Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

828 Dosage > Barriers: Metabolism > Flashcards

Barriers: Metabolism Flashcards

1
Q

Sites of drug metabolism

A

-first pass: GI epithelium and liver
-systemic: in organs and blood stream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Classes of Metabolism

A

3 phases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Phase 1 of metabolism

A

of main compound
-ex: decarboxylases, oxygenase, deamidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Phase 2 of metabolism

A

through addition, conjugation
ex: glucuronisation, sulfation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Phase 3 of metabolism

A

transport-multidrug resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Metabolism goals

A

-eliminate activity of drug
-make a compound more soluble until it cannot escape excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How to achieve Metabolism

A

-change shape to block binding to receptors
-change lipophilic character to hydrophilic for increased solubility
-increase molecule size to be cleared by bile or urine
-make more recognizable by efflux pumps

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

very lipophilic

A

-normally reside in fatty tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Phase 1 CYP (oxidation, reduction) enzymes

A

2D, 2C, 3A, 1A, 2B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Phase 2 conjugation enzymes

A

-SULT
-methyl transferase
-UGT
-NAT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PHase 3: Transporter (ABC, SLC) enzymes

A

-P-gp
-OATP1B1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Metabolism of tamoxifen SLIDE 42

A

TAM –(CYP3A4)–> NDM –(CYP2D6)–>4OH-NDM aka Endoxifen, active metabolite

PRODRUG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CYPs

A

-17 CYPs in humans
-grouped into families with around 40% amino acid homology
-70 mammalian CYPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cytochrome P450 family

A

-CYP3A4 major focus of phase 1 metabolism
-though CYP3A5 might metabolize what we though CYP3A4 did (similar isoforms)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Drug-Drug interactions

A

can alter drug elimination
-xenobiotics like grapefruit and orange juice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Nonlinear PK

A

leads to nonlinear TK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Rectum epithelia

A

-simple columnar (upper half)
-stratified squamous non-keratonized region transitions to strat squamous keratinized region (lower half near anal sphincter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Absorption by surface area

A
  1. stomach
  2. jejunum
  3. cecum (way lower)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Role of stomach

A

-digest food and control its flow
-food reservoir
-food to fluid chyme for absorption
-pH protects against most bacteria, allows pepsin to function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Stomach

A

-fasting pH < 3
-fed pH 5 to 7
-30 min emptying half
-fasting state: 4 phases of emptying ending with Housekeeper wave
-fed state, no defined cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Stomach organization

A

-fundus
-body
-antrum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

fundus of stomach

A

-upper
-contains gas
-produces contractions to move food

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Body of stomach

A

-middle
-reservoir for food/fluids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Antrum of stomach

A

-lowest
-funnel shaped
-pyloric region
-controls flow to small intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Emptying cycle

A

-cycle of 4 phases
-eating stops the progression of the cycles
-starts over when stomach empties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Phase 1

A

-40-60 min no activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Phase 2

A

-mixing contractions in stomach and small intestine
-40-60 min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Phase 3

A

-powerful contractions empty stomach
-peristalsis by small intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Phase 4

A

-contractions diminish
-stomach empty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Cold carbonated drinks

A

-rapidly induce emptying

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

big-mac

A

-basically halt gastric motility

32
Q

The intestine

A

-3 hour transit time
-site of most absorption
-pH=5-6.5

33
Q

colon drug absorption

A

occurs in ascending region nearest to small instestine

34
Q

Small Intestine

A

-site of most absorption
-house most transporters
-5-6m long

35
Q

colon

A

fluid and electrolyte absorption

36
Q

small intestine regions

A
  1. duodenum
  2. jejunum
  3. Ileum
37
Q

small intestine compostition

A

serosa, muscles, submucosa, mucosa
-villi and crypts

38
Q

upper small intestine

A

mixing

39
Q

lower small intestine

A

electrolyte absorption

40
Q

Intestinal absorbing surface area

A

-increases due to folding
cylinder< folds < villi < microvilli

41
Q

Columnar epithelial cells

A

-form single continuous layer of absorptive cells covering each villus
-separated from lamina propia by basal lamina
-crypt region and villus region
-crypt cells, goblet cells, M cells

42
Q

basal lamina

A

-separates columnar epithelium from lamina propia
-comprised of glycoproteins
-penetrable by lymphocytes

43
Q

lamina propia

A

blood vessle and lymph

44
Q

crypt region

A

-3x more crypt than villi
-undifferentiated cells that proliferate
-Goblet, Paneth, Argentaffin cells

45
Q

goblet cells

A

-crypt region
-some in villus region
-mucus secreting

46
Q

paneth cells

A

-regulate microflora
-crypt region

47
Q

Argentaffin cells

A

-secrete mucos component
-crypt region

48
Q

Villus region

A

-absorptive enterocytes
-few goblet cells
-M cells overlay the peyer’s patch or lymphoidal tissue

49
Q

GI tract turnover

A

-every 2-4 days
-cells from crypt migrate up to villus tip and then sloughed off
-enterocyte life span 2-3 days

50
Q

Intestinal muscle

A

-can affect integrity and absoprtion
-contractility changes by IBS, crohn’s, etc alter transit time and absorption

51
Q

Colon

A

-slower transport
-varies in thickness from sigmoid to caecum region
-water and electolyte absorption
-promote solid stool
-ileocaecal valve
-ascending, transverse, descending

52
Q

Ileocaecal valve

A

-limits blood flow from ileum into caecum and vice versa

53
Q

Colon structure

A

-serosa
-muscularis externa
-submucosa and mucosa

54
Q

serosa

A

squamous epithelium covered with adipose tissue

55
Q

muscularis externa

A

-inner circular muscle layer and incomplete outer longitudinal layer

56
Q

Colonic Mucosa layers

A

-muscularis mucosae
-lamina propia
-epithelium

57
Q

Proximal colon

A

usually where eneteric coated formulations target by oral administration

58
Q

Distal colon-rectal administration

A

-suppositories
-some young and old patients with gag reflexes
-low residence time
-high absorption

59
Q

Gastrointestinal rates

A

SLIDE 81
-slowest in elderly people

60
Q

Relationship between stomach emptying and colonic retention

A

As stomach empties, colon absorbs

61
Q

Rectum

A

-upper and lower half
-highly folded
-high absorption
-low residence time
-route of administration

62
Q

Upper rectum

A

simple columnar

63
Q

Lower rectum

A

-stratified squamous, non-keratinized region near anal sphincter
-this epithelium allows high drug absorption

64
Q

Variabilities in drug response

A

-genetic factors (drug targets, transporters, enzymes)
-environmental factors (induction and inhibition)
-physiological factors (age, disease)

65
Q

Considerations for Oral Absorption

A

-Disintegration/ Deaggregation of particle
-Dissolution to crystalline or amorphous form
-Free API to intestinal flora, bile, nucleate, absorption

66
Q

Potential barriers of drug absorption

A

-food
-pH
-protein binding

67
Q

Biorelevant Dissolution Times

A

-effects of formulation and food on dissoulution and availability of orally administered drugs

68
Q

Mean residence time

A

average time drug stays in body

69
Q

Stomach volume

A

lower when fasting

70
Q

small intestine volume

A

higher when fasting

71
Q

large intestine volume

A

lower when fasting

72
Q

GI transit time variation

A

-residence differs
-emptying controls colonic retention
-more residence = more absorption
-pH and residence changes occur even when drug taken before meals

73
Q

GI luminal fluids

A

-jejunum
-ileum
-colon

74
Q

jejunum fluids

A

-lowest pH of the luminal fluids (7.08-7.6)
-lowest buffer capacity (3.23-4.5)
-ONLY one with bile salt content (2.88-4.6)

75
Q

Factors influencing solubility

A

-buffer capacity
-bile salts
-regional fluids
-other drugs
-endogenous substrates

76
Q

Variables along the GI tract

A

-transporters and enzymes
-fluid composition
-diet and chemical exposure
-pharmacogenetics and genomics
-interindividual variation
-drug-nutrient and drug-drug interactions

77
Q
A

828 Dosage (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions