Pharmacology: Drug Distribution and Binding

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Questions and Answers

What is the relationship between the volume of distribution and the location of the drug in the body?

The larger the volume of distribution, the more likely the drug is confined to the circulatory system.

The larger the volume of distribution, the more likely the drug is found in the tissues of the body. (correct)

The smaller the volume of distribution, the more likely the drug is found in the tissues of the body.

The volume of distribution has no effect on the location of the drug in the body.

What is the primary function of albumin in drug distribution?

To bind sex hormones

To bind basic drugs

To bind thyroid hormone

To bind acidic drugs (correct)

What is the effect of binding to plasma proteins on a drug's concentration in tissues?

It has no effect on the concentration of the drug in tissues

It limits the concentration of the drug in tissues (correct)

It is dependent on the type of protein bound

It increases the concentration of the drug in tissues

What is the role of fat in the body regarding lipid-soluble drugs?

It serves as a reservoir for lipid-soluble drugs Signup and view all the answers

What is the term for the process by which a drug is distributed into tissues?

Distribution Signup and view all the answers

What determines the rate of delivery and potential amount of drug distributed into tissues?

Cardiac output, regional blood flow, capillary permeability, molecular size, degree of ionization, lipid solubility, and binding to serum proteins Signup and view all the answers

What is the effect of reversible binding to plasma proteins on the concentration of active, unbound drug?

It limits the concentration of active, unbound drug Signup and view all the answers

What is the term for the proteins that specifically bind to certain hormones?

Hormone carrier proteins Signup and view all the answers

What happens to the concentration of active, unbound drug in intracellular water after distribution equilibrium is achieved?

It is the same as that in plasma, except when carrier-mediated transport is involved Signup and view all the answers

Which of the following is NOT a factor that affects drug transfer across the placenta?

Drug's half-life Signup and view all the answers

What is the primary mechanism by which the effect of a drug is terminated after withdrawal?

All of the above Signup and view all the answers

What is the primary determinant of drug penetration into the brain?

The lipid solubility of the nonionized and unbound species of the drug Signup and view all the answers

What is the main function of Phase I functionalization reactions?

To introduce or expose a functional reactive group on the parent compound Signup and view all the answers

Which of the following statements about the blood-brain barrier is TRUE?

It is primarily composed of tight junctions between endothelial cells in brain capillaries Signup and view all the answers

What is the primary role of drug metabolism?

To convert the drug into a more water-soluble form for easier excretion Signup and view all the answers

Which of the following is a characteristic of Phase II biosynthetic reactions?

They often result in the formation of inactive metabolites Signup and view all the answers

Which of the following statements about the termination of drug effect is TRUE?

It can be influenced by factors like drug distribution Signup and view all the answers

What happens to lipophilic compounds filtered through the glomerulus?

They are reabsorbed into the systemic circulation Signup and view all the answers

What happens to the half-life (T1/2) of a drug as clearance decreases due to a disease process?

It increases Signup and view all the answers

Steady state in pharmacokinetics refers to what?

The dynamic equilibrium between drug intake and elimination Signup and view all the answers

What percentage of drugs administered to humans are eliminated primarily through renal excretion?

25–30% Signup and view all the answers

Which factor influences the amount of drug filtered into the tubular lumen during glomerular filtration?

Glomerular filtration rate and plasma binding Signup and view all the answers

What process allows for the majority of filtered drugs to be reabsorbed back into the bloodstream?

Passive tubular reabsorption Signup and view all the answers

Why do lipid-soluble drugs tend to be poorly excreted in renal excretion?

They are easily reabsorbed due to passive diffusion Signup and view all the answers

What is the primary effect of the ion-trapping phenomenon on basic drugs in acidic urine?

They are excreted more rapidly Signup and view all the answers

What happens to polar drugs of low tubular permeability during renal excretion?

They remain in the lumen and accumulate Signup and view all the answers

Which of the following factors does NOT affect the amount of drug entering the tubular lumen?

Renal blood flow Signup and view all the answers

Which of the following is NOT a factor in determining if two drug products are considered pharmaceutical equivalents?

They have identical chemical structures. Signup and view all the answers

What is the primary advantage of administering drugs via the pulmonary route?

It allows for rapid absorption into the bloodstream. Signup and view all the answers

Which of the following scenarios would necessitate direct injection of drugs into the spinal subarachnoid space?

Providing rapid pain relief during surgery. Signup and view all the answers

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

The reduction of bioavailability due to metabolism in the liver and intestines. Signup and view all the answers

Why is the volume of distribution (VD) an important pharmacokinetic parameter?

It reflects the extent to which a drug distributes to tissues compared to plasma. Signup and view all the answers

Which of the following is NOT a characteristic of the pulmonary administration route?

It guarantees complete absorption of the drug into the bloodstream. Signup and view all the answers

What is the primary function of the meninges in the central nervous system?

To protect the brain and spinal cord from injury. Signup and view all the answers

What is the relationship between bioavailability and the first-pass effect?

Bioavailability is decreased by the first-pass effect. Signup and view all the answers

Study Notes

Injection Techniques

Injection into deltoid or vastus lateralis leads to faster absorption compared to gluteus maximus.
Female patients show slower absorption in gluteus maximus due to subcutaneous fat distribution.
Drugs too irritating for subcutaneous injection can be administered intramuscularly.

Subcutaneous Injection

Subcutaneous injections should only involve non-irritating drugs to avoid severe tissue damage.
Absorption rate from subcutaneous injections is often consistent and slow, aiding sustained drug effects.
Incorporating a vasoconstrictor in a subcutaneous drug solution can slow absorption.

Intra-Arterial Injection

Direct intra-arterial injection localizes drug effects in specific tissues, beneficial for liver tumors and head/neck cancers.

Intrathecal Injection

Intrathecal injections bypass blood-brain and blood-cerebrospinal fluid barriers for immediate effects on CNS, useful in spinal anesthesia and acute CNS infections.

Pulmonary Administration

Non-irritating gaseous and volatile drugs can be inhaled, rapidly absorbed through pulmonary epithelium.
Pulmonary route allows immediate drug absorption and avoids hepatic first-pass metabolism, ideal for targeting pulmonary diseases.

Bioequivalence

Drug products are pharmaceutical equivalents if they share the same active ingredients and demonstrate similar bioavailability under test conditions.

Bioavailability

Bioavailability refers to the fraction of drug entering systemic circulation; high liver and intestinal metabolism may significantly reduce it (first-pass effect).

Distribution of Drugs

After absorption, drugs distribute into interstitial and intracellular fluids based on volume of distribution (VD).
Large VD suggests high likelihood of drug presence in body tissues, while small VD indicates confinement within the circulatory system.
Factors influencing drug distribution include cardiac output, blood flow, capillary permeability, molecular size, lipid solubility, and binding to serum proteins.

Plasma Proteins

Many drugs bind to plasma proteins like albumin and α1-acid glycoprotein; binding is generally reversible.
Concentration of drugs at their site of action is limited by binding to plasma proteins, as only unbound drugs can cross membranes.

Tissue Binding and Reservoirs

Lipid-soluble drugs are stored in fat, which can act as a reservoir, leading to drug redistribution post-administration.
Drug effect termination occurs primarily through metabolism, excretion, or redistribution from action sites to other tissues.

Blood-Brain Barrier

Drug penetration into the brain relies on transcellular transport through tight junctions of endothelial cells.
Lipid solubility and non-ionized forms are key determinants for brain drug uptake; inflammation can increase permeability.

Placental Transfer of Drugs

Drug transfer across the placenta is influenced by lipid solubility, plasma binding extent, and ionization degree of weak acids and bases.

Drug Metabolism (Biotransformation)

Biotransformation generally produces polar, inactive metabolites for easier excretion; lipophilic compounds may be reabsorbed in the renal tubules.
Classifications:
- Phase I: Functionalization reactions (oxidation, reduction, hydrolysis).
- Phase II: Biosynthetic reactions (conjugation).

Phase I Reactions

Introduce functional groups on drugs, making them reactive for further conjugation.
Liver performs significant Phase I reactions, and decreased clearance may lead to increased half-life.

Steady State

Achieved when drug intake is balanced with its elimination, indicating stable plasma concentrations.

Renal Excretion

Renal excretion accounts for a major route of elimination for 25-30% of drugs; it involves:
- Glomerular filtration: Dependent on filtration rate and drug binding; only unbound drugs are filtered.
- Passive tubular reabsorption: Lipid-soluble drugs are poorly excreted, while polar drugs concentrate as water is reabsorbed.
- Ion-trapping effect: Basic drugs are excreted faster in acidic urine, promoting their charged form and inhibiting reabsorption.

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Description

This quiz covers the principles of drug distribution, including the role of albumin and plasma proteins, and how drug binding affects tissue concentration. It also explores the distribution of lipid-soluble drugs in the body.