters and become sedated.



Pethidine: (rarely used at RCH)

• synthetic opioid• mu agonist• metabolite is nor-pethidine• pethidine infusions should be

avoided due to the concerns of nor-pethidine toxicity



Fentanyl:

• synthetic opioid• mu agonist • structurally similar to pethidine• short acting, but a lipophilic (fat

soluble) drug which may result in accumulation

• no metabolitesChildren's Pain Management

Service, RCH, Melbourne


Hydromorphone (DilaudidTM):

• synthetic opioid• related to oxycodone and

hydrocodone• varied formulations (oral, IV/IM/SC,

epidural)• the metabolites are H3G and H6G

• hydromorphone 3 glucuronide & hydromorphone 6 glucuronide



Oxycodone:

• synthetic opioid• related to hydrocodone and

hydromorphone

• similar strength to oral morphine• sustained release version available• OxycontinTM



Dextropropoxyphene:• synthetic opioid• weak mu agonist• preparations often mixed with

other analgesics• eg combined with paracetamol as DigesicTM



Methadone:• synthetic opioid• strong mu agonist• very long acting opioid• useful for neuropathic pain• no metabolites



Tramadol:

• not a true opioid • has opioid and non-opioid

properties• non-opioid effects are via nor-

adrenaline and serotonin pathways• active metabolite (M1) has mu

receptor affinity


Misbeliefs about opioids and children • ‘Children are more sensitive to opioids’• ‘Infants and neonates do not feel pain’• ‘Pain is character building’• ‘Children have little requirements for

opioids’• ‘Children can be easily overdosed’• ‘The use of opioids leads to addiction’


Misunderstanding of definitions

• Confusion about the definitions of addiction, tolerance, withdrawal and the implications for patients are the main reason that opioids are under utilised


Definitions

• Addiction: psychological dependence with compulsive drug use, and craving for opioids for effects other than pain relief

• Tolerance: when increased doses of a drug is needed to produce the same pharmacological effect


Definitions

• Withdrawal: a cluster of physiological signs and symptoms, which occur after sudden ceasing of some drugs

• Dependency: when sudden absence of an opioid produces physical withdrawal syndrome


Fear of addiction• Fear of creating addiction in patients

contributes to the under use of opioid analgesics (Ferrell BR et al, J Pain & Sympt Manage, 1992)

• The risk of addiction for patients having opioids for medical reasons is extremely low

• Tolerance to an opioid does not mean the patient has an addiction


Caring for children receiving opioids• Accurate documentation• Correct dose of opioid• Correct and safe delivery of opioid• Observation of vital signs• Minimal side effects • Documented pain scores • Adequate analgesia achieved


Caring for children receiving opioids• Monitoring

sedation score pain score respiratory effort, rate, depth oxygen saturation heart rate


Combining opioids• It is not good practice to administer more

than one opioid at a time, as this increases the risk of side effects

• At RCH we do not administer morphine and codeine together

• An exception is when long-acting and short-acting formulations of the same opioid are administered for optimal analgesia in patients with severe pain eg MS Contin & morphine mixture OR Oxycontin & oxycodone


Optimising opioid analgesia

• The child needs to be comfortable• The child needs to be able to

breathe deeply/cough without pain• The child needs to be able to

mobilise freely without being limited by pain


Optimising opioid analgesia• Pre-emptive pain management is

important• Treat side effects early and adequately• Adjunctive analgesia may be required• Children should not be sedated• Believe the child’s pain assessment • Act on assessment


Children's Pain Management Service• The Children's Pain Management

Service supervises most patients with opioid infusions at Royal Children's Hospital

• CPMS can be contacted at all times on pager 5773


Finally…

Optimal pain management is the right of all patients and the responsibility of all health professionals


Documents

Pre-reading about Opioid Analgesia for Children Royal Children’s Hospital Melbourne Australia