dr.husni - paracetamol iv as a safety analgesic
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Paracetamol iv as a Safety Analgesic
A. Husni Tanra
Department of Anesthesiology IC and Pain ManagementFaculty of Medicine Hasanuddin University
Makassar
Pain ControlAnalgesic Drugs
Opioid Non Opioid
NSAIDs Paracetamol
Now, almost all pain control managed with Multimodal Analgesia
Using Combination of Opioid with Non-Opioid Drugs
1. Opioids• Originally derived from poppies• Body possesses endogenous
opioids– enkephalins– endorphins
• Opiate Receptors– mu ()– delta ()– kappa ()– sigma ()
• Opioid is a srong analgesic• Opioids don’t damage organ.
Papaver somniferum
Ref. 2,5
Pharmacology of Opioids• 1: inhibit transmission of pain• 2: respiratory depression, euphoria, constipation, physical dependence• : inhibit transmission of pain• : inhibit transmission of pain• : autonomic effects, dysphoria, hallucinations
Ref. 5
Sensory nerve terminal
Secondary neurons
Afferent neurons
Mechanism of Opioids: How it works?
Substance Pgultamates
Minami et al : OPIOID, pp.20-32, Kasseido, Tokyo (2005)
Stimulation
NMDA receptor
NK1 receptor
Pain stimuli
μ-opioid receptor
Opioids
Releasing transmitter substances
Descen
ding
inhibito
ry nerv
e
terminals
Activate
inhibitory nerve
α2 adrenaline
receptor
noradrenaline
μ-opioid receptor
OPIOIDS
Inhibits excitationPain
Side Effect of OpioidsCommon Side Effect
1. Nausea and vomiting
2. Sedation 3. Urticaria4. Constipation
Very rare/ almost none1. Tolerance2. Respiratory
depression 3. Dependence4. Addiction
These side effects are dose related
Conclusions of opioids• Opioid is strong or very strong
analgesic• Safe to our organs• But they have many annoying side
effects
Limited used as single drug
Non-Opioid Medications• “Ceiling effect” to
analgesia• Do not produce
constipation, tolerance or physical dependence
• Most work by inhibiting prostaglandin formation• Mild to moderate analgesic
Ref. 1
2. NSAID
TXA2
PGE2
PGI2 PGI2
Mechanism of Cox-1, 1971Invention of Cox-2, 1999
All NSAIDs have similar evicacy
NSAIDs (nonselective inhibitor)• Efficacy is similar amongst NSAIDs• Differences in potency, time of onset,
& duration of action• Side effects:
– GI bleeding– renal dysfunction– platelet dysfunction
Ref. 1,3
COX-1 vs Cox-2 Selective Inhibitor (COXIB)
Selective COX-2 more safety than Non-selective COX inhibitor
But, it still had disadvantages such as : Cardiovascular Problem
IbuprofenKetoprofen
DiclofenacMeloxicamNimesulide
CelecoxibRofecoxibValdecoxib
AcetosalKetorolac
IndomethacinPiroxicam
non-selective
COXinhibitor
preferentiallyCOX-2
selectiveinhibitor
COX-2selectiveinhibitor
COX-1selectiveinhibitor
preferentiallyCOX-1
selectiveinhibitor
COXIB
analgesicanti-inflammatory
Less GI side effects, but more CVA
More GI side effects
Cox-1 vs Cox-2 selective inhibitor
Side effects of Opioid vs NSAIDOpioids NSAIDs
Side effects Nausea /Vomiting GI tract ulcer
Constipation Renal dysfunction
Sedation ( Titration) Liver dysfunction
Pruritis Asprine asthma
Respiratory depression (very rare)
Coagulopathy (in some drugs)
13
● we can see it immediately⇒ Rapid effect of opioid
● Easily treated⇒No organ damage.
●Not immediately seen ⇒Slow effect, usually masking
●Sometimes life threatening ⇒ NSAID can damage GI & Kidney
3. Paracetamol iv NEW but OLD DRUG
Acetominophen/PAAP
Analgesic Effects Antipyretic Effect
Route of Administration Orally Rectally Intravenously available in Indonesia since 2009
Bertolini A, et al CNS Drugs reviews, 2006;12:250-275
No Anti-Histamine Effects
Safety of paracetamol
1. All Age - Infant - Children2. All Age – Elderly3. Pregnant and Lactating Woman4. Incidence of adverse effects
comparable to placebo5. Renal Impairment6. Mild Hepatic Impairment
Paracetamol As Single Analgesic Drugs
Safe for all age (infant to elderly)
1. Infant – Children
- For Mild Pain
- Similar to NSAIDs
- Adjunct to other treatments for more severe pain
- Useful in day care surgery (20-40 mg/kg), include
tonsillectomy
Paracetamol As Single Analgesic Drugs
Safe for all age (infant to elderly)
2. Elderly
- Paracetamol is preferred non opioid analgesic for older people
- No Need to Reduce the Dose of Paracetamol
Paracetamol As Single Analgesic Drugs
Safe for pregnant and lactating woman
3. During Pregnancy and Breastfeeding
- Analgesic of choice during pregnancy
- Prostaglandin actions may have adverse effects in woman
Slight increase in asthma in infants
- Safe for the treatment of migraine in mother who are
breastfeeding
Paracetamol As Single Analgesic Drugs
3. Safe for pregnant and lactating woman
During Pregnancy and Breastfeeding
- Effective for Perineal pain during the first 24 hours after
birth
- Modestly effective in treating uterine pain
Paracetamol As Single Analgesic Drugs
4. Incidence of adverse effects comparable to placebo
Paracetamol As Single Analgesic Drugs
Hepatic impairment- Safety in patients with liver disease
- Preferred than NSAIDs
- Need to reduce the dose for patient with significant degree of hepatic
impairment
- Cautions in patients who had depleted glutahione store (Cirrhosis, hepatitis
C, HIV, malnourished)
Interactions with warfarin- Increase INR
Paracetamol As Single Analgesic Drugs
5. Safe in Mild Hepatic Impairment
Effective for Mild To Moderate Pain
Post Dental Surgery
Post Orthopedic Surgery
Post Tonsillectomy
Post Adenoidectomy
Post Inguinal Surgery
Acute Pain Associated with
Pharyngitis
Migraine TTH (Tension-type headache)
Paracetamol As Single Analgesic Drugs
Combination of Opiodwith Paracetamol
Opioid
Paracetamol
- Effective in Moderate to Severe Pain
- Reduce Opioid Dose - Reduce Opioid Side
effects- Little Paracetamol Side
Efffects-
PARACETAMOL , NSAIDS & COXIBS
Guidelines line for postoperative pain management state that:
“Unless contraindication, all patients should receive an around-the clock (ATC) regiment on NSAIDs, COXIBs, or Paracetamol”.
American Society of Anesthesiologists Task Force on Acute Pain Management 2004;100:1573-1581
Hyllested M, Jones S, Pedersen JL et al (2002) Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth 88(2): 199–214.
Paracetamol can be the best alternative to NSAID especially for high risk patients
It is appropriate to administer paracetamol with NSAID, or COXIBs additive or synergistic effects
Intravenous form of paracetamol has more predictable onset and duration of actions
Qualitative Review of Paracetamol and NSAIDs
1. Sindet-Pedersen S.1997. Data on file.
* I.V. paracetamol was administered as a bio-equivalent dose of propacetamol.
Fast onset of action *1
Sindet-Pedersen S, 1997
Rapid onset: 5minPeak at ideal time: 30min
IV paracetamol for dental
Good residual effect at >6hrs
Qualitative Systemic Review 2010Paracetamol and NSAIDs
Current evidence suggests that combination of Paracetamol and an NSAIDs may offer superior
analgesia compared with either drug alone
(Anesth Analg 2010)
Combination of paracetamol and parecoxib may useful in patients
who are susceptible to hemorrhagic complications of NSAIDs
Parecoxib and Acetominophen
Paracetamol and Gabapentin
Paracetamol +
Gabapentin
Analgesic+
Antihyperalgesic
postoperative pain scores &
Rescue Analgesics
but more episodes of nausea and vomiting and higher levels of sedation
Wound infiltration with Bupivacaine 1mg/kg combined with rectal Paracetamol 30 mg/kg has a better and valuable
efficacy compared to the rectal Paracetamol 30 mg/kg alone following inguinal herniotomy, hydrocelectomy and
orchidopexy in children and earlier mobilization.
Paracetamol and Local Anesthetic Infiltrations
+ParenteralAnalgesia (iv paracetamol + NSAIDs or COX-2 )
+Regionalspinal/epidural
and/or nerve block
+ParenteralAnalgesia
+Regional
spinal/epiduraland/or
nerve block+
Oral + Opioid+
Oral NSAIDs or COX-2 inhibitor or
paracetamol
+Oral + Opioid
+Oral NSAIDs or COX-2 inhibitor Or paracetamol
+Oral NSAIDs or COX-2 inhibitor or paracetamol
Pa
in I
nte
nsi
tySevere
MildT I M E
WFSA AnalgesicLadder for
postopeative pain
Pain Intensity
Opiate And
NSAID and
Paracetamol
Oral route available – give orally
Oral route unavailable – Rectal paracetamol & NSAID Opiate: High Tech: PCA Low tech: IM algorithm Epidural infusion analgesia
NSAID and
Paracetamol
ParacetamolPain decreases as time passes
Take Home Message1. Paracetamol iv as a single analgesic is very
safe analgesic, but only for mild and moderate pain.
2. It can be combined with many analgesic or adjuvan drugs to provide strong analgesic for postoperative pain.
3. So, it can be the basic regiment for Multimodal Analgesia.
4. Because of its safety it can be the choice for high risk surgical patient
Thank youvery much