Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

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
Emptying cycle
-cycle of 4 phases -eating stops the progression of the cycles -starts over when stomach empties
26
Phase 1
-40-60 min no activity
27
Phase 2
-mixing contractions in stomach and small intestine -40-60 min
28
Phase 3
-powerful contractions empty stomach -peristalsis by small intestine
29
Phase 4
-contractions diminish -stomach empty
30
Cold carbonated drinks
-rapidly induce emptying
31
big-mac
-basically halt gastric motility
32
The intestine
-3 hour transit time -site of most absorption -pH=5-6.5
33
colon drug absorption
occurs in ascending region nearest to small instestine
34
Small Intestine
-site of most absorption -house most transporters -5-6m long
35
colon
fluid and electrolyte absorption
36
small intestine regions
1. duodenum 2. jejunum 3. Ileum
37
small intestine compostition
serosa, muscles, submucosa, mucosa -villi and crypts
38
upper small intestine
mixing
39
lower small intestine
electrolyte absorption
40
Intestinal absorbing surface area
-increases due to folding cylinder< folds < villi < microvilli
41
Columnar epithelial cells
-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
basal lamina
-separates columnar epithelium from lamina propia -comprised of glycoproteins -penetrable by lymphocytes
43
lamina propia
blood vessle and lymph
44
crypt region
-3x more crypt than villi -undifferentiated cells that proliferate -Goblet, Paneth, Argentaffin cells
45
goblet cells
-crypt region -some in villus region -mucus secreting
46
paneth cells
-regulate microflora -crypt region
47
Argentaffin cells
-secrete mucos component -crypt region
48
Villus region
-absorptive enterocytes -few goblet cells -M cells overlay the peyer's patch or lymphoidal tissue
49
GI tract turnover
-every 2-4 days -cells from crypt migrate up to villus tip and then sloughed off -enterocyte life span 2-3 days
50
Intestinal muscle
-can affect integrity and absoprtion -contractility changes by IBS, crohn's, etc alter transit time and absorption
51
Colon
-slower transport -varies in thickness from sigmoid to caecum region -water and electolyte absorption -promote solid stool -ileocaecal valve -ascending, transverse, descending
52
Ileocaecal valve
-limits blood flow from ileum into caecum and vice versa
53
Colon structure
-serosa -muscularis externa -submucosa and mucosa
54
serosa
squamous epithelium covered with adipose tissue
55
muscularis externa
-inner circular muscle layer and incomplete outer longitudinal layer
56
Colonic Mucosa layers
-muscularis mucosae -lamina propia -epithelium
57
Proximal colon
usually where eneteric coated formulations target by oral administration
58
Distal colon-rectal administration
-suppositories -some young and old patients with gag reflexes -low residence time -high absorption
59
Gastrointestinal rates
SLIDE 81 -slowest in elderly people
60
Relationship between stomach emptying and colonic retention
As stomach empties, colon absorbs
61
Rectum
-upper and lower half -highly folded -high absorption -low residence time -route of administration
62
Upper rectum
simple columnar
63
Lower rectum
-stratified squamous, non-keratinized region near anal sphincter -this epithelium allows high drug absorption
64
Variabilities in drug response
-genetic factors (drug targets, transporters, enzymes) -environmental factors (induction and inhibition) -physiological factors (age, disease)
65
Considerations for Oral Absorption
-Disintegration/ Deaggregation of particle -Dissolution to crystalline or amorphous form -Free API to intestinal flora, bile, nucleate, absorption
66
Potential barriers of drug absorption
-food -pH -protein binding
67
Biorelevant Dissolution Times
-effects of formulation and food on dissoulution and availability of orally administered drugs
68
Mean residence time
average time drug stays in body
69
Stomach volume
lower when fasting
70
small intestine volume
higher when fasting
71
large intestine volume
lower when fasting
72
GI transit time variation
-residence differs -emptying controls colonic retention -more residence = more absorption -pH and residence changes occur even when drug taken before meals
73
GI luminal fluids
-jejunum -ileum -colon
74
jejunum fluids
-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
Factors influencing solubility
-buffer capacity -bile salts -regional fluids -other drugs -endogenous substrates
76
Variables along the GI tract
-transporters and enzymes -fluid composition -diet and chemical exposure -pharmacogenetics and genomics -interindividual variation -drug-nutrient and drug-drug interactions
77

828 Dosage (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions