KARNATAKA COLLEGE OF PHARMACY

DEPARTMENT OF PHARMACOLOGY
2022-2023

SUBJECT – ADVANCED PHARMACOLOGY-I

TOPIC – NARCOTIC AND NON-NARCOTIC ANALGESICS

Submitted To
Submitted By
Mrs. Kusu Susan Cyriac
Satyanand Sahu
Assistant Professor
1st Sem M.PHARM M.Pharm
Department of Pharmacology Department of Pharmacology
 CONTENT
1. Pain
2. Types
3. Analgesic
4. Types
5. Narcotic Analgesic
6. Opioid Receptor
7. Opioid Antagonist
8. Non- Narcotic Analgesic

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 INTRODUCTION
 Algesia ( Pain) - unpleasant sensory & emotional experience associated
with actual or potential tissue damage.
Types of Pain
1. On the basis of site

Type Origin/ Site Cause Example

Somatic Pain Originated from outer layer of
body or from muscle
Visceral Pain Originated from Viscera part
Referred Pain Associated with other disease
Cut, Inflammation. Cut by a blade
Spasm, Ischemia, Stomach pain
Inflammation, etc.
Caused by some disease In case of Angina the
cardiac pain referred to
left arm

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 2) On the basis of Time of Duration
Type Example

Acute Wound, burn, cut, etc.

Chronic Arthritis, cancer, etc.

3) On the basis of Etiology

Type Etiology Example

Nociceptive Activation of sensory receptor Cut by a blade, Stomach

pain

Neuropathic Damage of CNS or PNS tissue Arthritis, cancer, etc.

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 ANALGESIC
Drug used to relieve the pain without loss of consciousness.

Classification
1. Narcotic / Opioid / Morphine like Analgesic e.g. Morphine, Codeine, etc.
2. Non- Narcotic / Non- Opioid / Antipyretic / Aspirin ( NSAIDs) like
Analgesic e.g. Aspirin, Nimesulide, etc.
3. Adjuvant Analgesic e.g. Anticonvulsant, Antidepressant, etc.

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 NARCOTIC ANALGESICS
Also known as opioid analgesic.
Opioid refers to all compound related to Opium.
Opium Contains two types of alkaloids i.e. Phenanthrene derivatives and
Benzoisoquinoline derivatives.
Phenanthrene Derivatives
i. Morphine
ii. Codeine
iii. Thebaine
Benzoisoquinoline Derivatives
iv. Papaverine
v. Noscapine
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 Narcotic analgesic are the drugs that relieve the pain by binding to opioid
receptor which are present on CNS as well as Peripheral tissues and gives
their analgesic activities.
OPIOID RECEPTORS
Opioid receptors belongs to GPCR.
These receptor are present on the CNS as well as Peripheral tissues.
There are three different type of opioid receptors, which are Mu (µ), Kappa
(κ), Delta (δ).

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 µ receptor this receptor has high affinity for morphine.
Morphine mainly binds to the µ receptor and exert their pharmacological
action.
Endogenous opioid peptide like Endomorphine also bind to µ receptor.
Subtypes - µ1, µ2
κ receptor this receptor has high affinity for Ketocyclazocine and
Dynorphin.
Subtypes – κ1, κ2, κ3
δ receptor this receptor has high affinity for Enkephalins which is a
endogenous opioid peptide.

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TYPES OF NARCOTIC (OPIOID) ANALGESIC
1. On the basis of Source
OPIOID ANALGESIC

Natural Opium alkaloids Semi-Synthetic opioids Synthetic opioids

Pethidine (Meperidine)
Morphine Diacetylmorphine (Heroin) Methadone
Codeine Pholcodine Fentanyl
Tramadol
Papaverine Ethyl morphine Tapentadol

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 2. On the basis of Action
Strong Agonist Moderate/Low Mixed Agonist/ Pure Antagonist
Morphine Antagonist
Agonist Buprenorphine Naloxone OPIOID
Heroin
Fentanyl
Codiene Nalbuphine Nalmefene ANALGESIC
Pentazocine
Methadone Butorphanol Naltraxone

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General Mechanism of Action of Narcotic Drugs

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Morphine
Principal alkaloid in opium, Prototype.
Administered orally, iv, rectally, subcutaneously, as well as through
inhalation or snorting.
Bind to µ opioid receptor.

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 Pharmacological Actions
1. CNS actions
a) Analgesic
b) Sedation
c) Respiratory centre
d) Antitussuve/Cough Centre
e) Euphoria
f) Miosis *
g) Nausea and emesis
i) Heat regulation

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 2. Peripheral Action
a) Cardiovascular System
b) Vagus
c) GIT
d) Urinary tract
3. Bronchi
4. Renal Function

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 Pharmacokinetics
 Oral route,
 Slow and incomplete absorption, due to 1st pass metabolism
bioavailability is 20-40%.
 Subcutaneously/ Intramuscular inj.
 Gives it’s effect in 15-20 min, peak plasma conc. 1 hr.
 T1/2 – 2-3 hr and duration of action is 3-5 hr, Elimination is almost
completed in 24 hrs. 90% through urine rest 10% from other route.

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 Adverse Effects
Sedation
mental clouding
Lethargy
Vomiting
Blurring of vision
BP may fall.
Apnoea in newborn

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 Acute morphine poisoning It may be accidental, suicidal or seen in drug
abusers. In the nontolerant adult, 50 mg of morphine i.m. produces
serious toxicity. The human lethal dose is estimated to be about 250 mg.
Tolerance and dependence If the drug is used repeatedly high degree of
tolerance can be developed to morphine and related opioids.

USES
 To relieve pain.
 Also used in Diarrhea.
 Also used in pain caused by heart attack or MI.

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Heroin
 Also known as Diacetyl morphine or Diamorphine.
 3 times more potent than morphine
 Act on µ receptor
 Highly lipid soluble
Pharmacological Action
a) Analgesic
b) Sedative
c) Respiratory depression
d) Euphoria
e) Physical dependence
f) Nausea and Emesis

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Pharmacokinetic
Given through oral, rectal, and IV/IM.
Metabolism in liver.
Onset of Action
Bioavailability orally(20-40%), rectally(36-71%), IV/IM(100%)
Elimination Half life- 2-3 hours
Adverse Drug Reaction
Constipation, Skin rashes, Dry mouth
Headache, Insomnia

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PETHIDINE
 First synthesized in 1939.
 Also known as Mepridine.
 Interact with µ receptor and it’s action is blocked by Naloxone.
 Better absorbed than morphine.
 But less potent than morphine. 100mg = 10 mg of morphine.
 Onset of action is more than morphine.
ADR
Similar to Morphine.
Uses
In analgesia
During labour
Preanaesthetic medication
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Opioid Antagonist
Drug which nullify(reduce) the action of opioid agonist.
It bind to OR with high affinity, but fails to initiate the receptor mediated
activity.
Types
1. Mixed agonist and Antagonist- Pentazocine, Cyclozocine, Buprenorphine,
Nalbuphine, Nalorphine
2. Pure opioid antagonist- Naloxone, Naltrexone, Nalmefene
Uses
 Used to reduce the action of opioid agonist.
 Also used to reduce opioid poisoning, abuse and over dosing of opioid
agonist/ drugs.
 Antagonized Coma and Respiratory depression caused by use of morphine.
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Mixed Agonist and Antagonist
Pentazocine
K receptor agonist and µ receptor antagonist.
Pharmacological Effects
1. CNS – similar to morphine.
2. CVS- increases BP and heart rate thus increase cardiac work. Hence not used
in MI.
3. Constipation
4. Tolerance and Dependence.

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Pharmacokinetics
Oral and IV,IM,SC route.
Exert their action in between 15- 30 min.
Metabolize in liver.
Half life- 2-3 hrs.
ADR
Sedation
Sweating
Nausea
dysphoria.
Uses
Used as analgesic
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Pure Antagonist
Naloxone
Competitive antagonist to all type of receptor.
Used to decrease the high dose of any kind of opioids analgesic.
At µ receptor on low dose and at k and delta receptor on high dose it give good
effect.
No addiction, dependence has been observed.
0.4-0.8mg used to antagonize the morphine action and 4-10 mg used to
antagonize the action of nalorphine.

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Mechanism of Action
Naloxone is a competitive inhibitor of the µ-opioid receptor. Naloxone
antagonizes the action of opioids, and reversing their effects. If a patient has
not taken opioids, Naloxone does not have a significant effect on patients.
Pharmacokinetics Naloxone is inactive orally because of high first pass
metabolism in liver. Injected i.v. it acts in 2-3 min. The primary pathway of
metabolism is glucuronidation. Plasma t½ is 1 hour in adults and 3 hours in
newborns. Duration of action is 1-3 hr.
ADR Adverse effects of naloxone are uncommon; may include rise in BP and
pulmonary edema.

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Uses
Naloxone is the drug of choice for morphine poisoning (0.4-0.8 mg i.v.
every 2-3 min: max 10 mg).
It is also used to treat overdose with other opioids and agonist-antagonists
(except Buprenorphine).
To reverse respiratory depression due to use of opioids: 0.1-0.2 mg i.v.
Diagnosis of opioid dependence precipitates withdrawal in dependent
subjects.
It also partially reverses alcohol intoxication.
 Naloxone has been found to elevate BP

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Non-Narcotic Analgesic

Also known as NSAIDs, Aspirin type, Non-opioid Analgesic.

NSAIDs Nonsteroidal Anti-Inflammatory Drugs.
In contrast to morphine, they do not depress CNS, do not produce physical
dependence.
May act by inhibiting the Cyclo-oxygenase enzyme.
Use for less severe pain i.e. for low or moderate type of pain, inflammation,
antipyretic(fever),platelet aggregation.

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Basic Mechanism of Action of NSAIDs

Phospholipase A2

PGE2, PGI1,TXA2 PGE1, PGI2, TXA2

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Classification of NSAIDs

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Non-selective COX Inhibitor
Aspirin
Prototype NSAIDs
10 times less potent than Morphine.
It is one of the oldest analgesic and anti-inflammatory drugs.
Also used in platelet aggregation.
Mechanism
Aspirin inhibits COX irreversibly by acetylating one of its serine residues which
result into the inhibition of TX A2.

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Pharmacological Actions
1. Analgesic, antipyretic, anti-inflammatory actions.
2. GIT
3. Blood vessel
4. Blood
5. Metabolic effects
6. Respiration

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Pharmacokinetics
Route- Oral
Absorption- Absorbed from the stomach & SI.
Poorly water soluble and rapidly deacetylated in the gut wall, liver, plasma
and other tissues to release salicylic acid.
The plasma t½ of aspirin as such is 15- 20 min.
However, metabolic processes get saturated over the therapeutic range; t½ of
anti-inflammatory doses may be 8- 12 hours while that during poisoning may
be as long as 30 hours.
Excreted through urine.

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Adverse effects
GI Disturbances– Nausea, vomiting, gpigastric distress and gastric mucosal
damage.
Hypersensitivity-Bronchospasm, rashes, urticaria.
Hepatotoxicity – Rise in serum transminases
Nephrotoxicity– Na+ and H2O retention causes renal failure
Prolongation of bleeding time
Respiration- Asthma

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Uses
Used to treat mild pain.
Used to treat fever.
Also used in Arthritis.
Also use to treat post MI.
Used to treat Preeclampsia.

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Nimesulide
Nimesulide is a non-steroidal anti-inflammatory drugs (NSAID)
with pain medication and fever reducing  properties.

Mechanism
weak inhibitor of COX-1 and moderately inhibitor of COX-2 selective.
reduced generation of superoxide by neutrophils inhibition of PAF synthesis
and TNFα release, free radical scavenging.
Pharmacokinetics
Nimesulide is almost completely absorbed orally, 99% plasma protein bound,
extensively metabolized and excreted main ly in urine with a t½ of 2- 5 hours.

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Pharmacological Action
Analgesic
Antipyretic
Anti-inflammatory activity

Uses
 Used in sports injury, sinusitis, dental surgery, post operative inflammatory
condition, fever, low back pain, ENT disorder.
Adverse Effects
 Epigastric pain, nausea, vomiting, loose motion, heart burn, rash, GIT
tolerant, etc.

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Celecoxib
Belongs to Selective COX-2 inhibitor class.
More potent than other NSAIDs (about 10 times).
It exerts anti- inflammatory, analgesic and antipyretic actions.
Mechanism
Selectively inhibit COX-2 without inhibiting COX-1, which may reduce PGI2
production and gives its action.
do not suppress TXA2 production, do not inhibit platelet aggregation & do not
prolong bleeding time.

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Pharmacokinetics
Celecoxib given via oral route and absorbed slowly, 97% plasma protein
bound and metabolized primarily by CYP2C9 with a t½ of - 10 hours.
Uses
It is used to treat the pain and inflammation in osteoarthritis, acute pain in
adults, rheumatoid arthritis, ankylosing spondylitis, painful menstruation, and
juvenile rheumatoid arthritis.
Adverse effects
Common side effects include abdominal pain, nausea, and diarrhea. Serious
side effects may include heart attacks, strokes, gastrointestinal perforation,
gastrointestinal bleeding, kidney failure, and anaphylaxis.

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Acetaminophen
Commonly known as Paracetamol.
Popular, safer alternate to Aspirin (as anti-pyretic and analgesic)
Domestic analgesic
Used in both adults and children
Over the counter drug (OTC

Mechanism of action
 The reduction of the COX pathway activity by acetaminophen is thought to
inhibit the synthesis of prostaglandins in the central nervous system.

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Pharmacological Action
Analgesic
Anti- Inflammatory
Antipyretics
Respiratory system- no action
CVS – no action
Pharmacokinetics
Paracetamol is well absorbed orally, it is uniformly distributed in the body.
Metabolism occurs mainly by conjugation with glucuronic acid and sulfate
Excreted through urine.
Plasma t½ is 2- 3 hours.
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Side effects
Allergic reaction
difficulty breathing or swallowing
swelling of your face, lips, throat, or tongue
severe itching.
peeling or blistering skin
Uses
Useful in mild to moderate pain like headache, pyrexia, myalgia etc.
In case of patients allergic to Aspirin
Used in hemophilia.
Used in PUD (peptic ulcer disease)

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Reference
1. Essential of Medical Pharmacology 8th edition by KD Tripathi. Page no.
Narcotic Analgesic (419-514) & Non Narcotic Analgesic (209-226).
2. A Text Book of Pharmacology-I PV publication by Dr. Madan Kaushik. Page
no. Narcotic Analgesic (343-356) & Non Narcotic Analgesic (609-626)
3. Pharmacology for Pharmacy Students by Padmaja Udaykumar . Page no.
Narcotic Analgesic (210-224) & Non Narcotic Analgesic (368- 379).

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 THANK YOU

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