5. SalicylatesSalicylates
Acetyl salicylic acid (Acetyl salicylic acid (aspirinaspirin).).
Sodium salicylates.Sodium salicylates.
Diflunisal (dolobid, difluorophenyl salicylate).Diflunisal (dolobid, difluorophenyl salicylate).
Acetyl salicylic acidAcetyl salicylic acid ((aspirinaspirin).).
Kinetics:Kinetics:
Well absorbed from the stomach, but better from the upper smallWell absorbed from the stomach, but better from the upper small
intestine (large surface area). Distributed allover the body, 50-80%intestine (large surface area). Distributed allover the body, 50-80%
bound to plasma protein (albumin).bound to plasma protein (albumin).
Metabolized to acetic acid and salicylates (active metabolite).Metabolized to acetic acid and salicylates (active metabolite).
Salicylates is conjugated withSalicylates is conjugated with glucuronic acid and glycine.glucuronic acid and glycine.
Excreted by the kidney.Excreted by the kidney.
Alkalinization of the urine increases the rate of salicylates excretion.Alkalinization of the urine increases the rate of salicylates excretion.
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6. Low dose of aspirin 0.6 gLow dose of aspirin 0.6 g is eliminated byis eliminated by
1st order kinetics1st order kinetics and its t 1/2 isand its t 1/2 is 3-5 h.3-5 h.
while high dose (more than 4 g/day)while high dose (more than 4 g/day) isis
eliminated byeliminated by zero-order kineticszero-order kinetics and its tand its t
1/2 may increase up to1/2 may increase up to 15 h.15 h.
Mechanism of action:Mechanism of action:
AspirinAspirin irreversibly inhibitsirreversibly inhibits cyclo-cyclo-
oxygenase enzyme, so blocks synthesis ofoxygenase enzyme, so blocks synthesis of
prostaglandins and thromboxane A2.prostaglandins and thromboxane A2.
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7. Pharmacological effects of aspirin:Pharmacological effects of aspirin:
Anti-infammatory effects:Anti-infammatory effects:
InhibitsInhibits prostaglandinprostaglandin synthesis.synthesis.
Blocks action ofBlocks action of kininskinins which are mediatedwhich are mediated
through prostaglandin synthesis.through prostaglandin synthesis.
InhibitsInhibits granulocytegranulocyte adherence to damagedadherence to damaged
vasculature.vasculature.
StabilizesStabilizes lysosomes.lysosomes.
Inhibits migration ofInhibits migration of PMN leukocytesPMN leukocytes &&
macrophages into the site of inflammation.macrophages into the site of inflammation.
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8. Analgesic effects:Analgesic effects:
CentrallyCentrally:: it inhibits prostaglandin synthesis, soit inhibits prostaglandin synthesis, so
increasingincreasing pain thresholdpain threshold in the thalamus.in the thalamus.
PeripherallyPeripherally:: inhibits prostaglandin synthesis, soinhibits prostaglandin synthesis, so
inhibitinginhibiting inflammationinflammation and diminishes activationand diminishes activation
of peripheral pain sensors.of peripheral pain sensors.
Aspirin alleviatesAspirin alleviates mild to moderate painmild to moderate pain ofof
muscular and dental origin, postpartum states,muscular and dental origin, postpartum states,
arthritis & bursitis.arthritis & bursitis.
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9. Antipyretic effect:Antipyretic effect:
It inhibits prostaglandin synthesis in the CNSIt inhibits prostaglandin synthesis in the CNS
Resetting of temperature control in theResetting of temperature control in the
hypothalamus.hypothalamus.
VD of the superficial BV, so increasing heatVD of the superficial BV, so increasing heat
dissipation & sweating.dissipation & sweating.
NBNB: aspirin lowers elevated temperature while: aspirin lowers elevated temperature while
normal body temperature is only slightlynormal body temperature is only slightly
affectedaffected..
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10. Platelet effect:Platelet effect:
Aspirin in small dose (75-100 mg /day)Aspirin in small dose (75-100 mg /day)
irreversibly inhibits thromboxane A2 synthesisirreversibly inhibits thromboxane A2 synthesis inin
the plateletsthe platelets without affecting prostacyclinwithout affecting prostacyclin
synthesis in the vascular endothelium.synthesis in the vascular endothelium.
Aspirin must be stopped one week prior toAspirin must be stopped one week prior to
surgery if potential bleeding complications are asurgery if potential bleeding complications are a
concern.concern.
Aspirin hasAspirin has longer durationlonger duration as antiplatelet thanas antiplatelet than
ticlopidine, dipyridamole and phenylbutazone.ticlopidine, dipyridamole and phenylbutazone.
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11. Uses:Uses:
Antipyretic (0.5-2 g / day).Antipyretic (0.5-2 g / day).
Analgesic for mild to moderate superficial painAnalgesic for mild to moderate superficial pain
(headache, arthritis, toothache, myalgia) 0.5-2 g/day.(headache, arthritis, toothache, myalgia) 0.5-2 g/day.
Acute rheumatic fever (6-12 g/ day).Acute rheumatic fever (6-12 g/ day).
Rheumatoid arthritis (6-8 g / day).Rheumatoid arthritis (6-8 g / day).
Prophylaxis in thromboembolic diseases e.g. transientProphylaxis in thromboembolic diseases e.g. transient
ischemic attack, unstable angina, & MI (75-100 mg /ischemic attack, unstable angina, & MI (75-100 mg /
day).day).
Other uses under investigation e.g. aspirin may reduceOther uses under investigation e.g. aspirin may reduce
cataract formation and the incidence of cancer colon.cataract formation and the incidence of cancer colon.
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12. A/E:A/E:
GIT upsetGIT upset: nausea, vomiting, gastritis, ulceration &: nausea, vomiting, gastritis, ulceration &
bleeding (prevented by misoprostol).bleeding (prevented by misoprostol).
HypersensitivityHypersensitivity:: bronchial asthma, angioedema &bronchial asthma, angioedema &
rashes.rashes.
IdiosyncracyIdiosyncracy:: aspirin causes hemolytic anemia inaspirin causes hemolytic anemia in
patient with G-6-PD deficiency.patient with G-6-PD deficiency.
HypoprothrombinemiaHypoprothrombinemia and bleeding tendency asand bleeding tendency as
aspirin competes with vitamin K, so decreasingaspirin competes with vitamin K, so decreasing
prothrombin synthesis.prothrombin synthesis.
Salicylism:Salicylism: aspirin in large doses for long time therapyaspirin in large doses for long time therapy
causes headache, tinnitus, hearing difficulty, blurring ofcauses headache, tinnitus, hearing difficulty, blurring of
vision, GIT upset, irritability & hyperventilation (thesevision, GIT upset, irritability & hyperventilation (these
symptoms disappear on stopping aspirin).symptoms disappear on stopping aspirin).
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13. At low toxic doseAt low toxic dose: aspirin produces: aspirin produces
respiratory alkalosis followed by acidosisrespiratory alkalosis followed by acidosis
TeratogenicityTeratogenicity
Nephropathy.Nephropathy.
Reye's syndromeReye's syndrome : aspirin in children with: aspirin in children with
viral infection may causeviral infection may cause liver injury andliver injury and
encephalopathy.encephalopathy.
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14. Acute aspirin poisoning:Acute aspirin poisoning:
Restlessness, tremors, convulsion, vomiting,Restlessness, tremors, convulsion, vomiting,
dehydration, hypotension, hyperventilation, hyperreflexia,dehydration, hypotension, hyperventilation, hyperreflexia,
hyperpyrexia & coma.hyperpyrexia & coma.
Treatment:Treatment:
Activated charcoalActivated charcoal 50g p.o to adsorb salicylates and50g p.o to adsorb salicylates and
prevents its absorption.prevents its absorption.
Alkalinization of urineAlkalinization of urine (to enhance excretion) by i.v Na(to enhance excretion) by i.v Na
HCO3 which also corrects acidosis.HCO3 which also corrects acidosis.
AnticonvulsantAnticonvulsant e.g. i.v diazepam.e.g. i.v diazepam.
Cold fomentationCold fomentation and ice bags.and ice bags.
Correct dehydration by i.vCorrect dehydration by i.v fluids (5% dextrose).fluids (5% dextrose).
CorrectCorrect acid / base balanceacid / base balance (alkalosis or mixed(alkalosis or mixed
alkalosis/acidosis need no specific treatment).alkalosis/acidosis need no specific treatment).
Correct hypoprothrombinemia by i.vCorrect hypoprothrombinemia by i.v vitamin K.vitamin K.
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15. Contraindications:Contraindications:
Peptic ulcer, esophageal varices,Peptic ulcer, esophageal varices,
bronchial asthma, idiosyncrasy, allergy,bronchial asthma, idiosyncrasy, allergy,
viral infection in children, bleedingviral infection in children, bleeding
tendency and small dose in gouttendency and small dose in gout
(competes with uric acid excretion).(competes with uric acid excretion).
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16. Interactions:Interactions:
Alcohol increases aspirin-induced GIT bleeding.Alcohol increases aspirin-induced GIT bleeding.
Aspirin displaces oral anticoagulants and oralAspirin displaces oral anticoagulants and oral
hypoglycemics from their plasma protein binding sites,hypoglycemics from their plasma protein binding sites,
so increasing their activities and may lead to toxicity.so increasing their activities and may lead to toxicity.
Aspirin inhibits the uricosuric effects ofAspirin inhibits the uricosuric effects of sulphinpyrazonesulphinpyrazone
and probenecid.and probenecid.
BarbituratesBarbiturates increase the analgesic effect of aspirin.increase the analgesic effect of aspirin.
NBNB:: DiflunisalDiflunisal (difluorophenyl salicylate): it has analgesic(difluorophenyl salicylate): it has analgesic
and anti-inflammatory effects like aspirin, but hasand anti-inflammatory effects like aspirin, but has nono
antipyretic action.antipyretic action.
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17. Locally acting salicylatesLocally acting salicylates
Salicylic acidSalicylic acid: keratolytic, antiseptic & fungistatic.: keratolytic, antiseptic & fungistatic.
Methyl salicylateMethyl salicylate (wintergreen oil): used as(wintergreen oil): used as
counterirritant for muscle and joint pain.counterirritant for muscle and joint pain.
SulfasalazineSulfasalazine : it is a combination of: it is a combination of
sulfapyridine and 5-aminosalicylic acid (5-ASA).sulfapyridine and 5-aminosalicylic acid (5-ASA).
Sulfasalazine liberatesSulfasalazine liberates 5-ASA5-ASA in the colon wherein the colon where
itit blocks the synthesis of leukotriene B4 locallyblocks the synthesis of leukotriene B4 locally
and used in ulcerative colitis.and used in ulcerative colitis.
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19. Non-acidic NSAIDsNon-acidic NSAIDs
Selective COX-2 inhibitors.Selective COX-2 inhibitors.
are not concentrated in the gastric mucosa.are not concentrated in the gastric mucosa.
and are less likely to produce peptic ulcersand are less likely to produce peptic ulcers
Examples:Examples:
NabumetoneNabumetone: it is a pro-drug, changed in the body to its: it is a pro-drug, changed in the body to its
active metabolite. It is relatively selectiveactive metabolite. It is relatively selective COX-2COX-2
inhibitor.inhibitor.
Meloxicam, rofecoxib & celecoxibMeloxicam, rofecoxib & celecoxib are selective COX-2are selective COX-2
inhibitors.inhibitors.
Rofecoxib and celecoxib may causeRofecoxib and celecoxib may cause cardiac toxicitycardiac toxicity
(myocarditis).(myocarditis).
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20. Acetaminophen (paracetamolAcetaminophen (paracetamol).).
It is only analgesic and antipyretic,It is only analgesic and antipyretic,
it has no anti-inflammatory effect as itit has no anti-inflammatory effect as it
acts centrally only.acts centrally only.
It doesn’t cause gastritis.It doesn’t cause gastritis.
It doesn’t cause bronchial asthma.It doesn’t cause bronchial asthma.
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21. KineticsKinetics::
Well absorbed orally and rectally,Well absorbed orally and rectally,
Conjugated with glucuronic acid andConjugated with glucuronic acid and
sulforic acidsulforic acid
Excreted in urine.Excreted in urine.
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22. DynamicsDynamics: inhibits PG synthesis in the CNS: inhibits PG synthesis in the CNS
only.only.
UsesUses: analgesic, antipyretic especially in: analgesic, antipyretic especially in
children and those who cannot toleratechildren and those who cannot tolerate
aspirin e.g. patients with bronchial asthma,aspirin e.g. patients with bronchial asthma,
peptic ulcer or gout.peptic ulcer or gout.
A/E:A/E: Rashes, blood dyscrasiasRashes, blood dyscrasias
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23. Toxicity of paracetamolToxicity of paracetamol
Large toxic dose causes liver cellLarge toxic dose causes liver cell
necrosis.necrosis.
Treated by:Treated by:
N-acetylcysteine and methioneine whichN-acetylcysteine and methioneine which
supply thesupply the S-HS-H group necessary togroup necessary to
detoxify the toxic metabolites.detoxify the toxic metabolites.
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24. Thank youThank you
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