Pharmacology of analgesics and

opioids - I

- Dr Purna Radha Shrestha

NAMS
• The word ‘analgesic’ derived from the greek
word – ‘an, without’ ; ‘algesia, pain’
 Classification of pain
Pain

Pain classified Pain classified

by duration by nature

Acute Chronic Nociceptive Non-

nociceptive

Somatic Visceral Neuropathic Sympathetic

 Classification of analgesics
Analgesics

Non-opioids Opioids

Examples: Examples:
Acetaminophen Morphine
NSAIDs Fentanyl
Alpha-2 agonists Pethidine
NMDA receptor antagonists
Anticonvulsants
 Multimodal analgesia
• Combines different classes of medications, having
different (multimodal) pharmacological
mechanisms of action

• Improves analgesia due to additive or synergistic

effects

• Permits the reduction of individual drugs thereby

reducing the incidence and severity of adverse
effects
 Paracetamol
• Lacks significant antiinflammmatory effects

• Doesnot produce gastric irritation

• Doesnot inhibit platelets

• Mechanism of action: Strong central inhibition of

prostaglandin synthesis

• Opioid sparing property in postopeartive setting

 Intravenous paracetamol
• Formulation: 10 mg/ml aqueous solution (100 ml bottle); 150
mg/ml ampoule

• Infusion over 15 mins

• Dose: 15 mg/kg if < 50kgs, 1 gm if > 50 kgs

• If needed, repeat dose only after 4 hrs of first dose, not

exceeding 4 gm daily

• Peak analgesic effect: 1 hour

• Duration: approx. 4-6 hours
 Paracetamol suppositories
• Much less reliable as absorption is slower and much less
predictable

• Bioavailabilty between 24%-98%

• Undergoes partial first-pass hepatic metabolism

• Peak analgesic effect: 2-3 hrs

• Dose: Upto 40 mg/kg

• Used in pediatric age group

 Metabolism of paracetamol
• Metabolism: major and minor pathways

• Major: sulfated conjugation

• Minor: oxidation forming reactive metabolic product

(N-acetyl- p-benzoquinone-imine): 5-8% of a
therapeutic dose of paracetamol, removed by
conjugation with glutathione
 NSAIDs
• Salicylates – Aspirin, salicylic acid
• Propionic acid derivatives – Ibuprofen, naproxen,
ketoprofen
• Acetic acid derivatives – ketorolac, Indomethacin,
Diclofenac

* Inhibit cyclooxygenase pathway

 Cyclooxygenase (COX) pathways
Membrane phospholipid
Phospholipase A2

Arachidonic acid
COX-1 COX-2
“Constituitive” “Inducible”

Prostaglandins Prostaglandins

Gastric protection Pain

Hemostatis Inflammation
Renal function Fever
• Opioids requirements for postoperative pain
management are decreased 20% to 50% by
NSAIDs.
 Adverse effects of NSAIDs
• Renal injury
• Bleeding
• Gastrointestinal ulceration
 Factors increasing NSAIDs induced
nephrotoxicity
• Hypovolemia
• Preexisting renal disease
• Congestive heart failure
• Sepsis
• Combination with other potentially
nephrotoxic drugs
• Cirrhosis
 Ketorolac
• Nonspecific cyclooxygenase inhibitor

• Potent analgesic with moderate antiinflammatory

activity

• Route of administration: Intravenous / intramuscular

• Formulation: 30 mg/ml vial

• Metabolized in liver by glucoronic acid conjugation

• Ketorolac, 30 mg IM, produces analgesia that is
equivalent to 10 mg of morphine or 100 mg of
pethidine

• Onset of action: 15-20 mins

• Duration of action: 4-6 hrs

• Absence of ventilatory and cardiovascular depression

• Has little or no effect on biliary tract dynamic

• Useful for providing postoperative analgesia both
as the sole drug and to supplement opioids

• Exhibits a ceiling effect with respect to

postoperative analgesia

• Decreases opioid related side-effect of nausea

and vomiting
 IV magnesium
• NMDA receptor antagonist

• Decreases central sensitization

• 40 mg/kg prior to induction, followed by a 10 mg/kg/hr

infusion results in reduction of perioperative analgesic
requirements
 Alpha2- agonists

• Clonidine, Dexmedetomidine

• Mechanism of action: inhibit release of norepinephrine

in central presynaptic neurons

• Clonidine: IV form 1-3 mcg/kg

• Dexmedetomidine in IV formulation, loading dose at 1

mcg/kg over 10 min followed by an infusion at 0.2–0.7
mcg/kg/hr
• α 2 :α 1 specificity ratio is 200:1 for clonidine and
1600:1 for dexmedetomidine

• Dexmedetomidine has a shorter half-life (2–3 h) than

clonidine (12–24 h).
 Effects of alpha2 agonists
• Sedation
• Analgesic
• Anxiolytic
• Does not depress respiration

* Side effects: bradycardia, hypotension

 Anticonvulsants (gabapentinoids)
• Gabapentin and pregabalin are anticonvulsants that
decrease perioperative pain and limit long-term wound
hypersensitivity

• Only oral form available

• Preoperative use has been shown to have opioid sparing

effects (approx. a 40% decrease)

• Bind presynaptic voltage-gated calcium channels of the

dorsal root ganglion and spinal cord
• Which type of pain is suppressed by opioids?
a) Somatic
b) Visceral
c) Neuropathic
d) Sympathetic
• Which of the following NSAIDs is selective
COX2 inhibitor?
a) ketorolac
b) Ibuprofen
c) Parexocib
d) Diclofenac
• Advantage of alpha2 agonist over opioids is
a) Analgesia
b) Sedation
c) Hypotension
d) Doesnot depress ventilation
THANK YOU