First Pass Metabolism

First Pass Metabolism


INTRODUCTION & MOA:

  • First-pass effect – 
  • Phenomenon of drug metabolism whereby drug concentration is greatly reduced before reaching systemic circulation & its concerned target tissue.
  • Mostly occurs with orally administered drug – Due to vulnerability to metabolizing enzymes in intestinal wall & liver.
  • Finally transported via portal vein to liver for metabolization.
  • Hence, referred as “Presystemic metabolism”.
  • Drug bio-availability is greatly reduced.
  • Can be avoided by adminstering drug via sublingual, transdermal or parentral routes.

DRUGS EXPERIENCING FIRST PASS METABOLISM:

  • Notable drugs:
  • Imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.

ALTERNATIVE ROUTES OF ADMINISTRATIONS:

Avoid first-pass effect because they allow drugs to be absorbed directly into systemic circulation. 

  • Suppository
  • Intravenous
  • Intramuscular
  • Inhalational aerosol – 
  • Limited first pass metabolism occurs.
  • Especially for drugs via veins.
  • Transdermal (via Skin)- 
  • Limited presystemic metabolism occurs. 
  • Sublingual or buccal routes – e.g. Isosorbide mononitrate.
EXTENT OF FIRST PASS METABOLISM:
  • Refers to drug fraction lost during absorption process that is generally related to liver & gut-wall.
LOW INTERMEDIATE HIGH-NOT GIVEN ORALLY HIGH ORAL DOSE
Phenobarbitone Aspirin Isoprenaline Propranolol
Phenylbutazone Quinidine Lignocaine Alprenolol
Tolbutamide Desipramine Hydrocortisone Verapamil
Pindolol Nortriptyline Testosterone Salbutamol
Isosorbide mononitrate Chlorpromazine   Glyceryl trinitrate
  Pentazocine   Morphine 
  Metaprolol   Pethidine

DRUGS PROPERTIES:

  • Drugs with high first pass effect have considerably higher oral dose than  sublingual or parenteral dose. 
  • There is marked individual variation in oral dose due to differences in extent of first pass metabolism. 
  • Oral bioavailability is apparently increased in patients with severe liver diseases like Cirrhosis.
  • Increased effect seen if another drug competing with it in first pass metabolism given concurrently. 
  • Eg. Propranolol & chlorpromazine
Exam Question
 
  • A drug administered through oral route undergo high first pass metabolism.
  • High first pass metabolism causes for less bioavailability.
  • High first pass metabolism is seen in Lignocaine, Propranolol & Salbutamol.
  • Isosorbide mononitrate bypasses first pass metabolism.
  • Sublingual route escape first pass metabolism.
  • Theophylline escape first pass metabolism.
Don’t Forget to Solve all the previous Year Question asked on First Pass Metabolism

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