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FIRST PASS METABOLISM
GUIDED BY- DR.DHANANJAY SANGLE
• first-pass metabolism:- a process in which a drug
administered by mouth is absorbed from the
gastrointestinal tract and transported via the portal
vein to the liver, where it is metabolized. As a
result, in some cases only a small proportion of the
active drug reaches the systemic circulation and its
intended target tissue. First-pass metabolism can
be bypassed by giving the drug via sublingual or
buccal routes.
• The first-pass effect (also known as first-pass
metabolism or pre systemic metabolism) is a
phenomenon of drug metabolism whereby the
concentration of a drug is greatly reduced before it
reaches the systemic circulation. It is the fraction of
drug lost during the process of absorption which is
generally related to the liver and gut wall. Notable
drugs that experience a significant first-pass effect
are imipramine, morphine, propranolol,
buprenorphine, diazepam, midazolam, demerol,
cimetidine, and lidocaine.
 After a drug is swallowed, it is absorbed by the
digestive system and enters the hepatic portal
system. It is carried through the portal vein into
the liver before it reaches the rest of the body.
The liver metabolizes many drugs, sometimes to
such an extent that only a small amount of active
drug emerges from the liver to the rest of the
circulatory system. This first pass through the
liver thus greatly reduces the bioavailability of
the drug.
• The four primary systems that affect the first
pass effect of a drug are the enzymes of the
gastrointestinal lumen, gut wall enzymes,
bacterial enzymes, and hepatic enzymes.
• In drug design, drug candidates may have good
drug likeness but fail on first-pass metabolism,
because it is biochemically selective.
• The four primary systems that affect the first
pass effect of a drug are the enzymes of the
gastrointestinal lumen, gut wall enzymes,
bacterial enzymes, and hepatic enzymes.
• In drug design, drug candidates may have
good drug likeness but fail on first-pass
metabolism, because it is biochemically
selective.
• Alternative routes of administration like
suppository, intravenous, intramuscular,
inhalational aerosol, transdermal and
sublingual avoid the first-pass effect because
they allow drugs to be absorbed directly into
the systemic circulation. Note that the
intravenous route also avoids the absorption
phase.
• Drugs with high first pass effect have a
considerably higher oral dose than sublingual
or parenteral dose. There is marked individual
variation in the oral dose due to differences in
the extent of first pass metabolism. Oral
bioavailability is apparently increased in
patients with severe liver diseases like Cirrhosis.
It is increased if another drug competing with it
in first pass metabolism given concurrently. Eg.
propranolol and chlorpromazine
What is the meaning of first pass
effect?
• Hepatic first pass effect:- All drug dose
absorbed from the gastrointestinal tract is first
delivered to the liver by the portal vein. A
fraction of the drug can then be metabolized in
the liver before it even reaches the systemic
circulation. Therefore the oral bioavailability of
the drug is reduced.
What drugs are metabolized in the
liver?
• Drug metabolism also known as xenobiotic
metabolism is the biochemical modification of
pharmaceutical substances or xenobiotics
respectively by living organisms, usually
through specialized enzymatic systems. Drug
metabolism often converts lipophilic chemical
compounds into more readily excreted
hydrophilic products.
What drugs have significant first pass
effect?
• Notable drugs that experience a significant
first-pass effect are imipramine, morphine,
propranolol, buprenorphine, diazepam,
midazolam, demerol, cimetidine, and
lidocaine. After a drug is swallowed, it is
absorbed by the digestive system and enters
the hepatic portal system.
First pass metabolism- Buddhabhushan dongre

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First pass metabolism- Buddhabhushan dongre

  • 1. FIRST PASS METABOLISM GUIDED BY- DR.DHANANJAY SANGLE
  • 2. • first-pass metabolism:- a process in which a drug administered by mouth is absorbed from the gastrointestinal tract and transported via the portal vein to the liver, where it is metabolized. As a result, in some cases only a small proportion of the active drug reaches the systemic circulation and its intended target tissue. First-pass metabolism can be bypassed by giving the drug via sublingual or buccal routes.
  • 3. • The first-pass effect (also known as first-pass metabolism or pre systemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.
  • 4.  After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug.
  • 5. • The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes. • In drug design, drug candidates may have good drug likeness but fail on first-pass metabolism, because it is biochemically selective.
  • 6. • The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes. • In drug design, drug candidates may have good drug likeness but fail on first-pass metabolism, because it is biochemically selective.
  • 7. • Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. Note that the intravenous route also avoids the absorption phase.
  • 8. • Drugs with high first pass effect have a considerably higher oral dose than sublingual or parenteral dose. There is marked individual variation in the oral dose due to differences in the extent of first pass metabolism. Oral bioavailability is apparently increased in patients with severe liver diseases like Cirrhosis. It is increased if another drug competing with it in first pass metabolism given concurrently. Eg. propranolol and chlorpromazine
  • 9.
  • 10. What is the meaning of first pass effect? • Hepatic first pass effect:- All drug dose absorbed from the gastrointestinal tract is first delivered to the liver by the portal vein. A fraction of the drug can then be metabolized in the liver before it even reaches the systemic circulation. Therefore the oral bioavailability of the drug is reduced.
  • 11. What drugs are metabolized in the liver? • Drug metabolism also known as xenobiotic metabolism is the biochemical modification of pharmaceutical substances or xenobiotics respectively by living organisms, usually through specialized enzymatic systems. Drug metabolism often converts lipophilic chemical compounds into more readily excreted hydrophilic products.
  • 12. What drugs have significant first pass effect? • Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine. After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system.