BIOTRANSFORMATION
FATE OF DRUG
DEFN……
• Drug undergoes some changes in the
body & then it is excreted out, it is
known as fate of drug.
• alteration of drug in living
organism is known as
biotransformation.
sites
• Liver
• Kidney
• Intestine
• Lung
• plasma
Normal fate
• After absorption of drugs, it may
have ----
• 3 fates
• ---metabolize by enzymes
• ---spontaneous change into another
substance without help of enzyme.
• ----spontaneous excretion
process
• Metabolism lead to following changes into
drugs.
-→non polar compd… to make polar compd….
So it is water soluble and can be easily
excreted by kidney.
→if compd.. Is already high polar & water
soluble, then it is excreted as such.
So it may lead to
• 1-inactivation of drug.
•
• e.g- phenobarbitone,
• morphine,
• .
2
• Forming active metabolites
from an active drug.e.g.
• Phenacetin . →paracetamol
• Digitoxin--→digoxin
3
• Activation of inactive drug.i.e.
conversion of prodrug into active
drug.
• Levodopa->dopamine
• Prednisone→prednisolone
classification
• Reaction are classified into two
type.
• 1—non synthetic—or phaseI
• 2-synthetic—conjugation—phase II
Nonsynthetic-phaseI
• 5 types
• 1.oxidation
• 2.reduction
• 3.hydrolysis
• 4.cyclisation
• 5.decyclisation
oxidation
• Addition of O2 or –ve charge ion
• Or removal of H ion or +ve charge
radicle.
• it is occurred with the help
of enzyme, so drug become more
water soluble & easily excreted out
reduction
• Converse to oxidation.i.e. addition of
+ve charge ion or removal of O2 or
_ve charge ion.
• many halogenated and
nitrated compd… are reduced by this
way.
hydrolysis
• In this process , splitting of drug
molecule take place with addition of
water.
• enz. esterase take major part
• in this .e.g
• .Ach, atropine ,phenytoin
cyclisation
• Formation of ring structure from
straight structure of drug.
• e.g.proguanil
decyclisation
• In this, opening of ring structure is
taking place.
• e.g.-phenobarbitone.
Synthetic reaction
conjugation
phaseII
• In this process drug or its
metabolites is combine with an
endogenous substance to form highly
ionised organic acid which is easily
excreted in bile or urine. It is done
by 7 ways .
7-types
• 1-glucuronide conjugation
• 2-acetylation
• 3-methylation
• 4.sulfate conjugation
• 5.glycine conjugation
• 6.glutathione conjugation
• 7.ribonucleoside/nucliecacid synthesis
Glucuronide conjugation
• This can be done by help of glucuronic
acid.
• e.g.chloramphenicol,
aspirin,morphine
• Even bilirubin, steroid hormone etc.
excreted in bile and hydrolysed by gut
bacteria and again reabsorbed. Such type
of process is known as eneterohepatic
cycling, which prolong action of drugs
acetylation
• Mainly drugs having amino. And
hydrazine group are metabolised by
this way.
• enz, acetyl-co A take part in this.
• E.g. sulpha, PAS
methylation
• Drugs having amino and phenole
group are metabolised by this way.
• Methionine is important factor for it.
• E.g.adrenaline,histamine
Sulphate conjugation
• For phenole group. And steroids.
• Enz-sulphokinase
• E,g.-chloramphenicol,sex hormone
Glycine conjugation
• Drug having carboxylic acid group are
conjugated with glycine.
• e..salicylates
Glutathione conjugation
• By this way, with help of glutathione
it inactivate highly reactive
quinolones
Ribonucleoside
synthatase
• By this reaction-
• inactivation of purine and cancer
drugs- take place
Microsomal enz.system
• The drug can be metabolised by
enz,.or co.enz. Or intermidiary
metabolites.
• one enz can metabolites so
many drugs.such enz. Are of two
types->microsomal
• -→non microsomal
sites
• Micosomal enz. System is located in t
smooth endoplasmic reticulum of
liver
• Kidney
• intestine
• lung. etc
enzymes
• Monooxinase
• Cytochrome p-450
• Glucuronyl transferase. Etc
• They catalyse most of
oxidation,reduction, hydrolysis
&glucuronyl conjugation
Induction of enz.system
• This is induced by drugs, diet,
bacteria, carcinogen, insecticides and
other compd…
• they by acting on DNA,
increase synthesis of enz.
Cytochrome p450 & gluc.transferase
drugs
• Following drugs are known to induce the
system
• -phenobarbitone
• --rifampicin
• --macrolide antibiotics
• --isoniazid
• -alcohol
• -DDT etc.
effects
• 1.reduce intensity &reduce duration
of action, of drugs , which are
inactivated by system.
• 2-increased intensity of drugs which
are activated by system. e,g.
paracetamol
cntd
• 3.drug tolerance.e.g. carbamezapine
• 4.faster metabolism of endogenous
substance .e.g. steroid,bilirubin
• 5.precipitation of acute intermittent
porphyria due to increased enz .of
porphyrin
cntd
• 6. interference of action of other
drugs. e.g. ocpills & anticoagulants.
• 7.interfering in chronic toxicity
Duration of effect
Induction of enz, take place within 4-
14 days, & maintains till inducer drug
is given.
as & when drug is stopped, enz.
Comes to its normal level within 1-3
weeks.
uses
• 1- congenital non- heamolytic
jaundice-in this .adding of
phenobarbitone will lead to rapid
clearance of jaundice,.
• 2- cushing sydrome—phenytone is
help ful in reducing symptoms
cntd
• 3—chronic poisoning
• 4-liver disease
Non micrososmal reaction
• These are present in into cytoplasm
and mitochondria of liver and plasma.
• Enz-oxidase. Esterase, amidase, etc.
• Reaction-oxidation,
reduction.hydrolysis,all conjugation
except glucuronidation.
Hoffman elimination
• In this type , drug is metabolised or
inactivated in the body fluid, by
molecular rearrangement without
help of enz. Or co-enz.
• E.g .atracurium
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