Opioid Analgesics - Part 1

OPIOID
ANALGESICS - 1
Dr. Jayesh Balat

Assistant Professor
Pain
= Algesia
Pain is an unpleasant sensation produced
when nociceptive (injurious) stimulus is
received
Pain
A sensory modality (objective
feeling) – nociception
DISABLING,
UNPLEASANT
SENSATION EVOKED
BY NOXIOUS STIMULI
An emotional reaction
(subjective feeling)
PSYCHOLOGICAL
RESPONSE
ASSOCIATED WITH
PAIN
Analgesic
A drug that selectively relieves pain by acting
in the CNS or on peripheral pain mechanisms,
without significantly altering consciousness.

Pain pathway
Pain receptors
Pain carrying fibers
Pathway
Algogenic substances
• Bradykinin, serotonin, histamine, K ions,

Ach, proteolytic enzymes, ATP, Caspaicin
• PGs and substance P –enhance the sensitivity
of pain nerve endings but do not direct excite
them
Pain receptors
Free (bare) nerve endings

Pain carrying fibers
Aδ
C
Pain pathway
TRANSMISSION
FIRST ORDER SECOND ORDER TRACTS

NEURON NEURON IMPULSES
NOCICEPTORS SYNAPSED TO FIRST ASCENDS TO BRAIN
(PRIMARY ORDER NEURON IN VIA VARIOUS
DORSAL HORN OF ASCENDING
SENSORY TRACTS MAINLY
SPINAL CORD &
AFFERENTS) CROSS TO OPPOSITE LATERAL
HAVE CELL BODY AT THE SAME LEVEL SPINOTHALAMIC
IN DORSAL ROOT AND CONTINUE AS TRACT
GANGLIA ASCENDING TRACT
LATERAL
SPINOTHALAMI
C TRACT
The Lateral spinothalamic
tract has two pathways for
nociceptive information to
reach the brain,
1.Neospinothalamic tract
for "fast spontaneous
pain" and
2.Paleospinothalamic
tract for "slow increasing
pain"
Treatment of pain
Eliminate cause
Interrupt pain pathways
Alter perception or reaction to pain

Opioid analgesics are more effective against slow than
fast pain
At low dose, opioid drugs markedly ↑ ability to tolerate
pain, while at high dose can interfere with the detection

of pain
Mechanism of actions
of opioid analgesics
Effects are mediated via opioid receptors
m (mu)
d (delta)
k (kappa)
μ (Mu) receptors Κ (Kappa) receptors δ (Delta) receptors
Analgesia (spinal μ1 + Analgesia (spinal Κ1+ Analgesia (spinal +
supraspinal μ2) supraspinal Κ3) supraspinal)
Respiratory Respiratory Respiratory
depression depression (lower depression
ceiling)
Euphoria Dysphoria Affective behavior
Reduced GI motility Constipation Constipation
(Constipation)
Sedation Sedation Proconvulsant action
Miosis Miosis
Physical dependence Physical dependence
Cellular Mechanism of Action
Opioid receptors are linked to G proteins. Activation of Gi
leads to decreased cAMP and

Opioid Analgesics
Opium:
A dark brown,
resinous
material
obtained form
poppy capsule.
Papaver somniferum
It contained two types of alkaloids

1. Phenanthrene derivatives: Morphine, Codeine, Thebaine
2. Benzoisoquinoline derivatives: Papaverine, Noscapine
Classification of Opioids
Natural opium alkaloids
Morphine, codeine, thebaine, papaverin, noscapine
Semisynthetics opiates
Diacetylmorphine (Heroin), pholcodeine
Synthetics opioids
Pethidine, fentanyl, methadone, tramadol
Pharmacological Actions
Prototype Drug- Morphine

CNS
Depressant Effect
Analgesia Dull, poorly localized visceral pain is relieved
better than sharp defined somatic pain
Not only pain but emotional component of pain
relieved MOA- Spinal Supraspinal
Sedation Drowsiness, and mental clouding
Subjective Euphoria, feeling of well being, pleasant

feeling sensation
Respiratory ↓ sensitivity of respiratory centre to CO2
centre drive.
↓ both rate and depth of respiration.
Cough Centre Suppression - anti-tussive action
Thermoregulatory center Hypothermia
Vasomotor center Suppression – Fall in BP

CNS
Stimulant Effect
CTZ Vomiting
Edinger Westphal - Miosis

nucleus
Vagal Bradycardia
Centre
CVS
Depression of VMC
Histamine Release Vasodilatation Fall in BP
Direct action on Blood vessels
Blood shifts from pulmonary to systemic circulation – useful in Acute LVF, pulmonary
oedema
GIT
Increased tone
Inhibit GI motility
Constipation
Decrease GI Secreions
Other smooth muscles

Spasm of sphincter of Oddi- biliary Colic
Urinary bladder- tone of both detrusor and sphincter is increased
Bronchi – increase release of histamine-broncho-constriction

Pharmacokinetics
Morphine can be administered by oral and parenteral
route.
Oral route – unreliable – high first pass metabolism
Widely distributed in body with concentration in liver,
spleen and kidney. It also crosses the placenta
Metabolized in liver by glucuronidation (morphine 6
glucuronide and morphine 3 glucuronide)
Glucuronides are excreted by kidney
Half life of 2-3 hours. Effect of a parenteral dose lasts
for 4-6 hours.
MARPHINE CVS
M Miosis
A Analgesia
R Respiratory depression
P Physical dependence
H Hypotension, hypothermia, histamine release
I Itching
N Nausea vomiting
E Euphoria
C Cough suppression, Constipation
V Vagal stimulation
S Sedation
ADR
Sedation Respiratory centre
Hypotension Hypothermia Hypersensitivity
Vomiting Constipation
Apnea to fetus Tolerance
Dependence
Treatment – withdrawal of
morphine and substitution with
oral methadone, - gradual
withdrawal
Acute Morphine Poisoning
Lethal dose – 250 mg
pinpoint pupils, respiratory depression,
Fall in BP.
Death due to respiratory failure.
Treatment-
Maintain respiration and circulation
Gastric lavage with potassium permanganate
Specific antidote – Naloxone 0.4 to 0.8 mg iv,
repeated every 1-4 hour.
Precautions and contraindications
Infant and elder- more susceptible to respiratory depression
Respiratory insufficiency- Bronchial asthma

Head injury
Hypotensive state
Undiagnosed abdominal pain- can aggravate certain colicy pain
Hypothyroidism, liver and kidney disease patients

Unstable personalities
Pethidine (Mepiridine)
Imp differences in comparison to morphine
Less potent analgesic
Rapid onset, short duration
Does not suppress cough

Spasmodic action less prominent
Miosis is less prominent

Tachycardia – anticholinergic action
Less histamine release – safe in asthmatics

Fentanyl – pethidine congener
80 – 100 times more potent than morphine
High lipid solubility – enters brain rapidly and

produces peak analgesia in 5 min after i.v.
administration
Short duration of action (30-40 mins) --- redistribution
Has less propensity to release histamine
Transdermal fentanyl – available for use in

cancer / terminal illness or other types of
chronic pain for patients requiring opioid
analgesia
USES
As an analgesic
Traumatic , visceral, ischemic pain(MI), post operative burn,

cancer pain
Pethidine – used
Anesthesia for obstetric analgesia.
and preanesthetic medication
Relief of anxiety and apprehension
Acute left ventricular failure
Cough- codeine, noscapine
Diarrhea – loperamide, diphenoxylate.

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OPIOID

Dr. Jayesh Balat

A drug that selectively relieves pain by acting

in the CNS or on peripheral pain mechanisms,

without significantly altering consciousness.

• Bradykinin, serotonin, histamine, K ions,

Free (bare) nerve endings

FIRST ORDER SECOND ORDER TRACTS

Interrupt pain pathways

Alter perception or reaction to pain

pain, while at high dose can interfere with the detection

leads to decreased cAMP and

It contained two types of alkaloids

Prototype Drug- Morphine

Subjective Euphoria, feeling of well being, pleasant

Vasomotor center Suppression – Fall in BP

Edinger Westphal - Miosis

Histamine Release Vasodilatation Fall in BP

Direct action on Blood vessels

Other smooth muscles

Urinary bladder- tone of both detrusor and sphincter is increased

Bronchi – increase release of histamine-broncho-constriction

H Hypotension, hypothermia, histamine release

C Cough suppression, Constipation

Hypotension Hypothermia Hypersensitivity

Apnea to fetus Tolerance

Respiratory insufficiency- Bronchial asthma

Undiagnosed abdominal pain- can aggravate certain colicy pain

Hypothyroidism, liver and kidney disease patients

Less potent analgesic

Rapid onset, short duration

Does not suppress cough

Miosis is less prominent

Less histamine release – safe in asthmatics

High lipid solubility – enters brain rapidly and

Has less propensity to release histamine

Transdermal fentanyl – available for use in

Traumatic , visceral, ischemic pain(MI), post operative burn,

Relief of anxiety and apprehension

Acute left ventricular failure

Cough- codeine, noscapine

Diarrhea – loperamide, diphenoxylate.

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