Non steroidal anti inflamatory Drugs.ppt

Dr. Adenwali Hassan Ahmed
CMNs, medical Doctor, Obstetrics & gynecology
Dr. Adenwali Hassan Ahmed
CMNs, medical Doctor, Obstetrics & gynecology

1. Non-steroidal anti-inflammatory
drugs
{NSAIDs}
Dr. Adenwali Hassan Ahmed:
(CMNs, Bsc-Medical Doctor, Bsc- Public Health Officer,
Msc-Gyn/Obest. PhD Candidate

2. Introduction
Non-steroidal anti-inflammatory drugs
(NSAIDS) have:
1.Analgesic-to relieve pain
2.Antipyretic-to relieve fever
3.Anti-inflammatory - A medicine intended to
reduce inflammation

3. Continue
NSAIDS, also known non-narcotic, non
Opiod or aspirin like analgesics because of:
1.They donot depress CNS
2.They donot produce physical dependence
3.They have no abuse liability
4.They are weaker analgesics
5.They are more commonly employed and many
are OTC.

4. Classification of Drugs Classification of Drugs
A. Non-selective COX inhibitors:
1.Salicylates, e.g Aspirin.
2.Propionic acid derivatives, e.g ibuprofen,
naproxen, ketoprofen.
3.Aryl-acetic acid derivatives, e.g diclofenac
and aceclofenac.
4.Pyrrolo-pyrrole derivative, e.g ketorolac.
5.Indole derivatives, e.g Indomethacin
KETOROLAC: Nonsteroidal anti-inflammatory
(trade
 name Torodal) that is given only orally

5. Cont---
Cox-1: Cyclooxygenase-1, an enzyme that acts to speed
up the production of certain chemical messengers, called
prostaglandins, in a variety of areas of the body such as the
stomach, kidneys, and sites of inflammation.
Cox-2: Cyclooxygenase-2, an enzyme that acts to speed
up the production of certain chemical messengers, called
prostaglandins that play a key role in in promoting
inflammation.
Cyclooxygenase-1: An enzyme that regulates prostaglandins
that are important for the health of the stomach lining and
kidneys

6. Continue
B. Selective COX-2 inhibitors
1.Celecoxib : A Cox-2 inhibitor (trade name
Celebrex) that relieves pain and inflammation
without harming the digestive tract.
2.Etoricoxib: helps to reduce the pain and swelling
(inflammation) in the joints and muscles of people 16
years of age and older with osteoarthritis, rheumatoid.
(90mg)
3.Parecoxib: is a selective COX-2 inhibitor and NSAID
used for the short-term management of perioperative pain.

7. Continue
Analgesic-antipyretic with poor anti-
inflammatory action
1. Paraaminophenol derivatives, e.g paracetamol
(acetominophen)
2. Pyrazolone derivatives, e.g metamizol
(dipyrone) and propiphenazone.
3. Benzoxazocine derivatives, e.g nefopam.
Nefopam: is a
painkiller. It treats moderate pain, for example after an operation
or
a serious injury, dental pain, joint pain and muscle pain, or pain from cancer.
You
can also take nefopam for other types of long-term pain when weaker
painkillers
no longer work.

8. Prostaglandin:
A potent substance that acts like a hormone and is found
in many bodily tissues (and especially in semen);
produced in response to trauma and may affect
blood pressure and metabolism and smooth muscle
activity.

9. What is the difference between selective
and non-selective NSAID?
Nonselective NSAIDs – Nonselective NSAIDs inhibit
both COX-1 and COX-2 enzymes to a significant
degree.
Selective NSAIDs – Selective NSAIDs inhibit COX-2, an
enzyme found at sites of inflammation, more than COX-
1, the type that is normally found in the stomach, blood
platelets, and blood vessels

10. Mechanism of action
NSAIDS blocked prostaglandin generation.
Beneficial actions due to prostaglandin
synthesis inhibition:
1.Analgesia
2.Anti-pyretic
3.Anti-inflammatory
4.Anti-thrombotic
5.Closure of ductus arteriosus in newborn.

11. Continue
Shared toxicities due to prostaglandin
synthesis inhibition:
1.Gastric mucosal damage
2.Bleeding- inhibition of platelet function.
3.Limitation of renal blood flow- sodium and
water retention.
4.Delay- prolongation of labour
5.Asthma and anaphylactoid reactions in susceptible
individuals.

12. Aspirin
Aspirin is acetylsalicylic acid and it is rapidly
converted in the body to salicylic acid which is
responsible for most of the actions.
It is one of the most oldest analgesic anti-
inflammatory drugs and is a still widely used.

13. Pharmacological actions
Analgesic
Antipyretic
Anti-inflammatory
Metabolic effects
Respiration, e.g hyperventilation
Acid-base and electrolyte balance
CVS

14. Continue
GIT- e.g nausea, vomiting and epigastric distress.
Urate excretion- dose related effect.
Blood- irreversibly inhibits TXA2 synthesis.
Acute rheumatic fever
Rheumatoid arthritis
Osteoarthritis
Dysmenorrhoea
Post-myocardial infarction and post stroke patients.
TXA2:Thromboxane:

15. Continue
Aspirin is available 1oomg, 300mg, 325mg and
650mg tabs.
Ecosprin 75, 150, 325 mg tabs.
Loprin 75, 162.5 mg
Thromboxane
A2 (
TXA2)
is a type of thromboxane that is produced by
activated
platelets ... 
Synthesis and
breakdown. 
TXA2 is
generated
from
prostaglandin H2 by thromboxane-A synthase in a metabolic
reaction
which generates approximately equal ...
Chemical
formula: C20H32O5, vasoconstriction

16. Adverse Effects
Nausea
Vomiting
Epigastric pain
Peptic ulceration
Hypersensitivity
Rash.

17. Ibuprofen
 Ibuprofen was the first member of this class to
be introduced in 1969 as a better tolerated
alternative to aspirin.
 Inhibit prostaglandin synthesis.
 It is used for analgesic, anti-inflammatory and
anti-pyretic.
 Inhibition of platelet aggregation is short lasting
with ibuprofen.

18. Therapeutic uses Therapeutic uses
 Analgesia
 Antipyretic
 Anti-inflammatory
 Rheumatoid arthritis
 Osteoarthritis
 Musculoskeletal disorders
 Soft tissue injuries
 Fractures
 Suppress swelling.

19. Adverse EffectsAdverse Effects
Gastric discomfort
Nausea
Vomiting
Headache
Dizziness
Blurring vision
Depression
Rash
Precipitate aspirin induced asthma.

20. Diclofenac sodium
 It is well absorbed drug.
 It inhibits prostaglandin synthesis.
 Metabolized and excreted both in urine and bile.
 The plasma half life is 2 hours.
 Available as 50mg TID, then 75mg BID oral.

21. Therapeutic Uses
Rheumatoid
Osteoarthritis
Toothache
Dysmenorrhoea
Analgesia
Antipyretic
Anti-inflammatory

22. Side-Effects
Epigastric pain
Nausea
Headache
Dizziness
Rashes
Gastric ulceration
Bleeding

23. IndomethacinIndomethacin
It is a potent anti-inflammatory drug with prompt
anti-pyretic action.
Indomethacin relieves only inflammatory or
tissue injury related pain.
It is a highly potent inhibitor of prostglandin
synthesis.
Indomethacin is well absorbed orally and rectal
absorption is low.

24. Therapeutic uses Therapeutic uses
Potent anti-inflammatory.
Analgesia.
Closure of ductus arteriosus BID, 0.1-0.2mg/kg.

25. Side-Effects
Gastric irritation
Nausea
Anorexia
Gastric bleeding
Diarrhea
Frontal headache
Mental confusion
Hallucination
Dizziness
Depression.

26. Metamizol (Dipyrone)
 Metamizol is a derivative of amidopyrine is a
potent and promptly acting analgesic and
antipyretic, but having poor anti-inflammatory
effect.
 It can be given:
1.Orally
2.IM
3.IV

27. Continue
 Metamizol has:
1.Pain during injection.
2.Gastric irritation
Few cases of agranulocytosis were reported and
metamizol is banned in USA and Europe.
Available 0.5-1.5mg oral/IM/IV.

28. NSAIDS case studiesNSAIDS case studies
ID/CC: A 22 year old white female who is a
professional skier presents to the emergency
room complaining of severe malaise, dizziness,
jaundice, very low urinary volumes and fatigue.
HPI: Following a recent skin accident, in which
she sprained her shoulder and knee, she took a
total of 20 tablets of diclofenac over a 3-day
period.
Malaise:
Physical discomfort (as mild
sickness
or depression)
Dizziness:
A reeling sensation; a feeling
that
you are about to fall

29. Continue
PE: Mild hypotension, no fever, severe dehydration
and tenderness to palpitation in epigastric area.
Labs: Hyperkalemia (Higher than normal levels of potassium in
the circulating blood; associated with kidney failure or sometimes
with the use of diuretic drugs)
Treatment: volume replacement, immediate
withdrawal of NSAIDS, supportive therapy,
metabolic correction, and avoidance of all
nephrotoxic medications.

30. Continue
Discussion: Use of NSAIDS, such as diclofenac can
lead to acute renal failure via two mechanisms.
Unopposed renal vasoconstriction by Angiotensin II
and norepinephrine.
Reduction in cardiac output caused by the associated
rise in systemic vascular resistance.
Thus, inhibition of prostaglandin synthesis by an
NSAIDS can lead to reversible renal ischemia, a
decline in glomerular hydrostatic pressure (the major
driving force for glomerular filtration) and acute renal
failure.

31. Indomethacin case studyIndomethacin case study
ID/CC: A 28 year old male comes to his family
medicine clinic and complains of increased bruising
over the past 3 days as well as bleeding from the gums
while brushing his teeth.
HPI: The patient is an amateur weight lifter who
recently tried to lift an excessive amount of weight but
strained a muscle and has been taking Indomethacin for
pain.
PE: Normal
Labs: increased PT. (Prothrombin time)

32. Continue
Treatment: Discontinue Indomethacin; vitamin K
may be used in patients with an elevated PT.
Discussion: NSAIDS are extensively metabolized
and protein bound. NSAIDS inhibit the COX
enzymes, there by inhibiting prostaglandin
production, which in turn produces their anti-
pyretic, anti-inflammatory and analgesic effects.
Moderate doses of NSAIDS can bring out subclinical
platelet defects in otherwise healthy individuals.

33. Continue
THANK YOU…