OPIOID ANALGESICS

MOTTO AND VISION

• To impart evidence
based research oriented
medical education
• To provide best possible
patient care
• To inculcate the values
of mutual respect and
ethical practice of
medicine
 Reference books)
(Digital Library,
INTEGRATION

Clinical Subject
INTEGRATION
BIOETHICS
RESEARCH

MEDICINE
VERTICAL
Vertical
4rd Year Pharmacology LGIS

10%
5%
Prof. Umar’s Clinically Oriented Integration Model

Core Subject – 60%

05%
Pharmacology

&
10% Re
s
Horizontal Integration – 10%
For Basic Sciences Interactive Lectures

ch B i e ar
ar c s oe c h • Eye
e se ethi th &
ic s
Same Year Subjects
R io • Pathology
B

Vertical Integration – 10%

Clinical Subjects • Medicine
• Surgery
10%
3.55 10% HORIZONTAL Spiral Integration – 15%
INTEGRATION
OEye Different Year Basic • Physiology (10%)
Sciences Subjects • Biochemistry (5%)

ic
s B
Re io e Research & Bioethics, Digital library – 05%
th & se th
oe c h ar i c s
B i se a r ch
e &
15%
R

05%
BIOCHEMISTRY
Basic Sciences
INTEGRATION
Different Year

PHYSIOLOGY
Subjects
SPIRAL
15%
 LEARNING OBJECTIVES
After this session, you should be able to:
• Classify opioids
• Describe opioid receptor distribution and the
mechanism of action of opioid analgesics
• Discuss pharmacological effects, adverse effects
and contraindications of opioids
• Outline salient features of various opioid agonists,
partial agonists and opioid antagonist.
 SPIRAL INTEGRATION-
PHYSIOLOGY AND ANATOMY
Pain
An unpleasant sensory and emotional experience
associated with actual or potential tissue damage

Pain can be either acute or chronic

• Receptors
• receptors distributed throughout the body, Stimulated by touch,
mechanical, thermal or chemical injury

• Nerves
• Sensation from periphery to the spinal cord (dorsal horn) ascend
in the crossed spinothalamic tract
• A delta fibers (large diameter myelinated) touch
• C fibers (non/thinly mylenated nerves) mechanical, thermal &
chemical

• Pain centre
• Hypothalamus
Pain Center
CORE SUBJECT
MORPHINE - HISTORY
Friedrich Wilhelm Serturner
A German Pharmacist
Isolated Morphine in 1803 and named it after the Greek
god of Dreams “MORPHEUS”
OPIOID RECEPTORS
Supraspinal & Spinal Analgesia
Sedation, Miosis
Decrease GI motility
Resp. depression
↑ Prolactin & GH release
Inhibit Ach & Dopamine release
Physical dependence

.
 CLASSIFICATION OF OPIOIDS
NATURAL OPIUM ALKALOIDS
Morphine, Codeine
Papaverine, Noscapine, Thebaine

SEMI-SYNTHETIC OPIOIDS
Hydromorphone, Oxymorphone
Hydrocodone, Oxycodone
Pholcodeine, Diacetylmorphine (Heroin)
SYNTHETIC OPIOIDS
• Pethidine(Meperidine)
• Methadone,
• Dextropropoxyphene,
• Tramadol,
• Fentanyl, Afentanil , Sufentanil, Remifentanil etc.
Based on RECEPTOR INTERACTIONS
PURE AGONISTS
1.Morphine, Hydromorphone, Oxymorphone
2.Methadone, Meperidine
3.Fentanyl

MILD TO MODERATE AGONIST(Partial agonists)

1. Codeine, oxycodone
2. Hydrocodone,
3.Dihydrocodone
MIXED AGONISTS-ANTAGONISTS
1. Buprenorphine(partial u agonist, k & d antagonist)
2.Nalbuphine(strong k agonist, partial u antagonist)
3.Pentazocine(weak u agonist, k agonist)

PURE ANTAGONISTS
• Naloxone
• Naltrexone
• Nalmefene
MORPHINE
• Morphine is the principal alkaloid in
opium Therefore it is described as
prototype.
PHARMACOKINETICS

Absorption
Readily absorbed after oral, I/M & S/C administration
Significant first-pass effect
R.O.A: Oral, S/C, I/M, & I/V , nasal insufflation
Widely distributed – brain, liver, spleen, kidney
Highly liphophilic opioids may accumulate in fat tissue
Readily crosses placental barrier – dependence in fetus
PHARMACOKINETICS
Metabolism
In Liver by glucoronidation – water soluble metabolites
• Morphine-6- Glucoronide
• Morphine-3-glucoronide
Excretion
• Via kidney in urine
• Completely eliminated in 24 Hrs
MECHANISM OF ACTION
μ, κ and δ are GPCRs
• Distributed widely in brain & spinal cord; and also outside
CNS – vascular tissues, airway/lung, gut & cells of immune
system.

• Decrease NTs release (glutamate, substance P) from primary

afferents at spinal cord, by closing presynaptic voltage
gated Ca2+ channels
• Hyperpolariztion by opening postsynaptic K+ channels on
ascending secondary afferent neurons of pain pathways.
OPIOID RECEPTORS (contd.)
• Upon activation of the receptors , Gi/Gs coupling
occurs leading to a large no. of intracellular events:
• Inhibition of adenylyl cyclase activity
• Reduced opening of voltage-gated Ca2+ channels
• Stimulation of K+ current through GIRKs
(G protein-activated inwardly rectifying K+ channels)
• Activation of PKC & PLCβ
PHARMACOLOGICAL
ACTIONS
STIMULANT ACTIONS
Miosis
Nausea & vomiting
Truncal rigidity
Vagal stimulation – Bradycardia
INHIBITORY ACTIONS
Analgesia
Sedation
Mood and subjective effects : euphoric effect
Respiratory depression
Cough suppression
Temperature regulating centre – depressed
Vasomotor centre – high doses cause fall in BP
VERTICAL INTEGRATION-
MEDICINE/ ANESTHESIA
CLINICAL USES OF OPIOIDS
1- AS ANALGESIC

2- Cough suppression

3- Acute Pulmonary Edema with LVF

4- Diarrhea

5. Anesthesia
ACUTE ADVERSE EFFECTS
HORIZONTAL INTEGRATION-
FORENSIC
ADVERSE REACTIONS

Generally direct extensions of their pharmacological actions.

• Respiratory depression, apnea
• Nausea & vomiting
• Dizziness, orthostatic hypotension, edema
• Mental clouding, drowsiness
• Tolerance & dependence
CORE SUBJECT
Drug interactions
Sedative hypnotics:

Antipsychotic tranquilizers.

MAO inhibitors.

Amphetamines increase analgesic effect.

 OPIOID ANTAGONISTS

NALOXONE, NALTREXONE & NALMEFENE

All are pure opioid antagonist

• Strong binding affinity for the mu receptors
 NALOXONE

Competitive antagonist at all opioid receptors

• Given parenterally - short DOA (1-2 h)

• Reverses opioids effects within 1-3min
• Drug of choice for opioid overdosage
• Reverses respiratory depression due to intraoperative use of
opioids.
• Diagnosis of opioid dependence---- precipitates withdrawal
in dependent individuals.
NALTREXONE
• It is more potent than Naloxone
• Given orally & have long DOA(1-2days)
• Used in treatment of alcohol addict, reduce craving in them
• Can block effects of Heroin for 48 hrs

• Methylnaltrexone --- useful for treating constipation with

late stage advanced disease , without precipitating
abstinence syndrome.
• Alvimopan: For treatment of post operative ileus
following bowel resection surgery

NALMEFENE:
I/V pure opioid antagonist,
DOA:8-10 hrs
 METHADONE
• Synthetic long acting potent µ receptor agonist
• Agonist at NMDA receptors Inhibits monoamines reuptake
transporters.

• Has analgesic, respiratory depression, emetic, antitussive,

constipating & biliary actions like morphine.

• Use for relief of chronic pain, detoxification of heroin/

morphine dependent addict
MEPRIDINE (PETHIDINE)
 FENTANYL
• Most widely used
• Others subgroups members are, SUFENTANIL, ALFENTANIL,
REMIFENTANIL

• Fentanyl is 100 times more potent than morphine, has

relatively shorter time to peak analgesic effect (15-20 min)
rapid termination of effect & relatively cardiostability (do
not release histamine).
Mixed agonist-antagonist
• Buprenorphine, pentazocine and nalbuphene
• Buprenorphine is µ receptor agonist and ĸ and δ
receptor antagonist

• Pentazocine and Nalbuphene are strong ĸ receptor

agonist and µ receptor antagonist

• Management of opioid withdrawal as well as in

detoxification program.
 BIOETHICS/ FAMILY
MEDICINE/AI
• Rodríguez-Fernández JL, Criado-García O. A meta-analysis
indicates that the regulation of cell motility is a non-intrinsic
function of chemoattractant receptors that is governed
independently of directional sensing. Frontiers in
Immunology. 2022 Oct 20;13:1001086.

• Ghaddaf AA, Alsharef JF, Alhindi AK, Bahathiq DM, Khaldi SE,
Alowaydhi HM, Alshehri MS. Influence of perioperative
opioid-related patient education: A systematic review and
meta-analysis. Patient Education and Counseling. 2022 Sep
1;105(9):2824-40.

• Shetty A, Delanerolle G, Cavalini H, Deng C, Yang X, Boyd A,

Fernandez T, Phiri P, Bhaskar A, Shi JQ. A Systematic review
and Network Meta-analysis of pharmaceutical interventions
used to manage chronic pain. medRxiv. 2023:2023-02.
EOLA