This presentation will cover several areas starting theoretically and moving through to practical application


Slide (27) 23 Pain window diagrams



Download 0.65 Mb.
Page3/6
Date02.12.2016
Size0.65 Mb.
1   2   3   4   5   6

Slide (27) 23 Pain window diagrams

Slide (28) 24 Tree of analgesia

So how do we know what drugs to use: understanding the different pharmogenics of each sub group of analgesia and their sites of action in the pain pathways will help. However this is a very complex process as new areas of pain pathway sites of actions are being discovered almost daily. Nevertheless drawing a line in the sand & starting somewhere is required. This knowledge is then coupled with either an understanding of the ascending and descending and brain registration areas functions in pain pathway interruption and modulation. In the late 1960’s the was the Gate Theory – today this has grown markedly . (Far to broad a topic to cover in this presentation. However the ANZCA Acute pain management book has done a lot of the leg work if you can achieve an effective thorough pain assessment.



Lipid soluble narcotics (hydromorphone (Dilaudid), fentanyl) Water soluble narcotics (preservative-free (PF) morphine, Duramorph

Why Use Opioids



  • Mode of Action:

    • Mimic action of endorphins.

    • Attach to receptor sites to produce analgesia.

    • Majority of receptor sites are found within the substantia gelatinosa of the dorsal horn (spinal cord).

    • Inhibit the release of substance P a neurotransmitter required for nociceptive transmission.

  • Opioid Recptors

Receptor

Action

Mu 1

Analgesia, euphoria and dependence

Mu 2

Respiratory depression, bradycardia, purities, miosis, nausea and vomiting, inhibition of gut motility

Kappa

Analgesia, sedation, miosis

Delta

Analgesia, dysphoria

sigma

Dysphoria, hallucinations, mydriasis


Achieving analgesia in the recovery room Opioids and Adjunctive therapy

  • Maximize regional analgesia

  • Analgesia is titrated to patient’s report of pain and functional ability.

  • Analgesia frequently achieved with opioid loading doses(s) with consideration given to:

    • sedation score, respiration rate, BP, and age

  • Use Adjunctive: paracetamol, NSAID, Tramadol, and ketamine may also be appropriate.

APP Order

  • Morphine 1-2 mg 5 minutely up to 10 mg PRN

  • Fentanyl 20-40 mcg 5 min. up to 200 mcg PRN

Notice which pain settles with opioid. Is there a pain that appears not to be responsive?



Has a non-opioid been considered?
Opioid Recovery room loading

  • Small amounts often to gain rapid analgesia

  • Peak effect of morphine ~ 15 minutes

  • Load then allow time for medication to peak

  • Minimum wait of 20- 30 minutes in recovery following parenteral opioid administration

  • Ketamine improves analgesia in patients with severe pain that is poorly responsive to opioids (level 11) ANZCA 2005


Practice points

  • Opioid requirement decreases with increasing age

  • Continuous Intravenous Infusions

  • Difficult to predict the infusion rate required to achieve consistent analgesia in each individual.

  • It takes 5 half-lives of a drug to reach a constant plasma drug concentration following changes in infusion rate

  • Programmed bolus doses should be used to achieve patient comfort, before rate changes.


Practice Points Pain and opioids

  • Pain acts as a physiological antagonist to the central depressant effects of opioids

  • As tolerance develops to the analgesic effect, so to does a greater tolerance develop to the respiratory depressant effect.

  • Respiratory effects of opioids

  • May produce a decrease in tidal volume and respiratory rate, or changes in respiratory rhythm.

  • Respiratory depression more likely when:

    • first dose is given

    • pain subsides (e.g. IDC insertion)

    • drug dose error

    • the dose not reviewed in renal failure

Adverse effects of opioids

    • CNS:sedation;euphoria ;constriction of pupils (miosis)

    • GIT Emesis stimulation of the chemoreceptor trigger zone in the medulla.

    • worst in ambulatory patients.

    • Constipation:delayed gastric emptying, inhibition of bowel motility.

    • Urinary retention: increased tone in the bladder sphincter

    • CVS: Hypotension- Arteriole and vein vasodilatation;

    • histamine release:Pruritus; histamine release which may result in local or generalised itching, not associated with a rash.

    • Allergy: rare, but similar to other allergic reactions.

Management options for opioid induced side effects.

  • Decrease the dose of opioid (e.g. PCA dose).

  • Regular concurrent use of other analgesics and non drug therapies.

  • Monitoring sedation levels will help prevent clinically significant respiratory depression.

  • Decrease the dose of opioid if constantly drowsy thus preventing respiratory rate depression

  • Sedation and respiratory depression can be exaggerated by the co - administration of e.g. diazepam, temazepam, or prochlorperazine with an opioid.

  • .


Opioid requirement decreases with increasing age
Continuous Intravenous Infusions

  • Difficult to predict the infusion rate required to achieve consistent analgesia in each individual.

  • It takes 5 half-lives of a drug to reach a constant plasma drug concentration following changes in infusion rate

  • Programmed bolus doses should be used to achieve patient comfort, before rate changes.


Pain and opioids

  • Pain acts a a physiological antagonist to the central depressant effects of opioids

  • As tolerance develops to the analgesic effect, so to does a greater tolerance develop to the respiratory depressant effect.

Respiratory effects of opioids



  • May produce a decrease in tidal volume and respiratory rate, or changes in respiratory rhythm.

  • Respiratory depression more likely when:

  • first dose is given

  • pain subsides (e.g. IDC insertion)

  • drug dose error

  • the dose not reviewed in renal failure.

STATEMENT OF EVIDENCE



  • As significant background and /or intermittent hypoxaemia may occur for a number of days postoperatively, Supplemental oxygen is recommended for at least the first 48-72 hours following major surgery and in elderly or high-risk patients regardless of the analgesic method used.

NHMRC Reader et al 1992a
Adverse effects of opioids

  • Central Nervous system

  • sedation

  • euphoria

  • constriction of pupils (miosis)

  • Emesis

  • stimulation of the chemoreceptor trigger zone in the medulla.

  • worst in ambulatory patients.

  • Constipation

  • delayed gastric emptying, inhibition of bowel motility.

  • Urinary retention

  • increased tone in the bladder sphincter

  • Hypotension

  • arteriole and vein vasodilatation

  • histamine release

  • Pruritus

  • histamine release which may result in local or generalised itching, not associated with a rash.

  • Allergy

  • rare, but similar to other allergic reactions.

Management options for opioid induced side effects.



  • Decrease the dose of opioid (e.g. PCA dose).

  • Regular concurrent use of other analgesics and non drug therapies.

  • Monitoring sedation levels will help prevent clinically significant respiratory depression.

  • Decrease the dose of opioid if constantly drowsy thus preventing respiratory rate depression

  • Sedation and respiratory depression can be exaggerated by the co - administration of e.g. diazepam, temazepam, or prochlorperazine with an opioid.


Morphine

  • Gold standard

  • Receptors: Mu +++ kappa + delta + agonist

  • short half life 2-3 hours.

  • Two main metabolites M3G and M6G, M6G is approximately twice as potent an analgesic as morphine.

Bupamorphine 7 days 72 hr to peak

  • Partial agonist may antagonize the effects of a previously administered agonist Opioids - depending on

    • proportion of receptors occupied

    • time interval between the administration of the two drugs



Buprenorphine patches are available as low-dose 7d release patches or in higher dose

patches replaced every 72hr.

Steady plasma concentrations occur on average 12hr after application of the transdermal

patch.


Dangerously high plasma concentrations can occur if patients are actively warmed whilst

wearing a transdermal patch, also pressure sensitive

BD label checking and signing safe guide


  • Example: Buprenorphine was compared with naloxone for reversal of prepoperative fentanyl (Boysen K et al 1988)



Acute Pain in Buprenorphine Maintained Patients

Use some form of opioid maintenance medication prefer Tramadol

Acute pain in hospitalized patient

provide analgesia as indicated for the condition

Caution: avoid high dose analgesic medication compounded with paracetamol in patient with Hepatitis B or C

consider maintenance with methadone pre operative 7/7 weaning Norspan



Methadone—long-acting pure opioid agonist.

In the acute pain setting methadone should be continued at the same dose.

If the patient is unable to take methadone orally, substitution with parenteral methadone or

other opioids may be required in the short term



Oxycodone

  • Synthetic opioid with better oral bioavailability than morphine and a slightly longer duration of action than oral morphine.

Receptors: Mu+++, Kappa+ and Delta+ agonist



  • 20mg oral oxycodone ~ 10 mg IM morphine

  • Oral oxycodone will take ~ 40 minutes to act

Also available in a control release tablet – 40% of drug dose is released in first hour(

enteric coated (functioning gut required)

Synthetic opioid with better oral bioavailability than morphine and a slightly longer duration

of action than oral morphine.




Codeine


Receptor: Mu+++ kappa+ and delta+ agonist

Well absorbed orally but a low affinity for opioid receptors.

Owes its analgesic effects to conversion by CYP2D6 to morphine, a pathway that is inactive

in about 10% of the population.

Number Needed to Treat = 16.7 for 60mg dose and 1.9 for combination 1gm paracetamol

with 60mg codeine.


Synthetic Opioids

Pethidine Rarely used

`synthetic opioid



Receptor Mu ++ kappa+ and delta + agonist.

  • elimination half life 2 - 6 hours.

  • norpethidine is its main metabolite, it has a long half life of 15 - 20 hours and will provide analgesia.

  • build up of norpethidine can cause irritability, tremors and convulsions.

  • Pethidine has been reported to more than double the risk of delirium.

  • Muscle fibrosis can occur when administered by IM route


Intra Operative

Remifentanil

  • Ultra short acting synthetic opioid

  • half-life is ~ 3 minutes. Usually delivered by infusion and rapid recovery when stopped.

  • Long acting analgesics may be needed before discontinuation.

  • Not for epidural or spinal route use as contains glycine


Alfentanil

  • derived from fentanyl

  • onset of analgesia in 15-120 seconds

  • duration of analgesia is dose related.

  • when compared to fentanyl, alfentanil is 25% more potent.

  • elimination half life of 90 minutes is significantly shorter than other opioids.

  • secondary serum peak levels reported.


Fentanyl

  • Receptors: Mu+++ and delta+ agonist

  • Onset of analgesia 30 - 120 seconds

  • Half life 1-2 hours

  • Peak onset 1 -5min, duration 30min, metabolite <72hrs (lipid soluable)/inert

  • No active metabolite - safer opioid in the presence of renal impairment.

  • Secondary serum peak levels reported @ 4hr (caution with continuos IV infusion ) leak taken up in fat cell with rebound release reported

  • Life threatening respiratory depression has been reported when transdermal or IV route fentanyl has been administered to opioid naïve patients (particularly early patch design)

  • spinal anaesthesia. Fentanyl 10–30µg has a rapid onset (10–20 min) and a short duration

  • Transdermal administration. Very lipid-soluble opioids are absorbed through skin. Fentanyl patches are available in five sizes (12–100µg/hr) and patches are replaced every 72hr of action (4–6hr)



Tramadol racemic mixture

  • synthetic centrally acting opioid-like drug

  • Less than half of its analgesic activity is at the µ-opioid receptor. It inhibits noradrenaline and serotonin uptake at nerve terminals, thereby enhancing the inhibitory pathway.

  • Lower tolerance & abuse potential, less respiratory depression, & constipation compared to other opioids reported.

  • Metabolised in the liver & excreted in the kidney. Main metabolite of tramadol is O-desmethyltramadol (M1) which is more potent. Formation of M1 also depends on the presence of CYP2D6 within the cytochrome P450 system (see codeine).

  • Parenteral load give slowly (15-30 minutes) to reduce incidence of adverse reaction

  • Nausea and dizziness - very common > 1/10

  • Drug interactions with anti-convulsants, and anti-depressants .Serotonin syndrome

  • Minimal respiratory and gastro-intestinal stasis.

  • Drug interaction with warfarin, and not recommended if coexisting condition of epilepsy exists

Equianalgesia (note equianalgesia differ from text to text slightly)

Drug

Oral dose (mg)

Parental dose (mg)

Morphine

30

10

Pethidine

300

75

Oxycodone

20 – 30

-

Codiene

200 - 240

-

  • Systemic Medications: Opioids

  • Opioid Receptors: ì, ê and ä receptors

  • Location of receptors: Periphery following inflammation;Spinal cord dorsal horn; Supraspinally in the brainstem, thalamus and cortex; PAG, nucleus raphe magnus and RVM in descending pathway

  • Mechanism of Action:

  • Spinal

  • Inhibition of Ca++ influx presynaptically

  • Enhacing K+ efflux postsynaptically

  • Activation of descending inhibitory GABAergic circuit

  • Peripheral

  • Inhibition of release of pro inflammatory and pro nociceptive substances

  • Adverse Effects & Problems: Respiratory Depression;Nausea and Vomiting;Sedation;Urinary Retention

  • Euphoria/Dysphoria;Constipation;Tolerance;Dependence and Addiction

  •  

  • Transdermal Fentanyl Delivery System (Ionsys)

  • Needle free, patient activated system for in-hospital use

  • Iontophoresis

  • Low intensity electrical field used to transport fentanyl across skin into circulation

  • Each double click delivers 40mcg over 10 min; For us in adults > 18 years; Used for 24 hours or 80 doses

  • Tramadol: Reasemtic noradrenaline /serotonin

  • Moderate affinity ì receptor agonist 5ht3 agonist.

  • Acts on spinal modulating pathways

  • Inhibition of neuronal NA and Serotonin uptake

  • Stimulation of presynaptic serotonin release

  • Adverse Effects:

  • Nausea & Vomiting: Ondansetron interferes with analgesic effect

  • Non addictive, less sedation

  • Dose: 3 mg/kg IM/IV/PO for moderate to severe pain

  •  

  • Buprenorphine:Semisynthetic, Agonist-Antagonist

  • Routes of administration:

  • IV, IM, Neuraxial, SC, SL, Trasdermal

  • Useful in morphine intolerant patient;Ceiling effect for respiratory depression, but not for analgesia.

  • Antiflammatory action:Useful in intra-articular injections; Prolongs duration of analgesia in peripheral nerve blocks with LA

  • Methadone:Synthetic broad spectrum opioid;Mu receptor agonist;NMDA antagonist;Inhibitor of monoamine transmitters

  • Useful in treatment of neuropathic pain; Orally well absorbed; No dose adjustment in renal disease; Drug most commonly used for opioid rotation

  •  



ANZCA’s Opioid Key messages

1. Dextropropoxyphene has low analgesic efficacy (U) (Level I [Cochrane Review]).

2. Tramadol is an effective treatment for neuropathic pain (U) (Level I [Cochrane Review]).

3. Gabapentin, non-steroidal NSAIDs and ketamine are opioid-sparing medications and reduce opioid-related side effects (N) (Level I).

4. In appropriate doses, droperidol, metoclopramide, ondansetron, tropisetron, dolasetron, dexamethasone, cyclizine and granisetron are effective in the prevention of postoperative nausea and vomiting (N) (Level I [Cochrane Review]).

5. Alvimopan and methylnaltrexone are effective in reversing opioid-induced slowing of gastrointestinal transit time and constipation (N) (Level I [Cochrane Review]).

6. Droperidol, dexamethasone and ondansetron are equally effective in the prevention of postoperative nausea and vomiting (U) (Level I).

7. Paired combinations of 5HT3 antagonist, droperidol or dexamethasone provide superior prophylaxis of postoperative nausea and vomiting than either compound alone (N)(Level I).

8. Naloxone, naltrexone, nalbuphine, droperidol and 5HT3 antagonists are effective

treatments for opioid-induced pruritus (N) (Level I).

9. Opioids in high doses can induce hyperalgesia (N) (Level I).

10. Tramadol has a lower risk of respiratory depression and impairs gastrointestinal motor function less than other opioids at equianalgesic doses (U) (Level II).

11. Pethidine is not superior to morphine in treatment of pain of renal or biliary colic (U) (Level II).

12. Morphine-6-glucuronide is an effective analgesic (N) (Level II).

13. In the management of acute pain, one opioid is not superior over others but some opioids are better in some patients (U) (Level II).

14. The incidence of clinically meaningful adverse effects of opioids is dose-related (U) (Level II).

15. High doses of methadone can lead to prolonged QT interval (N) (Level II).

16. Haloperidol is effective in the prevention of postoperative nausea and vomiting (N) (Level II).

17. Opioid antagonists are effective treatments for opioid-induced urinary retention (N) (Level II).PTER 4

18. In clinically relevant doses, there is a ceiling effect for respiratory depression with

buprenorphine but not for analgesia (N) (Level III-2).

19. Assessment of sedation is a more reliable way of detecting early opioid-induced

respiratory depression than a decreased respiratory rate (S) (Level III-3).

20. The evidence for risk of cardiac arrhythmias following low-dose droperidol is poor (N) (Level III-3).

21. In adults, patient age rather than weight is a better predictor of opioid requirements, although there is a large interpatient variation (U) (Level IV).

22. Impaired renal function and the oral route of administration result in higher levels of the morphine metabolites morphine-3-glucuronide and morphine-6-glucuronide with increased risk of sedation and respiratory depression (S) (Level IV).

The following tick box þ represents conclusions based on clinical experience and expert opinion.

;; The use of pethidine (U) and dextropropoxyphene (N) should be discouraged in favour of other opioids.

 

Paracetamol


  • Used as a component of multimodal therapy.

  • Importance of around the clock regular dosing.

  • Intravenous route option (give over 15 minutes 6/24hr)

  • Commence ASAP

  • 4g daily in adult (warfarin interaction at 3 g per week ↑ INR potential)



ANZCA’s Paracetamol Key Message

Paracetamol (acetaminophen) is the only remaining para-aminophenol used in clinical practice and is an effective analgesic (see below) and antipyretic. It is absorbed rapidly and well from the small intestine after oral administration with a bioavailability of between 63% and 89% (Oscier & Milner, 2009). It can also be given rectally and intravenously (see below and Section 6).

The mechanism of action of paracetamol remains unclear. In contrast with opioids,

paracetamol has no known endogenous binding sites, and unlike NSAIDs, apparently does not inhibit peripheral cyclo-oxygenase activity. There is increasing evidence of a central antinociceptive effect. Although the mechanism of analgesic efficacy of paracetamol remains elusive, it may involve direct and indirect inhibition of central cyclo-oxygenases, but the activation of the endocannabinoid system and spinal serotonergic pathways also appear to be essential (Bertolini et al, 2006; Botting, 2006; Pickering et al, 2006; Mallet et al, 2008; Pickering et al, 2008). Paracetamol has also been shown to prevent prostaglandin production at the cellular

transcriptional level, independent of cyclo-oxygenase activity (Mancini et al, 2003).

As one of the mechanisms of action of paracetamol appears to be linked to the serotonergic system, it is possible that other drugs with serotonergic effects could affect pain relief. In volunteers, coadministration of tropisetron or granisetron blocked the analgesic effects of paracetamol (Pickering et al, 2006 Level II; Pickering et al, 2008 Level II). The significance of this in the clinical setting has not yet been elucidated.


NSAIDs

The term NSAIDs is used to refer to both nsNSAIDs and coxibs (COX-2 selective inhibitors). NSAIDs have a spectrum of analgesic, anti-inflammatory and antipyretic effects and are effective analgesics in a variety of acute pain states. Many effects of NSAIDs can be explained by inhibition of prostaglandin synthesis in peripheral tissues, nerves, and the CNS (Botting, 2006). However, NSAIDs and aspirin may have other mechanisms of action independent of any effect on prostaglandins, including effects on basic cellular and neuronal processes. Prostaglandins are produced by the enzyme prostaglandin endoperoxide (PGH) synthase,

which has both cyclo-oxygenase and hydroperoxidase sites. Two subtypes of cyclo-oxygenase enzyme have been identified – the ‘constitutive’ COX-1, the ‘inducible’ COX-2: a COX-3 is also being investigated (Simmons et al, 2004; Gajraj & Joshi, 2005; Botting, 2006; Kam & So, 2009).




Share with your friends:
1   2   3   4   5   6


The database is protected by copyright ©dentisty.org 2019
send message

    Main page