A brief description of the liver functions in detoxificcation

1. DETOXIFICATION
OF IBUPROFEN
BY: HERMAN NDJAMEN
GROUP: 205

2. STRUCTURE
OF
IBUPROFEN
CHEMICAL
SYNTHESIS
CONCLUSION
ADVERSE
EFFECTS AND
OVERDOSE
OUTLINE
USES OF
IBUPROFEN
MECHANISM
OF
DETOXIFICATIO
N
MECHANISM
OF ACTION

3. STRUCTURE OF IBUPROFEN
IBUPROFEN ALSO KNOWN CHEMICALLY AS
2-(4-isobutylphenyl)propanoic acid OR
2-(4-(2-methylpropyl)phenyl)propanoic
acid (IUPAC ID) is a non-steroidal antiinflammatory drug which is widely used
nowadays as pain relief.
It exist chemically in two forms:
- R-2-(4-(2METHYLPROPYL)PHENYL)PRAPANOIC ACID
- S-2-(4-(2METHYLPROPYL)PHENYL)PROPANOIC
ACID.
THEY ARE JUST ENANTIOMERS OF
EACH OTHER, THE S FORM BEING MORE
ACTIVE THAN THE R.

4. INDUSTRIAL PREPARATION
(CHEMICAL SYNTHESIS)
Ibuprofen is produced industrially as a racemate
mixture of the R&S forms but since the S form is
more active, there is a need of converting the R
into S form. For this purpose an enzyme is used;
alpha-methylacyl-CoA racemase (Isomerase).
R-IBUPROFEN
(levibuprofen)
S-IBUPROFEN
(DEXIBUPROFEN)

5. SYNTHESIS
THE IMPROVED SYNTHESSIS OF IBUPROFEN OCCURS IN THREE MAIN STEPS:
I. FRIEDEL-CRAFTS ACETYLATION OF ISOBUTYLBENZENE (FORMS ISOBUTYLPHENYL
ETHANONE
II. HYDROGENATION WITH RANEY NICKEL PRODUCES (ISOBUTYLPHENYLETHANOL)
III. CARBONYLATION USING PALLADIUM AS CATALYST ( FORMS IBUPROFEN)

6. USES OF IBUPROFEN
• IBUPROFEN IS PRIMARILY USED FOR FEVER,
PAIN, DYSSMENORRHEA (MENSTRUAL PAIN)
• IT IS ALSO USED DURING INFLAMMATORY
DISEASES LIKE RHEUMATOID ARTHRITIS
• IT IS USED FOR PERICARDITIS AND PATENT
DUCTUS ARTERIOSUS

7. MECHANISM OF ACTION
• Nonsteroidal anti-inflammatory drugs such as
ibuprofen work
by inhibiting the enzyme cyclooxygenase (COX)
, which converts arachidonic
acid to prostaglandin H2 (PGH2). PGH2, in turn, is
converted by other enzymes to several
other prostaglandins (which are mediators of
pain, inflammation, and fever) and to thromboxane
A2 (which stimulates platelets aggregation leading
to blood clots formation.
• They may also inhibit chemotaxis, alter lymphocyte
activity and inhibit neutrophil aggregation.

8. DETOXIFICATION
• THE GENERAL PRINCIPLE UNDERLYING
DETOXIFICATION OF DRUGS BY THE LIVER IS A
SERIES OF REACTIONS WHICH WILL RENDER
THE HYDROPHORBIC TOXIC DRUG MORE
HYDROPHILIC.
• DETOXIFICATION BY THE LIVER GENERALLY
OCCURS IN TWO STEPS:
PHASE 1: OCCURS IN THE RIGHT LOBE
PHASE 2: OCCURS IN THE LEFT LOBE

10. MECHANISM OF DETOXIFICATION
• IBUPROFEN IS PROCESSED IN THE LIVER IN TWO
DIFFERENT WAYS; OXIDATION & CONJUGATION
WITH GLUCURONIC ACID (GLUCURONIDATION)
• THE SERUM HALF-LIFE OF IBUPROFEN IS 1.8 TO 2.0
HOURS.

11. * OXIDATION OF IBUPROFEN IN THE LIVER OCCURS
MAINLY BY ADDITION OF OXYGEN MOLECULE TO
IBUPROFEN. THIS REACTION IS CATALYSED BY
MONOXYGENASES AND USES NADPH AS Co-ENZYME,
REASON FOR WHICH THE REACTION IS USUALLY TERMED
A HYDROXYLATION REACTION
* 25 PERCENT IS OXIDIZED BY THE LIVER TO FORM 2
HYDROXY IBUPROFEN AND 37 PERCENT TO
CARBOXYIBUPROFEN USING MONOXYGENASES AS
ENZYMES.
GENERAL EQUATION
RH+ O2 + NADPH + H+
R-OH + H2O + NADP

12. THE PRINCIPLE OF CONJUGATION IS THE SAME
AS THAT SEEN DURING BILIRUBIN
CONJUGATION. THIS INVOLVES THE REACTION
OF IBUPROFEN WITH UDP-GLUCURONIC ACID
IN THE PRESENCE OF THE ENZYME
GLUCURONYLTRANSFERASE TO FORM THE
IBUPROFEN GLUCURONIDE.
14% OF IBUPROFEN IN THE LIVER IS BEING
EXCRETED AS IBUPROFEN GLUCURONIDE IN
URINE AND FAECES.

14. ADVERSE EFFECTS
Adverse effects that may arise due to frequent
usage (long-term) of ibuprofen are divided into
common and infrequent.
* common adverse effects include: nausea,
dyspepsia, gastrointestinal ulceration/bleeding,
raised liver enzymes, diarrhea, constipation,
epistaxis, headache, dizziness, priapism, rash,
salt and fluid retention, and hypertension.
* Infrequent adverse effects include: heart
failure, hyperkalemia, renal impairment,
confusion, and bronchospasm and sometimes
allergy.

15. CARDIOVASCULAR RISK
• chronic ibuprofen use has been found correlated
with risk of hypertension and myocardial infarction
(heart attack), particularly among those chronically
using high doses.
EFFECT ON THE SKIN
• Along with other NSAIDs, ibuprofen has been associated
with the onset of bullous pemphigoid or pemphigoid-like
blistering. This is because Ibuprofen has been reported
to be photosensitising although weaker than other
NSAID’s
NB: DRINKING ALCOHOL WHEN TAKING IBUPROFEN
INCREASES RISK OF STOMACH BLEEDING.

16. This is the term used to describe a more than
normal intake of a drug.
NORMAL DOSAGE:
In medical practice the maximum amount for
an adult is 800mg per dose or 3200mg per day
but preparations generally advice a maximum of
1200mg per day.
Human response in cases of overdose ranges
from absence of symptoms to fatal outcome
despite intensive-care treatment.

17. • Most symptoms are an excess of the
pharmacological action of ibuprofen, and
include:
- abdominal pain, nausea, vomiting,
drowsiness, dizziness, headache, tinnitus, and
nystagmus.
- Rarely, more severe symptoms, such as
gastrointestinal bleeding, seizures, metabolic
acidosis, hyperkalaemia, hypotension,
bradycardia, tachycardia, atrial fibrillation,
coma, hepatic dysfunction, acute renal failure,
cyanosis,respiratory depression, and cardiac
arrest have been reported.

18. Some new medical terms used
• DYSPEPSIA: A painful, difficult or disturbed digestion
accompanied by symptoms of nausia, vomiting and
heartburn.
• EPISTAXIS: Bleeding from the Nose.
• PRIAPISM: Presence of a persistent, usually painful,
erection of the penis unrelated to sexual stimulation or
desire.
• TINNITUS: Hearing ringing, buzzing, or other sounds
without an external cause.
• BULLOUS PEMPHIGOID: An acute or chronic autoimmune
skin disease, involving the formation of blisters at the space
between the skin layers epidermis and dermis.
• PHOTOSENSITIZATION: development of abnormally
heightened reactivity of the skin or eyes to sunlight.

19. CONCLUSION
• Doctors should always take time to prescribe
the appropriate drug with it’s appropriate
dosage.
• Patients should always seek for the advice of a
medical personnel before beginning any
treatment.

20. THANKS
FOR YOUR
ATTENTION