Absorption - The Pharmacokinetics Series

Summary

This video delves into the process of drug absorption, explaining how drugs enter the systemic circulation and factors influencing bioavailability. The speaker highlights the differences in absorption depending on how a drug is administered (oral vs intravenous), as well as factors like pH, gut motility, and patient conditions (e.g., bariatric surgery, diarrhea). Key concepts such as lipid solubility, ionization, and the first-pass effect are explored. The video emphasizes the importance of understanding bioavailability when adjusting drug dosages, especially when converting from oral to intravenous forms.

Takeaways

• 😀 Absorption is the process by which a drug enters the systemic circulation, influenced by how the drug is administered.
• 😀 Bioavailability (F) refers to the percentage of a drug that reaches the bloodstream. Intravenous administration has 100% bioavailability.
• 😀 Oral drugs undergo absorption through the stomach and intestines, and only a portion reaches systemic circulation due to various factors.
• 😀 The first-pass effect refers to the metabolism of a drug by the liver before it reaches systemic circulation, reducing its effective concentration.
• 😀 Factors like stomach acidity, food, and other medications can influence drug absorption. For example, calcium and iron can decrease absorption of certain antibiotics.
• 😀 Conditions such as bariatric surgery, diarrhea, and ileus can alter drug absorption due to changes in the gastrointestinal tract.
• 😀 Gut motility impacts absorption, with drugs like metoclopramide increasing motility and opioids slowing it down.
• 😀 Decreased blood flow (e.g., in shock or atherosclerosis) reduces drug absorption by affecting splanchnic blood flow.
• 😀 Lipid solubility is essential for a drug to cross cell membranes. Non-ionized (uncharged) molecules are more lipid-soluble and easier to absorb.
• 😀 Transporters like P-glycoprotein (P-gp) on the intestinal membrane can actively pump drugs out, affecting drug absorption and distribution.
• 😀 Knowledge of bioavailability is important for adjusting dosages when switching between oral and intravenous routes, such as in the case of furosemide.

Q & A

What is bioavailability and how is it related to drug absorption?

Bioavailability refers to the proportion of a drug that reaches the systemic circulation after administration. When a drug is administered intravenously, its bioavailability is 100%, but for oral administration, it may be lower due to absorption limitations in the digestive system.

How does drug absorption differ between oral and intravenous routes?

When a drug is given intravenously, it directly enters the bloodstream, resulting in 100% bioavailability. In contrast, when taken orally, only a portion of the drug is absorbed through the gut, and its bioavailability is less than 100%, depending on various factors like drug stability and absorption efficiency.

Why is the drug furosemide used as an example in this video?

Furosemide is used as an example because its bioavailability is 50% when taken orally, meaning only half of the dose reaches the systemic circulation. This highlights the importance of adjusting dosages when switching between oral and intravenous administration.

What are some factors that can influence drug absorption?

Several factors can influence drug absorption, including the pH of the environment, food in the stomach, the surface area of the intestine, drug stability in stomach acid, and the presence of transporters like P-glycoprotein that may actively pump the drug out of the cells.

How does the stomach’s acidity affect drug absorption?

The acidity of the stomach can degrade certain drugs, especially those that are chemically unstable, such as penicillin G. The pH of the environment also affects the ionization of drugs, influencing their lipid solubility and ability to cross cell membranes.

What role do transporters like P-glycoprotein play in drug absorption?

Transporters like P-glycoprotein (P-gp) actively pump drugs out of cells, reducing the drug's absorption into the bloodstream. These transporters can be induced or inhibited by other drugs, affecting overall drug absorption and distribution.

How does bariatric surgery affect drug absorption?

Bariatric surgery can reduce the surface area of the stomach and small intestine, leading to decreased absorption of drugs. As a result, patients who undergo these surgeries may need higher doses or supplementary treatments, such as iron, to ensure proper drug absorption.

What is the first pass effect and how does it impact drug effectiveness?

The first pass effect refers to the metabolism of a drug by the liver before it reaches the systemic circulation. Drugs with a significant first pass effect, like nitroglycerin, may require alternate routes of administration (e.g., sublingual or spray) to bypass the liver and ensure therapeutic effectiveness.

Why is it important to adjust drug doses when switching from oral to intravenous administration?

Adjusting drug doses is crucial because the bioavailability of orally administered drugs is often lower than 100%. For instance, if a patient typically takes 80mg of furosemide orally (with 50% bioavailability), they would need only 40mg intravenously to achieve the same therapeutic effect.

What impact does the pH of the environment have on the ionization of drugs?

The pH of the environment influences whether drugs are ionized or non-ionized. Non-ionized (uncharged) drugs are more lipid-soluble and can more easily cross cell membranes, whereas ionized drugs are less likely to be absorbed.