Drugs acting on CNS as per the PCI Syllabus

1. Opioids analgesics
Mrs. Asha Suryawanshi
Asst. Professor
M. Pharm(Pharmaceutical Chemistry)
SDDVCOP & RC New Panvel

2. Opioids are the narcotic analgesics that relieve pain by binding to opioid
receptors, which are present in the central and peripheral nervous system.
It can cause numbness and induce a state of unconsciousness
DEFINATION

3. Receptor CNS Location Response on
activation
µ Brain( laminae III & IV of the
cortex, thalamus) spinal cord
µi suprasipnal analgesics,
physical dependence .
µ2 Respiratory
depression,Miosis
sulphoria reduced
gastrointestinal motility
K Brain (hypothalamus,periqueuctal
gray, clustrum)
Spinal
analgesia,diuresis,dysph
oria, sedation, miosis,
depersonalization and
derealization
σ Brain (pontine nucleus olfactory
bulbs, deep cortex)
Analgeia ,may be
associated with mood
change
OPIOIDS RECEPTORS

4. MECHANISM OF ACTION
All opioid receptors are G-protein coupled
receptors and inhibit adenylate cyclase.
They are also involved in
Post synaptic µ receptor activation-
Increasing K+ Efflux .increases
hyperpolarization
Pre synaptic µ receptor activation- Reducing
pre synaptic Ca++ influx
Thus inhibit neuronal activity

5. CLASSIFICATION OF OPIOIDS
1) OPIOID AGONIST
A) Natural opium alkaloid: Eg. Morphine, Codeine
B) Semisynthetic opiates : Eg. Hydromorphone, Oxymorphone
C) Synthetic opioids: Eg. Pethidine, Tramodol, Methadone, Fentanyl Alfentanil, Remifentanil
2) Opioid agonist- antagonist:
Eg. Pentazocine
3) Partial receptor agonist:
Eg. Buprenorphine
4) Receptor antagonist:
Eg. Naltrexone

6. Natural opium alkaloid
Morphine
Morphine is the major analgesic drug contained in crude opium and is
prototype strong agonist.

7. MOA
Opioid drugs, typified by morphine, produce their pharmacological actions,
including analgesia, by acting on receptors located on neuronal cell membranes.
The presynaptic action of opioids to inhibit neurotransmitter release is considered to be their
major effect in the nervous system.
Uses :
1) This medication is used to treat severe pain.
2) Morphine belongs to a class of drugs known as opioid analgesics.
3)It works in the brain to change how your body feels and responds to pain.

8. Structural Activity Relationship of Morphine Analogue

9. Codeine
Codeine is an opiate and prodrug of Morphine

10. MOA
Codeine is an opioid and an agonist of the mu opioid receptor.
It acts on the central nervous system to have an analgesic effect.
It is metabolized in the liver to produce morphine which is ten times more potent
against the µ receptor.
Uses
1) Codeine is used to treat mild to moderate pain and to relieve coughing.
2) It is also used to treat diarrhea and diarrhea-predominant irritable bowel syndrome.
3) It is a weak analgesic.
4) It is used in combination with paracetamol or with ibuprofen to relieve pain

11. Hydromorphone
Hydromorphone, also known as dihydromorphinone

12. MOA
It is an opioid agonist that binds to several opioid
receptors. Its analgesic characteristics are through its effect on the
mu-opioid receptors. It also
acts centrally at the level medulla,
depressing the respiratory drive and suppressing cough.
Uses
An opioid analgesic used to treat moderate to severe pain when the use
of an opioid is indicated.

13. Oxymorphone
MOA: An opioid analgesic with actions and uses similar to those
of morphine, apart from an absence of cough suppressant activity.
Uses:
It is used in the treatment of moderate to severe pain, including pain in
obstetrics.

14. Synthetic opioids
Pethidine

15. MOA:
Pethidine is often employed in the treatment of
postanesthetic shivering. The pharmacologic mechanism of
this antishivering effect is not fully understood,but it may
involve the stimulation of κ-opioid receptors
Uses:
Pethidine is the most widely used opioid in labour and
deliverybut has fallen out of favour
Pethidine is the preferred painkiller for diverticulitis,
because it decreases intestinal intraluminal pressure

16. Tramodol
Tramadol induces analgesic effects through a variety of
different targets on the noradrenergic system, serotoninergic
system and opioid receptors system

17. MOA:
Tramadol is a centrally acting analgesic with a multimode of action. It acts on
serotonergic and noradrenergic nociception, while its metabolite
O-desmethyltramadol acts on the µ-opioid receptor.
Its analgesic potency is claimed to be about one tenth that of morphine.
Uses:
Tramadol (a schedule IV drug in the US) is used primarily to treat mild to
severe pain, both acute and chronic. There is moderate evidence for use
as a second-line treatment for fibromyalgia but is not FDA approved for
this use

18. Methadone

19. MOA:
Methadone hydrochloride is a µ-agonist; a synthetic opioid analgesic with
multiple actions qualitatively similar to those of morphine, the most
prominent of which involves the central nervous system and organs
composed of smooth muscle
Uses:
The principal therapeutic uses for methadone are for analgesia and for
detoxification or maintenance in opioid addiction. The methadone
abstinence syndrome, although qualitatively similar to that of morphine,
differs in that the onset is slower, the course is more prolonged, and the
symptoms are less severe.

20. Remifentanil
Remifentanil is a specific μ-receptor agonist

21. Uses:
Remifentanil is used as an opioid analgesic that has a rapid onset and
rapid recovery time. It has been used effectively during craniotomies ,
spinal surgery,cardiac surgery , and gastric bypass surgery .While
opiates function similarly, with respect to analgesia,
the pharmacokinetics of Remifentanil allows for quicker post-
operative recovery.

22. Fentamyl
Synthesis

23. MOA:
It is a µ agonist. It has high lipophilic character and can
easily crosses blood brain barrier and enters central Nervous system
Uses
1) It is opioid analgesic. It is about 80 times more active than
Morphine.
2) It is given in combination with general analgesthetics to produce surgical analgesic
3) It helpful in maintaining the state of neuroleptanalgesia

24. Opioid agonist- antagonist:
Pentazocine

25. Uses:
Pentazocine is used primarily to treat pain, although its analgesic effects
are subject to a ceiling effect.
It has been discontinued by its corporate sponsor in Australia, although
it may be available through the special access scheme
MOA:
It is believed to work by activating (agonizing)
κ-opioid receptors (KOR) and blocking (antagonizing) μ-
opioid receptors

26. Partial receptor agonist:
Buprenorphine

27. Uses:
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic
pain.
It can be used under the tongue (sublingual), in the cheek (buccal), by injection
(intravenous) as a skin patch (transversal), or as an implant.
MOA:
Buprenorphine is a partial agonist at the mu receptor, meaning that
it only partially activates opiate receptors.
It is also a weak kappa receptor antagonist and delta receptor
agonist. It is a potent analgesic that acts on the central nervous
system (CNS).

28. Receptor antagonist:
Naltrexone
Naltrexone hydrochloride is a relatively pure
and long-lasting opioid antagonist

29. MOA:
Uses:
Naltrexone belongs to a class of drugs known as opiate antagonists.
It works in the brain to prevent opiate effects
(e.g., feelings of well-being, pain relief).
It also decreases the desire to take opiates. This medication is also
used to treat alcohol abuse.