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