R.

Santhosh Krishna
 WHAT ARE OPIOIDS?
 Opioids are substances that act on opioid
receptors to produce morphine like effects
 Opioid analgesics are drugs that relieve
pain by acting on the CNS without
altering consciousness
 The most common opioid drugs used are
morphine, codeine, thebaine etc
 The strongest opioid drug used in the
community is fentanyl which in
intravenous form is 80-100 times more
potent than morphine
 HISTORY
 The Sumerians in Mesopotamia were
among the first to have cultivated the
poppy plant around 3400 BC for medical,
recreational purposes
 They named it as “Hul Gil” a “plant of
joy”
 In 1804 morphine, an opioid analgesic
was extracted from opium by
Dr.Friedrich Serturner of Germany
 In 1832 codeine was discovered by
Pierre Jean Robert. This discovery led to
a development of a generation of
antitussives and antidiarrheal medicines
based on codeine
 MECHANISM OF ACTION
 Opioid drugs produce analgesia by acting on
receptors located on neuronal cell
membranes
 Opioid receptors are of 3 types mu, delta
and kappa
 These receptors decrease pain transmission
by causing activation of nerve fibres coming
from the periaqueductal gray within the
midbrain and raphe nuclei within the
medulla
 In addition, opioids directly inhibit afferent
nerve transmission by binding to mu-opioid
receptors presynaptically and
postsynaptically within the dorsal horn of
the spinal cord
 As a result, the ascending pathways for pain
stimuli are decreased thereby providing pain
relief
 PHARMACOLOGICAL ACTIONS
 Central Nervous System
1. Analgesia
Most effective in relieving dull, continuous and poorly localised pain
arising from deeper structures, for example the gut. Less effective against
superficial and sharp pain
2. Sedation
Drowsiness, feeling of heaviness and difficulty in concentrating are
common.
3. Hallucinations
These are more common with kappa opioid receptor agonists, but
morphine and other mu opioid receptor agonists may also cause hallucinations

 Cardiovascular system
1. Mild bradycardia
Common as a result of decreased sympathetic drive and a direct effect
on SA node
2. Peripheral vasodilatation
Caused by histamine release and reduced sympathetic drive may result
in a slight fall in blood pressure that may be significant in hypovolemic
patients
Respiratory System
1. Respiratory depression
Mediated via MOP receptors at the respiratory
centres in the brainstem. Respiratory rate falls more than the
tidal volume and the sensitivity of the brain stem to carbon
dioxide is reduced. Its response to hypoxia is less affected
2. Cough suppression
Codeine suppresses coughing to a degree
similar to morphine, but has lesser analgesic activity.

 Gastrointestinal System
o Stimulation of the chemoreceptor trigger zone causes
nausea and vomiting.
o Smooth muscle tone is increased but motility is decreased
resulting in delayed absorption, increased pressure in the
biliary system (spasm of sphincter of Oddi) and
constipation.
 Endocrine System
The release of ACTH, prolactin and gonadotrophic
hormone is inhibited. Secretion of ADH is increased

 Renal System
It may cause urinary retention by increasing tone of
urethral sphincter

 Immunity
The immune system is depressed after long-term opioid
abuse
 PHARMACOKINETICS
 Most opioid analgesics are well absorbed when administered via
subcutaneous, intramuscular, and oral routes

 Distribution is wide; concentration in liver, spleen and kidney is higher

than that in plasma

 Opioids like morphine are metabolized in liver by glucoronide

conjugation, and are then readily excreted by the kidneys

 Opioids are basic drugs that, with the exception of alfentanil, have
pKa values greater than 7.4, so that the ionized form of the drug
predominates in the blood

 The pKa of alfentanil is 6.5 so that 90% of alfentanil is non-ionized at

pH 7.4. This facilitates its access into the CNS
 pKa is also an important determinant of absorption from the
gastrointestinal tract
 Plasma t1/2 of morphine averages 2-3 hours. Effect of parenteral dose
last 4-6 hours
THERAPEUTIC USES OF
OPIOIDS
 as Analgesic
o Opioid analgesics appear to be most effective to control severe
pain in terminal stages of cancer patients
o They are most potent hence used for treating moderate to
severe pain like acute myocardial infarction, burns, pulmonary
embolism, bullet wound etc
o In renal and biliary colic, atropine is used with morphine to
counteract spasmogenic effect of morphine
 Preanaesthetic medication
Opioids like morphine and pethidine are used about half an
hour before anesthesia because of their sedative, analgesic and
euphoric effects
 Cough
Codeine or more commonly its substitutes are widely used for
suppressing dry, irritating cough
 Diarrhoea
Opioids from the phenylpiperidine subclass of opioids, which
consists of synthetic opiates, are often used to control diarrhoea
due to their selective GI effects. Examples of these agents include
loperamide

 Acute Pulmonary Oedema

Intravenous morphine relieves breathlessness associated with
acute left ventricular failure due to
a) Reducing preload on heart by peripheral vasodilatation
b) Shifting blood from pulmonary to systemic circulation
Adverse effects