An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain. Analgesic drugs act in various ways on the peripheral and central nervous systems. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down a high temperature. They're often used to relieve symptoms of headaches, painful periods, sprains and strains, colds and flu, arthritis, and other causes of long-term pain.

1. Non-narcotic Analgesics, Antipyretics
& Anti-inflammatory Drugs
Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of Pharmaceutical Sciences, Nashik

2. Pain
Pain is an unpleasant feeling, such as a prick, tingle, sting, burn, or ache.
Pain may be sharp or dull. It may come and go, or it may be constant.
You may feel pain in one area of your body, such as your back, abdomen, chest, pelvis,
or you may feel pain all over.
(टोचणे, मुंग्या येणे, डुंकणे, जाळणे ककुं वा वेदना होणे)

3. Pyrexia
Pyrexia, also known as fever, is an
increase in the body temperature of
an individual beyond the normal
range.
This increase in temperature is
usually considered dangerous, but it
is a natural defensive mechanism of
the body to fight against infections.

4. What is inflammation?
Inflammation happens in everyone, whether you’re aware of it or
not.
Your immune system creates inflammation to protect the body
from infection, injury, or disease.
There are many things you wouldn’t be able to heal from without
inflammation.
5 SIGNS OF
INFLAMMATION

7. Acute inflammation usually occurs for a short (yet often severe)
duration. It often resolves in two weeks or less. Symptoms
appear quickly such as Heat, Pain, Redness, Swelling and Loss of
function
Chronic inflammation is a slower and generally less severe form
of inflammation. It typically lasts longer than six weeks. It can
occur even when there’s no injury, and it doesn’t always end
when the illness or injury is healed. Chronic inflammation has
been linked to autoimmune disorders and even prolonged stress.

8. • These are the drugs which relieve pain by
blocking the pain impulse generation and
transmission.
Analgesics
• These are the drugs which reduce the elevated
body temperature i.e. hyperpyrexia.Antipyretics
• These are the drugs used to treat inflammation,
swelling and edema.
Anti-inflammatory
agents

9. Classification

10. Non-Narcotic Analgesic, Antipyretics & Anti-Inflammatory
Salicylates
• Ex. Aspirin, Methyl Salicylates, Magnesium Salicylic acid, Sodium
Salicylates, Salicylic acid, Salfasalazine.
Para-amino phenol
• Ex. Paracetamol, Phenacetin,
Pyrazolones
• Ex. Phenyl butazone, oxyphenbutazone, analgin.

11. Non-Steroidal Anti-inflammatory Drugs (NSAIDS)
• Ex. Indomethacin, Sulindic, TolmetinIndole derivatives
• Ex. Ibuprofen, Ketoprofen, Fenoprofen, Naproxen,
Dexibuprofen,
Propionic acid derivatives
• Ex. Meclofenamate, Mefenamic acid, Flufenamic
acid, Tolfenamic acid
Fenamates
• Ex. Diclofenac, Ketorolac, Aceclofenac.Phenyl acetic acid derivatives
• Ex. Piroxicam, Tenoxicam, Dioxicam, Lornoxicam,
Meloxicam.
Oxicam acid derivatives
• Ex. Nimesulide.Sulfonamide

12. Miscellaneous
• Ex. Hydroxychloroquine, Penicillamine.
Gold Compounds
• Ex. Aurothioglucose.
Selective COX-2 inhibitors
• Ex. Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Firocoxib
Anti-gout drugs
• Ex. Allopurinol, Colchicine, Probenecid

13. Salicylates: ASPIRIN

14. Mechanisms of action
Aspirin causes several
reduction of
inflammation,
analgesia (relief of
pain), the prevention
of clotting, and the
reduction of fever.
Aspirin's suppress the
production of
prostaglandins and
thromboxane is due
to inhibition of the
cyclooxygenase (COX)
enzyme.
Cyclooxygenase is
required for
prostaglandin and
thromboxane
synthesis.

15. Prostaglandin PGI-2 Prostaglandin PGE-2
PG synthatase

16. Pharmacological actions of Aspirin

17. Analgesic action
Salicylates block
pain impulse
generation and
transmission to
the pain receptor
due to inhibition
of prostaglandin
synthesis.

18. Anti-inflammatory action
Salicylates show anti-inflammatory
action due to inhibition of enzymes
cyclooxygenase (COX).
Thus, inhibit prostaglandin synthesis.
Prostaglandins are required for
edema, pain, fever, itching,
inflammation, and swelling.

19. Anti-Rheumatic action
Salicylates reduce pain, swelling
and fever in rheumatoid arthritis
and rheumatic fever by three
actions.
• Inhibition of prostaglandin synthesis.
• Stimulation of adrenal medulla to
secrets steroidal hormones to show anti-
inflammatory action
• By rising the pain threshold value.

20. Antipyretic action
Salicylates reduce the
elevated body temperature
by sweating and inhibition
of synthesis and release of
prostaglandin-E2 in
hypothalamic temperature
regulating center.

21. Anti-platelet action:
Salicylates reduce
thromboxane-A2 alpha
synthesis hence, they
inhibit platelet
aggregation thereby
show anti-platelet
action.

22. Uric acid excretion
Salicylates
increase urinary
excretion of uric
acid hence, used
in acute Gout.

23. Gastrointestinal action
Salicylates can cause acute gastritis and gastric ulceration due to
damage of mucus layer that result in gastric hemorrhage [gastric
bleeding], bloody stool, iron deficiency anemia etc.
The mucus production is take place because of prostaglandins
but salicylates inhibit prostaglandin synthesis and affect mucus
production in stomach.
Because of this gastric acid attacks on the gastric mucosa and
results in ulcer, erosion and gastric bleeding.

24. Therapeutic uses of aspirin
Analgesia:
• Mild to moderate pain of
musculoskeletal origin,
headache, myalgia, neuralgia,
toothache, dysmenorrhea and
backache.
Antipyretic:
• Lowers elevated body
temperature (pyrexia) for
symptomatic relief.
Anti-inflammatory
activity:
• Rheumatoid arthritis,
osteoarthritis, bursitis, and
acute rheumatic fever.
Prophylaxis of
thromboembolism,
cerebral ischemia, and
venous emboli.
Prevention of re-
infarction in patients
with previous history of
acute myocardial
infarction.
Dose: 350-650 mg

25. Adverse drug reaction of aspirin
Salicylism
• headache, confusion, tinnitus, deafness, sweating, palpitation.
Hemorrhage
• major gastric bleeding and GIT hemorrhage
Hypersensitivity reactions
• skin rash, pruritus, bronchospasm, edema, shock
Reye’s syndrome
• aspirin in children with influenza or small pox has been associated with Reye’s
syndrome, a life threatening condition marked by severe vomiting, lethargy, delirium,
coma, and death. Permanent brain damage may occur in survivors.

26. Contraindications
Pregnancy, Severe bleeding,
Allergy,
Impaired renal
function,
Hemophilia, Ulcer,
Influenza, Chickenpox

27. Aspirin should not be given in peptic ulcer?

28. • Aspirin is weakly acidic drug causing
gastric acidosis leading to gastric
discomfort (distress) i.e. hyperacidity,
nausea, vomiting and headache.
• If aspirin is taken in empty stomach,
gastric acidosis causes damage to GIT
mucosa and erosion.
• That results in gastric ulcer, gastric
bleeding and anemia.

29. COX-I and COX-II (cyclooxygenase) enzymes are
required for prostaglandin synthesis and
ultimately for inflammatory reactions.
But COX-I is an enzyme which is present in
stomach mucosa and other sites of inflammation.
COX-1 is also required for synthesis of gastric
mucus to protect and lubricate the internal
mucosa layer of stomach from the gastric acid
erosion.
The COX-2 is present in variety of tissue as
including site of inflammation.

30. • Common NSAIDs and salicylates inhibit both enzymes COX-I and COX-II
thereby inhibiting prostaglandin synthesis and hence show anti-
inflammatory action.
• But blocking of COX-I enzyme also inhibit gastric mucus secretion hence
gastric mucosa expose to gastric acid and shows erosion and damage.
• This leads to gastric upset, peptic ulceration, gastric bleeding, intestinal
bleeding and bloody stools.
• Therefore Aspirin should not be given in peptic ulcer.

31. Aspirin is generally taken after meal or in
association with sodium bicarbonate?
OR Aspirin is not taken in empty stomach?

32. • Aspirin is weakly acidic drug causing gastric acidosis leading to gastric
discomfort (distress) i.e. hyperacidity, nausea, vomiting and
headache. If aspirin is taken in empty stomach, gastric acidosis shows
damage to GIT mucosa and erosion causing peptic ulcer, GI bleeding
and anemia.

33. • If aspirin is given after meal, this secreted gastric acid is utilized for
food digestion process and loaded stomach avoids direct contact of
acid with GI mucosa. Sod bicarbonate if given along with aspirin,
neutralizes gastric acid and avoid peptic ulceration.

34. Why Aspirin (Salicylate) therapy is always
supported with Vitamin K?

35. • Salicylate causes gastric acidosis, peptic ulcer and GIT bleeding at
large doses up to 500mg. At low dose of 150mg, it inhibits platelet
aggregation and prolongs bleeding time.
• Vitamin K activates blood clotting factor. Hence, initiates blood
coagulation and prevents hemorrhages (blood loss). So Salicylate
therapy is always supported with Vitamin K.

36. Acute Salicylates Poisoning

37. Causes:
• Accidental overdose more than 650 mg
Symptoms:
• Gastrointestinal Symptoms: Nausea, Vomiting, Abdominal pain, Gastric
bleeding and bloody stools.
• Metabolic symptoms: metabolic acidosis, hypoglycemia
• Electrolyte imbalance: dehydration, hypokalemia,
• Respiratory symptoms: hyperventilation and respiratory alkalosis
• Cardiovascular symptoms: CV collapse
• CNS Symptoms: Tinnitus, lethargy, seizures,tremor, Hallucination,
Convulsion, Vertigo Coma.
• Others: Hyperpyrexia

38. Treatment is Symptomatic and Includes
• Patient should be hospitalized immediately.
• Gastric lavage to eliminate unabsorbed drugs from the stomach.
• Temperature is brought down by external cooling with cold water
sponges.
• Activated charcoal 1g/kg may be indicated in massive overdose, ideally
within 1 hour of ingestion. It adsorbs the aspirin in the gastrointestinal
tract.
• Intravenous fluids such as dextrose 5% are recommended to increase a
urinary output. The IV fluids should contain Na+, K+,HCO3 and glucose
(to treat hypokalaemia and acidosis). Blood pH should be monitored.

39. In severe cases, forced alkaline diuresis with sodium bicarbonate and a diuretic
like frusemide is given along with IV fluids. Sodium bicarbonate ionizes salicylates
making them water soluble and increases their excretion through kidneys.
Diuretics must be given to increase urinary elimination of salicylates.
If hemorrhagic complications are seen, Vitamin K and Protamine must be given to
prevent hemorrhage.
Hemodialysis can be used to enhance the removal of salicylate from the blood.
Hemodialysis is usually used in those who are severely poisoned.

40. PARACETAMOL

41. MECHANISM OF ACTION
Paracetamol has analgesic and antipyretic actions like aspirin. It has
poor anti-inflammatory action in comparison to aspirin because it
has weak inhibitory activity on cyclooxygenase enzyme.
Paracetamol is thought to relieve pain by reducing the production
of prostaglandins in the brain and spinal cord.
Paracetamol reduces fever by affecting an area of the brain that
regulates our body temperature (the hypothalamic temperature-
regulating center).

42. Dose
Paracetamol
tablet 500
mg
Paracetamol
syrup 125
mg/5mL

43. USES OF PARACETAMOL
Fever:
• Paracetamol is used to provide temporary relief from fever without treating the underlying
cause.
Headache:
• Paracetamol is used to relieve acute headaches including a migraine.
Muscle Pain:
• Paracetamol is used to relieve mild to moderate pain in the muscles.
Menstrual Cramps:
• Paracetamol is used to relieve pain and cramping associated with menstrual cycles in women.
Post Immunization Pyrexia:
• Paracetamol is used in the treatment of pain and fever that sets in after one has taken
vaccinations.

44. ADVERSE DRUG REACTIONS
Liver damage
• A paracetamol overdose is dangerous and capable of causing serious damage to
the liver and kidneys.
Allergic skin reaction
• Paracetamol can cause red spots on skin, rashes, hives and itching.
Anemia
• Paracetamol can cause anemia like symptoms in some patients.
Stevens-Johnson Syndrome
• Paracetamol can cause this rare but potentially fatal allergic reaction of the skin
that requires immediate treatment.

45. CONTRAINDICATIONS
Liver Disease
• Paracetamol is metabolized by the liver and is not
recommended if you suffer from impaired liver function.

46. NSAIDS [Non-Steroid Anti-Inflammatory Drugs]

47. NSAIDs are most popularly used as pain killer
and anti-inflammatory agents.
They do not contain steroidal ring in their
chemical structure.
They should not be used for minor headache
and fever.

48. NSAIDs mainly use for relieving the
pain like osteoarthritis, rheumatoid
arthritis, ankylosing spondylitis, lower
back pain, migraine, gouty arthritis,
menstrual pain, dysmenorrhea,
postoperative pain, muscle stiffness,
renal stones pain, dental pain, and
tennis elbow and athlete injury.

49. Mechanisms of NSAIDs
NSAIDs inhibit
cyclooxygenase and
prostaglandin synthesis.
This enzyme are
responsible for formation
of prostaglandin PGF2,
PGF2 alpha, thromboxane
form the arachidonic acid.
Inhibition of Prostaglandin
E, Prostaglandin F2 alpha
show potent analgesic
anti-inflammatory action.

50. Therapeutic uses
NSAIDs mainly use for relieving the pain like osteoarthritis, rheumatoid
arthritis, ankylosing spondylitis, lower back pain, migraine, gouty arthritis,
menstrual pain, dysmenorrhea, postoperative pain, muscle stiffness, renal
stones pain, dental pain, and tennis elbow and athlete injury.

51. Adverse drug reaction
• Nephrotoxicity,
• Peptic ulcer,
• Abdominal pain,
• Gastric bleeding
Contraindications
• Kidney diseases [nephrotoxicity].
• Peptic ulcer.
• Pregnancy.

52. Summary of nonsteroidal anti-inflammatory agents (NSAIDs).

53. GOUT
Gout is medical condition characterized by abnormally
high levels of uric acid in the blood, recurring attacks
of joint inflammation (arthritis), and deposits of hard
crystals of uric acid in and around the joints, and
decreased kidney function and kidney stones.

54. Gout is a purine metabolism disorder resulting
from an excess of uric acid in the blood due to
either its overproduction or faulty elimination.

55. Antigout agents
Xanthine oxidase inhibitors
• Ex. Allopurinol, Oxypurinol, Tisopurine, Febuxostat
Uricosuric agent
• Ex. Probenecid, Sulphinpyrazine, Benzbromarone, Isobromindione,
Azapropazone
Others
• Ex. Rasburicase, Pegloticase

56. Prof. Amol Deore