NSAID drug

By Dr. Ganesh Jaiswal

NSAIDS DRUGS ( Nonsteroid anti-
inflammatory drugs)
All the drugs in this class have analgesic, antipyretic and anti-inflammatory actions.
Compared to opioids drugs they are weaker analgesics.
They don't depress CNS.
Do not produce physical dependence and have no abuse liablity so they are also called as non-
narcotic, non-opoid.
They act primarily on peripheral pain mechanism.
What is pain?
- Pain can be defined as unpleasant sensory and emotional experience associated with actual
or potential tissue damage.
- Pain can be acute or chronic
- Acute pain lasts for short times and occurs during trauma, surgery and other conditions.
- Chronic pain lasts for longer period of time.
Inflammation
It is defined as localized physical condition in which part of the body
becomes red, swollen, hot and often painful, especially as a reaction to
injury or infection.
Fever
The increase in body temperature above the normal range is called
fever.
Normal body temperature is 98 degree Fahrenheit.
Salicylates
Aspirin (acetyl salicylic acid)
Aspirin is acetyl salicylic acid converted in to salicylic acid in to our body
which responsible for its action.
IUPAC name- 2-acetoxy benzoic acid

Structure of aspirin
Starting material for synthesis- salicylic acid + acetic anhydride
Basic ring – salicylic acid
Mechanism of action
Inhibits irreversibly cyclooxygenase, an enzyme require for the synthesis of
prostaglandlin ( PG mediates pain, inflammation and fever)
And by potentiating thromboxane A2 receptor it causes platelet
aggregation.
USES
Analgesic, antipyretic, arthritis, antiplatelet etc.
ADR-
GI bleeding, peptic ulcer, REYES syndrome
Overdose may causes tinnitus (unusual disturbing sound in ear)
Headache ,reversible vision impairment and hearing loss etc
Hyperuricemia by decrasing the execration of uric acid.
Pharmacokinetics
Aspirin is absorbed in acidic medium
Elimination aspirin follows first order at low dose and zero order at high dose.
Aspirin is metabolized in liver by glycine and glucuronide conjugation.
Q.1 mechanism of action of aspirin is
a) irreversibly inhibit cox enzyme
b) reversibly inhibit cox enzyme
c) inhibit cox-2 enzyme
d) donot inhibit any enzyme .
Propionic acid derivative
Ibuprofen, Naproxen, Flubiprofen, ketoprofen.
Ibuprofen
IUPAC name – 2-(4-isobutylphenyl) propionic acid
Basic moiety- phenyl-1-methyl acetic acid
Starting material for synthesis- isobutyl benzene
MOA
Reversible inhibit Cox enzyme
USES
Analgesic, antipyretic, Dysmenorrhea, osteoarthritis, musculoskeletal
disorder etc
Anthranilic acid derivative or Fenamates
Mephenamic acid
 Structure of Mephenamic acid
Basic moiety- phenyl Anthranilic acid
IUPAC Name- N-2,3-Xylyl anthranilic acid
Starting material for synthesis
2,3-xylidine + 2-chloro benzoic acid
Mechanism of action
Inhibit cyclooxygenase enzyme require for the synthesis of prostaglandin.
Uses
Analgesic but weak anti-inflammatory, Dysmenorrhea, menorrhea etc.
Aryl acetic acid dervatives
Diclofenac, aceclofenac

Structure of diclofenac
Basic moiety- Biphenyl ring
IUPAC name – 2-[(2,6-dicholorophenyl)-amino]phenyl acetate
Starting material for synthesis
2-cholorobenzoic acid and 2,6-dichloro aniline.
MOA
Same as above
USES
Pain, inflammation, Arthritis, spondylitis etc
ADR
Epigastria pain
Nausea, headache, Rashes.
Aceclofenac

Structure of aceclofenac
 Basic moiety- Diphenyl amine or phenyl acetic acid derivative
Oxicam Derivatives
Piroxicam, Tenoxicam
Basic moiety- Dioxo Benzthi-azine and pyridine
IUPAC name -4-hydroxy-2-methyl-1,1-dioxo-N-pyridine-2-yl-{6},2-benzothiazine-
3-carboxamide.
MOA
Reversible inhibitor of cox.
Reduces production of IgM rheumatoid factor and leucocyte chemo taxis.
USES
Same as above
Indole derivative
indomethacin
Basic moiety- indole derivatives
IUPAC Name – 1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-ylacetic acid
Starting material for synthesis- P-anisidine +NaNo2/HCL
Mechanism of action
Same as above
ADR
Frontal, headache , mental confussion, depression and psychosis.
Contraindicates in pregnant woman and children, machinery worker, driver
and kidney patients
Suldinac
Basic moiety –indane derivative
Starting material for synthesis –Glyoxalic acid
Mechanism of action – same as above
Preferential COX-2 inhibitor
Eg. Nimesulide,Meloxicam, Nambumetone
MOA
They relivately inhibit COX-2
USES
Sport injuries, dental pain, postoperative pain, osteoarthritis
ADR
Epigastic pain, Nausea, loose motion, rashes, Diziness etc .
Selective COX-2 inhibitors
Eg Celecoxib, Etoricoxib, parecoxib
MOA
Slectively inhibit cox-2
Analgesic antipyretic with poor anti-inflammatory action
Paracetamol
IUPAC name – acetaminophen, N-(4 hydroxy phenyl) acetamide.

structure of paracetamol
Starting material for synthesis- p-nitro phenol
MOA
paracetamol is more active on COX in brain
USES
OTC drug analgesic for headache, migraine Dysmennorhea
ADR
Nephrotoxicity on chronic use, hepatotoxicity on high dose
Poisioning can occur at high dose
N-acetyl-p-benzoquinonemine (NABQI) is the toxic metabolite
N-acetylcystine is antidote .
Q.Naproxen is a derivative of
a) Arylpropionic acid
b) Arylacetic acid
c) Arylpropionic ether
d) Indole
Q. One of the following is a pro drug
a) Ketoprofen
b) Naproxen
c) Suldinac
d) Phenylbutazone
Q. One of the following is selectively
COX-2 inhibitor
a) Paracetamol
b) Nimesulide
c) Valdecoxib
d) Aspirin
Q.Phenylbutazone is a
a) Propionic acid derivative
b) Pyrazolidine derivative
c) Anthranilic acid derivatrive
d) None
Q. Non opoid analgesic which
doesnot inhibit PG synthesis is
a) Celecoxib
b) Nefopam
c) Ketorlac
d) Antipyrine
explanation
Nefopam acts by inhibiting monoamine reuptake in the cental nervous
system and glutamatergic pathway.
Q. Which of the following drug is
prodrug
a) Nimuslide
b) Indomethacin
c) Diclofenac
d) Nabumetone
Explanation
Nabumetone is a prodrug which is metabolized to an active metabolite
6-methoxy-2-naphthylacetic acid (6-MNA)
Q. Which isomer of ibuprofen is
more active ?
a) S (-) isomer
b) S(+) isomer
c) R (+) isomer
d) R (-) isomer
Q starting material for ibuprofen is
a) Isobutyl benzene
b) Isopropyl benzene
c) Isobutyl acetophenone
d) None
Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune disease in which there is joint
inflammation, synovial proliferation and destruction of articular cartilage.
Anti-rheumatoid drug
These are the drug which can suppress the rheumatoid process, bring
about the remission and retard the disease progression.
Classification
A. Disease modifying antirheumatic drugs (DMARD)
methotrexate, Azathioprine, sulfasalazine, chloroquine,
hydroxychloroquine, lefunamide, aurnafin, d-pencillanmine.
B. Biological response modifiers
TNF alpha inhibitor- Adalimumab, infliximab,Entanercept
Interleukin-1 antagonist- Anakinra
Adjuvant therapy
Prednisolones and other glucocorticoids
Methotrexate
It is the first line of drug for rheumatoid arthritis
Basic moiety- 2,4-diamino pteridine
Starting material for synthesis
N-(4-methylamino-benmethylamino-benzoyl)glutamic acid + 2-amino-4-
hydroxyl-6-bromomethylpteridine.
Derivative – aminosalicylates
Mechanism of action
Methotraxate acts by inhibiting dihydrofolate reductase inhibitor.
Inhibit cytokine production, chemotaxis and cell mediated immune
response.
ADR
Nodulosis, GI upsets, Dose dependent liver damage, megaloblastic anaemia and
pancytopenia.
Contraindication
Pregnancy, breast feeding, liver disease, active Infection and peptic ulcer
Important points
Not recommended in renal impairment patient
Trimethoprin causes bone marrow suppression
Follinic acid is prescribed with methotrexate.
Sulfasalazine
It is second line of drug for rheumatoid arthritis.
Mechanim of action
Sulfasalzine is a prodrug and is cleaved by bacteria in the colon in to sulfapyridine and
5-amino salicyclic acid and sulfapyridine inhibits the production of inflammatory
cytokines (Ils, TNF-alpha) by monocytes by monocyte so the component which is
effective in rheumatoid arthritis is sulfapyridine
Uses
Rheumatoid arthritis
- second line drug
- combined with methotrexate
Inflammatory bowel disease
ADR
-Neutropenia, thrombocytopenia
- Hepatitis
HYDROXY CHLOROQUINE/chloroquine
It is primarily use as antimalarial.
Mechanism of action
mechanism of action is not known now.
Possible explanation
- Reduce monocyte IL-1→ B-lymphocyte inhibited

Advantages
Hydroxychloroquine have relatively low toxicity compared to chloquine
As chloroquine have incidence of retinal damage.
Disadavantages
Slower acting
- remission seen in 3-6 month
USES
Rheumatoid arthritis (HCQ-400mg/d for 4-6 weeks followed by 200mg/d.
-needs to give for long duration
- can be combined with methotrexate
 malaria
ADR
Due to accumulation in melanin containing tissue there is chance of retinal
damage which is less with Hydroxy chloroquine
Rashes, greying of hair, myopathy, neuropathy
LEFUNAMIDE
Lefunamide is a potent immunomodulator
Mechanism of action
Inhibit dihydro-orotate dehydrodenase enzyme
Pyrimidine synthesis inhibited.
Antibodies production by B-cell is depressed
USES
Use in rheumatoid arthritis
Efficacy compared to Mtx
symptoms improve
Faster onset of benefits : 4 weeks
Dose- 100mg/d for 3 days followed by 20 mg/day
Lefunamide should not to be combined with Mtx.
ADR
Thrombocytopenia, leukopenia
Incresae chance of infection
Nausea, headace, diarrohea etc
TNF alpha inhibitor
eg Etanercept, infliximab, Adalimumab
These are soluble TNF-receptor protein or antibodies
Mechanism of action
Acts by
binding to TNF alpha cytokines and neutralize it
function of T-cell macrophases is suppressed.
Quicker response than Dmard and corticosteroids
Generally added with MTX.
Q. Which of the following is not a
disease modifying Antirheumatic
Drug?
a) Sulfasalazine
b) Methotrexate
c) Chloroquine
d) infliximab
Q which of the following is first line
of drug for rheumatoid arthritis
a) Methotrexate
b) Sulfasalazine
c) Lefunamide
d) Hydroxychloroquine
Q. Methotrexate works by inhibiting
a) Cell wall synthesis
b) Cellmembrane synthesis
c) Dihydrofolate reductase enzyme
d) Dihydo orotate dehydrogenase
Q. Which of the following
supplement should be given with
methotrexate
a) Pyrodoxine
b) Follinic acid
c) Cynocobalamine
d) Thiamine
Q. Abtacept is used in
a) Rheumatoid arthritis
b) Osteoarthritis
c) Gout
d) None
explanation
Abtacept is a T-cell modulating drug which is used in rheumatoid
arthritis
Q. All of the following is tumor
necrosis factor blocking agent
except
a) Adalimumab
b) Etanercept
c) Infliximab
d) Abciximab
explanation
Abaciximab is a glycoprotein which Platelet aggregration.
Q. Fully humanized antibodies used
for the treatment of rheumatoid
arthritis
a) Anakinra
b) Adalimumab
c) Infliximab
d) Lefunamide
explanantion
Adalimumab is the first first fully human monoclonal antibody
approved by the USFDA
It is a medication which is used for the treatrment of Rhrumatoid
arthritis, psoriasis, ulcerative colitis etc.