MEDICINAL CHEMISTRY-1

1. ASSIGNMENT
ON
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
SUBMITTED BY: SUBMITTED TO:
MARY MELNA PROF. N.S. HARI NARAYAN
ENROLL NO: MOORTY SIR
1801024022

2.  What’s Inflammation-Importance and sign of
inflammation
 NSAIDS-Introduction,Mechanism,Physiology of
pain,Classification
 Salicylate(Aspirin)-Introduction, Synthesis,
Pharmacology, Adverse
Effects,Uses,Interaction,Precaution& Contraindication
 Propinoic Acid Derivatives(Ibuprofen)-Introduction,
Pharmacology, Uses, Side Effects.

3.  It produces anti-inflammatory action means it acts
against the inflammation.
What’s Inflammation?
 Inflammation is derived from latin word
inflammatio which means to set on fire.
 It’s a complex biological responses of body tissues
to harmful stimuli,such as pathogens,damaged
cells or irritants.
 This complex process involves several immune
cells,blood vessels and molecular mediators.

4.  Inflammation occurs in the body to eliminate the
initial causes of cell injury ,clear out necrotic cells
and tissue damage.
5 Signs of Inflammation
LATIN WORD
Calor
Dolor
Rubor
Tumor
Functio laesa
MEANING
Heat
Pain
Redness
Swelling
Loss of Functions
DUE TO
Local vessel Dilation
Local Releas of enzyme
&increased tissue
pressure
Local Vessel dilation
Influx of plasma protein&
phagocytes cells into the tissue
spaces
Lack of oxygen or nutrient,and
insufficient blood flow to the area

5.  The drugs which comes under NSAIDs category have
analgesic ,antipyretic and anti-inflammatory action.
 These are the drugs without steroidal ring.
 NSAIDs don’t depress CNS,don’t produce physical
dependence,have no abuse liability and are weaker
analgesic instead morphine shows all characteristics.
 It’s also known as Non-narcotic ,Non-opoids or
aspirin like analgesics.
 Mainly NSAIDs act on peripheral pain
mechanisms,but also in the CNS to raise pain
threshold.

6. Mechanism of Action of NSAIDs
Biochemical
Mechanism
1. Inhibition of Hydrolytic enzyme.
2.Inhibition of Arachidonic
metabolism.
3.Inhibition of COX & LOX pathway
4.Inhibition of free radical
generations.
Cellular or Immunologic
Mechanism
1.Inhibition of Polymorphonuclear
leucocytes.
2.Monocyte Modification.
3.Action through lymphocytes.

7. Mechanism of action of NSAIDs:

8. Sources (Chemical/Thermal)
Pain Receptors
Discharge Impulse
Electrical activity to spinal cord and into the brain
In brain elcetrical activity become the experience of
PAIN
PHYSIOLOGY OF PAIN

9. CLASSIFICATION OF NSAIDs
ACIDIC DRUGS
Classical and non classical
(gold compounds)
BASIC DRUGS
Timegadine
(which inhibit neutrophile
degranulation)
NON-ACIDIC DRUGS
Indoxle,Nicotindole,
Nambumetone
CLASSIFICATION OF ACIDIC/CLASSICAL
NON-
SELECTIVE
COX
INHIBITOR
SELECTIVE
COX-II
INHIBITOR
PREFERENTIAL
COX-II
INHIBITORS
ANALGESIC &
ANTIPYRETICS

10. • Sodium Salicylate,Aspirin,SalolSalicylates
• Tenoxicam,PiroxicamOxicam
• Sulindac,IndomethacinAryl Acetic Acid
• Diclofenac,Acelofenac
Aryl Acetic Acid
Derivatives
• Naproxen,IbruprofenPropionic Acid Derivatives
• Phenylbutazon,OxyphenbutazonPyrazolone Derivatives
•Mefanamic acid,Meclofenamic acidFenamate
• Trick:-SOAAPP-F
NON SELECTIVE COX INHIBITOR:

11. SELECTIVE COX-II INHIBITOR
PREFERENTIAL COX-II INHIBITORS
ANALGESIC & ANTIPYRETICS
Celecoxib,Valdecoxib,Etoricoxib,Parecoxib
Nimesulide,Meloxicam,Nabumetone
1.Para-aminophenol Derivatives-Paracetamol
2.Pyrazolone Derivatives-Metamizol,Propiphenazone
3.Benzoxazocine Derivatives-Nefopam

12. INTRODUCTION:
 Aspirin is a nonsteroidal anti-inflammatory drug (NSAID).
NSAIDs are a class of drugs. Other NSAIDs include ibuprofen
(Advil, Motrin) and naproxen (Aleve, Naprosyn). They work in a
similar way to reduce the amount of prostaglandin your body
makes.
 Prostaglandin is a natural substance that most cells in your body
make. Your cells release prostaglandins when you’re injured.
They contribute to your body’s inflammation, which causes a
variety of effects, including swelling, fever, and increased
sensitivity to pain.
 By blocking your body’s production of prostaglandins, NSAIDs
such as aspirin can help prevent and relieve these symptoms of
injury.

13.  SYNTHESIS OF ASPIRIN:

14. PHARMACOLOGY:
 Aspirin (acetylsalicylic acid) is the best-known salicylate and
belongs to the non steroid anti-inflammatory drug class. Despite
wide use being made since more than 100 years, knowledge
about mechanism of action and therapeutic issues continually
evolves. The main mechanism of action is prostaglandin
synthesis inhibition. This is achieved through inhibition of
prostaglandin endoperoxide synthase (PGHS) or
cyclooxygenase (COX) synthesis. Most of the therapeutic uses of
aspirin are explained by this mechanism. Nevertheless aspirin
uses change as time goes by: if the main one during the first
fifty years was an analgesic, anti-pyretic and anti-inflammatory
one, the last fifty years saw aspirin being used mainly as an
anti-thrombotic agent, in primary and secondary thrombo-
embolic prevention. Better knowledge of mechanism of action
points today at, on one hand, more selective and therefore better
tolerated molecules, and, on the other hand, at new therapeutic

15. SIDE EFFECTS:
 Common side effects of aspirin can include:
Nausea,vomiting,stomach pain,heartburn
 Serious side effects of aspirin are rare, but can include:
 Allergic reactions. Symptoms can include:
 Hives,rash,swelling of your eyes, face, lips, tongue, or throat,wheezing or
difficulty breathing
 Changes in your acid-base balance, which affects how systems in your body
work. Symptoms can include:
 Hoarseness,fast heartbeat,fast breathing,cold and clammy skin
 Salicylate toxicity. Early symptoms can include:
 ringing in your ears,hearing loss
 Stomach bleeding. Symptoms can include:
 bloody vomit,vomit that looks like coffee grounds,bright red blood in your
stools,black or tarry stools

16. USES:
 Aspirin is used in the treatment of a number of conditions,
including fever, pain, rheumatic fever, and inflammatory
conditions, such as rheumatoid arthritis, pericarditis, and
Kawasaki disease. Lower doses of aspirin have also been
shown to reduce the risk of death from a heart attack, or
the risk of stroke in people who are at high risk or who
have cardiovascular disease, but not in elderly people who
are otherwise healthy.There is some evidence that aspirin
is effective at preventing colorectal cancer, though the
mechanisms of this effect are unclear.In the United States,
low-dose aspirin is deemed reasonable in those between
50 and 70 years old who have a risk of cardiovascular
disease over 10%, are not at an increased risk of bleeding,
and are otherwise healthy.

17. INTERACTION:
 Aspirin is known to interact with other drugs. For example,
acetazolamide and ammonium chloride are known to enhance
the intoxicating effect of salicylates, and alcohol also increases
the gastrointestinal bleeding associated with these types of
drugs. Aspirin is known to displace a number of drugs from
protein-binding sites in the blood, including the antidiabetic
drugs tolbutamide and chlorpropamide, warfarin,
methotrexate, phenytoin, probenecid, valproic acid (as well as
interfering with beta oxidation, an important part of valproate
metabolism), and other NSAIDs. Corticosteroids may also
reduce the concentration of aspirin. Ibuprofen can negate the
antiplatelet effect of aspirin used for cardioprotection and
stroke prevention.The pharmacological activity of
spironolactone may be reduced by taking aspirin, and it is
known to compete with penicillin G for renal tubular
secretion.Aspirin may also inhibit the absorption of vitamin C.

18. PRECAUTIONS:
 Use an immediate-release aspirin in such an event. Make sure
your doctor knows if you are pregnant or breastfeeding. Do not
use this medicine during the later part of a pregnancy unless your
doctor tells you to. This medicine may increase risk for bleeding
problems, including stomach ulcers or bleeding.
CONTRAINDICATION:
 Many medicines should not be used together by the same person.
For instance, a person who takes warfarin to thin the blood
should not take aspirin, which is a blood thinner. This is an
example of a relative contraindication.

19. INTRODUCTION:
 Ibuprofen is a medication in the nonsteroidal anti-
inflammatory drug (NSAID) class that is used for
treating pain, fever, and inflammation. This
includes painful menstrual periods, migraines,
and rheumatoid arthritis. It may also be used to
close a patent ductus arteriosus in a premature
baby. It can be used by mouth or intravenously. It
typically begins working within an hour.

20.  PHARMACODYNAMICS:Ibuprofen is a
nonsteroidal anti-inflammatory drug (NSAID) that
possesses anti-inflammatory, analgesic and
antipyretic activity. Its mode of action, like that of
other NSAIDs, is not completely understood, but may
be related to prostaglandin synthetase inhibition.
 PHARMACOKINETICS:Ibuprofen pharmacokinetics
are only minimally influenced by advanced age, the
presence of alcoholic liver disease, or rheumatoid
arthritis. Levels of ibuprofen in breast milk are
negligible. In addition, ibuprofen can be combined
with acetaminophen without altering the
pharmacokinetic profile.

21. USES:
 Ibuprofen is used primarily to treat fever (including
post-vaccination fever), mild to moderate pain
(including pain relief after surgery), painful
menstruation, osteoarthritis, dental pain, headaches,
and pain from kidney stones. About 60% of people
respond to any NSAID; those who do not respond well
to a particular one may respond to another.
 It is used for inflammatory diseases such as juvenile
idiopathic arthritis and rheumatoid arthritis. It is also
used for pericarditis and patent ductus arteriosus.

22. SIDE EFFECTS:
 Adverse effects include nausea, dyspepsia, diarrhea,
constipation, gastrointestinal ulceration/bleeding, headache,
dizziness, rash, salt and fluid retention, and high blood pressure.
 Infrequent adverse effects include esophageal ulceration, heart
failure, high blood levels of potassium, kidney impairment,
confusion, and bronchospasm. Ibuprofen can exacerbate asthma,
sometimes fatally.
 Ibuprofen may be quantified in blood, plasma, or serum to
demonstrate the presence of the drug in a person having
experienced an anaphylactic reaction, confirm a diagnosis of
poisoning in people who are hospitalized, or assist in a
medicolegal death investigation. A monograph relating
ibuprofen plasma concentration, time since ingestion, and risk of
developing renal toxicity in people who have overdosed has
been published.