Med Chem Unit 4

What is the definition of 'Drug Release'?

The process by which drug particles (solute) migrate from a dosage form and contact biological fluid (solvent).

The process where a solid drug particle dissolves in a liquid vehicle to yield a solution is known as _____.

Dissolution

What are the standard units for the 'Dissolution Rate' ($dM/dt$)?

Mass per unit time (e.g., mg/min).

List three examples of liquid dosage forms provided in the source material.

Solutions, suspensions, and emulsions.

List four types of solid dosage forms categorized under drug formulation factors.

Powders, ODT (Orally Disintegrating Tablets), chewables, and capsules.

Which semisolid dosage form is specifically mentioned alongside hydrogels and creams?

Gummies

What four 'Release Profiles' are identified as formulation factors?

Immediate, Delayed, Extended, and Pulsatile.

Formula: Noyes-Whitney Equation

$\frac{dM}{dt} = \frac{D \times S}{h} \times (C_S - C_M)$

In the Noyes-Whitney equation, what does the variable $D$ represent?

The diffusion coefficient for the drug in the media.

In the Noyes-Whitney equation, what does the variable $S$ represent?

The surface area of the drug particles.

In the Noyes-Whitney equation, what does the variable $h$ represent?

The unstirred aqueous layer thickness.

In the Noyes-Whitney equation, what does $C_S$ signify?

The saturated concentration at the solid particle-diffusion interface.

In the Noyes-Whitney equation, how is $C_M$ defined?

The media concentration based on the volume of fluid in the GIT.

How does decreasing the particle size of a drug affect the dissolution rate?

It increases the surface area ($S$), thereby increasing the dissolution rate.

Between crystalline and amorphous solid-state structures, which generally has higher drug solubility?

Amorphous

How does the salt form of an API typically affect its dissolution rate compared to the pure API?

It increases the dissolution rate by increasing solubility.

Which two formulation additives are listed as tools to increase drug solubility?

Cosolvents and surfactants.

Generally, is the ionized or unionized form of a drug more soluble in the solvent/media?

The ionized form.

What effect does increasing media agitation have on the diffusion layer thickness ($h$)?

It decreases the thickness, which increases the dissolution rate.

How does high media viscosity affect the rate of drug dissolution?

It increases the diffusion layer thickness ($h$), which decreases the dissolution rate.

What is the definition of 'Bioavailability' ($F$)?

The fraction or percentage of a drug substance that reaches the bloodstream or systemic circulation.

Bioavailability ($F$) values range from _____ to _____.

0 to 1

Name the two kinetic steps that occur between a tablet being administered and the formation of drug particles.

Disintegration (into granules) and deaggregation (into particles).

Which physicochemical factor refers to a drug's lipophilicity?

$LogP$

What are the three general factors that systemic drug absorption depends on?

Physicochemical properties of the drug, nature of the drug product (formulation), and anatomy/physiology of the absorption site.

Plasma membranes are 'selectively permeable,' meaning they restrict molecules based on which four characteristics?

Size, electrical charge, molecular structure, and lipid/water solubility.

Which type of drugs possess high membrane permeability: small lipophilic drugs or large hydrophilic drugs?

Small, lipophilic drugs.

To cross a lipid bilayer, a polar substance must either pass through an aqueous protein channel or bind to a _____.

Carrier protein

True or False: Ionized (charged) drugs can never cross cell membranes.

False, because they exist in equilibrium with an unionized state that can cross.

What is the fundamental difference between active and passive transport regarding energy requirement?

Active transport requires energy (ATP), while passive transport does not.

Identify the two types of passive transport processes.

Simple diffusion and facilitated diffusion.

Identify the two main types of active transport processes.

Carrier-mediated active transport and vesicular transport.

What is 'Paracellular Transport'?

The passive diffusion of drugs through aqueous channels in intercellular junctions (e.g., tight junctions).

The process by which molecules move spontaneously from high concentration to low concentration is called _____.

Diffusion

What is the driving force for drug absorption by passive diffusion?

The concentration gradient.

In Fick's Law of Diffusion, what does the partition coefficient ($P$) represent?

The drug's lipid solubility (ratio of solubility in lipid vs. water).

According to Fick's Law, how does increasing membrane thickness ($h$) affect the diffusion rate?

It decreases the diffusion rate.

Which anatomical part of the gastrointestinal tract allows for rapid absorption due to microvilli increasing surface area?

The duodenum.

In the context of drug absorption, what are 'sink conditions'?

Conditions where the rate of drug exit (blood flow/clearance) is much higher than entry, maintaining a high concentration gradient ($C_P \ll C_A$).

Passive diffusion is considered a _____ process, meaning the rate increases proportionally with concentration.

First-order

Why might a drug have better absorption in the small intestine than the stomach, even if the pH favors the stomach?

The small intestine has a much larger surface area and higher blood flow.

How can food components like calcium interfere with the absorption of drugs like fluoroquinolones?

By forming complexes with the drug, which prevents absorption.

What is another name for 'Pore Transport'?

Convective transport (or bulk transport).

Which specific passive transport mechanism involves drugs complexing with oppositely charged ions to cross membranes?

Ion-pair transport

How does 'Facilitated Diffusion' differ from 'Simple Diffusion'?

Facilitated diffusion requires a carrier protein, whereas simple diffusion involves moving directly through the lipid bilayer or channels.

Which type of active transport uses energy directly from ATP hydrolysis to move molecules against a gradient?

Primary active transport

Explain the mechanism of 'Secondary Active Transport'.

One molecule moves against its gradient by coupling with another molecule moving down its gradient.

The $Na^+/K^+$ ATPase is an example of which type of transport?

Primary active transport

The $Na^+/Glucose$ co-transporter (SGLT) is an example of which type of transport?

Secondary active transport

What is 'Endocytosis'?

A process where the cell membrane surrounds and engulfs outside material to bring it inside the cell.

Which type of transport system is 'saturable' at high drug concentrations?

Carrier-mediated transport.

What happens to the absorption rate of a drug using passive diffusion if its concentration at the absorption site is doubled?

The absorption rate doubles (linear relationship).

What are the two major superfamilies of transporters involved in drug transport?

ABC (ATP Binding Cassette) and SLC (Solute Carrier) transporters.

Which transporter superfamily typically favors larger, lipophilic drugs and functions mostly as efflux pumps?

ABC transporters

Which transporter superfamily typically favors smaller, hydrophilic drugs and functions mostly as uptake transporters?

SLC transporters

Transporters that pump molecules out of cells are called _____.

Efflux transporters

Transporters that bring molecules into cells are called _____.

Uptake transporters

What is the clinical role of transporters in the liver?

They bring drugs into liver cells for metabolism (uptake) and pump drugs into bile (efflux).

How do transporters at the Blood-Brain Barrier (BBB) affect drug therapy?

They can prevent drug access to the brain via efflux or allow entry via uptake.

What clinical drug target is inhibited by SSRIs to treat depression?

SERT (Brain serotonin transporter)

Proton pump inhibitors (PPIs) target which primary active transporter in the stomach?

$H^+/K^+$ ATPase

Which renal transporter is the target of loop diuretics used for edema and hypertension?

$Na^+-K^+-Cl^-$ cotransporter

SGLT2 inhibitors used in diabetes target transporters located in which organ?

The kidney

Why does loperamide not typically cause central opioid effects at clinical doses?

It is a substrate for the efflux transporter P-gp, which keeps it out of the brain.

What happens to drug entry if an efflux transporter in the intestine becomes saturated?

Drug entry into the body increases because the drug is no longer being pumped back out.

According to the Noyes-Whitney equation, what is the relationship between the dissolution rate and the concentration gradient $(C_S - C_M)$?

The dissolution rate is directly proportional to the concentration gradient.

Term: Diffusion Coefficient ($D$)

Definition: A constant describing the amount of drug diffusing across a membrane per unit time at a fixed concentration gradient.

Which process involves the packaging of molecules into membrane-enclosed vesicles for transport?

Vesicular transport

True or False: Facilitated diffusion requires ATP because it uses a carrier protein.

False, it is a passive process because it occurs down a concentration gradient.

Which mechanism of transport is used by glucose in most tissues via GLUT transporters?

Facilitated diffusion

In the kidney, which glucose transporter is used to move glucose against its concentration gradient to prevent loss in urine?

SGLT (Sodium-Glucose Linked Transporter)

What is the primary absorption process for 'most drugs' according to the source material?

Simple diffusion

Which specific drug transporter is mentioned as being present in the kidney, though not shown on a specific intestinal diagram?

BCRP

How does increasing the temperature of the fluid affect the diffusion coefficient ($D$)?

It increases the diffusion coefficient.

Which transport process is 'non-saturable' and allows water-soluble drugs of MW less than 100 to pass?

Pore transport

The brain serotonin transporter (SERT) is an example of what kind of transporter?

Secondary active transporter

What is 'Exocytosis'?

A process where a vesicle inside the cell fuses with the membrane to expel contents outside.

Which factors influence the diffusion coefficient ($D$) of a drug?

Molecular weight/structure of the drug, membrane composition, viscosity, and temperature.

According to the slide on saturable transport, when is carrier saturation 'uncommon'?

At clinical doses.

What describes the condition where blood flow carries a drug away immediately after absorption?

Sink conditions