By Shahirah Zainudi, R.Ph 3960
Pharmacist

Introduction
Objective Pain Free Hospital
Principle in pain control
Ladder to treat pain
Types of analgesic in pain management
Conclusion

 Pain is the most common reasons patients
visit the emergency department1,2.
 Pain, as a presenting complaint, account for
up to 78 % of visits to the ED1.
 Definition of pain3
 Pain is an unpleasant sensory and emotional
experience associated with actual or potential tissue
damage, or described in terms of such damage
 mental suffering or distress.
1 Ministry of Health Malaysia. Guidelines for pain management in emergency department 1ST edition.
2 Ministry of Health Malaysia, Pain as the Fifth Vital Sign Guideline handbook, 2nd edition.
3 "International Association for the Study of Pain: Pain Definitions". Retrieved 31st July2017. Accessed from
https://www.iasp-pain.org/Taxonomy Pain. 1979;6(3):247–3

Pain free surgery
Pain free labor
Pain free procedures
Pain free rehabilitation
Pain free discharge

1 Ministry of Health Malaysia. Guidelines for pain management in emergency department 1ST edition.

 1Pain will be managed holistically by
 a) psychological,
 b) non-pharmacological and
 c) pharmacological method.
 Emergency department manages more acute
pain rather than chronic pain

Analgesic Medications for Acute Pain Management

Tablet Paracetamol 500mg Syrup Paracetamol 120MG/5ML
@250MG/5ML
Suppository ParacetamoI
125mg @ 250mg
Injection Paracetmol 10MG/ML IN 100ML

Form & Strength Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @
250mg
Injection
Paracetmol
10MG/ML IN 100ML
Prescribing category C+ C+ 125MG (C+) &
250MG (B)
A
Use Treatment of mild to moderate pain and fever Add ix: mx of moderate
to severe pain when
combined with opioid
analgesia
Pharmacokinetics Onset: Oral: <1 hr. IV: 5-10 min (analgesia); w/in 30 min (antipyretic).
Duration: 4-6 hr (analgesia). IV: ≥6 hr (antipyretic).
Absorption: Readily absorbed from the GI tract. Time to peak plasma
concentration: Approx 10-60 min (oral).
Distribution: Distributed into most body tissues; crosses the placenta
and enters breast milk. Plasma protein binding: Approx 25%.
Antipyretic properties - reduced amount of PG E2 in the CNS,
lowers the hypothalamic set-point in the thermoregulatory
centre, resulting in peripheral vasodilation, sweating and hence
heat dissipation

Form &
Strength
Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @ 250mg
Injection
Paracetmol
10MG/ML IN
100ML
Pharmacokinetic Metabolism: Hepatic via glucuronic and sulfuric acid conjugation. N-
acetyl-p-benzoquinoneimine (minor hydroxylated metabolite), is usually
produced in very small amounts by CYP2E1 and CYP3A4 isoenzymes in the
liver and kidneys.
Excretion: Mainly via urine (as glucuronide and sulfate conjugates, <5%
as unchanged drug). Elimination half-life: Approx 1-3 hr
Administration May be taken with or without food.
Dosage Details Intravenous
Mild to moderate pain and fever
Adult: 33-50 kg: 15 mg/kg as a single dose, at least 4 hrly. Max: 60 mg/kg
(up to 3 g) daily;
>50 kg: 1 g as a single dose, at least 4 hrly. Max: 4 g daily. Admin by
infusion over 15 min.
Child: <10 kg: 7.5 mg/kg as a single dose, at least 4 hrly. Max: 30 mg/kg
daily; 10-33 kg: 15 mg/kg as a single dose, at least 4 hrly. Max: 60 mg/kg
(up to 2 g) daily; >33-50 kg: 15 mg/kg as a single dose, at least 4 hrly.
Max: 60 mg/kg (up to 3 g) daily. Admin by infusion over 15 min.

Form &
Strength
Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @ 250mg
Injection
Paracetmol
10MG/ML IN
100ML
Dosage
Details
Normal patient
Oral
Mild to moderate pain and fever
Adult: 0.5-1 g 4-6 hrly. Max: 4 g daily.
Child:10-15mg/kg/dose every 4-6hours as needed. 3 to <6 mth 60
mg; 6 mth to <2 yr 120 mg; 2 to <4 yr 180 mg; 4 to <6 yr 240 mg; 6 to <8
yr 240 or 250 mg; 8 to <10 yr 360 or 375 mg; 10 to <12 yr 480 or 500
mg; 12-16 yr 480 or 750 mg. Given 4-6 hrly if necessary. Max: 4 doses in
24 hr.
Oral
Post-immunisation pyrexia
Child: 2-3 mth 60 mg. If necessary, a 2nd dose may be given after 4-6 hr.
Rectal
Mild to moderate pain and fever
Adult: As supp: 0.5-1 g 4-6 hrly. Max: 4 g daily.
Child: 3 mth to <1 yr 60-125 mg; 1 to <5 yr 125-250 mg; 5-12 yr 250-500
mg. Given 4-6 hrly if necessary, up to 4 times daily.
Rectal
Post-immunisation pyrexia
Child: 2-3 mth 60 mg. If necessary, a 2nd dose may be given after 4-6 hr.

Form &
Strength
Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @
250mg
Injection
Paracetmol
10MG/ML IN 100ML
Dosing interval
in renal
impairment
Oral
Children
CrCl < 10-50mL/min : Administer every 8 hours
Intermittent HD or PD: Administer every 8 hours
CRRT: No adjustment necessary
Adults
CrCl 10-50mL/min : administer every 6 hours
CrCl <10mL/min : Administer every 8hours
Intermittent HD or PD:No adjustment necessary
CRRT: Administer every 8 hours
Injection:
CrCl <30mL/min: Use with caution; consider decreasing daily dose and
extending dosing interval

Form &
Strength
Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @
250mg
Injection
Paracetmol
10MG/ML IN 100ML
Dosing
adjustment in
hepatic
impairment
Oral : Use with caution. Limited, low dose therapy is usually well
tolerated in hepatic disease/ cirrhosis. However, cases of hepatotoxicity
at daily acetaminophen dosages < 4gm daily have been reported. Avoid
chronic use in hepatic impairment.
Injection:
Mild to moderate impairment: Use with caution in hepatic impairment or
active liver disease; manufacturer’s labeling suggests a reduced total
daily dosage may be warranted, although no specific dosage adjustments
are provided.
Severe impairment: Use is contraindicated.
Food Interaction
Alcohol may increase risk of hepatotoxicity.
Adverse Drug
Reactions
Thrombocytopenia, leucopenia, pancytopenia, neutropenia, agranulocytosis,
pain and burning sensation at inj site. Rarely, hypotension and tachycardia.
Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute
generalised exanthematous pustulosis, acute renal tubular necrosis and
hepatotoxicity.

Form & Strength Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @ 250mg
Injection
Paracetmol
10MG/ML IN
100ML
Pregnancy category PO: category B; IV: category C
Overdosage Symptoms: Pallor, nausea, vomiting, abdominal pain, anorexia, CNS
stimulation, excitement, delirium, metabolic acidosis, glucose
metabolism abnormalities. In severe poisoning, liver damage may lead
to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema
and death. Management: Admin activated charcoal if taken w/in 1
hr and >150 mg/kg has been ingested. Determine plasma
paracetamol concentration at 4 hr or later after ingestion. Treatment
w/ N-acetylcysteine may be used up to 24 hr after ingestion (most
effective if given w/in 8 hr). If needed, admin IV N-acetylcysteine.
Oral methionine may be a suitable alternative for remote areas if
vomiting is not a problem.
Drug interaction May reduce serum levels w/ anticonvulsants (e.g. phenytoin,
barbiturates, carbamazepine). May enhance the anticoagulant effect
of warfarin and other coumarins w/ prolonged use. Accelerated
absorption w/ metoclopramide and domperidone. May increase serum
levels w/ probenecid. May increase serum levels of chloramphenicol.
May reduce absorption w/ colestyramine w/in 1 hr of admin. May
cause severe hypothermia w/ phenothiazine.

Form & Strength Tablet
Paracetamol
500mg
Syrup
Paracetamol
120MG/5ML
@250MG/5ML
Suppository
ParacetamoI
125mg @
250mg
Injection
Paracetmol
10MG/ML IN 100ML
Precaution
Hepatic insufficiency.
Severe renal insufficiency (Creatinine clearance ≤ 30 mL/min).
G6PD deficiency (may lead to haemolytic anaemia).
Chronic alcoholism or excessive alcohol intake.
Anorexia, bulimia or cachexia, chronic malnutrition (low
reserves of hepatic glutathione).
Dehydration and hypovolemia.

 Non opiod analgesic
 Paracetamol ( Acetaminophen)
NSAIDs
Non Cox inhibitors selective COX Inhibitors Selective
Diclofenac- tablet, injection
suppositori, oinment
Mefenamic Acid- Capsul
Methyl salicylate- Ointment
Ketoprofen- Oinment
Ibuprofen- Tablet
Naproxen- Tablet
Indomethacin- Capsule
Celecoxib
Etoricoxib
Parecoxib

Form &
Strength
Tablet Diclofenac 50mg/ tab Injection Diclofenac 75mg/vial
Picture
Form &
Strength
Capsul Mefenamic Acid
250mg/cap
Picture

Mefenamic Acid Diclofenac Sodium
Prescribing
category
B B
Dosage Oral
Adult: 500 mg tid.
Child: >6 mth 6.5 - 25 mg/kg daily
3 - 4 times daily for not longer than
7 days
Oral
Pain and inflammation : 50-150 mg/day. Max:
150 mg/day
Child > 6mo: 0.3-1mg/kg/day . Max 150mg/day
3mg/kg/day for only a maximum of 2
days
Injection
IV Post-op pain 75 mg infusion, may repeat 4-6 hr
later if needed. Max period: 2 days.
Prophylaxis of post-op pain As diclofenac Initial:
25-50 mg via infusion after surgery followed by 5
mg/hr, may repeat after 4-6 hr. Max: 150
mg/day. Max period: 2 days.
IM Pain and inflammation As diclofenac Na: 75
mg once daily, may increase to 75 mg bid in
severe conditions. Max period: 2 days
Gel
Local symptomatic relief of pain and
inflammation As diclofenac Na (1% gel): Apply
onto affected area 3 or 4 times daily.
Rectal
Adult: 75-150mg/day in div doses (Max com oral

Active
Ingredients
Mefenamic Acid Diclofenac Sodium
Dosage
adjustment in
renal impairment
Use is not recommended Not recommended in patients
with advanced renal disease or
significant renal impairment
Dosage
adjustment in
hepatic
impairment
No dosage adjustment provided in
manufacturer’s labeling (has not
been studied). However,
adjustment may be necessary dua
to extensive hepatic metabolism.
Elderly: no spesific dosing
recommendation, elderly may
demonstrate adverse effects at
lower doses than younger adults
and 60% may develop
asymptomatic peptic ulceration
with or without hemorrhage;
monitor renal f(x).
Administration Should be taken with food.
May impair ability to drive or
operate machinery.
Should be taken with food. Take
immediately after meals.

Active
Ingredients
Mefenamic Acid Diclofenac Sodium
Pharmacoki
netics
Duration: ≤6 hr.
Absorption: Rapidly absorbed from
the GI tract. Time to peak plasma
concentration: Approx 2-4 hr.
Distribution: Enters breast milk
(small amounts). Volume of
distribution: 1.06 L/kg. Plasma
protein binding: >90%.
Metabolism: Metabolised by
CYP2C9 isoenzyme to 3-
hydroxymethyl mefenamic acid,
which may then be oxidised to 3-
carboxymefenamic acid.
Excretion: Via urine (approx 52%)
as unchanged drug and
metabolites; faeces (approx 20%).
Elimination half-life: Approx 2-4
hr.
Absorption: Rapidly absorbed as oral soln,
sugar-coated tab, rectal supp, or by IM inj;
more slowly as enteric-coated tab esp when
given w/ food.
Bioavailability: 55%. Time to peak plasma
concentration: W/in 1 hr (conventional tab);
2-3 hr (enteric-coated tab); w/in 10-30 min
(oral soln); approx 1 hr (rectal supp).
Distribution: Penetrates synovial fluid; enters
breast milk (small amounts). Plasma protein
binding: >99%.
Metabolism: Undergoes first-pass
metabolism; converted to 4'-
hydroxydiclofenac, 5-hydroxydiclofenac, 3'-
hydroxydiclofenac, and 4',5-
dihydroxydiclofenac.
Excretion: Mainly via urine as glucuronide
and sulfate conjugates (approx 60%) and bile
(approx 35%); as unchanged drug (<1%).
Terminal plasma half-life: Approx 1-2 hr.

Active Ingredients Mefenamic Acid Diclofenac Sodium
Contraindication
Hypersensitivity to mefenamic
acid, aspirin or other NSAIDs.
Patient w/ inflammatory bowel
disease, active ulceration or
chronic inflammation of the
upper or lower GI tract, renal
failure. History of asthma,
urticaria, allergic-type
reactions. Treatment of
perioperative pain in the
setting of CABG surgery.
Hypersensitivity. Patients in whom
asthma, urticaria, or other sensitivity
reactions are precipitated by aspirin
or other NSAIDs. Active or suspected
peptic ulcer or GI bleeding, ulcerative
or acute inflammatory conditions of
the anus, rectum (proctitis) and
sigmoid colon. Treatment of
perioperative pain in CABG surgery.
High dose of systemic diclofenac (150
mg/day) for >4 wk in patients w/
established CV disease or uncontrolled
HTN. IV diclofenac should not be
given in patients w/ hypovolaemia,
dehydration, history of haemorrhagic
diathesis, cerebrovascular bleeding
(including suspected), undergoing
surgery w/ a high risk of
haemorrhage. Pregnancy (3rd
trimester).
Pregnancy Category
(US FDA) PO: C, D (in 3rd trimester or
near delivery)
PO/Topical: Category C;
Parenteral: Catogory B

Non Cox inhibitors selective COX Inhibitors Selective
Diclofenac
Ibuprofen
Indomethacin
Ketoprofen
Mefenamic Acid
Celecoxib
Etoricoxib
Parecoxib
Form &
Strength
Tablet Celecoxib 200mg Injection Parecoxib 40mg
Picture
Form &
Strength
Tab Eterocoxib 90mg & 120mg
Picture

Active
Ingredients
Capsule Celecoxib Eterocoxib Parecoxib
Strength 200mg & 400mg 90mg & 120mg 40mg
Prescribing
Category
A A* A*
Uses Acute pain Acute pain Management of post
operative pain in the
immediate post
operative setting only
Dosage 400mg as a single dose
on first day followed by
200mg once daily on
subsequent days
Maintenance: 200 mg
bid.
90mg @120 mg once
daily (Given the
exposure to COX-2
inhibitors, doctors are
advised to use the
lowest effective dose
for the shortest
possible duration of
treatment)
40 mg followed by 20
or 40 mg every 6 to 12
hours, as required.
Use limited to two
days only with a
maximum dose of 80
mg/day.
Elderly: <50 kg: Half
the usual dose. Max:
40 mg/day.

Active
Ingredients
Capsule Celecoxib Eterocoxib Parecoxib
Dosage
adjustment in
renal impairment
CrCl <30 mL/min:
Contraindicated.
CrCl <30 mL/min:
Contraindicated.
CrCl <30 mL/min:
Contraindicated.
Dosage
adjustment in
hepatic
impairment
Moderate (Child-Pugh
category B): Reduce dose by
50%. Severe (Child-Pugh
category C or ≥10 score):
Contraindicated.
Mild (Child-Pugh score of
5-6): 60 mg once daily.
Moderate (Child-Pugh 7-9):
Max 60 mg every other day
or 30 mg once daily.
Severe (Child-Pugh ≥10):
Avoid.
Mild (Child-Pugh score 5-6):
No dosage adjustment
needed. Moderate (Child-
Pugh score 7-9): Half the
usual dose. Max: 40 mg/day.
Severe (Child-Pugh score
≥10): Contraindicated
Administration
May be taken with or without
food.
This drug may cause dizziness,
if affected do not drive or
operate machinery.
May be taken with or
without food.
May impair ability to
drive or operate
machinery.
Interaction with
food May delay absorption w/ high
fat meal.
No documentation No documentation

Active
Ingredients
Capsule Celecoxib Eterocoxib Parecoxib
Pharmacoki
netics:
Absorption: Absorbed from
the GI tract. May delay
absorption w/ high fat meal.
Time to peak plasma
concentration: Approx 3 hr.
Distribution: Enters breast
milk. Volume of distribution:
Approx 400 L. Plasma protein
binding: Approx 97% (mainly
albumin).
Metabolism: Hepatically via
CYP2C9 isoenzyme to form
inactive metabolites.
Excretion: Mainly via faeces
and urine (as metabolites; <3%
as unchanged drug). Terminal
half-life: Approx 11 hr.
Absorption: Well absorbed
from the GI tract. Time to
peak plasma concentration:
Approx 1 hr (w/o food);
approx 2 hr (w/ food).
Distribution: Volume of
distribution: Approx 120 L.
Plasma protein binding:
Approx 92%.
Metabolism: Extensively
metabolised via CYP3A4
isoenzyme to form 6'-
hydroxymethyl derivative of
etoricoxib then oxidised to
6'-carboxylic acid derivative
(major metabolite).
Excretion: Mainly via urine
(70%); faeces (20%). Half-
life: Approx 22 hr.
Parecoxib is the prodrug of
valdecoxib. It is a selective
cyclo-oxygenase-2 (COX-2)
inhibitor primarily responsible
to reduce mediators of pain
and inflammation. Its action is
due to inhibition of
prostaglandin synthesis via
inhibition of COX-2.
Pharmacokinetics:
Distribution: Plasma protein
binding: Approx 98%.
Metabolism: Immediately
hydrolysed in the liver to its
active metabolite, valdecoxib,
and propionic acid.
Excretion: Mainly via urine as
inactive metabolites (approx
70%); faeces (trace amounts).
Plasma half-life: Approx 22
min.
Pregnancy
Category (US
FDA)
PO: C, D (in 3rd trimester or near
delivery)
Pregnant: special
precaution.
Contraindicated for lactating
mothers
Contraindicated in
pregnancy (3rd trimester)
and lactation.

 Opioid analgesic
 Dihydrocodeine Tartrate (DF118)
 Fentanyl
 Morphine HCl/ Morphine Sulphate
 Nalbuphine HCl
 Oxycodone HCl IR/ PR
 Remifentanil
 Tramadol
 Moderate pain score (4-6)

Opioid analgesic Prescribing
Category
Strength & Form
Dihydrocodeine Tartrate
(DF118)
B 30mg in tablet form
Fentanyl A* & A A*- 25mcg/hr & 50mcg/hr for transdermal
A- 50mcg/ml injection
Morphine HCl/ Morphine
Sulphate
B B-Morphine Sulphate 10 mg/ml Injection
B- Solution Morphine HCl 10mg/5m
A- Morphine Sulphate Controlled Release
10mg, 30mg & 60mg
A*- Morphine Sulphate 10 mg Immediate
Release Tablet
Nalbuphine HCl B Injection 10mg/ml
Oxycodone HCl IR/ PR A* A* - Oxycodone HCl 5mg,10 mg, 20mg Immediate
Release Capsules
A*- Oxycodone HCl 10 mg, 20mg & 40mg Prolonged
Release Tablet
A*- Oxycodone Hydrochloride 10 mg/ml Injection
Pethidine B B- Inj Pethidine 50mg/ml , 100mg/2ml
Remifentanil A* Remifentanil 5 mg Injection
Tramadol A & A/KK A- Tramadol HCl 50 mg/ml Injection
A/KK- Tramadol HCl 50 mg Capsule

Opioid analgesic Dihydrocodeine Tartrate
(DF118)
Tramadol
Dosage details ADULT: 30 - 60 mg every 4 -
6 hours. (max 240mg/day)
Child 4-11 y.o: 0.5 - 1 mg/kg
body weight every 4-6 hours
(max per dose 30mg)
Child 12-17 y.o : 30mg every
4-6 hours (max 240mg/day)
Elderly: Dosage should be
reduced in the elderly.
Oral
Moderate to severe pain
Adult: 50-100 mg 4-6 hrly. Extended-release tab:
50-100 mg once or twice daily. Max: 400 mg/day.
Elderly: >75 yr Increase dosing interval. (Max:
300mg/day)
Parenteral
Postoperative pain
Adult: Initially, 100 mg followed by 50 mg every 10-
20 min if necessary, to a total of 250 mg in the 1st
hr including initial dose. Thereafter, 50-100 mg 4-6
hrly up to a total daily dose of 600 mg.
Elderly: >75 yr Increase dosing interval. (Max:
300mg/day)
Parenteral
Moderate to severe pain
Adult: IM/IV: 50-100 mg 4-6 hrly over 2-3 min.
Elderly: >75 yr Increase dosing interval. (Max:
300mg/day)

Opioid analgesic Dihydrocodeine Tartrate
(DF118)
Tramadol
Dosage adjustment
in renal
impairment
Avoid use or reduce dose;
opioid effects increased and
prolonged and increased
cerebral sensitivity occurs
Oral
CrCl < 10mL/min : Contraindicated
CrCl 10 to < 30mL/min : increase dosing interval to
12 hourly. Max dose 200mg/day. Contraindicated
for extended release tablet
Parenteral:
CrCl < 10m
CrCl 10 to 30mL/min : Increase dosing interval to
12 hourly
Dosage adjustment
in hepatic
impairment
Dihydrocodeine should be
avoided, or the dose
reduced in patients with
hepatic impairment
Oral:
Severe: Increase dosing interval to 12 hrly;
Contraindicated (extended-release).
Parenteral:
Severe: Increase dosing interval to 12 hrly.
Administration It is recommended that this
product should be taken
during or after food.
This medicine can impair
cognitive function and can
affect a patient's ability to
drive safely.
May be taken with or without food.
May impair ability to drive or operate
machinery.

Opioid analgesic Dihydrocodeine Tartrate
(DF118)
Tramadol
Contraindication Hypersensitivity to the active
substance or to any of the excipients
listed in section
• Respiratory depression
• Obstructive airways disease
• Acute alcoholism
• Risk of paralytic ileus
• Head injuries or conditions in which
intracranial pressure is raised.
Suicidal patients; acute intoxication w/
hypnotics, centrally acting analgesics, opioids,
psychotropic drugs or alcohol; uncontrolled
epilepsy, acute or severe bronchial asthma,
hypercapnia or significant resp depression in
unmonitored settings or absence of resuscitative
equipment.
Not intended for narcotic withdrawal treatment.
Severe renal and hepatic impairment. Co-
administration w/ MAOIs or w/in 2 wk after
withdrawal.
Special
Precautions
Dihydrocodeine should be given in
reduced doses or with caution to
patients with asthma and decreased
respiratory reserve.
Use in caution in those with a history of
drug abuse.
Alcohol should be avoided whilst under
treatment with dihydrocodeine.
Patients who suffer from emotional disturbance
or depression, history of epilepsy or risk of
seizure, head injury, increased intracranial
pressure. Renal and hepatic impairment. Elderly.
Pregnancy and lactation.
Adverse Drug
Reactions
Abdominal pain, diarrhea,
paraesthesia, paralytic ileus,
seizure
Resp depression, seizure, dizziness, headache, somnolence,
weakness, CNS stimulation (e.g. anxiety, euphoria,
hallucinations), asthenia, sweating, confusion, coordination
disturbance, paraesthesia, hypoaesthesia, amnesia,
cognitive dysfunction, depression, dysphoria, constipation,
nausea, vomiting, dyspepsia, diarrhoea, abdominal pain,

Opioid analgesic Dihydrocodeine Tartrate
(DF118)
Tramadol
Pregnancy
Category (US FDA)
Pregnancy
May cause respiratory depression in
the new-born infant
Breast-feeding
Dihydrocodeine passes into breast
milk in very small. Avoided if the
mother is breast feeding.
Category C: Either studies in animals have
revealed adverse effects on the foetus
(teratogenic or embryocidal or other) and
there are no controlled studies in women or
studies in women and animals are not
available. Drugs should be given only if the
potential benefit justifies the potential risk
to the foetus.
Drug Interactions Dihydrocodeine may cause the
release of histamine; hence this
product should not be administered
during an asthmatic attack and
should be administered with
caution in patients with allergic
disorders.
Increased risk of convulsions or serotonin
syndrome w/ SSRI, serotonin-norepinephrine
reuptake inhibitors (SNRI), TCA and other
seizure threshold lowering drugs (e.g.
bupropion, mirtazapine,
tetrahydrocannabinol). Decreased serum
concentrations w/ carbamazepine. May
potentiate the anti-depressant effect of
norepinephrine, 5-HT agonists or lithium.
Increased INR and ecchymoses w/ coumarin
derivatives (e.g. warfarin).
Potentially Fatal: Increased risk of seizures
w/ MAOIs.
Food Interaction Not documented
Enhanced CNS depressant effect w/ alcohol.

Opioid analgesic Dihydrocodeine Tartrate
(DF118)
Tramadol
Pharmacokinetics Absorption
Dihydrocodeine is well
absorbed after oral
administration. Peak plasma
levels occur 1.6 - 1.8 hours
after ingestion.
Biotransformation
After oral administration the
bioavailability of the drug is
approximately 20%,
indicating that the pre-
systemic metabolism plays a
substantial role in reducing
the bioavailability of
dihydrocodeine.
Elimination
Dihydrocodeine is excreted
in the urine as unchanged
drug and metabolites. The
mean elimination half life
ranges between 3.5 – 5
hours.
Onset: Approx 1 hr.
Duration: 9 hr.
Absorption: Readily absorbed from the GI tract.
Bioavailability: Approx 70-75% (oral); 100% (IM).
Distribution: Widely distributed. Crosses the
placenta and enters breast milk.
Metabolism: Extensive hepatic first-pass
metabolism. Converted to O-desmethyltramadol
(active) via N- and O-demethylation by CYP3A4 and
CYP2D6 isoenzymes and also via glucuronidation or
sulfation.
Excretion: Via urine (as metabolites). Elimination
half-life: Approx 6 hr.

Opioid analgesic Fentanyl
Dosage Details Intramuscular
Premedication before anaesthesia
Adult: 50-100 mcg to be given 30-60 min prior to induction of anaesth.
Elderly: Dose reduction may be needed.
Intravenous
Adjunct to general anaesthesia
Adult: Patients w/ spontaneous respiration: Initially, 50-200 mcg followed by
supplements of 50 mcg. Max: 200 mcg. Admin infusion rates of 0.05-0.08
mcg/kg/min. Patients w/ assisted ventilation: Initially, 300-3,500 mcg (up to 50
mcg/kg) followed by supplements of 100-200 mcg depending on patient's
response. Loading dose (alternatively via bolus): Approx 1 mcg/kg/min given for
the 1st 10 min followed by infusion of approx 0.1 mcg/kg/min.
Child: 2-12 yr Initially, 2-3 mcg/kg followed by supplements of 1 mcg/kg.
Elderly: Dose reduction may be needed.
Dosage adjustment
in renal impairment
Avoid use or reduce dose;
opioid effects increased and prolonged and
increased cerebral sensitivity occurs

Opioid analgesic Fentanyl
Contraindication
s
Opioid nontolerant patient. Treatment of acute pain other than breakthrough
pain (e.g. migraine or other headaches) or post-op pain; acute or severe resp
depression or obstructive lung disease; paralytic ileus
Special
Precautions
Head injury; increased intracranial pressure; renal or hepatic impairment;
myasthenia gravis, cardiac bradyarrhythmias, pre-existing pulmonary disease
(e.g. COPD) or condition (e.g. hypoxia). Cachetic or debilitated patients. Rapid
IV infusion may cause skeletal muscle and chest wall rigidity. Prolonged use may
cause tolerance, psychological and physical dependence. Abrupt withdrawal
may lead to withdrawal symptoms, gradually taper down the dose to avoid this
risk. Elderly. Pregnancy and lactation.
Adverse Drug
Reactions
Abdominal pain, aesthenia, anorexia, anxiety, appetite changes, tremor,
diarrhea
Pregnancy
Category (US
FDA)
Parenteral/Transdermal: C, D (if prolonged use/high doses at term)

Opioid analgesic Fentanyl
Overdosage Symptoms: Altered mental status, loss of consciousness, hypotension, resp
depression, resp distress and resp failure. Management: Immediately remove
patch, buccal film or tab followed by naloxone admin. Stimulate patient
physically or verbally. Establish and maintain patent airway, if needed.
Drug Interactions Concomitant use w/ CYP3A4 inhibitors (e.g. erythromycin, clarithromycin,
troleandomycin, azole antifungals, ritonavir, amiodarone, nefazodone,
aprepitant, diltiazem and verapamil) increases serum levels of fentanyl and may
potentiate fatal resp depression. Increased risk of life-threatening serotonins
syndrome w/ SSRIs, SNRIs and MAOIs. May reduce serum levels w/ rifamycin
derivatives. Enhanced depressant effect w/ general anaesth, tranquilisers,
barbiturates and narcotics. May increase excretion w/ ammonium Cl. May
increase hypotensive effect w/ phenothiazines. May reduce efficacy of
pegvisomant
Food Interaction May enhance depressant effect w/ alcohol. Serum levels may be increased by
grapefruit juice. May reduce serum levels w/ St John's wort.

Opioid analgesic Fentanyl
Pharmacokineti
cs:
Onset: IV: Rapid; IM: Approx 7-15 min;
Semi-synthetic opioid with high lipid solubility
Faster onset of action compared to morphine
Duration: IV: 30-60 min; IM: 1-2 hr;
Absorption: Transmucosal: Rapidly absorbed from buccal and nasal mucosa, the
remainder is swallowed and slowly absorbed from the GI tract. Transdermal:
Slow absorption after application. Bioavailability: Buccal film: 71%; buccal tab:
65%; lozenge: Approx 50%; sublingual spray: 76%; sublingual tab: 54%. Time to
peak plasma concentration: Buccal film: 0.75-4 hr; sublingual spray: 10-120
min; sublingual tab: 15-240 min; transdermal patch: 20-72 hr.
Distribution: Highly lipophilic, distributes rapidly from blood into the lungs and
skeletal muscles then into deeper fat compartments. It crosses the placenta,
enters the breast milk and appears in the CSF. Volume of distribution: 4-6 L/kg.
Plasma protein binding: Approx 80%.
Metabolism: Hepatic via N-dealkylation and hydroxylation by CYP3A4
isoenzyme.
Excretion: Via urine (75%, primarily as metabolites; <7-10% as unchanged drug);
faeces (approx 9%). Elimination half-life: IV: 2-4 hr; transdermal patch: 20-27
hr; transmucosal: 3-14 hr (dose-dependent); nasal spray: 15-25 hr.

Opioid analgesic Pethidine
Pharmacokinetics Absorption: Absorbed from the GI tract; only 50% reaches the
circulation due to 1st-pass effect. Peak plasma concentrations after
1-2 hr (oral). Variable absorption (IM).
o IM pethidine demonstrates variable absorption and is associated
with widely fluctuating plasma concentrations with variable levels
of analgesia.
Metabolism:
Metabolised in liver to active metabolite (Norpethidine) which has
a long half life and is neurotoxic (tremors and convulstions)
It is believed that long term pethidine usage may have a higher
risk of addiction compared to morphine.
There is no evidence that pethidine is better than morphine in the
management of renal colic or obstetric pain.
NOT RECOMMENDED FOR USE IN ACUTE OR CHRONIC PAIN
Distribution: Crosses the placenta; enters breast milk; appears in
CSF. Protein-binding: 60-80%.
Excretion: Via urine (small amounts as unchanged drug);
elimination half-life: 3-5 hr (unchanged drug), 20 hr (norpethidine).

Opioid analgesic Pethidine
Dosage details Intravenous
Adjunct to anaesthesia
Adult: As hydrochloride: 10-25 mg by slow IV inj.
Parenteral
Preoperative medication
Adult: As hydrochloride: 25-100 mg IM/SC given 1 hr before surgery.
Child: As hydrochloride: 1-2 mg/kg given IM 1 hr before surgery.
Parenteral
Moderate to severe acute pain
Adult: As hydrochloride: 25-100 mg IM/SC inj or 25-50 mg by slow IV inj repeated after 4 hr.
Child: As hydrochloride: SC/IM: 2 mth to 12 yr: 0.5-2 mg/kg; 12-18 yr: 20-100 mg. Repeat
dose every 4-6 hr if needed. IV inj: Neonates and children ≥12 yr: 0.5-1 mg/kg IV inj every 10-
12 hr if needed in those up to 2 mth and every 4-6 hr if needed in older children. 12-18 yr:
25-50 mg every 4-6 hr if needed. Alternatively, ≥1 mth: Loading dose: 1 mg/kg by IV inj
followed by 100-400 mcg/kg/hr via continuous IV infusion adjusted according to response.
Elderly: 25 mg every 4 hr.
Parenteral
Postoperative pain
Adult: As hydrochloride: 25-100 mg IM/SC inj every 2-3 hr if necessary.
Child: As hydrochloride: 0.5-2 mg/kg IM every 2-3 hr if necessary.
Parenteral
Obstetric analgesia
Adult: As hydrochloride: 50-100 mg by IM/SC inj as soon as contractions occur at regular
intervals; repeat after 1-3 hr if needed. Max: 400 mg in 24 hr.

Opioid analgesic Pethidine
Dosage in Renal
Impairment
Dose reductions may be necessary.
Hepatic
Impairment
Dose reductions may be necessary.
Special
Precautions
Elderly and debilitated patients. Withdraw gradually. Pregnancy (avoid
prolonged use or high doses at term) and lactation.
Pregnancy
Category (US
FDA)
Parenteral/PO: B, D (if prolonged use/high doses at term)
Food Interaction
Increased CNS depression with valerian, St John's wort, kava
kava, gotu kola.

 Methods include non- pharmacological and pharmacological approaches.
Non-pharmacological approaches
Techniques proven to be useful in acute pain management:
 1. Psychological approaches: including music, preoperative information,
distraction, cognitive methods, relaxation training, hypnosis, guided imagery
 Music- reduction in postoperative pain and opioid consumption.
 Pre-operative information- effective in reducing procedure-related pain.
 Distraction- effective in procedure-related pain in children
 Cognitive methods-training in coping methods or behavioural instruction
prior to surgery, reduces pain and analgesic use.
 Hypnosis and relaxation-inconsistent evidence of benefit in the
management of acute pain
 2. Complementary therapies and other techniques: including massage,
acupuncture, TENS, hot and cold packs

 Pharmacological approaches
 Oral analgesics- NSAIDs / COX2 Inhibitors / Opioids
 Intravenous injection – NSAIDs / COX2 Inhibitors /
Opioids
 Patient-controlled analgesia (PCA) - Morphine /
Fentanyl
 Epidural analgesia – Intermittent / infusion/ PCEA
 o Mixtures of local anaesthetics and opioids (“cocktail”)
 o Opioids
 Intrathecal analgesia
 o Opioids
 Subcutaneous morphine
 Peripheral nerve blocks

 Some of the reasons for poor pain
management include:
 a. Pain relief is not considered a priority In
medical practice.
 b. Medical staff often lack sufficient
knowledge about pain and pain management.
 c. There are still many barriers to the use of
opioid analgesics.

http://www.moh.gov.my/index.php/pa
ges/view/1071

 Category A: Controlled studies in women fail to demonstrate a risk to the foetus in
the 1st trimester (and there is no evidence of a risk in later trimesters), and the
possibility of foetal harm remains remote.
 Category B: Either animal-reproduction studies have not demonstrated a foetal risk
but there are no controlled studies in pregnant women or animal-reproduction
studies have shown an adverse effect (other than a decrease in fertility) that was
not confirmed in controlled studies in women in the 1st trimester (and there is no
evidence of a risk in later trimesters).
 Category C: Either studies in animals have revealed adverse effects on
the foetus (teratogenic or embryocidal or other) and there are no controlled studies
in women or studies in women and animals are not available. Drugs should be given
only if the potential benefit justifies the potential risk to the foetus.
 Category D: There is positive evidence of human foetal risk, but the benefits from
use in pregnant women may be acceptable despite the risk (e.g., if the drug is
needed in a life-threatening situation or for a serious disease for which safer drugs
cannot be used or are ineffective).
 Category X: Studies in animals or human beings have
demonstrated foetal abnormalities or there is evidence of foetal risk based on
human experience or both, and the risk of the use of the drug in pregnant women
clearly outweighs any possible benefit. The drug is contraindicated in women who
are or may become pregnant.