Absorption Flashcards
What are the 4 factors that determine a drug’s ability to cross biological membrane?
1) Molecular size/weight
2) Lipid solubility
3) Degree of ionization
4) Concentration gradient
How does molecular weight affect a drug’s ability to cross biological membrane
Small MW drugs absorbed more readily
Remember: plasma protein binding to drug also increases size (duh)
How does lipid solubility affect a drug’s ability to cross biological membrane?
Increased lipid solubility —> increased absorption
Drug can easily cross lipid bilayer of membranes
Estimated by oil:water partition coeff.
How does the degree of ionization affect a drug’s ability to cross biological membrane?
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
How does the concentration gradient affect a drug’s ability to cross biological membrane?
High concentration created at side of drug administration
Drugs moves from [high] to [low]
What are the 3 mechanisms by which drugs cross the biological membrane?
1) Passive diffusion
2) Carrier mediated diffusion
3) Endocytosis
Describe passive diffusion as it relates to drug transport
Most important route — driven by [gradient]
Through:
1) aqueous diffusion/filtration
2) lipid diffusion
Describe aqueous diffusion/filtration as it related to drug transport
Drug flows through aqueous channel
- Limited capacity
- Channel size varies (drugs w/ MW <100-200)
Describe lipid diffusion as it related to drug transport
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
What are the 2 types of carrier mediated diffusion as it related to drug transport
1) facilitated diffusion
2) active transport
Describe facilitated diffusion as it related to drug transport
driven by [gradient]
no E required
Describe active transport as it related to drug transport
- E dependent
- selective, saturable, unidirectional
- for drugs that resemble endogenous compounds
Describe endocytosis as it related to drug transport
Minor importance for drug passage
Pinocytosis or phagocytosis
What is enteral absorption? Name two types of administration.
Absorption via GI tract
1) Oral
2) Rectal
What is parenteral absorption? Name six types.
Absorption outside GI tract
1) Sublingual/buccal
2) Intravenous
3) Intramuscular
4) Subcutaneous
5) Inhalation (gaseous/suspension)
6) Transdermal
What is the bioavailability of oral drug administration?
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)
What is the onset effect rate of oral drug administration?
Slow (15-30 min for immediate release)
Slower (hours) for enteric/sustained release
What are other factors to consider with oral drug administration?
- 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
What is an enteric drug coat?
- Protects stomach from irritation
- Protects drugs from low stomach pH
What is a drug with controlled-release prep?
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
What is the bioavailability of rectal drug administration?
Variable
Generally greater than oral
What is the onset effect rate of rectal drug administration?
Not rapid
What are other factors to consider with rectal drug administration?
- 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
What is the bioavailability of sublingual/buccal drug administration?
Generally high
What is the onset effect rate of sublingual/buccal drug administration?
Within minutes (5-10)
What are other factors to consider for sublingual/buccal drug administration?
- 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)
Compare and contrast absorption of non-ionized and ionized drugs.
Non-ionized = uncharged (readily absorbed)
Ionized = charged (cannot be absorbed)
Describe weak acids as drugs.
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
Describe weak bases as drugs
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
Describe bioavailability (F) with regards to dose adjustment
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
How is bioavailability used?
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)
