COX-2 Inhibitors

Examples Parecoxib (Dynastat)

Celecoxib (Celebrex)
Etoricoxib (Arcoxia)
Dosage IV/IM 40 mg, then 20 or 40 mg 6-12 hrly
Max: 80 mg/day.
Indication Analgesia
Anti-inflammatory effects
Mechanism of Action COX-2 = in response to tissue injury and inflammation
Side Effects Nausea and vomiting
Abdominal pain
Back pain
insomnia, dizziness
MI, deep-vein thrombosis, pulmonary embolism, stroke
renal impairment, increased blood creatinine
Potentially Fatal: Anaphylaxis, Stevens-Johnson syndrome,
toxic epidermal necrolysis.
 Tramadol
Class Weak opioid
Half Life 4-6 hours
Indication/Dosage Mod to Sev Pain (Oral)
50-100 mg 4-6 hrly
Ext-rel tab: 50-100 mg 1-2 times/day
Max: 400 mg/day

Post-op Pain (Intravenous)

100 mg→50 mg every 10-20min if needed
Max: 250 mg for the 1st hour

Maintenance: 50-100 mg 4-6 hrly

Max: 600 mg/day
Mechanism of Action • Inhibition of the reuptake of norepinephrine, serotonin and
enhances serotonin release.
• It alters perception and response to pain by binding to mu-
opiate receptors in the CNS.
 Tramadol
Side effects Sweating
Itchiness and rashes
Nausea and vomiting
Dizziness or vertigo
Agitation
Serotonin symptoms: agitation, fever, nausea, muscle stiffness,
lack of coordination, or loss of consciousness.
DRUGS USE in MODERATE to
SEVERE PAIN
 OPIODS
• Natural – morphine
• Synthetic- pethidine, fentanyl nalbuphine,
tramadol, diamorphine
 INDICATION
• Moderate to severe acute postoperative pain
• Moderate to severe cancer pain
• Chronic pain
 SIDE EFFECTS
• Nausea and vomiting
• Sedation
• Respiratory depression
• Ileus/constipation
• Urinary constipation
• Pruritus
 MORPHINE
• naturally occuring opiod, derived from unripe
seed capsule of the poppy plant
• Available in oral and parenteral administration
• Parenteral formulation is most commonly used
for acute postoperative pain
• Oral preparation may be immediate release (IR)
e.g. aqueous morphine or controlled/sustained
release (SR) e.g MS Contin
• Metabolised in the liver to Morphine-3-
Glucuronide and morphine-6-glucuranide
 PETHIDINE
- Synthetic opiod with low oral bioavailability
- Available in parenteral formulation only
- Metabolised in liver to active metabolite
(Norpethidine) which has a long half life and is
neurotoxic (tremors and convulsion)
- It is believed that long term use of pethidine
may have higher risk of addiction compared to
morphine
 Remifentanil

• is a potent ultra short-acting synthetic opioid analgesic drug.

• It is given to patients during surgery to relieve pain and as an adjunct
to an anaesthetic.
• Remifentanil is a specific mu-type-opioid receptor agonist. Hence, it
causes a reduction in sympathetic nervous system tone, respiratory
depression and analgesia.
• The analgesic effects of remifentanil are rapid in onset and offset.
• Half life = 0.2-0.3 hours
• Metabolised by : tissue esterase By hydrolysis of the propanoic acid-
methyl ester linkage by nonspecific blood and tissue esterases.
• Excretion: kidney
Patient Controlled Analgesia (PCA)
• A method of opioid delivery where a
computerized syringe pump is set to deliver
bolus doses whenever the patient presses a
button (patient demand).
• It allows small amounts of an opioid to be
given at frequent intervals.
• Hence the patient titrates the required dose of
the analgesic according to individual needs
Indications Contraindications
• post operative pain • patient preference
• severe acute pain • patient inability to
• patients unable to take safely comprehend the
oral medications technique
• who are unable to use
PCA
Advantages
• Effective for severe pain
• Analgesics dose met patient
requirement
• Patients are actively involved
with their own recovery and
feel better.(high rating for
patient satisfaction)
• Nursing made easy as patient
is comfortable, and nurses do
not have to administer
medication for pain relief.
• Risk of overdose is low
Disadvantages
• Not suitable for all patients.
• Need to educate patients and
relatives.
• Doctors and nurses need to
be trained on the safe and
effective use of PCA.
• High cost of PCA machine and
disposables.
• Human and pump errors
 General Guidelines
• Must be mentally alert and able to comply with Patient monitoring :
instructions. 1. Pain Score,
• ONLY the patient should activate the machine. 2. Sedation Score,
3. Respiratory rate,
• The PCA is delivered through an IV line which has a one
4. blood pressure
way “anti-reflux valve” to prevent accidental opioid
5. pulse rate,
overdose. If an anti-reflux valve is not available, use a
6. amount of drug used
dedicated line for the PCA.
7. complications
every hour for the first 4
hours, then every 4 hours.
• Patients on PCA are NOT to receive other opioids or
sedatives.
• Recommended settings: Age affects opioid dosing but
not gender and body weight.
• Drug concentration should be standardised to reduce
the chance of programming errors.
Drug concentration:
• Morphine 1 mg/ml OR
• Fentanyl 10 mcg/ml
Lock-out interval:
• 5 minutes
 Adverse effects of PCA opiods

1. Respiratory Depression
• Possible causes:
• drug interaction – especially if patient is on another drug with
sedative effect
• continuous (background) infusion
• inappropriate use of PCA by relatives
• human error
• programming error
• equipment error
2. Nausea & vomiting
3. Pruritus
4. Sedation
 Epidural analgesia
This is the introduction of analgesic drugs into
epidural space, usually via an indwelling
epidural catheter.
Indications

• Acute pain in adults and children, particularly

after surgery, and in procedures involving the
thorax, abdomen, perineum or lower limbs
• Post trauma pain
• For labour analgesia
Contraindications

• Patient refusal
• Untrained staff
• Local infection or general sepsis
• Central neurological disorders e.g. stroke, head
injury, brain tumour
• Coagulation disorders / patient on anticoagulants
• Hypovolemia
• Severe fixed cardiac output states
Advantages

• Good quality of analgesia at rest and at movement

(incident/dynamic pain), early mobilization and resume
normal activities unlimited by pain.
• Less sedation.
• Less nausea and vomiting
• Faster return to normal lung function, decreased incidence
of pulmonary infection especially patients with lung
disease, chest injury, thoracotomy and upper abdominal
surgery.
• Reduced duration of ileus in colorectal surgery
• Reduced rate of arrhythmias, earlier extubation, reduced
intensive care unit (ICU) stay, reduced stress hormone
cortisol and glucose concentrations as well as reduced
incidence of renal failure.
Disadvantages

• Technical difficulty
• High cost of equipment
• Weakness and numbness with local anaesthetics

Drugs used

• Two classes of drugs are commonly used

o Local anaesthetics
e.g.bupivacaine,ropivacaine,levobupivacaine
o Opioids e.g. fentanyl, morphine

• Usually a combination of local anaesthetics and fentanyl

(“cocktail”) is used for postoperative epidural analgesia.
Mechanism of action of drugs used
Opioids Local Anaesthetics

An opioid introduced into the epidural space Block the conduction of

diffuses across the dura into the CSF and reaches impulses along nerves and
the opioid receptors in the dorsal horn of the spinal spinal cord
cord to bring about analgesia

Antinociception is further augmented by

descending inhibition from mu‐opioid receptor

Activation in the periaqueductal gray (PAG) area of

the brain

Affect the modulation of nociceptive input but do

not cause motor or sympathetic blockade
Epidural analgesia using mixtures of LA and
opioids (“cocktail”)

• Methods of administration include

o Continuous infusion
o Patient controlled (PCEA)

Side effects occur as a result of:

o sympathetic blockade
o motor blockade
o sensory blockade
Drugs “cocktail”

• 0.1% Bupivacaine + 2 mcg/ml Fentanyl

• 0.2% Ropivacaine + 2 mcg/ml Fentanyl
• 0.1% Levobupivacaine + 2 mcg/ml Fentanyl

Rate of infusion

• Varies according to the site of the epidural and surgical

wound
• Recommended rates of infusion
o Thoracic 4-8 mls/hr
o Lumbar 6-12 mls/hr
Patient Controlled Epidural Analgesia
(PCEA)
PCEA decreases the requirement for epidural
top-ups, lowers consumption of LA and
decreases incidence of motor block and reduces
the consumption of systemic rescue analgesia,
with a consequent reduction in the requirement
for intervention by ward nurses, physicians, and
the APS
Epidural analgesia using opioids alone

• Epidural opioids alone have limited benefit and are not commonly
used.
• Risk of delayed respiratory depression is greater with morphine
when compared to fentanyl.
• Concurrent opioids and sedatives must not be given by other
routes.
• Opioid solutions used must be preservative-free (as preservative
may be neurotoxic).
• Patients receiving epidural opioids alone may ambulate, as there is
no motor blockade.
• A bolus dose of epidural morphine alone may provide up to 24
hours of analgesia. Epidural fentanyl alone is not used as the
duration of action is too short to be of any significant benefit.