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Pharmacology > Drug Absorption > Flashcards

Flashcards in Drug Absorption Deck (73):
1

Pharmacokinetic processes involve...

the passage of drugs across membranes

2

factors influencing drug membrane passage (4)

molecular size
lipid solubility
degree of ionization
concentration gradient

3

Molecular size --> can be affected by

drug binding to plasma protein

4

Lipid solubility --> estimated by

oil:water partition coefficient

5

Degree of ionization --> affected by

tissue pH, will influence lipid solubility

6

Concentration gradient --> created at...

site of administration

7

For most drugs, cell membranes act as...

lipid bilayers

8

mechanism of membrane passage (3)

passive diffusion
carrier mediated diffusion
endocytosis

9

passive diffusion is driven by?

concentration gradient

10

passive diffusion occurs across (2)

aqueous diffusion - filtration
lipid diffusion

11

aqueous diffusion occurs when?

limited capacity, channel size varies (generally for drugs of molecular weight

12

when is lipid diffusion favored?

if the drug has high lipid:water partition coefficient, often pH dependent; unionized moiety crosses membrane down concentration gradient

13

what is the most imporant mechanism of membrane passage (with mw 500-800)?

lipid diffusion

14

carrier mediated diffusion

many cell membranes contain specialized transporters that regulate entry and exit of important physiologic molecules (sugars, amino acids, neurotransmitters), but some also transport foreign chemicals (xenobiotics) including drugs with structural similiarity

15

is endo / exo-cytosis important to drug passage?

of minor importance

16

what is ... substance engulfed by membrane, taken into cell in newly formed vesicle, then released
examples?

endocytosis
iron and vit B12

17

what is... responsible for secretion of substances from cell. Many NTs are released from vesicles into extracellular space upon neuronal activation?

exocytosis

18

The effect of any given dose of drug on the plasma concentration of that drug (Cp) will depend on the? (2)

rate (time to peak) and
extent (bio-availability)
of transfer of drug from the site of administration to the blood

19

the fraction of unchanged drug reaching the systemic circulation following administration by any route

bioavailability

20

How do we determine bioavailability?

By comparing AUC (area under the curve from Cp vs time) obtained following a single dose of drug given by any route (most commonly oral route) to the AUC obtained following a sinlge dose by the IV route

F = AUCroute/AUCiv

21

What does knowledge of drug bioavailability allow for?

Dosage adjustments when the drug is given be different routes of administration (e.g. between the oral and intravenous routes)

22

IV administration: fraction of dose reaching general circulation [F] is ...

100% as no absorption step is involved (AUC for IV route is taken as the 100% value)

23

Oral administration: F varies from ...

100% to zero depending on several factors

24

What factors influence F for oral administration of drug?

Survival of drug in GI environment (acidity, digestive enzymes)

Ability to cross GI membranes

Efficiency of drug metabolism by gut wall or in liver (termed first pass effect);

25

What characteristics of a drug determine its ability to cross GI membranes

lipid solubility
size (molecular weight)
% of drug in the unionized state

26

first pass-effect =

efficiency of drug metabolism by the gut wall or in liver - wide variation among drugs and between individual patients

27

What can be a significant factor with oral route drugs?

Patient compliance

28

Other routes of administration for systemic drug action (other than oral and IV) (4)
F?

IM/SC/Inhalation/Sublingual
F approaches 100% (75 to 100) as tissue environment is generally non-destructive to drugs

29

Rate of absorption ... generally estimated as ...

The peak Cp or time to attain peak Cp plasma levels
Marked interpatient variation exists

30

Rate of absorption from the oral route.... the drug formulation can be a factor in and the rate can be increased for ______ or ______
or decreased for ____________ or ____________

Increased rate (time to peak is shortened)
liquid preparations
rapidly disintegrating tablets
Decreased rate (time to peak is slowed and Cp max is blunted)
enteric coated products
sustained release preparations

31

Rate of absorption from parenteral routes: generally determined by....

the specific route rather than the individual drug characteristics

32

From fastest to slowest rate, order of parenteral routes

intravenous = inhalation > intramuscular > subcutaneous > oral

33

Determining equivalency of Drug Products (given vial oral route) --> FDA requires that manufacturers of generic drugs demonstrate their formulation is bioequivalent to brand name formulation. A generic drug formulation is said to be bioequivalent to a brand name drug formulation if... (2)

rate (estimated by max of peak drug concentration Cmax) and
extend (bioavailability) that the active ingredient drug is absorbed and become available at the site of action (drug entering systemic ciruclation) is similar (Within set limits) to the brand name product

34

Drugs are considered bioequivalent if ....

the 90% confidence interval of the mean AUC and the mean Cmax of the generic product (T test) is within 80-125% of the brand product

35

General factors affecting drug absorption (from any site of administration): 5

solubility in biological fluids

rate of dissolution of solid for oral dosage formula or suspended particles for parenteral formulation (can result in differences due to manufacturing considerations [brand vs generic])

concentration of drug at site of administration (creation of concentration gradient)

circulation at site of absorption (can be altered by disease state or exercise)

area of absorbing surface (e.g. stomach vs intestine vs. lungs)

36

In what way does drug solubility in biological fluids influence absorption?

biological fluids are aqueous (not lipid), the the drug formulation must have some hydrophillicity to dissolve in biological fluids, yet the drug molecule itself must also be lipophilic to cross membranes and distribute to its site of action

37

What are the most imporant consideration when considering the route of drug administration?

bioavailability
relative rates of onset

38

Routes for systemic effects (8)

Oral
Rectal
Sublingual (buccal)
intravenous
intramuscular
subcutaneous
inhalation
transdermal

39

Routes for local effects

inhalation
topical

40

What is the most common route for systemic effects?

oral

41

oral route
onset? bioavailability?

slow onset
bioavailability can vary widely (0-100%)

42

Where are oral drugs mostly absorbed?

GI tracts via passive diffusion - thereby favoring absorption when the drug is in the nonionized (more lipophilic) form

43

When would you predict that weak acid drugs would be absorbed better?

in the intestine (based on the pH partition effect)
this is because the pH of the stomach is much lower (more protons) than the upper intestine

44

When would you predicts that weak bases would be absorbed better?

in the upper intestine (based on the pH parition effect) because the pH of the upper intestine is higher (fewer protons)

45

Where will the rate of absorption of a drug be greater... the small intestine or the stomach... what role does ionization play?

Well... because the extremely large surface area of the intestine, relative to the stomach, the rate of absorption of a drug from the intestine will be greater than that from the stomach, even for drugs predominately ionized in the intestine and largely unionized in the stomach

46

In what way does gastric emptying time effect drug absorption?

generally, increased GI motility will increase speed of emptying and increase rapidity of absorption by allowing drug to reach the increased absorptive area of small intestine faster

47

How does food influence drug absorption?

delays by delaying gastric emptying

48

Purpose of enteric coating

drugs that cause GI irritation or drugs destroyed by gastric secretions can be administered with enteric coating the prevents dissolution until the more basic intestine is reached

49

controlled release preparations - the rate of drug absorption is slowed by slowing rate of product dissolution allowing a slower, sustained, and uniform absorption of drug lasting 8 hours longer
ADVANTAGES?
DISADVANTAGES?

Advantages - decreased frequency of administration (increasing compliance), maintenance of therapeutic effective overnight, and elimination of peaks (decreased incidence/intensity of undesired effects) and nontherapeutic troughs in plasma levels

Drawback - greater interpatient variabilty in systemic levels obtained and dosage form filure resulting in "dose dumping" and drug toxicity

50

Rectal administration
onset?
bioavailability

onset not rapid
bioavailability - variable - generally greater than oral route

51

When is rectal useful?

when oral route precluded by vomiting, unconsciousness, post-GI surgery, presence of GI irritation, or uncoorperative patient (baby)

52

Rectal and liver?

Approximately 50% of dose will bypass the liver, thus first pass metabolism is less than for oral route -

53

Rectal absorption

absorption is irregular and incomplete, solution absorbed more reliably than suppositories in children

54

Sublingual
onset?
bioavailability

onset - within minutes
bioavailability - generally high

55

sublingual absorption

after absorption from the oral mucosa, venous drainage from mouth is to the superior vena cava protecting drug from rapid hepatic first pass metabolism plus faster onset of action

56

sublingual is useful when?

for drugs that are lipid soluble and relatively potent (

57

Intravenous
onset?
bioavailability

most rapid onset of action (

58

what is the most direct route of drug aministration?

IV
because factors relevant to absorption (membrane passage) are circumvented
Accuracy and immediacy of drug delivery exceeds all other routes

59

What is the most hazardous route of drug administration?

IV

60

Intramuscular
Bioavailability?
Rate?

Generally approaches bioavail of IV route (100%)
aqueous solutions are absorbed rapidly with rapid onset (5-10min)

61

What influence IM onset?

onset and extent of absorption can be affected by blood flow at site of injection. Degree of muscle activity can be a factor (via effect on blood flow to area)

62

Depot forms of IM?

in oil or suspended in other vehicles
exhibit slower, more sustained absorption (drug molecules must be released from vehicle or dissolve prior to absorption)

63

Subcutaneous
Bioavailability?
Rate?

Generally approaches bioavail of IV (100%)
route often utilized to provide slower, constant rate of absorption

64

Subcutaneous and rate of absorption alteration?

Period of drug absorption can be altered intentionally as with insulin preparations (varying particle size, protein complexation, and pH)

65

Inhalation (Gas/volatile liquid)
Rate and Bioavail?

Rate of onset (

66

inhalation has what type of effect?

systemic
rapid onset

67

What is reponsible for rapid rate in inhalants?

large surface area and high blood flow in pulmonary tissue

68

Transdermal
treatment of what kind of conditions
what is avoided?

systemic conditions

first pass metabolism is avoided

69

Transdermal
pros
cons

pros - prolonged drug levels can be achieved
cons - potential for unexpected drug accumulation and toxicity
cons - drug must be potent (doses

70

Local effect
Inhalation (aerosol/microparticles)

application of aerosolized particles at site of action in lungs increases local topical effects and reduces systemic effect (dependent on particle size) asthma

71

inhalation (Aerosol) size dependence

effects dependent on particle size
0.5 microM exhaled (no effect)
1-5 microM deposited into small airways (therpeutic)
10 microM deposited into oropharynx side effects

72

topical

localized application via skin or mucous membrane for treating local conditions (e.g. inflammation / infection)

73

topical - systemic absorption?

generally minial systemic absorption but can be significant under some conditions, e.g., application over larger area, to denuded area, use of occlusive dressing or with highly lipid soluble drugs. Greater potential for systemic availabilty in children due to greater ratio of body SA to weight