ADME Flashcards
Q: What are the four stages of the ADME pathway?
A: Absorption, Distribution, Metabolism, Excretion.
Q: What must a drug presented in the intestine do to act in the body?
A: It has to negotiate a number of processes to get into the body and then into systemic circulation.
Q: What happens to a drug immediately upon absorption?
A: Drugs must pass through the intestine and then the portal circulation, which takes them to the liver, ensuring any foreign chemical is taken to the liver to minimize the amount of drug entering the body.
Q: What is the fate of a drug after oral absorption? Serum conc
Absorption: After a drug is ingested orally, it is absorbed through the gastrointestinal tract into the bloodstream. The drug must reach a certain concentration in the blood (serum) to be effective, known as the effective serum concentration.
Therapeutic Effect: Once the drug reaches this concentration, it can exert its therapeutic effects on the target tissues or organs.
the drug dissolves in the stomach and intestines.
It is then absorbed into the blood through the walls of the intestines and enters the portal circulation, which carries it to the liver.
Q: What is the role of the liver in drug absorption?
A: The liver acts to convert foreign chemicals, including drugs, into forms that are more readily eliminated.
In the liver, a portion of the drug may be metabolized before it reaches the systemic circulation. This is known as the first-pass effect.
The remaining drug that is not metabolized enters the systemic circulation, where it can reach its target sites.
Q: What does Fick’s Law say about drug absorption?
Fick’s Law states that the rate of diffusion of a drug across a membrane is proportional to the concentration gradient, the surface area of the membrane, and the permeability coefficient of the drug.
A higher concentration gradient, larger surface area, and higher permeability all increase the rate of absorption.
Q: What are SLC influx transporters and their role in drug absorption?
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Solute Carrier (SLC) transporters facilitate the uptake of drugs into cells.
These transporters, such as OATs (Organic Anion Transporters) and OCTs (Organic Cation Transporters), help move drugs from the intestinal lumen into the portal circulation.
They are crucial for the absorption of many drugs, especially those that are not readily absorbed by passive diffusion
Q: How does P-glycoprotein affect drug levels in the blood?
A:
P-glycoprotein decreases drug absorption in the intestines by pumping drugs back into the intestinal lumen.
This action reduces the amount of drug that enters the portal circulation and, subsequently, the systemic circulation.
By limiting absorption, P-glycoprotein helps regulate drug bioavailability and can contribute to drug resistance.
Q: How does drug ionization affect its disposition in tissues?
A:
Ionized drugs are less likely to cross cell membranes because they are more water-soluble and less lipid-soluble.
Non-ionized (neutral) drugs can more easily penetrate cell membranes due to their higher lipid solubility.
The degree of ionization depends on the drug’s pKa and the pH of the surrounding environment.
Q: What is the significance of tissue pH in drug absorption and disposition?
A:
Tissue pH affects the ionization state of a drug.
For example, weak acids are more likely to be non-ionized in the acidic environment of the stomach, enhancing their absorption.
Conversely, weak bases are more likely to be non-ionized in the more basic environment of the intestines, enhancing their absorption there.
Q: What is presystemic drug metabolism?
A:
Presystemic metabolism, also known as first-pass metabolism, refers to the metabolism of a drug in the liver and intestines before it reaches the systemic circulation.
This process can significantly reduce the bioavailability of orally administered drugs, as a portion of the drug is metabolized and inactivated before it can exert its therapeutic effect.
Q: How does plasma protein binding affect drug distribution?
A:
Drugs often bind to plasma proteins such as albumin.
Only the unbound (free) drug can cross cell membranes and exert a therapeutic effect.
Extensive protein binding can limit the amount of free drug available for distribution to tissues and can also slow down drug elimination.
Q: What is the first-pass effect?
A:
The first-pass effect is the rapid uptake and metabolism of an orally administered drug by the liver before it reaches the systemic circulation.
This effect can significantly reduce the bioavailability of the drug, as a large portion may be metabolized and inactivated on the first pass through the liver.
Q: What is bioavailability and how does it differ between oral and intravenous administration?
A:
Bioavailability is the fraction of an administered dose of a drug that reaches the systemic circulation in an active form.
Intravenous (IV) administration provides 100% bioavailability because the drug is delivered directly into the bloodstream.
Oral administration typically results in lower bioavailability due to first-pass metabolism and incomplete absorption.
Q: What are some methods to avoid the first-pass effect?
A:
Routes of administration that bypass the gastrointestinal tract and liver, such as intravenous (IV), sublingual (under the tongue), rectal, and transdermal (through the skin) routes, can avoid or reduce the first-pass effect.
These methods allow more of the drug to reach the systemic circulation directly.
Q: Why is intraocular and intranasal delivery advantageous?
A:
These routes target the local area directly, reducing the need for higher systemic doses.
They bypass the gastrointestinal tract and first-pass metabolism, leading to quicker onset and higher local drug concentrations with fewer systemic side effects.
Q: What is biotransformation and where does it mainly occur?
A:
Biotransformation is the process by which the body chemically alters drugs to make them more water-soluble and easier to excrete.
This process mainly occurs in the liver, but also in the kidneys, intestines, and other tissues.
Q: What is the role of CYP450 enzymes in drug metabolism?
A:
Cytochrome P450 (CYP450) enzymes are responsible for phase I reactions in drug metabolism, including oxidation, reduction, and hydrolysis.
These enzymes convert lipophilic drugs into more hydrophilic metabolites that can be more easily excreted.
Q: What are prodrugs and give an example?
A:
Prodrugs are inactive compounds that are metabolized in the body to produce an active drug.
An example is codeine, which is metabolized to morphine by the enzyme CYP2D6, providing its analgesic effect.
Q: How does genetic polymorphism affect drug metabolism?
A:
Genetic variations in metabolic enzymes, such as those in the CYP450 family, can lead to differences in how individuals metabolize drugs.
These variations can result in differences in drug efficacy and toxicity among individuals, requiring personalized dosing regimens.
Q: What are some important properties of CYP450 enzymes that can influence therapy?
A:
Readily Inhibited: CYP450 enzymes can be easily inhibited by drugs and chemicals because they have low substrate specificity, allowing for competition between different drugs.
Inducible: Exposure to certain drugs and chemicals can increase the amount of CYP450 enzymes present, enhancing the metabolism of drugs.
