Absorption

Question 1

What are the 4 factors that determine a drug’s ability to cross biological membrane?

Answer 1

1) Molecular size/weight
2) Lipid solubility
3) Degree of ionization
4) Concentration gradient

Question 2

How does molecular weight affect a drug’s ability to cross biological membrane

Answer 2

Small MW drugs absorbed more readily

Remember: plasma protein binding to drug also increases size (duh)

Question 3

How does lipid solubility affect a drug’s ability to cross biological membrane?

Answer 3

Increased lipid solubility —> increased absorption

Drug can easily cross lipid bilayer of membranes

Estimated by oil:water partition coeff.

Question 4

How does the degree of ionization affect a drug’s ability to cross biological membrane?

Answer 4

Affected by pH —> affects lipid solubility

• More unionized = more lipid soluble = increased absorption (ions are charged —> can’t cross membranes)

Use H-H eqn for this

Question 5

How does the concentration gradient affect a drug’s ability to cross biological membrane?

Answer 5

High concentration created at side of drug administration

Drugs moves from [high] to [low]

Question 6

What are the 3 mechanisms by which drugs cross the biological membrane?

Answer 6

1) Passive diffusion
2) Carrier mediated diffusion
3) Endocytosis

Question 7

Describe passive diffusion as it relates to drug transport

Answer 7

Most important route — driven by [gradient]

Through:

1) aqueous diffusion/filtration
2) lipid diffusion

Question 8

Describe aqueous diffusion/filtration as it related to drug transport

Answer 8

Drug flows through aqueous channel

• Limited capacity
• Channel size varies (drugs w/ MW <100-200)

Question 9

Describe lipid diffusion as it related to drug transport

Answer 9

Drugs pass via hydrophobic bonding w/membrane lipids

• Favored if drug has high lipid:water partition coef.
• Often pH dependent
• Most important for drugs w/ MW of 500-800

Question 10

What are the 2 types of carrier mediated diffusion as it related to drug transport

Answer 10

1) facilitated diffusion

2) active transport

Question 11

Describe facilitated diffusion as it related to drug transport

Answer 11

driven by [gradient]

no E required

Question 12

Describe active transport as it related to drug transport

Answer 12

• E dependent
• selective, saturable, unidirectional
• for drugs that resemble endogenous compounds

Question 13

Describe endocytosis as it related to drug transport

Answer 13

Minor importance for drug passage

Pinocytosis or phagocytosis

Question 14

What is enteral absorption? Name two types of administration.

Answer 14

Absorption via GI tract

1) Oral
2) Rectal

Question 15

What is parenteral absorption? Name six types.

Answer 15

Absorption outside GI tract

1) Sublingual/buccal
2) Intravenous
3) Intramuscular
4) Subcutaneous
5) Inhalation (gaseous/suspension)
6) Transdermal

Question 16

What is the bioavailability of oral drug administration?

Answer 16

0-100%

Depends on …

1) survival in GI environment
2) ability to cross GI membrane
3) efficiency of drug metabolism by gut wall or liver (1st pass)

Question 17

What is the onset effect rate of oral drug administration?

Answer 17

Slow (15-30 min for immediate release)

Slower (hours) for enteric/sustained release

Question 18

What are other factors to consider with oral drug administration?

Answer 18

• Most common
• Drug admin via passive diffusion (aka favors lipophilic/ nonionized drugs)
• drug absorption rate from intestine > stomach
• increased GI motility and empty stomach —> increased absorption

Question 19

What is an enteric drug coat?

Answer 19

• Protects stomach from irritation

- Protects drugs from low stomach pH

Question 20

What is a drug with controlled-release prep?

Answer 20

Rate of absorption slowed by slowing rate of product dissolution

PROS: fewer doses, increase compliance, no peaks/troughs, overnight use

CONS: greater interpatient variability, formulation could fail to give entire dose

Question 21

What is the bioavailability of rectal drug administration?

Answer 21

Variable

Generally greater than oral

Question 22

What is the onset effect rate of rectal drug administration?

Answer 22

Not rapid

Question 23

What are other factors to consider with rectal drug administration?

Answer 23

• Useful when oral route not available (aka: vomiting, unconscious, post-GI surg, uncooperative)
• 50% of dose will bypass liver
• first pass metabolism is less than for oral
• absorption irregular/incomplete

Question 24

What is the bioavailability of sublingual/buccal drug administration?

Answer 24

Generally high

Question 25

What is the onset effect rate of sublingual/buccal drug administration?

Answer 25

Within minutes (5-10)

Question 26

What are other factors to consider for sublingual/buccal drug administration?

Answer 26

• Most direct route
• Circumvent all factors related to membrane passage/absorption
• accurate/fast drug delivery
• Used for drugs w/ narrow TI
• requires aseptic technique
• very hazardous (easy to reach irreversible toxic levels)

Question 27

Compare and contrast absorption of non-ionized and ionized drugs.

Answer 27

Non-ionized = uncharged (readily absorbed)

Ionized = charged (cannot be absorbed)

Question 28

Describe weak acids as drugs.

Answer 28

Always think:
R-COOH R-COO(-) + H(+)

Have lower pKas

At pH’s above pKa they are ionized [COO(-)] —-> can be ion trapped in basic solutions

Question 29

Describe weak bases as drugs

Answer 29

Always think:
R-NH3(+) R-NH2 + H(+)

Have higher pKas

At pH’s below pKa they are ionized [NH3(+)] —-> can be ion trapped in acidic solutions

Question 30

Describe bioavailability (F) with regards to dose adjustment

Answer 30

Fraction of unchanged drug reaching the systemic circulation

Compare AUC following single dose of drug given by any route to the AUC following a single dose by IV route

Question 31

How is bioavailability used?

Answer 31

Info on extent of absorption (aka F) by oral route available for most drugs

Use this for dosage adjustments when drug is given by a different route
(common to switch fro oral to IV)