Non narcotic: Agonist antagonist

1. NON NARCOTIC ANALGESICS
OR
ANTI-INFLAMATORY AGENTS
Presented by,
Prof. Sonali R. Pawar
Pharmaceutical Chemistry Department

2. 1
Introduction
2
Classification
3
MOA & SAR
4
Details of
Drugs
5
Narcotic
Antagonist
6
Drugs
information
Drug produce analgesia by binding to the CNS Receptor

3.  Drug acting on Central Nervous system.
 General anesthesia are CNS depressant Induced non awareness of sensation and loss of pain.
 Anesthesia Greek origin= Without perception/ insensibility
 Narcotic analgesic- act on CNS and increased pain threshold without disturbing
consciousness/ changing other sensory modalities thus, they relieve pain.
 Various analgesic- have inflammatory properties.
 Example : Aminopyrine and phenybutazone

4. SEVERAL DRUG WHICH USED FOR-
 Relieve pain from producing unconsciousness
 Antispasmodic (used to relieve spasm/contraction of involuntary muscle)
 Relax smooth muscles for relieving pain
 Local anesthetic block peripheral nerve fibers for preventing pain and
 Adrenal coracoids relieve rheumatoid arthritis (destructive joint disease caused by
inflammation) pain by anti-inflammatory action.

5. Analgesic are
classified as:
Opioid
Analgesic
narcotic
analgesic
centrally acting
Non opioid
Analgesic
Peripheral
acting
Naturally occurring,
semisynthetic and synthetic
drug:
Having morphine like action
Agonist- Antagonist:
Antagonist Block narcotic effect and cause withdrawal symptoms when another narcotic is present.

6. CLASSIFICATION OF NARCOTIC ANALGESIC
Morphine Analogues
Synthetic Derivative with
structure unrelated to Morphine
Morphine
Analogues
Codeine Naloxone Levorphane Nalophine Diamorphine (Heroin)
Phenylpiperidine
Series
Fentanyl
Pethidine
Methadone
Methadone
Dextra
propoxyphene
Pentazocine Cyclazocine
Benzomorphan
Semisynthetic
thebaine
Etorphine
Buprenorphine

7.  Three types of Opioid receptors: μ (mu), δ (delta)
and κ (kappa) has been cloned.
 All are G- Protein coupled receptor situated on
prejunctional neurons.
 They exercise inhibitory modulation by decreasing
the release of junctional transmitter.
 In opioid action various monoamines (NA, DA &
5HT) , GABA, Glutamate pathway are involved.

8.  Activation of opioid receptors by:
1) Reduced the formation of intracellular cAMP (Secondary messenger in biological process)
2) Open K+ ion channel (through μ and δ receptor)
3) Or Suppresses voltage gated N type Ca ++ ion channel.
RESULT
 Result:
 In neural hyperpolarization
 Reduce availability of intracellular Ca++ ions.
 Thus decreasing the release of neurotransmitter by CNS.

9. 1) Respiratory depression.
2) Treating compulsive users of opioids.
3) Nalorphine removes the withdrawal symptoms in patients
abusing heroine and methadone.
4) In acute poisoning caused by morphine and related
compounds.
5) Combination drugs also used to treat the disease.
6) Reducing the intensity of various problematic
effects of opioids:
 Euphoria (feeling high, unrealistic)
 Drowsiness (strong desire for sleep)
 Vomiting
 Muscle incoordination
 Abdominal pain
 Irritability
 Cold sweats (response to stress / diaphoresis)
 Diarrhea and Nausea.
Opioid analgesic are
used as

10. a) Analgesia:
 NASAID like aspirin/ibuprofen used instead of morphine in mild somatic pain (burn/ fracture) as they induced
sleep
 Chronic pain in case of cancer
 Labour pain
 Myocardial infraction
b) Diarrhoea: Opioid origin drug used as anti diarrhoeal drug. They act by increasing the tone and decreased the
motility of smooth muscles.
c) Relief of cough: codeine of dextromethorphan (antitussive action )
d) Anesthesia and pre anesthesia: IV rout 8-12 mg dose
e) Used in cardiovascular shock caused by an injury, burn etc.

11. Morphine is an example of opioid and specific for μ opioid receptors.
5 Fused rings and five chiral centers having absolute stereochemistry
I.e.; 5(R), 6(S), 9(R), 13(S) and 14 (R)
Levo (-) rotatory is naturally occurring isomer of morphine
Dextro (+) rotatory not containing any analgesic and other opioid activities is synthesized.
Structure
consist of:

12.  Alkaloid in opium
 Prototype opiate analgesic and narcotic
 Extensive effects on the CNS and smooth muscle
Mechanism of action:
 CNS opioid receptor responsible for the analgesic effect of morphine.
 Morphine initially act on μ (mu) opioid receptor.
 Bind initially to GABA inhibitor, which inhibit the descending pain inhibition pathway
 And thus, without the inhibitory signals pain modulation advance downstream.
Uses: To treating and relieving severe pain.

13.  Codeine is morphine related opioid analgesic
 Which less potent analgesic properties and mild sedative effects.
 Suppresses cough by acting centrally.
Mechanism of action:
 Opiate receptor bind to G- Protein receptor
 Serve as + or – ve regulators of synaptic transmission via G- protein which activate effector protein.
 Opiate bind stimulates GTP exchange with GDP on the G- protein complex.
 Opioids decrease the intracellular cAMP by inhibiting adenylate cyclase
 Therefore; inhibiting release of NT (GABA, DA, NA).
 Release of vasopressine, Somatostatin, insulin and glycogen is also inhibited by opioids.
 Opioid open calcium dependent channel inwardly potassium channel and closed N type
 voltage operated calcium channel to hyperpolarization and reduces neuronal excitability.
Uses: To treating and managing pain (systematic) and as an antidiarrheal and a cough suppressant .

14.  Meperidine hydrochloride is narcotic analgesic
 It may cause morphine dependence on prolonged use.
Uses: It is used for controlling moderated to severe pain.
Used for relieving moderate to severe pain (such as postoperative and labour pain.)
Mechanism of action:
 Meperidine having local anesthetic effect is an agonist of κ-opiate receptor.
 Opiate receptor bind to G- Protein receptor;
 Serve as + or – ve regulators of synaptic transmission via G- protein which activate effector protein.
 Opiate bind stimulates GTP exchange with GDP on the G- protein complex.
 Opioids decrease the intracellular cAMP by inhibiting adenylate cyclase
 Therefore; inhibiting release of NT (GABA, DA, NA).
 Codeine is converted to morphine.
 Opioid open calcium dependent channel inwardly potassium channel and closed N type
 voltage operated calcium channel to hyperpolarization and reduces neuronal excitability.

15.  Anileridine is a synthetic opioid and a strong analgesic.
 It is a narcotic pain reliever and treats moderate to severe pain.
Uses: It is used for treating and managing pain (systematic).
Used as an adjunct in anaesthesia.
Mechanism of action:
 Same as morphine

16.  Diphenoxylate hydrochloride is meperidine congener used with atropine as an antidiarrhoeal
 It acts like morphine in higher doses.
Mechanism of action:
 Diphenoxylate is an opiate receptor agonist which constricts the sphincters and decreases
peristalsis by stimulating the μ-receptors in GIT.
 Results into: segmentation and prolongation of GIT trasit time, as it has a direct effect on
circular smooth muscles of bowel.
 Clinically it due to increased segmentation which increases the contact of intraluminal
contents with the intestinal mucosa.
Uses: It is used as an adjunctive therapy in managing diarrhoea.

17.  Loperamide is a long acting synthetic antidiarrhoel drug.
 Which is not absorbed by gut.
 No effect on the adrenergic or CNS system, but antagonizes histamine.
Uses: It is used for controlling and relieving the symptoms of acute non specific diarrhoea
and chronic diarrhoea related to inflammatory bowel disease and gastroenteritis.
Mechanism of action:
 In Vitro and animal studies suggested that this drug slow down
intestinal motility
 Affect water and electrolyte movement through the bowel.
 It is non selective calcium channel blocker which bind to opioid μ
receptor and inhibit peristaltic activity.

18. Uses: Used in a regular narcotic therapy for treating cancer patients having severe pain.
Mechanism of action:
 Same as codeine
 Fentanyl citrate is a potent narcotic analgesic.
 μ opioid agonist.
 Used as an anesthetic drug.

20.  Pentazocine has mixed agonist- antagonist effect
 It is act as agonist at the κ and δ-opioid receptor
 And as an antagonist at μ opioid receptor
Mechanism of action:
 Pentazocine shows competes for the same receptor sites,
especially at μ opioid receptor
Uses: Used for relieving moderate to severe pain.

21. Methadone is a synthetic opioid analgesic which is a at μ opioid
agonist and inhibit actions and uses similar as morphine
Mechanism of action:
 Methadone is a μ opioid agonist and synthetic opioid analgesic which act on the CNS and organs
composed of smooth muscle similar to morphine.
Uses: Treating dry cough, pain, drug
withdrawal syndrome and opioid
drug dependence.

22. Drugs studied
below
1
• Antagonist are substances which oppose the action of
something.
2
• Opioid antagonist has a greater affinity for a cell receptor
than an opioid agonist.
3
• It prevent a response to opioid by binding to the cell
hence an opioid antagonist reverses the opioid actions.
4
• It restore the respiratory depression related to opioid.
5
• Used to treat alcohol dependence
6
• and blocking the effect of opioids used by a person
being treated for alcohol dependence

23. 1) Nalorphine hydrochloride
Mechanism of action:
 Nalorphine produces direct antagonistic affect against morphine.
 It causes respiratory depressant which potentiate the already existing
depression produced by morphine.
Uses:
 Used for reversing opioid overdose.
 Nalorphine Hydrochloride is a mixed opioid agonist- antagonist which act at
two opioid receptor.
 It has antagonist effects at the μ receptor and exert high efficacy agonist
characters at the κ- receptor

24. 2) Levallorphane Tartrate
 It is an opioid antagonist having similar properties of
naloxone
Uses:
 Used for completely or partially reversible narcotic
depression such as respiratory depression by opioids.
Mechanism of action:
 Levellorphane competes for the use the same receptor
sites and antagonist the opioid effects.
 It binds with the μ opioid receptor and nicotinic
acetylcholine receptors α2/ α3.

25. 3) Naloxone hydrochloride
Uses:
 Used for completely or partially reversible narcotic depression by opioids.
 Increasing blood pressure while managing septic shock.
Mechanism of action:
 antagonist the opioid effects.
 It binds with all three opioid receptors.
 Naloxone is an opioid antagonist used for reversible or
blocking the effects of opioid drugs.