Pharmacology Drug Distribution

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Questions and Answers

Which factor is crucial for a drug to effectively bind to a receptor and elicit the desired pharmacological response?

A complex interaction involving different types of chemical bonds, such as covalent and ionic bonds.

The drug's ability to induce significant structural changes in the receptor.

High concentration of the drug, regardless of its structural compatibility with the receptor.

A precise fit between the drug's structure and the receptor's binding site. (correct)

What is the potential consequence of even slight alterations in a drug's structure?

Reduced binding affinity but consistent pharmacological action.

Minimal change in biological activity, unless the alteration affects a critical functional group.

Significant changes in biological activity, including increased, decreased, or altered activity (e.g., agonist to antagonist). (correct)

Conversion of the drug into a completely inactive compound with no pharmacological effect.

The initial receptor model was based on a rigid lock-and-key concept. What is a more recent realization about receptors?

Receptors maintain a rigid structure at all times, ensuring high specificity for drug binding.

The drug fits into the receptor in an 'all-or-none process'.

Both the drug and receptor can have considerable flexibility, allowing for structural adjustments upon drug contact. (correct)

Drugs are the only molecules with flexibility; receptors remain unchanged ensuring binding.

What is the likely outcome of strong drug-receptor associations that lead to unproductive changes in the configuration of the macromolecule?

An antagonistic or blocking response. Signup and view all the answers

How do a drug’s acid–base properties influence its behavior in the body?

They greatly influence its biodistribution and partitioning characteristics. Signup and view all the answers

What is the definition of a base?

Base is a proton acceptor. Signup and view all the answers

According to the passage, what happens when un-ionized acids, such as carboxylic acids, donate their protons?

They form ionized conjugate bases, known as carboxylates. Signup and view all the answers

What happens when ionized acids, such as ammonium compounds, donate a proton?

They yield un-ionized conjugate bases (amine derivatives). Signup and view all the answers

Why is palmitic acid added to chloramphenicol to create chloramphenicol palmitate?

To mask the intense bitter taste of chloramphenicol, making it easier to administer orally. Signup and view all the answers

What is the primary purpose of using a prodrug approach?

To improve drug absorption or mask unfavorable properties, with the drug being converted to its active form after administration. Signup and view all the answers

How does enalapril, as a prodrug, enhance the efficacy of enalaprilic acid?

By improving the oral absorption of the active drug. Signup and view all the answers

What is the primary reason for using parenteral (injectable) drug administration?

To bypass the intestinal barrier in patients who cannot take drugs orally or when the drug is significantly metabolized in the liver. Signup and view all the answers

Which of the following is NOT a consideration for drug distribution in the gastrointestinal tract?

The density of the red blood cells in venous circulation. Signup and view all the answers

Why is chloramphenicol palmitate considered a prodrug?

Because it needs to be hydrolyzed into chloramphenicol to become an active antibiotic. Signup and view all the answers

Which of the following characteristics makes a drug a good candidate for parenteral administration?

Extensive first-pass metabolism. Signup and view all the answers

What happens to chloramphenicol palmitate once it reaches the intestinal tract?

It is hydrolyzed by digestive esterases into active chloramphenicol and palmitic acid. Signup and view all the answers

What is a key feature of intravenous drug administration that distinguishes it from subcutaneous or intramuscular injections?

Intravenous administration bypasses the need for the drug to diffuse into systemic circulation, causing rapid distribution. Signup and view all the answers

Why might a drug administered parenterally still not effectively target the brain?

The blood-brain barrier (BBB) restricts the passage of many drugs and chemicals into the brain. Signup and view all the answers

What is the primary purpose of using the prodrug approach in drug formulation?

To alter the solubility characteristics of the drug, which can increase flexibility in formulating dosage forms. Signup and view all the answers

What is the 'first-pass effect' in drug metabolism?

The metabolism of a drug by hepatic enzymes in the liver, reducing its concentration before it reaches systemic circulation. Signup and view all the answers

Which of the following statements accurately describes the characteristics of methylprednisolone acetate?

It is essentially water-insoluble and found in topical ointments and intramuscular suspensions. Signup and view all the answers

Why are esterases important for the effectiveness of methylprednisolone acetate and methylprednisolone sodium succinate?

Esterases hydrolyze these ester forms into the active methylprednisolone. Signup and view all the answers

Why is lidocaine typically administered intravenously?

Lidocaine is ineffective when administered orally due to the first-pass effect. Signup and view all the answers

Why was tocainide developed as an analog of lidocaine?

To prolong the drug's half-life and duration of action. Signup and view all the answers

What is a potential disadvantage of a drug with a maintenance dose based on weekly administration?

Adverse reactions may take a significant time to resolve due to slow clearance. Signup and view all the answers

How does injecting a drug directly into the spinal fluid or brain bypass the blood-brain barrier (BBB)?

These routes deliver the drug directly to the target site, circumventing the need to cross the BBB. Signup and view all the answers

What advantage does methylprednisolone sodium succinate have over methylprednisolone for drug administration?

It is water-soluble, allowing for intravenous administration Signup and view all the answers

In the context of drug metabolism, what is a 'metabolic labile site'?

A site on a drug molecule that is susceptible to metabolic reactions. Signup and view all the answers

How does the drug-protein binding phenomenon lead to drug-drug interactions?

One drug displaces another from the binding site, increasing the free concentration of the displaced drug. Signup and view all the answers

Why might drugs undergo distributive phenomena similarly after subcutaneous, intramuscular, oral and intravenous administration?

Once in systemic circulation, the drugs distribute similarly before reaching the target receptor. Signup and view all the answers

Which of the following is an example of an inactive parent drug that is converted to an active metabolite?

Sulindac being reduced to an active sulfide metabolite. Signup and view all the answers

What is the consequence of warfarin being displaced from its albumin-binding sites by another drug?

Increased prothrombin time, potentially leading to hemorrhage. Signup and view all the answers

What is the significance of studying the metabolic fate of a new drug product?

To understand how the drug is processed in the body, including its metabolites and excretion pathways. Signup and view all the answers

Why do lipophilic drugs tend to concentrate in tissue depots?

Neutral fat, a major component of tissue depots, has a high affinity for lipophilic substances. Signup and view all the answers

Why does thiopental's concentration rapidly decrease below its effective concentration after administration?

It disappears into tissue protein, redistributes into body fat, and then slowly diffuses back out of the tissue depots. Signup and view all the answers

Imipramine is N-demethylated to desipramine. What does this indicate?

Imipramine and desipramine are both active. Signup and view all the answers

Why can the body's ability to metabolize foreign molecules (xenobiotics) be considered fortunate?

It allows the body to eliminate potentially harmful substances. Signup and view all the answers

How does increasing the lipophilicity of a barbiturate affect its duration of action and CNS depression?

Decreases duration of action but increases CNS depression. Signup and view all the answers

Which characteristic is associated with barbiturates that have the slowest onset and longest duration of action?

Polar side chains. Signup and view all the answers

Why is the liver the first organ encountered by most molecules absorbed from the gastrointestinal tract?

Molecules absorbed from the gastrointestinal tract enter the portal vein, which leads directly to the liver. Signup and view all the answers

Why is acitretin, with its shorter half-life, preferred over etretinate for women who may become pregnant?

Acitretin clears from the body faster, reducing potential fetal exposure. Signup and view all the answers

How does protein binding affect the effective solubility of a drug?

It can maintain therapeutic concentrations even for poorly water-soluble drugs. Signup and view all the answers

How does protein binding contribute to a drug's half-life in the body?

By preventing rapid excretion of the drug through the renal glomerular membranes. Signup and view all the answers

What is one way protein binding affects drug biodistribution?

It may limit access to certain body compartments, such as the placenta. Signup and view all the answers

How might prodrug design alter the biological half-life of a drug?

By creating a drug with a slower rate of metabolism, thus altering a drug's half-life. Signup and view all the answers

The large, polar trypanocide suramin remains in the body for an extended period due to what?

Its protein-bound form. Signup and view all the answers

How does the albumin-drug complex affect the concentration of free drug at the receptor site?

It acts as a reservoir causing pharmacological response at the receptor. Signup and view all the answers

What is the terminal half-life of etretinate after 6 months of therapy, and how does it compare to acitretin?

Etretinate has a half-life of 120 days, significantly longer than acitretin. Signup and view all the answers

Study Notes

Drug Distribution

A drug, a chemical molecule, must pass through body barriers, avoid metabolic destruction, and reach its target receptor.
Drugs are introduced orally, intravenously, intramuscularly, or subcutaneously.
Drug distribution through different routes involves passing through membranes, systemic circulation, tissue depots, and subsequent metabolism.
Oral administration requires the drug to dissolve, pass through the gastrointestinal tract, and then be absorbed. Factors affecting drug dissolution include chemical structure, particle size/surface area, and crystal form.

Drug Distribution After Oral Administration

Drugs administered orally must dissolve to pass through the gastrointestinal mucosa (stomach lining).
Stomach acidity and intestinal alkalinity can affect drug dissolution.
Several factors influence a drug's ability to dissolve, including chemical structure, particle size, and crystal form.

Types of Tablet Coatings and Matrices

Tablet coatings and matrices can alter drug dissolution rates, allowing for controlled release or faster absorption.
Chemical modifications can help drugs reach their desired targets.

Prodrugs

Prodrugs are inactive compounds that are metabolized into active drugs in the body.
Examples include olsalazine (for ulcerative colitis) and chloramphenicol palmitate.
Prodrugs may be used to improve drug absorption, especially for drugs poorly absorbed from the gastrointestinal tract.
Prodrugs often improve bioavailability when compared to the parent drug.

Parenteral Administration

Parenteral administration (injections) bypasses the gastrointestinal tract, providing rapid drug distribution.
Factors like patient illness, rapid drug metabolism (first-pass effect), and targeting specific areas may need parenteral administration.
Subcutaneous, intramuscular, and intravenous injections are common routes.
These routes can result in direct access to the bloodstream, bypassing the digestive system

Drug-Protein Binding

Binding of drugs to proteins (especially albumin) in the bloodstream affects drug distribution, solubility, and biodistribution.
Protein binding can act as a reservoir, maintaining drug levels in the body for a longer period and delaying excretion.

Drug Metabolism

The liver is a primary site for drug metabolism.
Drugs may be metabolized to inactive forms during the first-pass through the liver.
Prodrugs are metabolized into active drugs in the body.

Excretion

The kidney is a major route for drug excretion.
Some drugs undergo enterohepatic circulation, where drugs are excreted in bile and re-absorbed into the intestines

Drug Receptors

Receptors are proteins to which drugs bind to produce pharmacological effects.
The location and type of receptors, the flexibility of the receptor, and structural similarity of drugs to the receptor all impact the effect of the drug.

Acid-Base Properties of Drugs

Most drugs are either acids or bases, and their acid-base properties affect their biodistribution and partitioning characteristics.
Acid-base properties can affect drug interactions and drug-receptor binding.

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Description

Explore the mechanisms of drug distribution within the body, focusing on the processes of drug administration routes and factors affecting dissolution. This quiz provides insight into the challenges drugs face in reaching their target receptors and the role of various coatings and matrices in tablet formulation.