Analgesic(NASIDs)

1. analgesic druganalgesic drug

2. AnalgesicsAnalgesics
• Medications that relieve pain withoutMedications that relieve pain without
causing loss of consciousnesscausing loss of consciousness

3. PainPain
• Is a protective reflex for self preservationIs a protective reflex for self preservation
due to presence of tissue damage.due to presence of tissue damage.
• There are 2 components of pain :There are 2 components of pain :
Perception and Reaction.Perception and Reaction.

4. • Perception is the physical component ofPerception is the physical component of
pain that carried of pain through the nervepain that carried of pain through the nerve
to the cortex .to the cortex .
• Reaction is psychological component ofReaction is psychological component of
pain and involve the patients emotionalpain and involve the patients emotional
response to the pain .response to the pain .

6. Analgesic (Drugs to Treat
Pain(
• What is pain?
– Sensory stimuli comes from
release of prostaglandins, NO,
bradykinins, histamine from
damaged tissue
– Substance P released from
sensory nerves, causes
spread of pain
– Stimuli carried by sensory
fibres to Thalamus &
Cerebrum
Sensory Cortex
Thalamus
Spinothalamic
Nerve
Tract

7. Classification ofClassification of ANALGESICANALGESIC
DRUGSDRUGS
NON OPIO1D OPIOIDNON OPIO1D OPIOID

8. Classification of AnalgesicsClassification of Analgesics
Aspirin Heroin
Codeine
OpiumIbuprofen
Acetaminophen
nonopioid
Analgesics
)Opioid(
Analgesics
Analgesics

9. Differences between opioid andDifferences between opioid and
non opioidnon opioid
1.1. Site of actionSite of action
2.2. Mechanism of actionMechanism of action
3.3. Uses for treatment painUses for treatment pain
4.4. Addiction and dependenceAddiction and dependence
5.5. Side effectSide effect
6.6. Have antiinflammatory effect .Have antiinflammatory effect .

10. AnalgesicsAnalgesics
opioidopioid
Site of Cortex & thalamus
Action
Antagonist Naloxone, nalorphine
& levallorphan
Uses Sever & deep pain e.g.
cancer, MI & anginal pian
Potency High
Side effect Addiction
MOA
‡ of opiates receptors
(µ, κ ,σ, δ) and relief the
pain through the release of
endorphines & encephalins
Non-opioid(NSAID)Non-opioid(NSAID)
Subcortical “thalamus”
No antagonist
Dull pain e.g. headache, toothache &
backache
Low
No addiction. ↑in bleeding tendency &
ulcer
Inhibits prostaglandin synthesis
by inhibition of cycloxygenase
enzyme

11. Categories of NSAIDsCategories of NSAIDs
There are two major categories forThere are two major categories for
non-steroidal anti-inflammatorynon-steroidal anti-inflammatory
drugs(NSAID).drugs(NSAID).
The first is non-selective anti-The first is non-selective anti-
inflammatory drugs.inflammatory drugs.
The second is selective anti-The second is selective anti-
inflammatory drugs, COX-2 inhibitors.inflammatory drugs, COX-2 inhibitors.

12. The Inflammatory ResponseThe Inflammatory Response
Inflammation typically represents the responseInflammation typically represents the response
to tissue injury and includes products ofto tissue injury and includes products of
activated mast calls, leukocytes and platelets;activated mast calls, leukocytes and platelets;
prostaglandins (PGs); leukotrienes;andprostaglandins (PGs); leukotrienes;and
complement-derived products.complement-derived products.
The body’s response to a stimuli which causesThe body’s response to a stimuli which causes
pain and/or tissue damage.pain and/or tissue damage.
Physiologically capillaries become “leaky”Physiologically capillaries become “leaky”
through vasodilation.through vasodilation.

13. histamine
serotonin
bradykinin - major contributors to symptoms of inflammation
leukotrienes - increase vascular permeability
- increase mobilization of endogenous
mediators of inflammation
prostaglandins PGE2
‑ promote edema and leukocyte infiltration
PGI2
‑ increase vascular permeability, enhance pain
properties of bradykinin
Mediators of the inflammatoryMediators of the inflammatory
responseresponse

14. Mediators of inflammationMediators of inflammation

15. Inflammation
The classical signs of
inflammation are:
1. Redness.
2. Swelling.
3. Heat.
4. Pain.
5. Loss of function.

16. NSAIDS
A therapeutic agent which relieves painA therapeutic agent which relieves pain
and fever by inhibiting the inflammatoryand fever by inhibiting the inflammatory
response.response.
These drugs are available over the counterThese drugs are available over the counter
and by prescriptionand by prescription
Non-steroidal. anti-inflammatory drugs
(NSAIDs( are one of the most common
pharmacological treatments prescribed for
osteoarthritis (one of the common
inflammatory disease(

17. NSAIDsNSAIDs
The NSAIDs are a group of chemicallyThe NSAIDs are a group of chemically
agents that differ in their antipyretic,agents that differ in their antipyretic,
analgesic, and anti-inflammatory activities.analgesic, and anti-inflammatory activities.
They act primarily byThey act primarily by
inhibiting the cyclooxygenase enzymes thatinhibiting the cyclooxygenase enzymes that
catalyze the first step in prostanoidcatalyze the first step in prostanoid
biosynthesis. This lead to decreasedbiosynthesis. This lead to decreased
prostaglandin synthesis withprostaglandin synthesis with
both beneficial and unwanted effects.both beneficial and unwanted effects.

18. ProstaglandinsProstaglandins
Prostaglandins were isolated from humanProstaglandins were isolated from human
semen in 1936. He named themsemen in 1936. He named them
Prostaglandins because he believed theyProstaglandins because he believed they
came from the prostate gland..came from the prostate gland..
They are synthesized in the same cell onThey are synthesized in the same cell on
which they act.which they act.

19. Biosynthesis of ProstaglandinsBiosynthesis of Prostaglandins
The goal is to inhibit the biosynthesis ofThe goal is to inhibit the biosynthesis of
prostaglandins in order to relieve theprostaglandins in order to relieve the
symptoms caused by the inflammatorysymptoms caused by the inflammatory
response.response.
Prostaglandins are synthesized fromProstaglandins are synthesized from
arachidonic acid in a pathway mediated byarachidonic acid in a pathway mediated by
the Cyclooxygenase enzymes.the Cyclooxygenase enzymes.

21. CyclooxygenaseCyclooxygenase
An enzyme involved in prostaglandinAn enzyme involved in prostaglandin
synthesissynthesis
– cyclooxygenase-1cyclooxygenase-1 (COX-1): beneficial(COX-1): beneficial
prostaglandinsprostaglandins
– cyclooxygenase-2cyclooxygenase-2 (COX-2): harmful(COX-2): harmful
prostaglandinsprostaglandins

22. COX Enzyme:Prostaglandin EffectsCOX Enzyme:Prostaglandin Effects
COX-1: beneficial COX-2
Peripheral injury
site
Inflammation
Brain Modulate pain
perception
Promote fever
(hypothalamus)
Vasodilation
Stomach protect mucosa
Platelets aggregation reduce
aggregation
Kidney vasodilation Maintain renal

23. COX Expression Function Inhibitors
COX-1
constitutively
throughout the body
organ pain, platelet
function, stomach
protection
NSAIDs including
aspirin
COX-2
Inducible and
constitutively in brain,
kidney
Inducible: inflammation,
pain, fever
Constitutive: synaptic
plasticity
NSAIDs, COX 2
inhibitors including
celecoxib
(Celobrex )
COX-3
Constitutively, high in
brain, heart
pain pathways, not
inflammation pathways
acetaminophen
some NSAIDs

24. Effects of COX InhibitionEffects of COX Inhibition
by Most NSAIDSby Most NSAIDS
COX-1
Gastric ulcers
Bleeding
Acute renal failure
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs : anti-platelet—decreases ability of blood to clot

25. ))NON Opioid Analgesic)non narcoticNON Opioid Analgesic)non narcotic
analgesicanalgesic
11..NSAIDS)nonselective CoxNSAIDS)nonselective Cox(.(.
22..COX-2 InhibitorsCOX-2 Inhibitors
33..AcetaminophenAcetaminophen

26. NON opioid ANALGESICNON opioid ANALGESIC
1.1.NSAID)COX(NSAID)COX(
• Salicylate group )Aspirin(Salicylate group )Aspirin(
• Propionic acid derivatives )Ibuprofen(Propionic acid derivatives )Ibuprofen(
• Indoleacetic acid )Indomethacin(Indoleacetic acid )Indomethacin(
• Oxicam derivaties )piroxicam(Oxicam derivaties )piroxicam(
• Fenamates )Mefenamic acid(Fenamates )Mefenamic acid(
• DiclofenacDiclofenac
• KetorolacKetorolac
• PhenylbutazonePhenylbutazone

27. NON opioid ANALGESICNON opioid ANALGESIC
2.Cox2 inhibitor2.Cox2 inhibitor ::
• CelecoxibCelecoxib
• RofecoxibRofecoxib
3.Paraaminophenol group3.Paraaminophenol group
• AcetaminophenAcetaminophen
• PhenacetinPhenacetin

28. Salicylates groupSalicylates group
• Aspirin)acetylsalicylic acid(Aspirin)acetylsalicylic acid(
• Sodium salicylateSodium salicylate
• Choline salicylateCholine salicylate
• DiflunisalDiflunisal
• Salicylic acidSalicylic acid
• Methyl salicylateMethyl salicylate

29. AspirinAspirin

30. Mechanism of actionMechanism of action
Inhibits the enzyme cyclooxygenase)cox1(Inhibits the enzyme cyclooxygenase)cox1(
• Irreversibly inactivating enzyme lead toIrreversibly inactivating enzyme lead to
inhibit prostaglandin synthesis.inhibit prostaglandin synthesis.
• All NSAIDS ,including aspirin have threeAll NSAIDS ,including aspirin have three
major therapeutic actions:major therapeutic actions:
1.1. Analgesic.Analgesic.
2.2. Anti- inflammatory.Anti- inflammatory.
3.3. Antipyretic.Antipyretic.

31. A Few Word About ProstglandinsA Few Word About Prostglandins
Arachidonic Acid
ProstaglandinsLeukotrienes
Lipoxygenase Cyclooxygenase
Phospholipase A2
Cell Membrane
(What’s the significance? We’ll talk later …)

32. Synthesis and effect ofSynthesis and effect of
prostoglandines on body organprostoglandines on body organ

33. Pharmacological effect ofPharmacological effect of
aspirinaspirin
1.Analgesic effect1.Analgesic effect
• PGE2 is thought to sensitize nerve endingPGE2 is thought to sensitize nerve ending
to the action of bradykinin, histamine, andto the action of bradykinin, histamine, and
other chemical mediators released locallyother chemical mediators released locally
by the inflammatory process.by the inflammatory process.
• Thus, by decreasing PGE2 synthesis,Thus, by decreasing PGE2 synthesis,
aspirin and other NSAIDs repress theaspirin and other NSAIDs repress the
sensationsensation of pain.of pain.

34. Pharmacological effect ofPharmacological effect of
aspirinaspirin
2.Antipyretic effect.2.Antipyretic effect. The salicylates lowerThe salicylates lower
body temperature in patients with fever bybody temperature in patients with fever by
impeding PGEimpeding PGE22 synthesis and release.synthesis and release.
Aspirin resets thermostat‌ toward normal,Aspirin resets thermostat‌ toward normal,
and it rapidly lowers the body temperatureand it rapidly lowers the body temperature
of febrileof febrile

35. • Fever be caused by PGE2 synthesis,Fever be caused by PGE2 synthesis,
which is stimulated when endogenouswhich is stimulated when endogenous
fever-producing agents )pyrogens(, suchfever-producing agents )pyrogens(, such
as cytokines, are released from WBCsas cytokines, are released from WBCs
that are activated bythat are activated by
infection,hypersensitivity, malignancy, orinfection,hypersensitivity, malignancy, or
inflammationinflammation

37. Pharmacological effect ofPharmacological effect of
aspirinaspirin
• 3.Antiinflammatory effect3.Antiinflammatory effect. PGs in. PGs in
inflammationinflammation  vasodilation and increasevasodilation and increase
vascular permeability.vascular permeability.
- Inhibition of PGs by NSAIDs attenuates,- Inhibition of PGs by NSAIDs attenuates,
not abolish, inflammation.not abolish, inflammation.

38. • 4.Antiplatelet effect4.Antiplatelet effect. .Low doses )60-81. .Low doses )60-81
mg daily( of aspirin can irreversibly inhibitmg daily( of aspirin can irreversibly inhibit
thromboxane production in platelets viathromboxane production in platelets via
acetylation of cyclooxygenase. Becauseacetylation of cyclooxygenase. Because
platelets lack nuclei, they cannotplatelets lack nuclei, they cannot
synthesize new enzyme, and the lack ofsynthesize new enzyme, and the lack of
thromboxane persists for the lifetime of thethromboxane persists for the lifetime of the
platelet )3-7days(.platelet )3-7days(.
..

39. 5.Uricosuric effect5.Uricosuric effect
6.Gastrointestinal6.Gastrointestinal effect.effect. NSAIDs block PGNSAIDs block PG
biosynthesis in the GI tract, they block thesebiosynthesis in the GI tract, they block these
cytoprotective processes. primary toxicity seencytoprotective processes. primary toxicity seen
with the NSAIDs is GIT irritation which maywith the NSAIDs is GIT irritation which may
lead to the production of ulcers when used inlead to the production of ulcers when used in
large doses over a long period of time.large doses over a long period of time.

40. 7.Respiratory action7.Respiratory action. At therapeutic doses, aspirin. At therapeutic doses, aspirin
increases alveolar ventilation., which leads toincreases alveolar ventilation., which leads to
elevated COelevated CO22 and increased respiration.and increased respiration.
Higher doses work directly on the respiratoryHigher doses work directly on the respiratory
center in the medulla, resulting incenter in the medulla, resulting in
hyperventilation and respiratory alkalosis thathyperventilation and respiratory alkalosis that
usually is adequately compensated for by theusually is adequately compensated for by the
kidney.kidney.
At toxic levels, central respiratory paralysis occurs,At toxic levels, central respiratory paralysis occurs,
and respiratory acidosis ensues due toand respiratory acidosis ensues due to
continued production of COcontinued production of CO

41. 8.Action on the kidney8.Action on the kidney. Cyclooxygenase inhibitors. Cyclooxygenase inhibitors
prevent the synthesis of PGEprevent the synthesis of PGE22 and PGIand PGI22
prostaglandins that are responsible forprostaglandins that are responsible for
maintaining renal blood flow, particularly in themaintaining renal blood flow, particularly in the
presence of circulating vasoconstrictorspresence of circulating vasoconstrictors
.Decreased synthesis of prostaglandins can.Decreased synthesis of prostaglandins can
result in retention of sodium and water and mayresult in retention of sodium and water and may
cause edema and hyperkalemia in somecause edema and hyperkalemia in some
patients.patients.

42. Clinical usesClinical uses
• 1.Control mild-moderate pain1.Control mild-moderate pain
• 2.Control fever2.Control fever
• 3.Treatment rheumatoid fever and arthritis3.Treatment rheumatoid fever and arthritis
and gout.and gout.
• 4.Prophylactic in MI)low dose(.4.Prophylactic in MI)low dose(.

43. Clinical usesClinical uses
• 5.Chronic use in colorectal cancer5.Chronic use in colorectal cancer
• 6.Facilitates closure of the patent ductus6.Facilitates closure of the patent ductus
arteriosusarteriosus
• 7.External applications: Salicylic acid is7.External applications: Salicylic acid is
used topically to treat acne,corns, calluses,used topically to treat acne,corns, calluses,
and warts. Methyl salicylate is usedand warts. Methyl salicylate is used
externally as a cutaneous counterirritant inexternally as a cutaneous counterirritant in
liniments.liniments.

44. ParmacokineticParmacokinetic
• Weak organic acid.Weak organic acid.
• Completely absorbed from the GIT.Completely absorbed from the GIT.
• Peak blood level 1 hour.Peak blood level 1 hour.
• Orally, rectally for children.Orally, rectally for children.
• Metabolize in liver and excreted in urine.Metabolize in liver and excreted in urine.

45. Adverse effectsAdverse effects
1.GIT effect.1.GIT effect.
2.Prolong bleeding time..2.Prolong bleeding time..
3.Allergic reaction.3.Allergic reaction.
4.4. Reye’s syndromeReye’s syndrome :: Salicylates must beSalicylates must be
avoided in children and teenagers (<15 yearsavoided in children and teenagers (<15 years
old) with varicella (chickenpox) or influenzaold) with varicella (chickenpox) or influenza
to prevent Reye's syndrome.to prevent Reye's syndrome. Although itAlthough it
occurs rarely there is a 20-30% mortality.occurs rarely there is a 20-30% mortality.

46. Drug interaction
• 1- with heparin or oral anticoagulant
hemorrhage .
• 2- antiacid reduce aspirin absorption
• 3- some Drug increase plasma
concentration of aspirin .

47. Over dose toxicityOver dose toxicity ((SalicylismSalicylism((
Symptoms:Symptoms:
• NauseaNausea
• VomitingVomiting
• HeadacheHeadache
• DizzinessDizziness
• tinnitustinnitus
• Mental confusionMental confusion
• Electrolyte imbalanceElectrolyte imbalance
• HyperthermiaHyperthermia
• HyperventilationHyperventilation
• convulsionsconvulsions
• Respiratory andRespiratory and
metabolic acidosismetabolic acidosis
• the end deaththe end death

48. TreatmentTreatment
1.Gastric levage.1.Gastric levage.
2. 02 supply .2. 02 supply .
3.Activated charcoal3.Activated charcoal
4. Sodium bicarbonate4. Sodium bicarbonate
5. .I.v.fluid.5. .I.v.fluid.
6. If sever hemodialysis6. If sever hemodialysis

50. PROPIONIC ACID DERIVATIVESPROPIONIC ACID DERIVATIVES
• IbuprofenIbuprofen
• FenoprofenFenoprofen
• KetoprofenKetoprofen
• NaproxenNaproxen
• OxaprozinOxaprozin
All these drugs haveAll these drugs have
anti-inflammatory,Analgesic, antipyretic effects.anti-inflammatory,Analgesic, antipyretic effects.

51. Therapeutic usesTherapeutic uses
1.1. Chronic treatment of rheumatoid arthritis andChronic treatment of rheumatoid arthritis and
osteoarthritis(less GIT effect than aspirin).osteoarthritis(less GIT effect than aspirin).
2.2. Headache painHeadache pain
3.3. Dental pain .Dental pain .
4.4. dysmenorrhea.dysmenorrhea.
5.5. Ibuprofen is used IV to close a patent ductusIbuprofen is used IV to close a patent ductus
arteriosus (PDA). It appears to have fewerarteriosus (PDA). It appears to have fewer
adverse effects than IVadverse effects than IV indomethacin.indomethacin.

52. • Ibuprofen, fenoprofen, and ketoprofen have short plasmaIbuprofen, fenoprofen, and ketoprofen have short plasma
half-lives (1 to 4 hours), whereas naproxen has a plasmahalf-lives (1 to 4 hours), whereas naproxen has a plasma
halflife of approximately 15 hours, which allows lesshalflife of approximately 15 hours, which allows less
frequent dosing.frequent dosing.
• Flurbiprofen has an intermediate half-life ofFlurbiprofen has an intermediate half-life of
approximately 6 hours; the half-life of oxaprozin isapproximately 6 hours; the half-life of oxaprozin is
approximately 50hours.approximately 50hours.
• A brief overview of some of the individual drugs use asA brief overview of some of the individual drugs use as
analgesic in patients with postsurgical dental painanalgesic in patients with postsurgical dental pain

53. Dose and preparationDose and preparation
Orally taken with dose of 200 mg every 6Orally taken with dose of 200 mg every 6
hours(Ibuprofen).hours(Ibuprofen).
• naproxen has long half live so is given oncenaproxen has long half live so is given once
daily.t1/2 (15hours) dose 500 mg two timesdaily.t1/2 (15hours) dose 500 mg two times
daily.daily.
• 25 to 50 mg of ketoprofen effective for mild25 to 50 mg of ketoprofen effective for mild
moderate pain In one dental study,100 mg ofmoderate pain In one dental study,100 mg of
ketoprofen was significantly more effectiveketoprofen was significantly more effective
than 400 mg of ibuprofen,than 400 mg of ibuprofen,

54. Side effectsSide effects
• GIT disturbance ranging from dyspepsia toGIT disturbance ranging from dyspepsia to
bleeding.bleeding.
• Side effects involving the central nervousSide effects involving the central nervous
system (CNS), such as headache, tinnitus,system (CNS), such as headache, tinnitus,
and dizziness, have also been reported.and dizziness, have also been reported.

55. Indoleacetic acidIndoleacetic acid
IndomethacinIndomethacin

56. IndomethacinIndomethacin
• Pharmacological effectPharmacological effect
1.1. Potent antiinflammatory(,acute goutyPotent antiinflammatory(,acute gouty
arithritis,osteoarthrits and ankylosingarithritis,osteoarthrits and ankylosing
spondylitis).spondylitis).
2.2. Control of pain.Control of pain.
3.3. Antipyretic effect.(not use to lower fever)Antipyretic effect.(not use to lower fever)
4.4. Delay labor.Delay labor.
5.5. Treatment of patent ductus arteriosus.Treatment of patent ductus arteriosus.

57. Side effectSide effect
1.GIT effect including1.GIT effect including
nausea,vomting,diarrhea,anorexia,abdominausea,vomting,diarrhea,anorexia,abdomi
nal pain,ulceration,perforation andnal pain,ulceration,perforation and
hemorrhage .hemorrhage .
2.CNS effect.2.CNS effect.
3.Chronic use decrease antihypertensive3.Chronic use decrease antihypertensive
drugs such as : Furosamide , Thiazid ,drugs such as : Furosamide , Thiazid ,
B- blocker, ACE inhibitors .B- blocker, ACE inhibitors .

58. Oxicam derivativesOxicam derivatives
PiroxicamPiroxicam
MELOXICAM (mobicMELOXICAM (mobic))

59. • Meloxicam inhibits both COX-1 and COX-Meloxicam inhibits both COX-1 and COX-
2, with preferential binding for COX-2, and2, with preferential binding for COX-2, and
at low to moderate doses shows less GIat low to moderate doses shows less GI
irritationthan piroxicamirritationthan piroxicam

60. • UsesUses
• Rheumatoid arthritis and osteoarthritis.Rheumatoid arthritis and osteoarthritis.
• Pharmacokinetic and dosePharmacokinetic and dose
• Piroxicam long half life 50 hours,20mg givenPiroxicam long half life 50 hours,20mg given
once daily.once daily.
• Meloxicam(15-20)half life,7.5-15 mgMeloxicam(15-20)half life,7.5-15 mg given oncegiven once
daily.daily.
Side effectSide effect
• GIT disturbances in 20% of patient.GIT disturbances in 20% of patient.

61. FenamatesFenamates
Mefenamic acid( ponstan)Mefenamic acid( ponstan)
Meclofenamic acidMeclofenamic acid

62. •Mefenamic acid is indicated for the reliefMefenamic acid is indicated for the relief
of moderate painand for relief of primaryof moderate painand for relief of primary
dysmenorrheadysmenorrhea
•and meclofenamate is indicated for mild-and meclofenamate is indicated for mild-
moderate pain, dysmenorrheamoderate pain, dysmenorrhea,,
•and arthritisand arthritis..

63. Mefenamic acidMefenamic acid
USES:USES:
– Dental pain.Dental pain.
– painful menstruation (dysmenorrhea)painful menstruation (dysmenorrhea)
No advantage over other NSAIDS.No advantage over other NSAIDS.
Dose:250-500 mgDose:250-500 mg

64. Side effectSide effect
The potential forThe potential for
• serious blood dyscrasiasserious blood dyscrasias
• GI side effects (dyspepsia, diarrhea)GI side effects (dyspepsia, diarrhea)
limits the use of mefenamic acid tolimits the use of mefenamic acid to
short-term, intermittent administration.short-term, intermittent administration.
(not used more than one week).(not used more than one week).

65. Diclofenac(voltarin)Diclofenac(voltarin)
• Uses:Uses:
• Rheumatoid arthritis..Rheumatoid arthritis..
• osteoarthritis.osteoarthritis.
• Reliefe of pain after third molarReliefe of pain after third molar
extraction(50-100 mg)extraction(50-100 mg)
• DysmenorrheaDysmenorrhea

66. DiclofenacDiclofenac
More potent than indomethacin andMore potent than indomethacin and
naproxen.naproxen.
Side effect:Side effect:
GIT disturbanceGIT disturbance
Rise in liver enzyme levelRise in liver enzyme level

67. 22--Paraaminophenol groupParaaminophenol group

68. Acetaminophen.Acetaminophen.
PhenacetinPhenacetin..
• Mechanism of actionMechanism of action
• These drugs act by inhibiting prostaglandinThese drugs act by inhibiting prostaglandin
Synthesis in CNS.Synthesis in CNS.
These drugs have antipyretic and analgesic effectThese drugs have antipyretic and analgesic effect
but weak anti-inflammatory effect because theybut weak anti-inflammatory effect because they
have less effect on Cox in peripheral tissues sohave less effect on Cox in peripheral tissues so
their weak anti-inflammatory activity . and notheir weak anti-inflammatory activity . and no
antiplatelet effect and lack many side effect ofantiplatelet effect and lack many side effect of
aspirin.aspirin.

69. How Do They Work?
• Inhibit prostaglandin synthesis centrally
Anti-inflammatory
Analgesic
Antipyretic
Analgesic
Antipyretic
N
S
A
I
D
s
A
C
E
T
A
M
I
N
O
P
H
E
N

70. PhenacetinPhenacetin

71. PhenacetinPhenacetin
• No longer use because of renal toxicityNo longer use because of renal toxicity
• Uses with other preparation with aspirinUses with other preparation with aspirin
and caffien.and caffien.

72. AcetaminophenAcetaminophen

73. AcetaminophenAcetaminophen
Pharmacological actionPharmacological action
• 11.Antipyretic.Antipyretic
2.2.AnalgesicAnalgesic
These effects due to inhibition of prostaglandinThese effects due to inhibition of prostaglandin
synthesis centrally. however has no effect onsynthesis centrally. however has no effect on
cyclooxygenase in peripheral tissues.cyclooxygenase in peripheral tissues.

74. Pharmacokinetic
• rapidly absorb from GIT
• Peak plasma (1-3) hr
• Dose 500 mg every 6 hr
• Metabolize in liver and excreted in urine .

75. Clinical usesClinical uses
1.1. Mild to moderate painMild to moderate pain
2.2. Reduce elevated body tempreture.underReduce elevated body tempreture.under
12 years(for children with viral infection).12 years(for children with viral infection).
3.3. In allergic to aspirinIn allergic to aspirin
4.4. Pregnant womenPregnant women
5.5. Gout patientsGout patients

76. Adverse effectAdverse effect
• No side effect with therapeutic dose.No side effect with therapeutic dose.
• Large dose 10-15 g (20-30) tablets causesLarge dose 10-15 g (20-30) tablets causes
hepatic necrosis (toxicity).hepatic necrosis (toxicity).
• SymptomsSymptoms::
• Start in the first 2 days.Start in the first 2 days.
• Nausea,vomting,,anorexia, abdominalNausea,vomting,,anorexia, abdominal
pain ,liver toxicity start in third day lead topain ,liver toxicity start in third day lead to
• Encephalopathy coma and death.Encephalopathy coma and death.

77. TreatmentTreatment
1.Gastric levage1.Gastric levage
2.Activated charcoal, sodium or magnesium2.Activated charcoal, sodium or magnesium
solution.solution.
3.Oral N-acetylcysten(antidote).3.Oral N-acetylcysten(antidote).
Note:Note: Acetaminophen should avoidedAcetaminophen should avoided
in alcoholic patient.in alcoholic patient.

78. 33--COX2 InhibitorCOX2 Inhibitor

79. Celecoxib, RofecoxibCelecoxib, Rofecoxib
Group of drugs that inhibit cox2 whichGroup of drugs that inhibit cox2 which
responsible for anti-inflammatory action.responsible for anti-inflammatory action.
Cox2 is;Cox2 is;
constitutive in kidney, brain.constitutive in kidney, brain.
inducible, in inflamed area.inducible, in inflamed area.

80. Celecoxib, RofecoxibCelecoxib, Rofecoxib
Pharmacokinetic.Pharmacokinetic.
long half live 11 hours.long half live 11 hours.
Side effect:Side effect:
GIT, reduce to 50% (less bleeding andGIT, reduce to 50% (less bleeding and
ulcer).ulcer).
Minimal renal & Cardiovascular side effect.Minimal renal & Cardiovascular side effect.
No effects on bleeding time(not inhibitNo effects on bleeding time(not inhibit
platelet).platelet).

81. Contraindication
• chronic renal insufficiency
• Heart disease
• Allergy to aspirin