2. Opium is a
narcotic formed
from the
latex(juice)
released by
lacerating the
immature seed
pods (fruits) of
PapaverPapaver
somniferum.somniferum.
Opium contains up to 12% morphine, an opiate alkaloid,
which is most frequently processed chemically to
produce heroin for the illegal drug trade.
Opioid AnalgesicsOpioid Analgesics
3. Opioid AnalgesicsOpioid Analgesics
µ- receptors are most important
CNS contains opioid peptides –
enkephalins, endorphins, dynorphins,
orphanin/nociceptin
Four receptors subtypes –
µ, κ, ∂, N/OFQ
(Gi-coupled - AC inhibition -
decrease cAMP)
Presynaptic and postsynaptic inhibition
6. Tissue injury
lead to
activation of
nociceptors
(pain receptors)
by differrent
substances
released by
injured tissues.
Thermal
Chemical
Mechanical
Electrical
Activated pain receptors generate
impulses that go into spinal cord
through primary afferent neurons.
7. Opioid ReceptorsOpioid Receptors
Opioid agonists inhibit
the release of excitatory
transmitters from these
primary afferents, and
they directly inhibit the
dorsal horn pain
transmission neuron.
Thus, opioids exert a
powerful analgesic
effect directly on the
spinal cord.
8.
9. It is well established that
the analgesic effects of
opioids arise from their
ability to directly inhibit
the ascending
transmission of
nociceptive information
from the spinal cord
dorsal horn and to
activate pain control
circuits that descend
from the midbrain to the
spinal cord dorsal horn.
10. Morphine inhibits the release of:
gonadotropin-releasing hormone (GnRH)
corticotropin-releasing hormone (CRH)
thus decreasing circulating concentrations of
luteinizing hormone (LH), follicle-stimulating hormone
(FSH), ACTH, and b-endorphin;
As a result plasma concentrations of testosterone and
cortisol decline.
11. Convulsions
• With most opioids, convulsions occur only at doses
far in excess of those required to produce profound
analgesia.
• High doses of morphine and related opioids produce
convulsions
12. Sedation
Drowsiness and clouding of mentation are
common effects of opioids. There is little or
no amnesia. Sleep is induced by opioids
more frequently in the elderly than in
young, healthy individuals. Ordinarily, the
patient can be easily aroused from this
sleep.
13. Respiratory depression
All of the opioid
analgesics can produce
significant respiratory
depression by inhibiting
brainstem respiratory
mechanisms acting on
receptors. The
respiratory depression is
dose-related. Opioid-
induced respiratory
depression remains one
of the most difficult
clinical challenges in the
treatment of severe pain.
14. Cardiovascular system
Most opioids have
no significant direct
effects on the heart
and, other than
bradycardia, no
major effects on
cardiac rhythm.
17. When we use OA for cough
suppression?
Cough is due to foreign body in
the lungs
Cough is due to lung cancer
Cough is due to pleura irritation
by broken ribs parts after trauma
18. The opioid
analgesics can
activate the
brainstem
chemoreceptor
trigger zone to
produce nausea
and
vomiting(action
on dopamine
receptors)
19. Histamine release
Morphine and some other opioids
provoke release of histamine, which
sometimes plays a large role in the
hypotension.
21. Type Drug name Properties
Full agonist Mepiridine
Methadone
Morphine
Fentanyl subgroup
Levorphanol
Antimuscarinic action(atropine-like action), no miosis,
tachycardia, no spasm of smooth muscles.
Long half-life, use for maintenance of opiate addicts
Partial
agonists
Codeine
Propoxyphene
Hydrocodone
Antitussive
Analgesic in combination with NSAIDs
and other drugs (Solpadeine)
22. Type Drug name Properties
Mixed opioid
agonist-
antagonists
Nalbuphine k-agonist – spinal analgesia,
dysphoria
m – antagonist – precipitation of
withdrawal
Antagonists Naltrexone
Naloxone
Nalmefene
IV, reversal of respiratory
depression, used in opiate addiction
23. Problems with opioid therapyProblems with opioid therapy
1.1. Acute toxicity(classic triad):Acute toxicity(classic triad):
- ComaComa
- Pinpoint pupilsPinpoint pupils
- Respiratory depressionRespiratory depression
Management of acute toxicity:Management of acute toxicity:
- SupportiveSupportive
- IV naloxoneIV naloxone
2.Tolerance(pharmakodynamic)2.Tolerance(pharmakodynamic) – decrease of drug efficiency over time with
multiple administrations. This is due to increased cAMP production in cells.
Tolerance can be overcome by dose increasing . Marked tolerance may develop to
the analgesic, sedating, and respiratory depressant effects, but not to the miotic,
convulsant, and constipating actions.
3.Dependence3.Dependence(psychological and physical symptoms on withdrawal)
24. 4.Withdrawal:4.Withdrawal: sweating, lacrimation, rhinorrhea,
anxiety, restlessness, insomnia, dilated pupils,
tachycardia, hypertension, nausea/vomiting,
abdominal pain, diarrhea,muscle aches.
Opioid withdrawal is not life threatening. Emergence
of withdrawal symptoms varies with half-life of the
particular opioid; within 6-12 hours after the last dose
of morphine/hydromorphone/oxycodone or 72-96
hours following methadone. Duration and intensity of
withdrawal symptoms can be variable and are related
to clearance of the drug; withdrawal from morphine is
short (5-10 days) but more protracted with
methadone.
26. Drug with specific action
Loperamide (Imodium) – antidiarrheal agent
Dextromethorphan – antitussive agent
Both are over-the-counter (OTC) drugs
27. NSAIDs• Non-steroidal anti-inflammatory drugs
• NAIDs have analgesic, antipyretic and, in higher doses, anti-
inflammatory effects
• Term "non-steroidal" is used to distinguish these drugs from
steroids, which have a similar anti-inflammatory action
• NSAIDs are non-narcotic analgesics
28. Burns
Chemical irritants
Frostbite
Toxins
Infection by pathogens
Physical injury
Immune reactions
Ionizing radiation
Foreign bodies
Tissue
Injury
Activation of the
arachidonic acid cascade
through membrane bound
phospholipase A2 (PA2).
29. o Arachidonic acid is a polyunsaturated fatty acid that is
present in the phospholipids of membranes of the body's
cells.
o Enzyme phospholipase A2 (PLA2) release arachidonic acid
from a phospholipid molecule
PLA2
Arachidonic
acid
32. COX-1 is expressed in most tissues including platelets and
GI
COX-2 is inducible; is expressed in brain, kidney and in sites
of inflamation.
COX-1 generates prostanoids for "housekeeping" such as
gastric epithelial cytoprotection,
COX-2 is the major source of prostanoids in inflammation
and cancer.
This distinction is overly simplistic, however; there
are both physiologic and pathophysiologic processes in
which each enzyme is uniquely involved and others in which
they function coordinately. For example, endothelial COX-2
is the primary source of vascular prostacyclin (PGI2),
whereas renal COX-2-derived prostanoids are important for
normal renal development and maintenance of function.
33. COX-1- selective Non-selective
COX-1,2
COX-2- selective
- Low-dose
aspirin
- (up to 325 mg
per day),
- 75 mg as
therapeutic
agent for MI
prevention
All other:
-Indomethacin
-Ibuprophen
-Naproxen
-Diclofenac
-Ketorolac
-Piroxicam
-Meloxicam
COXIBs:
-rofecoxib
-celecoxib
-lumaricoxib
-parecoxib
-valdecoxib
-etoricoxib
Nimesulide
34. 1)Antipyretic
2)Analgesic
3)Anti-inflammatory
All NSAIDs, including selective COX-2 inhibitors, are antipyretic,
analgesic, and antiinflammatory, with the exception of
acetaminophen(paracetamol), which is antipyretic and analgesic but is largely
devoid of antiinflammatory activity.
35. • Alleviate pain of low-to-moderate activity
• Have no opioid-like effects on CNS
• Pain arising from inflammation is controlled particularly well by
NSAIDs
• Effective for menstrual pain
• Lower body temperature by inhibiting PGE2 synthesis in
hypothalamic thermo regulating centers
• Do not lower normal body temperature
36. Antiplatelet action Most notable for aspirin.
Unlike other agents Aspirin is
irreversible inhibitor of
COX(COX should be
resynthesized)
No nucleus
– no new COX
synthesis – no new
TXA2
- no platelet
activation
- no thrombus
formation
37. Acetaminophen(Tylenol,
Panadol)
• No inhibition of COX in peripheral tissues
• Lack of significant anti-inflammatory action
• Analgesic and antipyretic activity due to COX inhibition in CNS
• No antiplatelet action
• Not increase bleeding
• Not cause Reye syndrime
• Minimal GI distress
Adverse effects
Hepatotoxicity in high dose
38. Adverse effects are generally
quite similar for all of the
NSAIDs:Central nervous system: Headaches, tinnitus(aspirin), and dizziness.
Cardiovascular: Fluid retention hypertension, edema, and rarely,
congestive heart failure.
Gastrointestinal: Abdominal pain, dysplasia, nausea, vomiting, and
ulcers or bleeding.(2,5% incidence in clinical trials)
Hematologic: Rare thrombocytopenia, neutropenia, or even aplastic
anemia.
Hepatic: Abnormal liver function tests and rare liver failure.
Pulmonary: Asthma.
Rashes: All types, pruritus.
Renal: Renal insufficiency, renal failure, hyperkalemia, and
proteinuria.
39. Coxibs controversy
• Rofecoxib and valdecoxib was withdrawn from the
market because of increased cardiovascular
mortality in chronic drug users
• Overall mortality was higher in patients on coxibs in
clinical trials
40. NSAIDs cannot be used (are
contraindicated) in the following
cases:
• Allergy to aspirin or any NSAID
• Aspirin should not be used under the age of 16 years (associated
with Reye syndrome)
• During pregnancy
• During breast feeding
• On blood thinning agents (anticoagulants)
• Suffering from a defect of the blood clotting system (coagulation)
• Active peptic ulcer
