Pharmaceutics Concepts

Front 1

Movement of drugs from a region of high concentration to low concentration. Does this requires energy? When does equilibrium occur?

Back 1

Diffusion; No ; equilibrium occurs when there is no concentration gradient (C1=C2)

Front 2

Explain the role of free energy in passive transport, as well as temperature and kinetic energy

Back 2

No energy is required for the transport itself, however, the molecules will move around to achieve the lowest free energy state. Increasing the temperature wil make molecules move faster, and increase kinetic energy (this will not determine whether or not diffusion will occur, only how FAST)

Front 3

Give some examples of diffusional transport systems

Back 3

Synthetic Polymeric Membranes:
- Transdermal patches (Clonidine and Duragesic)

Biological membranes:
- Absorption of drugs in the skin, GI tract, BBB and nephron

Front 4

Why might using a transdermal patch be desirable?

Back 4

Has approximately the same absorption and effectiveness as IV (which is much more than PO), with less side effects

Front 5

Catapress-TTS
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 5

Passive Transport

Front 6

Duragesic Patch;
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 6

PassiveTransport

Front 7

Reabsorption of water in the nephron:
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 7

Passive Transport

Front 8

Absorption of nutrients in the GI tract:
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 8

Passive Transport

Front 9

Diffusion of ionic molecules depends not only on the concentration gradient, but also on the _____________ gradient.

Back 9

Electrical

Front 10

Diffusion through the lipoidal bilayer

Back 10

Transcellular

Front 11

Diffusion through the spaces between the cell

Back 11

Paracellular

Front 12

What is convection? what is a classic example?

Back 12

Diffusion whereby molecules are transported by another liquid of gaseous molecule; example= diffusion of oxygen in the blood (transported by hemoglobin)

Front 13

When does facilitated transport happen instead of passive? What is the classic example?

Back 13

when the permeability of the drug-complex system is significantly greater than just the drug itself.

classic example is the absorption of vitamin B12 in the ileum of the intestine (forms complex with intrinsic factor secreted by parietal cells. Vit B12 will not be absorbed without intrinsic factor present)

Front 14

What type of molecules can diffuse paracellularly?

Back 14

Very small, water-soluble molecules

Front 15

what type of molecules would you expect to diffuse transcellularly?

Back 15

Larger, lipid (or non-water soluble) molecules

Front 16

Which type of transport would be more likely to expend energy? Transcellular or Paracellular?

Back 16

transcellular

Front 17

What is required in facilitated transport?

Back 17

No energy, but help of carrier is needed

Front 18

In which type of membrane would you expect to find facilitated transport (synthetic, biological, or both)?

Back 18

biological ONLY

Front 19

Explain ion-pair formation.

Back 19

Type of facilitated transport- occurs when the pH or charge of a complex is more favorable than the drug alone (leads to the transport of the more NEUTRAL complex)

Front 20

Describe the type of transport.
The basic drug, Propranolol, forms a neutral complex with Oleic acid for faster absorption rate

Back 20

Ion-pair formation (facilitated transport)

Front 21

Movement against the concentration gradient

Back 21

Active transport

Front 22

What is required for active transport?

Back 22

Energy (ATP) and a carrier (oftentimes a transmembrance protein, or "transporter")

Front 23

Absorption of Vitamin B12 in the GI intestine:
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 23

Facilitated transport

Front 24

Sodium-Potassium Pumps:
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 24

Active Transport

Front 25

Proton pump:
Which type of transport?
Passive Transport
Facilitated Transport
Active Transport

Back 25

Active Transport

Front 26

How are AAs, glucose, thiamine, riboflavine, and some vitamins absorbed in the intestine?

Back 26

They are large, lipid-insoluble molecules, therefore they cannot pass through the aqueous pores in the intestine. THEY MUST HAVE THE HELP OF A CARRIER IN THE MEMBRANE

Front 27

What happens to carrier molecules once they have transported the desired molecule across the membrane?

Back 27

They are typically "recycled," meaning they then go pick up another molecule

Front 28

Transport of material into the cell

Back 28

Influx

Front 29

Transport of material out of the cell / excretion

Back 29

Outflux ; Efflux

Front 30

What is Pgp? Where is it found?

Back 30

P-glycoprotein. A transmembrane protein found in the intestine and in tumors

Front 31

Give an example of a pump that actively effluxes drugs OUT of cells, leading to drug resistance

Back 31

P-glycoprotein (Pgp)

Front 32

Pgp (increases/decreases) the permeability of lipophilic and cytotoxic drugs

Back 32

decreases

Front 33

What type of drug do we need to use to limit tumor resistance to drugs? Why?

Back 33

P-glycoprotein (Pcp) inhibitor; that way the chemotherapy drug will stay inside the cell

Front 34

What is a drug that utilizes an amino acid transporter?

Back 34

Methyldopa

Front 35

What is a drug that utilizes an oligopeptide transporter?

Back 35

cephalexin ; captoril

Front 36

What is a drug that utilizes a phosphate transporter?

Back 36

Foscarnet (an antiviral... look out Tristan!)

Front 37

What is a drug that utilizes the Pgp efflux system?

Back 37

Vinblastin (used for leukemia)

Front 38

Why are certain drugs able to utilize transport systems?

Back 38

Because of structural similarities

Front 39

Fluorouracil is an anti-cancer drug that utilizes which transporter?

Back 39

Pyrimidine transporters

Front 40

Explain how we can use transport system competition to our advantage.

Back 40

Penicillin and Probenecid (both are acidic with carboxy groups, therefore use the same transport system.)
By adding Probenecid we are able to prolong the effect of penicillin because the Probenecid will block penicillin from being secreted by the kidney

Front 41

Which type(s) of transport are saturable?

Back 41

active transport

Front 42

What is the significance of Fick's law of diffusion?

Back 42

Shows the rate of diffusion depending on various factors associated with the membrane (DIRECTLY proportional to diffusivity, partition coefficient, surface area of the membrane, and concentration. INVERSELY related to the membrane thickness)

Front 43

What units do we use for Fick's law of diffusion?

Back 43

cm, cm3, or cm2/s

Front 44

What is the thickest biomembrane? Thinest?

Back 44

Skin; Scrotum

Front 45

What does a "sink condition" mean? An example?

Back 45

the concentration on the receptor side is significantly lower than on the donor side ; TTS (transdermal therapeutic system)

Front 46

In sink conditions, if C1= high, what does C equal?

Back 46

zero

Front 47

What is the permeability coefficient?

Back 47

Used in sink conditions when C2=0... P=DK/h

Front 48

Explain the variables in this equation. When is it used? What order process is this?
M=PSC1t

Back 48

M= amount being transported
P= permeability coefficient
S= surface area of the membrane
C1= concentration
t= time of diffusion

Used for sink conditions

First order (if the rate changes with concentration)
Zero-order (if surface area is constant and concentration is constant)

Front 49

Give an example of a sink condition that follows a zero-order process

Back 49

TTS, drinking half a bottle of whiskey

Front 50

Why is there a lag time present?

Back 50

There is time frame where the drug is simply saturating the membrane where there is no reaction

Front 51

What causes a burst effect?

Back 51

when the membrane is presaturated

Front 52

What effect does diffusivity have on the lag time?

Back 52

The greater the diffusivity, the shorter the lag time and vise versa

Front 53

Synthetic membranes are (non-porous / highly porous)?

Back 53

Can be either

Front 54

In which type of delivery system is "dose dumping" more common?

Back 54

Matrix transdermal patch

Front 55

Why is it important for a transdermal patch to be a zero-order system?

Back 55

Because blood cannot tolerate sudden changes in drug levels. Therefore, rate must remain constant and independent of concentration

Front 56

Instantaneous release of large excess of drug from reservoir

Back 56

Dose dumping

Front 57

What are three ways you could change the rate of release from a synthetic membrane?

Back 57

1. Change porosity
2. Change membrane thickness
3. Change the diffusion coefficient

Front 58

Give an example of a case in which more drug dissolves in the donor side as more molecules diffuse across the membrane

Back 58

A suspension

Front 59

matrix delivery systems start out as ______ order, then switch to ________ order. What is the equation associated with matrix systems?

Back 59

Zero ; First
Q= kt1/2

Front 60

Drugs diffuse when in their (unionized / ionized) form

Back 60

Unionized (lipophilic)

Front 61

What equation can tell you what percentage of a drug will diffuse through a lipophilic membrane?

Back 61

Henderson-Hasselbalch equation

Front 62

What is a "prodrug"?

Back 62

A form of a drug that allows it to stay unionized long enough to pass the biological membrane. Once inside, it get ionized

Front 63

Adding an ester group will (decrease/increase) diffusion through a lipid membrane.

Back 63

Increase

Front 64

Explain how Levodopa works

Back 64

Levodopa has a pH of like 8 or something (which is close to plasma pH). keeps dopamine in its unionzed form so it can cross the BBB. Once across BBB it is ionized by decarboxylase (dopamine alone has pH of 10+)

Front 65

In order for a drug to stay in its unionized form, pKa should be (close to / larger / smaller) than the pH

Back 65

close to

Front 66

a semipermeable membrane is permeable only to

Back 66

water (not solutes)

Front 67

Osmosis occurs from an area with ______ solute concentration to _______ solute concentration

Back 67

low ; high

Front 68

What is reverse osmosis? when is it used?

Back 68

When large molecules and ions are removed from the water.

Pressure is applied on the solute side, so that water passes through semipermeable membrane (like a filter)

*used during water purification (USP purified water)

Front 69

What is an OROS? explain what happens

Back 69

Oral osmotic system

Drug is surrounded by a semi-permeable membrane and has a hole drilled in the top... as water moves in, it forced drug out of the tablet through the little hole

Front 70

What are some advantages of a OROS osmotic pump? Disadvantages?

Back 70

Advantages;
zero-order release for 12-24 hrs
can delivery molecules of any size
the release rate is independent of pH or ionic strength

Disadvantages:
laser-drilled holes can get plugged
**do not break or chew. may see capsule in stool- that is normal**

Front 71

What would be a good option for a delivery of a large molecule that has a pH unsuitable for diffusion

Back 71

OROS osmotic pump

Front 72

When is the only time a drug is close to being 100% bioavailable

Back 72

IV administration

Front 73

True or false? Except for parental and oral administration of solution dosage forms, all other forms need to dissolve in the medium around the site of administration ito be absorbed.

Back 73

True

Front 74

The process by which a solid enters into a solution in a solvent

Back 74

Dissolution

Front 75

Why does the dissolution rate need to be determined (why run the dissolution test)?

Back 75

Tests in vitro can help up predict what will happen in vivo

Required for approval of a drug product (as part of quality control testing and uniformity testing)