Professional Documents
Culture Documents
NSAIDs
Dr: MANZOOR AHMED UNAR
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NSAIDs
Inflammation
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NSAIDs
Inflammation
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NSAIDs
Inflammation
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NSAIDs
Inflammation
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NSAIDs
Inflammation
Inflammation is characterized
(acute form ) by classical signs :
Pain (Dolor)
Heat ( Calor)
Redness (Rubor)
Swelling (Tumor) and
loss of function (Functio Leasa).
NSAIDs
Inflammation
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Metabolism of Arachidonic Acid
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NSAIDs
Inflammation
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NSAIDs
Inflammation
Mechanism of Prostaglandin:
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NSAIDs
Treatment of Inflammation
Drugs:
Non Steroidal Anti Inflammatory Drugs (NSAIDs).
Glucocorticoids.
Slow Acting Anti Rheumatic Drugs.
Disease Modifying Anti Rheumatic drugs. (methotrexate, gold
salts, salfasalazine).
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NSAIDs
Inflammation
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NSAIDs
Non – Selective Cox Inhibitors
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NSAIDs
Selective Cox - 2 Inhibitors
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NSAIDs
General Properties:
Mechanism of action:
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Mechanism of action of NSAIDs
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NSAIDs
Various NSAIDs have additional possible mechanism of action as
Inhibition of Chemotaxis,
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ASPIRIN
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NSAIDs
ASPIRIN
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NSAIDs
ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
Anti-inflammatory.
Analgesic.
Antipyretic.
Anti-rheumatic.
Anti-thrombotic.
Uricosuric.
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NSAIDs
ACTIONS OF ASPIRIN
Stabilizes lysosomes,
Interferes chemical mediators,
Inhibit granulocytes adherence to damage vasculature,
Inhibit the migration of polymorpho-nuclear leucocytes
and macrophages into site of inflammation.
Inhibit antigen induced release of histamine.
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
Increases sweating.
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
Uses of ASPIRIN
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NSAIDs
ASPIRIN
Side Effects
Gastritis
Gastric ulcers.
Duodenal ulcers.
Upper GIT bleeding.
Fecal blood loss.
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NSAIDs
ASPIRIN ( Adverse Effects )
Contraindications
Hemophilia.
Peptic ulcer.
Chronic renal failure
Asthma.
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NSAIDs
DOSES OF ASPIRIN
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Humanity has but three great enemies;
Fever, Famine and War.
Of these by far the most terrible , is
“ fever.”
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ASPIRIN INTOXICATION
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NSAIDs
ASPIRIN INTOXICATION
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NSAIDs
ASPIRIN INTOXICATION
2. Water metabolism :
Toxic doses causes dehydration, due to
Increased renal excretion of water.
Hyper ventilation.
Sweating.
3. Electrolyte metabolism:
Aspirin intoxication causes increased renal excretion of
Sodium, Potassium and Bicarbonate, result in hypokalemia,
Hypernatremia due to dehydration
Hyperkalemia due to9 renal impairment
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NSAIDs
ASPIRIN INTOXICATION
6. Lipid metabolism :
Inhibit synthesis, depress release and enhance break down
of tissue fatty acids.
Also lower plasma cholesterol level
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NSAIDs
ASPIRIN INTOXICATION
7. Other enzymes
Aspirin inhibit a large number of enzymes,
some of those involved in the conversion of
glutamic acid to glutamine and GABA,
result in aspirin poisoning convulsion
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NSAIDs
ASPIRIN INTOXICATION
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NSAIDs
Medical Treatment Of Aspirin Intoxication
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ASPIRIN
PARACETAMOL
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ACETAMINOPHEN / PARACETAMOL
Well tolerated.
Very safe drug
Rarely produce side effects.
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ACETAMINOPHEN / PARACETAMOL
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ACETAMINOPHEN / PARACETAMOL
Indications
Analgesic and Antipyretic (equivalent to aspirin)
Used in mild to moderate pain, headache, myalgia,
postpartum pain, alone or in combination with NSAIDs
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ACETAMINOPHEN / PARACETAMOL
Adverse Effects
Therapeutic doses may increases hepatic enzymes
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ACETAMINOPHEN / PARACETAMOL
Intoxication
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ACETAMINOPHEN / PARACETAMOL
Intoxication
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ACETAMINOPHEN / PARACETAMOL
Intoxication
90% Conjugation
NABQI Glutathione
NABQI
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ACETAMINOPHEN / PARACETAMOL
Intoxication
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ACETAMINOPHEN / PARACETAMOL
Intoxication
Clinical Features
First hours: Nausea, Vomiting, Abdomen discomfort
24 hours : Liver tenderness, Hepatic necrosis
Few days : Jaundice, Hypoglycemia,
Oliguria, Renal failure
Hepatic encephalopathy,
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ACETAMINOPHEN / PARACETAMOL
Intoxication
Treatment
Gastric lavage (with in one hour of ingestion)
if > 7.5g Paracetamol used
has unclear benefits,
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ACETAMINOPHEN / PARACETAMOL
Intoxication
NAC is indicated in
All patients with a serum Paracetamol concentration above the
possible hepatic toxicity line on the Rumack-Matthew nomogram
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ACETAMINOPHEN / PARACETAMOL
Intoxication
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ACETAMINOPHEN / PARACETAMOL
Intoxication
Dialysis
In the management of patients who present late in the course
(more than 24 hours) when NAC would be of limited value.
Liver transplantation
Liver transplantation should be considered in severe cases
which progress to stage three or four hepatic encephalopathy if the
patient is otherwise a suitable candidate
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NSAIDs
IBUPROFEN
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NSAIDs
INDOMETHACIN
Indol derivative.
Potent, non – selective, Cox inhibitor .
Well absorbed orally.
Metabolized in liver.
Excreted by bile, kidney.
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NSAIDs
COX-2 Inhibitors
CELECOXIB
Highly selective Cox-2 inhibitor (375 times more)
Absorption decreased by food
Half-life 11 hours
Highly protein bound
Dose not affect platelet aggregation
Dose 100-200 mg BID
Uses in rheumatoid arthritis, osteoarthritis
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Conjugation
Paracetamol Glucuronidation & 90%
Sulphation
P450
N-acetylcysteine
Toxic
Metabolite
Glutathione
(SH)
Non toxic
metabolites
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NSAIDs
ACTIONS OF ASPIRIN
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NSAIDs
IBUPROFEN
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NSAIDs
INDOMETHACIN
Indol derivative.
Potent, non – selective, Cox inhibitor .
Well absorbed orally.
Metabolized in liver.
Excreted by bile, kidney.
Half – life 11 hr
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NSAIDs
ROFECOXIB
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NSAIDs
Cox -2 – selective inhibitors
Osteo arthritis ,
Rheumatoid arthritis,
Acute gouty arthritis,
Muscular skeletal pain,
Ankylosis spondylitis.
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The brain is
part of an
entire body.
It is not a totally
separate entity
which functions
independently.
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BUT
Are there other peptide sequences with opioid or other
biological activity?
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Paracetamol Toxicity
90% Conjugation
NAPQI Glutathione
NAPQI
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Conjugation
Paracetamol Glucuronidation & 90%
Sulphation
P450
•N-acetylcysteine
•Methonine
Toxic
Metabolite
Glutathione
(SH)
Non toxic
metabolites
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steroid
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steroids
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prostaglandin
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Arachidonic acid
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Prostaglandins:
They are un – saturated fatty acid derivates,
contain 20 carbons with cyclic ring.
They also inhibit Peroxidase that converts
5 – HPETE (5-hydro peroxy eicosa tetra eicoic
acid ) to
5 – HETE ( hydrooxy eicosa tetra eicoic acid ).
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