INTRODUCTION

• Opioids are natural, semisynthetic, or synthetic

compounds that produce morphine-like effects
• These agents are divided into chemical classes based on
their chemical structure.
• All opioids act by binding to specific opioid receptors in
the CNS to produce effects that mimic the action of
endogenous peptide neurotransmitters like, endorphins,
enkephalins, and dynorphins).
• Although the opioids have a broad range of effects, their
primary use is to relieve intense pain, whether that pain
results from surgery, injury, or chronic disease.
• Analgesics- Drugs that selectively relieve pain by acting
on the CNS or on the peripheral pain mechanism, without
significantly altering consciousness- Opioids and NSAIDS.
• Opium – A dry powdered mixture containing 20 alkaloids
derived from unripe seed capsules of the plant poppy
(papaver somniferum).
• Opioid -All substances with morphine like properties that
bind to opioid receptors in the CNS. antagonised by
naloxone.
• Opiates -Agents derived from opium.
Chemical nature.
OPIOID
OPIOID RECEPTORS
• The major effects of the opioids are mediated by three
receptor families,
• which are commonly designated as μ (mu), κ (kappa), and
δ (delta).
• Each receptor family exhibits a different specificity for the
drug(s) it binds.
• All three opioid receptors are members of the G protein–
coupled receptor family and inhibit adenylyl cyclase.
• They are also associated with ion channels, increasing
postsynaptic K+ efflux (hyperpolarization)
• or reducing presynaptic Ca2+ influx,
cont,’
PHARMACOKINETICS OF OPIOIDS
• ABSORPTION; wide bioavailability range among different
opioids due to differences in first pass. Absorbed readily
from GIT, nasal or buccal mucosa. Rectal is adequate.
• DISTRIBUTION; target for opioids is the CNS. For
receptor activation, the drug must cross the BBB
• METABOLISM; in the liver. process may include
cytochrome P450 enzymes(CYP2D6, CYP34A) or UDP-
glucuronyltransferase.
• CYP2D6= codiene, hydrocodone, oxycodone and
tramadol
• CYP34A= fentanyl, methadone
• UDP-glucuronyltransferase= primary enzyme
responsible for metabolism of morphine, hydromorphone,
oxymorphone and tapentadol.

• EXCRETION; many excreted as metabolites through

kidneys with the exception of methadone which is
excreted via bile. Renal disease and failure causes a
decrease in clearance of drug
Fentanyl is responsible for post operative muscle rigidity whereas
succinylcholine causes post operative muscle pain and Fasciculation
Buprenorphine ·IS partial agonist at µ with κ and δ antagonistic
property and useful as an alternative to methadone for the
management opioid withdrawal.
• Nadlbuphine, pentazocine and dezocine are κ agonist and µ
receptor antagonists. These drugs can produce psychomimetic
effects with hallucinations, nighmares and anxiety.
Butuphano is a predominant κ agonist that produces equivalent
analgesia but more sedation than morphine.
Clinical use
• These are used as analgesic agents. Visceral, dull and
constant pain is relieved more effectively than inflammatory
pain.
• Morphine (i.v.) is useful in myocardial infarction as well as in
acute pulmonary edema.
• Codeine, pholcodeine, dextromethorphan and noscapine are
effective cough suppressants.
• Loperamide and diphenoxylate can be used for the treatment
of non-infective diarrhea.
• Morphine is useful as a pre-anaesthetic medication whereas
highly lipid soluble drugs (like fentanyl, alfentanil, sufentanil
etc) are used as adjuncts to other anaesthetic agents.
• Pethidine is used to reduce shivering after anesthesia [ its
action on α2 receptor]
CLINICAL USE
• MORPHINE
-Used in treating moderate to severe pain.
• PETHIDINE
-It’s a fast acting drug used to treat moderate to severe pain and
also used to control shivers after surgery
• CODEINE
-Mostly used to suppress cough centers.
-Mild to moderate pain
• MEPERIDINE
-Used in acute pain syndrome
-obstetric analgesia (prolongs labour)
• NALBUPHINE
-In moderate to severe pain associated with acute or chronic
disorders
• LOPERAMIDE
-Has minimal analgesic effect
-Used to treat diarrhea and does not cross the blood brain
barrier
• PENTAZOCINE
-Migraine headache pain
 CONTRAINDICATIONS
• Morphine is contraindicated in patients with head injury
• The drugs should be cautiously used in patients with pulmonary,
hepatic or renal dysfunction
• Caution should be taken in infants and the elderly
• They should not be administered to patients with hypothyroidism
• In biliary colic
• In asthma
cont’
• When taken by a pregnant woman it can cause in utero
dependence of the fetus and may cause several
withdrawal symptoms after birth
• In patients with acute psychiatric instability
• Patients with phoechromocytoma
ADVERSE EFFECTS/TOXICITY
AGONIST (Morphine)
• CNS- analgesia, euphoria, sedation, and respiratory depression

• CVS- bradycardia.

• GIT and UT- Constipation, nausea and vomiting ,urinary

retention.
• With repeated use, tolerance develops to most of the opioid

actions except miosis, constipation and convulsions.

 cont’

•ANTAGONIST (naltrexone)

Insomnia, restlessness, headache etc.

•MIXED AGONIST-ANTAGONIST (buprenorphine)

hallucinations, anxiety, blurred vision, dizziness, light headedness

IMPORTANT POINTS
• Heroin is a potent and a fast acting opioid but carries
high risk of abuse potential.
• Fentanyl is often used in cardiac surgery because of
negligible effects on cardiac contractility.
• Transdermal patch of fentanyl is contraindicated because
it can give rise to death due to hypoventilation .
• Codeine can be used as an antitussive because it depresses
the cough reflex.
• Loperamide , diphenoxylate and codeine is also used as
an anti-diarrheal drug as it decrease gastrointestinal tract
motility.
cont’
• Buprenorphine dissociates slowly from µ receptors and is
resistant to naloxone reversal.