test 1 part 2

Question 1

Absorption

Answer 1

• The transfer of a drug from the site of administration to the bloodstream

Question 2

Rate of absorption depends on

Answer 2

• Environment
• Chemical characteristics of drug
• Route of administration

Question 3

Absorption from the GI tract - oral cavity

Answer 3

• Slightly acidic
• Thin epithelium, high vascularity
• Bypasses hepatic metabolism (skips liver)

Question 4

Absorption from the GI tract - stomach

Answer 4

• Folds increase surface area
• Very acidic
-some drugs can be absorbed from the stomach but not the main site

Question 5

Absorption from the GI tract - small intestine

Answer 5

• Deep folds with villi and microvilli

-main site for absorption because of large surface area

Question 6

Absorption from the GI tract - large intestine

Answer 6

• Little absorption throughout
• Rectum- useful site because bypasses hepatic metabolism - lower part of rectum bypasses liver
-secretes mucous

Question 7

Passive Diffusion

Answer 7

-most common means for drugs to gain access to the body
• Concentration gradient is driving force
• Does not involve a carrier
• Not saturable
• Low structural specificity
• Major method of drug absorption
• 2 types (Aqueous and Lipid)

Question 8

Aqueous Diffusion

Answer 8

• Water soluble drugs penetrate the cell membrane through aqueous channels or pores

Question 9

Fick’s Law

Answer 9

Net diffusion ≈ Area for diffusion x Concentration gradient / Thickness of membrane

Question 10

Lipid Diffusion

Answer 10

• Lipid soluble drugs readily move across most biologic membranes
• Soluble in the lipid bilayer of membranes

Question 11

Facilitated Diffusion

Answer 11

• Passage into a cell through transmembrane carrier proteins
• Conformational changes allow passage
• High concentration to low concentration
• Does NOT require energy
• Saturable
• Inhibited by competitors for carrier protein

Question 12

Active Transport

Answer 12

• Drugs that closely resemble naturally occurring metabolites are transported via carrier proteins in the membrane
• Energy dependent
• Can move against gradient
• Saturable
• Selective
• Competitively inhibited by other cotransported substances

Question 13

Endocytosis & Exocytosis

Answer 13

• Transport of exceptionally large drugs across membranes

* Engulfment by membrane and transport into or out of cell by pinching off vesicle

Question 14

Factors Influencing Absorption

Answer 14

1. pH
2. Blood flow
3. Surface area
4. Contact time
5. P-glycoprotein

Question 15

If a drug is ionized, why won’t it cross the lipid bilayer?

Answer 15

-an ionized drug forms a hydrophilic polar non-lipophilic molecule with water meaning it will not want to cross the lipid bilayer

Question 16

the neutral form of a weak acid is

Answer 16

protonated

-weak base is not

Question 17

acidic drugs are more soluble at what pH

Answer 17

• more acidic pH

- pushes equation to the left (HA)= non-ionized form

Question 18

a weak base in an acidic environment

Answer 18

-cannot be absorbed

Question 19

lower the pKa

Answer 19

• more acidic the drug is
• BH+
• HA favored

Question 20

pH > pKa

Answer 20

B and A- favored

-deprotonated forms predominate

Question 21

Manipulation of drug excretion by the kidney

Answer 21

• ”Trap” drugs in the urine by ionizing them
• Acidic drugs excreted faster in alkaline urine
• Basic drugs excreted faster in acidic urine

Question 22

acidic drugs excreted faster in what urine pH

Answer 22

alkaline urine

Question 23

fluids that can trap drugs

Answer 23

• Stomach
• Small intestine
• Breast milk
• Aqueous humor
• Vaginal and prostatic secretions
-urine

Question 24

Blood Flow affecting absorption rate

Answer 24

• Blood flow to absorption site increases absorption

* Intestines receive more flow than stomach so absorption from intestine is favored

Question 25

Surface Area influencing absorption

Answer 25

* Increase in total surface area for absorption increases efficiency * Intestines have brush border which increases surface area 1000 fold to that of the stomach

Question 26

Contact time influencing absorption

Answer 26

* Stomach => Slow emptying = decreased absorption | * Intestine => Slow transit time = enhanced absorption

Question 27

P-glycoprotein influencing absorption

Answer 27

* Pumps drugs out of the cells => Reduces drug absorption | * Transmembrane transporter protein

Question 28

Bioavailability

Answer 28

how much drug can be absorbed into your bloodstream after any route of administration - 100 mg tablet - 70 mg unchanged - 70% bioavailability

Question 29

Determination of Bioavailability

Answer 29

• % Bioavailability= (AUC oral administration / AUC IV administration) X 100

Question 30

Bioavailability: First-pass Hepatic Metabolism

Answer 30

* Drugs absorbed from GI tract enter portal circulation before entering systemic circulation * Liver or gut metabolize drug to varying degrees * Drugs with high first-pass metabolism must be given in doses large enough to ensure enough active drug remains

Question 31

Bioavailability: Solubility of the Drug

Answer 31

• Hydrophilic drugs poorly absorbed • Extremely lipophilic drugs poorly absorbed • IDEAL: largely lipophilic, yet have some solubility in aqueous solutions -THIS IS WHY MOST DRUGS ARE WEAK ACIDS OR WEAK BASES

Question 32

Bioavailability: Chemical Instability

Answer 32

* pH of stomach can cause instability | * Degradative enzymes in GI tract

Question 33

Bioavailability: Nature of Drug Formulation

Answer 33

* Particle size * Salt form * Crystal polymorphism * Enteric coatings * Binders and dispersing agents

Question 34

Bioequivalence

Answer 34

• A way to compare two drug formulations • Comparable - Bioavailability - Time to peak blood concentration

Question 35

Pharmaceutical Equivalence

Answer 35

* Bioequivalent * Same amount of active drug * Same dosage * Same route of administration

Question 36

Therapeutic Equivalence

Answer 36

``` • Bioequivalent • Pharmaceutically equivalent • Comparable - Clinical effect - Safety profile GENERIC DRUGS ```