Drug Absorption And Oral Route

Front 1

What is passive diffusion?

Back 1

describes the passage of drug moleculesthrough a membrane that does not actively participate in theprocess. The process is governed by the concentration gradient and isdescribed by Fick’s Law.

Front 2

What is facilitated diffusion?

Back 2

or facilitated diffusion is a specializedtransport having similar characteristics to active transport exceptthat the molecules are not transferred against the concentrationgradient.

Front 3

What is active transport?

Back 3

a specialized transport that involves themembrane components (carriers). It requires energy, is saturable andcan be specific in the molecules it transports. It can be inhibited byprocesses that interfere with cellular energy or by substances thatcompete with the substrate for transport. It moves molecules againsta concentration gradient.

Front 4

what type of cells will drugs use if it is being absorbed in the lymph? what is this process called?

Back 4

M cells; transcellular transport

Front 5

What is absorption?

Back 5

the process by which a compound andits metabolites are transferred from the gastro-intestinal tract to the circulating system (parent +metabolites)

Front 6

What is the desired route we want a tablet to go through?

Back 6

Front 7

What is sink condition?

Back 7

saturation point is a lot lower than the drug entering it. So you can essentially ignore the receptor compartment. since the), then you can ignore the compartment 2 which can be blood as it will eventually dilute the compound (ansel p 169.)

Front 8

What is Fick's Law?

Back 8

Front 9

What isthe most important physicalproperty of a drug in relation to its absorption, distribution,potency, and elimination?

Back 9

Lipophilicity

Front 10

Lipophilicity deals greatly with:

Back 10

Solubility! Absorption! Bioavailability!

Front 11

What is partitioning?

Back 11

movement of molecules from one phase to another,e.g. from aqueous to lipid, from liquids to the plastic of containers,from outside to inside of membranes.

Front 12

another way that Dr. Prokai refers to partition coefficient is...

Back 12

LOGP

Front 13

The pH of GI fluid variesconsiderably along thetract. The absorption could beinfluenced by pH of theGI fluid by changing thefollowing:

Back 13

Solubility

pH-partition hypothesis

Chemical stability

Front 14

what is the pH partition hypothesis?

Back 14

Cell membranes are more permeable to the un-ionized forms (hydrophobic) ofdrugs than to their ionized forms (hydrophilic)

Front 15

T/F:

The degree of a drug’s ionization depends only on the pH of the environment not the pKa of the drug.

Back 15

False; it depends on both

Front 16

T/F:

Most drugs are absorbed through GI tract bypassive diffusion

Back 16

True

Front 17

T/F:

The molecule withlow molecularweight is easy for active transport.

Back 17

False; The molecule that has big MW, it will be through active transport. the low MW will be through diffusion!

Front 18

What is lipinski's rule of 5?

Back 18

Drug-like properties of molecules with potentialgood absorption

Front 19

How many rules are there for lipinski's rule of 5?

what are they?

Back 19

4 and they are...

1) Molecular weight < 500

2) logP < 5

3) < 5 H-bond donors (sum of NH and OH)

4)< 10 H-bond acceptors (sum of N and O)

Front 20

What Physicochemical Factors of DrugSubstance for Absorption are there?

Back 20

1. Chemical stability of a drug in GI tract greatly affectsabsorption.

2. Ionized drugs (quaternary ammonium compounds) canform ion pairing with other ions in GI tract to formabsorbable species (neutral) with a high lipid solubilitycan aid absorption. (Florence: pp 355-356)

3. The state of hydration of a drug can affect itssolubility and pattern of absorption, e. g. anhydrousAmpicillin has greater absorption than its trihydrateform.

4. Formationofotherformswiththecomponentandfood, e. g. formation of micelles with bile salt, canchange the absorption 5. Chemicalcomplexationofadrugwithothercomponents of GI tract can decrease solubility andreduce absorption, e. g. tetracycline analogues canform chemical complex with cations, such as Ca2+,Mg2+ and Al3+

4. Formation of other forms with the component andfood, e. g. formation of micelles with bile salt, canchange the absorption

5. Chemical complexation of a drug with othercomponents of GI tract can decrease solubility andreduce absorption, e. g. tetracycline analogues canform chemical complex with cations, such as Ca2+,Mg2+ and Al3+

Front 21

Dissolution-rate limited process (or absorption):

Back 21

theabsorption of these drugs will be dependent upon the amountof the drug in solution. The passage through the membrane isnot the rate-limiting step. The rate-limiting step is getting thedrug in solution.

Front 22

Absorption-rate limiting process (or absorption):

Back 22

The rate-limiting step is getting the drug across the membrane. Thedissolution of the drug is a rapid process and does not presenta problem.

Front 23

Define dissolution:

Back 23

The process by which a drug particle dissolves andgoes into solution.

Form the diffusion layer on the surface

Pass throughout the dissolving fluid and absorption ensures

Front 24

How can you increase dissolution?

Back 24

1) Increase of dissolution rate constant k

2) Increase Surface area

3) How to increase saturated solubility (cs)

Front 25

Describe crystalline:

Back 25

Low energy state

Ordered

Front 26

Describe polymorphs:

Back 26

Polymorphs: a drug could have various arrangements, leading tovarious crystal forms or polymorphs – the same molecule crystalizesinto more than one type of crystal: ! Polymorphs have the same chemical structure but different physicalproperties, e.g. solubility, density, hardness and compressibility. ! In general, the crystal form with the lowest free energy is the most stablepolymorph. ! Metastable polymorphs may convert to the more stable form over time.

Front 27

Describe Amorphous:

Back 27

Metastable state, not ordered

Gradually revert back to crystalline state over time

Front 28

T/F:

Lipophilic drugs are poorly soluble in water and are notwell absorbed orally because of failure of the drug todissolve in the fluids of GI tract.

Back 28

True

Front 29

what Factors affecting delivery rate from liquid forms?

Back 29

Vehicle viscosity

In emulsion, the rate depends upon the partitioncoefficient.

Front 30

Does solubility affect absorption?

Back 30

yes!

Front 31

Drugs that are suitable for the oral route can:

Back 31

Survive the acid of the stomach

Are resistant to enzymatic attack

Are absorbed across GI membranes

Front 32

How is absorption in the stomach?

Back 32

Harsh environment containing hydrochloric acid and gastric juice.

Food intake is very important for drug absorption.

Front 33

Three anatomical sections of the small intestine are?

Back 33

duodenum, jejunum and ileum

Front 34

T/F:

For most oral drugs, the optimum site for drug absorption isthe upper portion of the small intestine or ileum region.

Back 34

False:

its not the ileum, its the duodenum

Front 35

The _______ cells of the epithelium form mucus that acts as a protective mechanism, but may be a barrier for absorption.

Back 35

Goblet

Front 36

What are the characteristics of the Large intestine?

Back 36

No villi

For water absorption

Front 37

True or False:

Convective water flow (the movement of watermolecules) into and out of the GI tract will affectabsorption.

Back 37

True

Front 38

What makes up GI fluid?

Back 38

bile, Mucin, Enzymes

Front 39

surfactants are...

Back 39

highly surface active compounds

Front 40

Describe bile salts:

Back 40

Highly surface-active

Increases absorption by enhancing the dissolution rate for poor water-soluble drugs, e.g. griseofulvin

Reduces absorption by forming non-absorable complex drugs, e.g.neomycin

Front 41

Describe Mucin:

Back 41

A viscous mucopolysaccharide that lines and protects the intestinal epithelium

Binds with drugs, e.g. quarternary ammonium compounds, to reduceabsorption

Also a barrier to drug diffusion before reaching the intestinal membrane

Front 42

Describe Enzymes:

Back 42

Can degrade drugs in addition to digesting food

Front 43

The transit time of the drug in the GI tract dependsupon:

Back 43

The pharmacologic properties of the drug

Type of dosage form

Various physiologic factors

Food

****All enteric*****

Front 44

The factors that delay movement of drug from thestomach to the small intestine will influence the rateof absorption are:

Back 44

Consumption of meals high in fat

Cold beverages

Anticholinergic drugs, e. g. dicyclomine HCL,amitriptyline HCl

Front 45

A drug will remain in stomach for _____ hours. in the small intestine for _______hours.

Back 45

2-4 hours; 4-10 hours

Front 46

The presence of food in the GI tract can affect the bioavailability of thedrug. Food could:

Back 46

Front 47

Describe buccal or sublingual absorption:

Back 47