Mattingly "AI & Prompt Design: The Basics of Prompt Design"
Opioid analgesics 1 hwuegi-
1. Tripoli University
Faculty of Pharmacy
Drug Treatment of Pain
2011-2012
BY
PROF. ABDALLA SALEM ELHWUEGI (Ph.D.)
2. Main Goals
• To know mechanisms and pain pathways.
• To know Classification of analgesics.
• To know about narcotic analgesics (M.O.A.,
PA, S.E., C.I., T.U., Tolerance and
Dependence to opioids).
• To know about non-narcotic analgesics
(M.O.A., PA, S.E., C.I., T.U.)
3. Peripheral and central Pain pathways
• When a pain-producing
stimulus activates the
primary afferent nociceptor,
it generates electrochemical
impulses that propagate
through the peripheral nerves
to activate spinal cord nerve
cells. These nerve cells in turn
give rise to the pathways that
conduct the pain message to
higher centers in the
thalamus and cerebral cortex
that are required for the
conscious perception of pain.
4. Role of the Brain in Nociception
The brain is vital for 3 aspects of pain:
1. Perception of pain and its characteristics
(sensory-discrimination).
2. Reaction to pain (emotional aspects of
pain-affective-motivational).
3. Modulation of pain (especially by
descending control).
5. Types of Pain
Acute Pain Chronic Pain
1. An unpleasant sensory 1. Pain in the absence of or
or emotional experience following the removal of a
2. Caused by tissue injury. noxious stimulus. This is
also known as
It is also known as "pathological pain".
"physiological" or 2. The presence of chronic
"nociceptive" pain. pain implies a lesion or
3. Has a a role in malfunction in the "pain
protecting the organism pathway".
from injurious stimuli 3. Chronic pain has no
(noxious). protective role and is a
disease process.
6. Mechanisms of Pain Relief
1. Membrane lipid/protein disruption - general
anesthetics.
2. Ion channel blockade - local anesthetics.
3. GABA receptor modulation - general
anesthetics, IV anesthetics.
4. “Opioid” receptor activation - Narcotic
analgesics
5. Enzyme inhibition – Aspirin Like drugs
(NSAIDs).
7. Treatment of Pain
Drugs Known as analgesics
Types of Analgesics
• Opioid Analgesics • Non-opioid Analgesics
• Morphine like • Aspirin like
• Non-steroidal anti-
inflammatory
(NSAIDS)
8. I) Narcotic Analgesics &
Narcotic Antagonists
• Narcotic analgesics are those agents that are
distinguished from agents such as aspirin in that
they are used clinically for severe visceral pain
and possess an dependence (addiction) liability.
9. Classification Of Opioids
1. Classification based on Source
• Naturally occurring from the exudate of the seed
pod of the opium poppy. Contains over 20
alkaloids including morphine and codeine
(opiates).
• Commercial synthesis of compounds with
varying therapeutic properties.
• Endogenous Opiate Peptides - Endorphines
(Enkephalins, Beta-endorphin and Dynorphins).
10. 2. Classification based on action at opioid
receptors
Compound Mu Delta Kappa
(μ) (δ) (κ)
Morphine Ag Ag Ag
Fentanyl Ag Ag Ag
Methadone Ag
Pentazocine HCl pAg Ag
Butorphanol pAg Ag
tartrate
Nalbuphine HCl pAg Ag
Buprenorphine HCl pAg
Naloxone HCl Ant Ant Ant
Ag (Agonist) Ant (Antagonist) pAg (Partial agonist)
11. Examples
• Opioid drugs that are full agonists at mu
receptors: “morphine met me finally”:
(Morphine, methadone, meperidine, fentanyl)
• Opioid drugs that are partial agonists at mu
receptors: “partially b-blocks narcotics”:
(pentazocine, butorphanol, buprenorphine,
nalbuphine).
12. The “Opioid” Receptors
A. Characteristics
• High concentrations of these receptors are located in areas
of the CNS known to involve pain signal transmission
i. The dorsal horn of the spinal cord
ii. Periaqueductal gray
iii.Rostral ventral medulla, and several thalamic nuclei
• Selective binding sites for the opioids.
• Binding of Opioids to these receptors mediate diverse
pharmacological effects.
13. B. Properties
• Structural specificity - small modifications of the drug molecule cause
large changes in drug binding (and in drug effect in vivo).
• Stereospecificity - only the l (-) isomeric form of the agent binds with
high affinity (and is active as an analgesic).
• Competition between agonists and antagonists - drugs of partially similar
structure can bind to the receptor and block binding of agonists such as
morphine.
• Reversibility - bound drug can be displaced from the receptors by an
excess of other molecules that possess binding affinity.
• Binding affinity vs. potency - a good correlation exists between the
affinity for binding to the receptors and potency of agonist or antagonist
in vivo.
• All three major receptors are members of the G-protein-coupled family
of receptors.
