First Pass Metabolism

First pass metabolism refers to metabolism of a drug during its passage from the site of absorption into the systemic circulation.

Drugs administered through the oral route undergo high first pass metabolism since it is exposed to drug metabolizing enzymes in the intestinal wall and liver.

Reference:
Essentials of Medical Pharmacology by K D Tripathi 5th edition page 25.

Ans. is ‘a’ i.e., High first pass metabolism

o Causes for less bioavailability.

Incomplete absorption

o High first pass metabolism.

About other options

• Increased absorption increases bioavailability.

o I.V. administration has 100% bioavailahi I ity.

• High lipid solubility causes more absorption and better bioavailability.

Ans. is ‘a’ i.e., First pass metabolism

Bioavilability depends on :

i) Extent of absorption.

it) First pass metabolism.

Ans. is ‘a’ i.e., Lignocaine; ‘b’ i.e., Propranolol; ‘c’ i.e., Salbutamol

Ans. is ‘a’ i.e., Isosorbide mononitrate

o “All nitrates except isosorbide mononitrate undergo extensive but variable first pass metabolism in liver”.

Ans. A: Oral

It is the fraction of lost drug 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, Propranolol, 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.

Routes of administration like suppository/rectal, intravenous, intramuscular, inhalational aerosol and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. 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.

Ans. is ‘b’ i.e., Undergoes extensive first pass metabolism

Propranolol metabolism

• It is well absorbed after oral administration.
• It has low bioavailability due to high first pass metabolism in liver.
• It is lipophilic and easily penetrates into brain.
• Metabolism of propranolol is dependent on the hepatic blood flow.
• Bioavailability of propranolol is increased when it is taken with food. o Hydroxylated product of propranolol has beta blocking activity.
• Metabolites are excreted in urine mostly as glucuronides.
• More than 90% of propranolol is bound to plasma proteins.

Ans. is ‘b’ i.e., All drugs can be given

Sublingual route of administration

• The tablet or pellet containing the drug is placed under the tongue or crushed in the mouth and spread over the buccal mucosa.
• Only the lipid soluble and non-irritating drugs can be administered by this route
• Absoption is rapid and action can be produced in minutes
• Action can be easily terminated by spitting the drug after the desired effect is achieved.
• Liver is bypassed with this route, thus the drugs with high first pass metabolism can be easily given by this route.
• Drugs given by this route are: GTN, buprenorphine, desamino-oxytocin.

Ans: B.) All drugs can be given

The route of drug administration as shown in the image is the Sublingual route.

Sublingual route of administration

• The tablet or pellet containing the drug is placed under the tongue or crushed in the mouth and spread over the buccal mucosa.
• Only the lipid-soluble and non-irritating drugs can be administered by this route.
• For the sublingual route of administration, the drug should have high lipid solubility and also should be soluble in aqueous buccal fluids i.e.  biphasic solubility of the drug is necessary for absorption. 
• Absorption is rapid and action can be produced in minutes
• Action can be easily terminated by spitting the drug after the desired effect is achieved.
• The liver is bypassed with this route, thus the drugs with high first-pass metabolism can be easily given by this route.
• All drugs can’t be given by sublingual route.
• Drugs designed for sublingual administration, include some of the cardiovascular drugs, steroids, barbiturates, benzodiazepines, opioid analgesics with poor gastrointestinal bioavailability, enzymes and few vitamins and minerals.

Ans. b. It is most cardiotoxic local anesthetic

Ans. is ‘c’ i.e., Theophylline 

• Important drugs with high hepatic extraction ratio (with high hepatic first pass metabolism)

Propranolol (13 blockers)  Salbutamol        Pethidine              Theophylline

Isoprenaline                    Verapamil          Nitroglycerine        Lignocaine

Methyltestosterone          Hydrocortisone   TCA (imipramine)   Testosterone

Ans. is ‘c’ i.e., Theophylline