Drug Absorption and Lipophilicity

Questions and Answers

What is one advantage of using deuterium atoms to replace hydrogen atoms in drug metabolism?

It increases the rate of drug metabolism.

It yields a slower rate of metabolism. (correct)

It leads to stronger carbon-hydrogen bonds.

It results in a faster degradation of drugs.

What is indicated by the reduced transport of oxygen in tumors?

Increased drug efficacy.

Hypoxia that can be utilized for drug delivery. (correct)

Increased nutrient absorption.

Normal cellular metabolism.

What is the role of active targeting in drug administration?

To increase the overall drug distribution in the body.

To specifically deliver drugs to the tissue of interest using antibodies. (correct)

To decrease the drug concentration required for therapeutic effect.

To enhance the passive diffusion of drugs across membranes.

Which pharmacokinetic improvement is NOT mentioned as a benefit of using deuterated compounds?

Higher doses needed. Signup and view all the answers

Which statement regarding pharmacokinetic parameters is accurate?

They are calculated from plasma/serum drug concentrations post-administration. Signup and view all the answers

What type of targeting involves leveraging physical and chemical properties of tumor cells?

Passive targeting. Signup and view all the answers

What is the major barrier for orally administered drugs in the body?

The intestinal epithelium Signup and view all the answers

Which process primarily controls drug absorption across the epithelial layer?

Transcellular pathway Signup and view all the answers

What characteristic of a drug allows it to effectively penetrate the phospholipid bilayer?

Its lipophilicity Signup and view all the answers

How is lipophilicity of a drug typically estimated?

By calculating its partition coefficient using octanol and water Signup and view all the answers

What does a higher Log P value indicate about a drug?

It is more lipophilic Signup and view all the answers

Which of the following describes lipophilic substances?

They dissolve well in lipids and non-polar solvents Signup and view all the answers

Which configuration of Log P values is optimal for gastrointestinal absorption through passive diffusion?

Moderate Log P values Signup and view all the answers

What happens to very lipophilic compounds during absorption?

They tend to bioaccumulate in cell membranes Signup and view all the answers

Which of the following criteria is not part of Lipinski's rules for pharmacological activity?

Log P not greater than 4 Signup and view all the answers

What effect does pH have on Log P and drug absorption?

It alters the ionization of drugs affecting lipophilicity Signup and view all the answers

In terms of drug formulation, what is the purpose of excipients?

To facilitate the manufacturing process and improve drug release Signup and view all the answers

What is the significance of bioequivalence studies?

They compare the bioavailability of different drug formulations Signup and view all the answers

Which of the following statements about ionized compounds is true?

They are less lipophilic and thus have lower absorption Signup and view all the answers

Which of the following types of functional groups is classified as acidic?

Carboxylic acids (-CO2H) Signup and view all the answers

What aspect of the Active Pharmaceutical Ingredient (API) does not affect bioavailability?

Chemical stability in the body Signup and view all the answers

What is the primary route of administration for oral delivery of drugs?

Self-administration via the gastrointestinal tract Signup and view all the answers

Study Notes

Drug Absorption - Oral

Epithelial Barrier: Intestinal epithelium serves as the primary barrier for orally administered drugs.
Transcellular Pathway: Drug molecules traverse cell membranes via the transcellular route, entering cytoplasm from the apical side and exiting into systemic circulation at the basolateral side.
Passive Transport: Drug absorption is typically passive and occurs through simple diffusion, following a concentration gradient (high to low), favoring small lipophilic compounds.

Lipophilicity vs. Hydrophilicity

Lipophilic Substances: Dissolve well in lipids/non-polar solvents; can easily penetrate cellular membranes.
Hydrophilic Substances: Dissolve well in water/polar solvents; less capable of membrane penetration due to polarity.
Like Dissolves Like: Lipophilic molecules are more likely to cross cell membranes due to their solubility in the lipid bilayer.

Measuring Lipophilicity

Simulated Absorption: Drug lipophilicity is measured by shaking it with a lipophilic solvent (like octanol) and a hydrophilic solvent (like water) to determine the distribution ratio.
Partition Coefficient and Log P:
- Higher Log P indicates greater lipophilicity; lower Log P indicates greater hydrophilicity.

Log P and Drug Absorption

Optimal Log P Values: Essential for gastrointestinal absorption via passive diffusion; indicated rules such as Lipinski's:
- No more than 5 hydrogen bond donors
- No more than 10 hydrogen bond acceptors
- Molecular mass under 500 Da
- Partition coefficient limit of 5
Bioaccumulation: Compounds with Log P > 5 are prone to bioaccumulation (e.g., polychlorinated biphenyls).

Ionization and pH Effects

Ionization Impact: Most drugs ionize to some degree; their absorption is influenced by the pH of the medium (Log D).
Basic vs. Acidic Functional Groups:
- Basic: Amines (-NH2, NHR, NR2)
- Acidic: Carboxylic acids (-CO2H), sulphonic acids (-SO3H), phenols (Ar-OH)

Oral Administration Advantages

Common route due to self-administration, cost-effectiveness, and extensive gastrointestinal absorption ability.

Pharmaceutical Formulation

Active Pharmaceutical Ingredient (API): The physical state (crystalline or amorphous) and particle size of the API influence bioavailability.
Excipients: Include fillers and lubricants that aid in manufacturing processes (e.g., magnesium stearate).
Bioequivalence Studies: Compare the bioavailability of different formulations containing the same active ingredient. Variations in absorption are studied through plasma concentrations after administration.

Drug Delivery Mechanisms

Passive Targeting: Exploits tumor hypoxia due to rapid cell proliferation and abnormal blood vessels, activating drugs under low oxygen conditions.
Active Targeting: Links drugs to antibodies that specifically target desired tissues (e.g., Ivacaftor for cystic fibrosis).

Molecular Modification Impacts

Deuteration: Replacing hydrogen with deuterium forms a stronger carbon-deuterium bond, leading to slower metabolism, lower doses, and improved pharmacokinetics and safety.

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Description

This quiz explores the processes of drug absorption in the gastrointestinal tract, emphasizing the role of the intestinal epithelium and transport pathways. It also delves into the concepts of lipophilicity and hydrophilicity, highlighting their implications for drug solubility and membrane penetration. Test your understanding of these crucial pharmacological principles.