P-glycoprotein

Definition

P-glycoprotein is a membrane transporter protein that plays a crucial role in the absorption, distribution, and elimination of various drugs. It functions by actively pumping certain drugs and xenobiotics out of cells, particularly in tissues like the intestines, liver, and blood-brain barrier, impacting how effectively medications can enter systemic circulation. Understanding p-glycoprotein is essential because it influences drug bioavailability and can lead to drug interactions or resistance.

5 Must Know Facts For Your Next Test

1. P-glycoprotein is primarily located in the intestinal epithelium, liver, kidney, and blood-brain barrier, influencing drug absorption and elimination.
2. It actively transports many lipophilic drugs out of cells, reducing their overall bioavailability and effectiveness.
3. P-glycoprotein can lead to significant drug-drug interactions when two or more substances compete for the same transport pathway.
4. Certain foods and herbal supplements can inhibit or induce p-glycoprotein activity, affecting how well drugs are absorbed.
5. Genetic variations in the gene coding for p-glycoprotein can result in different responses to medications among individuals.

Review Questions

• How does p-glycoprotein influence drug absorption and what are the consequences of this interaction?
  • P-glycoprotein influences drug absorption by pumping drugs out of enterocytes in the intestines, which reduces the amount of drug that enters systemic circulation. This can lead to lower bioavailability for certain medications, making them less effective. The presence of p-glycoprotein is particularly significant for lipophilic drugs, as they are more likely to be affected by this transport mechanism during oral administration.
• Discuss the role of p-glycoprotein in drug-drug interactions and how this affects therapeutic outcomes.
  • P-glycoprotein can mediate drug-drug interactions by competing with other medications that are also substrates for this transporter. When two drugs are administered concurrently and both are p-glycoprotein substrates, one may inhibit the transport of the other. This can lead to increased plasma concentrations of the affected drug, potentially causing toxicity or enhanced effects. Therefore, understanding these interactions is crucial for optimizing therapeutic regimens.
• Evaluate how genetic polymorphisms in the p-glycoprotein gene affect individual responses to medications.
  • Genetic polymorphisms in the p-glycoprotein gene can result in variations in protein expression or function among individuals. These differences can significantly influence how well drugs are absorbed or eliminated from the body. For example, some individuals may have reduced p-glycoprotein activity leading to higher drug levels and increased risk of adverse effects, while others may have enhanced activity resulting in lower therapeutic effectiveness. Understanding these genetic differences is vital for personalized medicine approaches to ensure optimal drug therapy for each patient.

Related terms

Bioavailability: The proportion of a drug that enters the circulation when introduced into the body and is available for therapeutic effect.

Xenobiotic: A chemical compound that is foreign to a living organism, which includes drugs, pollutants, and other environmental chemicals.

ABC Transporters: A large family of membrane transport proteins, of which p-glycoprotein is a member, involved in transporting various molecules across cellular membranes using ATP.