Biopharmaceutics Presentation Topic- FIRST PASS METABOLISM
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A brief Biopharmaceutics Presentation on the Topic- FIRST PASS METABOLISM OF DRUGS, INCLUDES MECHANISM, APPLICATIONS AND DRUG DEVELOPMENT
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Biopharmaceutics Presentation Topic- FIRST PASS METABOLISM
- 2. “WHAT IS FIRST PASS METABOLISM ” ?? The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation. The first pass effect is often associated with the liver, as this is a major site of drug metabolism.
- 3. HEPATIC FIRST PASS METABOLISM :- Hepatic first pass occurs when drug absorbed from the gastrointestinal tract is metabolized by enzymes within the liver to such an extent that most of the active agent does not exit the liver and, therefore, does not reach the systemic circulation Phase I metabolic reactions can occur during the absorptive phase in the gut wall or liver before reaching the blood stream. This results in a reduction in the concentration of the drug before it reaches the circulation. In other words, there is a fraction of the drug that is lost.
- 6. However, the first pass effect can also occur in the lungs, vasculature, gastrointestinal tract, and other metabolically active tissues in the body. This effect can become augmented by various factors such as plasma protein concentrations, enzymatic activity, and gastrointestinal motility. 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, pethidine, tetrahydrocannabinol, ethanol (drinking alcohol), cimetidine, lidocaine, and nitroglycerin.
- 7. SOME EXCEPTIONS TO FIRST PASS METABOLISM INCLUDE :- In contrast some drugs are enhanced in potency: for example, the effect of the most commonly considered active ingredient in cannabis, THC, is enhanced by transformation of a significant portion into 11-hydroxy-THC that more readily crosses the blood-brain barrier and thus achieves greater potency than the original THC.
- 9. SOME COMMON EXAMPLES :- First pass metabolism may occur in the liver (for propranolol, lidocaine, chloromethiasole and GTN) or in the gut (for benzylpenicillin and insulin). In drug design, drug candidates may have good druglikeness 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.
- 10. EFFECT OF FIRST PASS METABOLISM ON DRUGS :- Drugs with high first pass effect typically 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, frequently among several other factors. Oral bioavailability of many vulnerable drug appears to be increased in patients with compromised liver function.
- 11. Bioavailability is also increased if another drug competing for first pass metabolism enzymes is given concurrently e.g. propranolol and chlorpromazine.
- 12. MECHANISM OF FIRST PASS METABOLISM:- 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 may greatly reduce the bioavailability of the drug.
- 15. SYSTEMS THAT AFFECT THE FIRST PASS EFFECT OF A 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.
- 16. CLINICAL SIGNIFICANCE :- Some drugs that undergo considerable first-pass metabolism include alprenolol, 5-fluorouracil, morphine, pentazocine, and mercaptopurine. When given orally, these drugs are quickly metabolized via the first- pass effect, requiring their oral dosages to be much larger than their intravenous dosages. The first pass effect also has an impact on peak drug concentrations, which may result in drug concentration peaks occurring much earlier than they would in a parenteral dose. It is critical to maintain proper serum concentrations of a drug that experiences the first-pass effect; this allows for the maintenance of a safe and effective dose of the drug.
- 19. THERAPEUTIC IMPLICATIONS OF FIRST PASS METABOLISM :- One major therapeutic implication of extensive first-pass metabolism is that much larger oral doses than intravenous doses are required to achieve equivalent plasma concentrations. For some drugs, extensive first-pass metabolism precludes their use as oral agents (e. g. lignocaine, naloxone and glyceryl trinitrate). Research has shown that monitoring blood levels of drugs that experience the first-pass effect is the most viable way to maintain therapeutic concentrations of these drugs.
- 20. NURSING, ALLIED HEALTH AND INTER-PROFESSIONAL TEAM MONITORING :- When monitoring patients that are taking drugs that experience the first-pass effect, it is critical to monitor the blood levels of these drugs to ensure that the patients' serum drug concentrations remain within their therapeutic windows. Doing so will maximize the efficacy of treatment and patient safety.
- 22. SUBMITTED TO:- DR. ASHIF KHAN MADE BY :- RISHABH SHARMA