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Drew 924 > Block 1 > Flashcards

Block 1 Flashcards

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1
Q

volume capacity of the stomach

A

1 L

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2
Q

daily acid production in the stomach

A

2L of 0.01M HCl / day

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3
Q

Fasted stomach pH

A

1.5

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4
Q

Fed stomach pH

A

4.5

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5
Q

majority of drugs are…

A

weak bases

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6
Q

H-H equation

A

pH = pKa + log (A- / HA)

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7
Q

Duodenum pH

A

4.9 - 6.4

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8
Q

Jejunum pH

A

4.4 - 6.6

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9
Q

Ileum pH

A

6.5 - 7.4

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10
Q

Large intestine pH

A

6.4 - 8

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11
Q

total drug solubility equation for weak acids

A

s_t = HA * (1 + Ka/H+)

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12
Q

total drug solubility equation for weak bases

A

s+t = B* (1 + H/Ka)

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13
Q

what does the noyes witney equation describe?

A

dissolution rate

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14
Q

What is a soluble dose number

A

< 250mL

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15
Q

Small intestine transit time =

A

2 - 5 hours

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16
Q

Large intestine transit time =

A

18 hours

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17
Q

Consequences of fast transit in terms of PK

A

shorter tmax, lower Cmax

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18
Q

What is an appropriate K1:1 for maximizing AUC?

A

1500 - 4000 M-1

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19
Q

To maximize AUC, large or small K1:1?

A

small

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20
Q

K1:1 equation

A

DrugCD / Drug + CD

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21
Q

How many glucose units in alpha, beta, gamma CD?

A 
a = 6
b = 7
g = 8
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22
Q

What are concerns for CD dosage forms?

A

1) concurrent drug administration

2) cholesterol extraction (parental, RBCs & kidneys)

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23
Q

Which CD is least toxic?

A

SBE-CD

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24
Q

What are the three phases of swallowing

A

oral
pharyngeal
esophageal

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25
what is the extrusion refelx?
only liquids allowed
26
when does the first tooth appear?
6 mos
27
stomach volume in neonate?
10 - 100mL
28
when do bile salts & phospholipids mature in the neonate
1 -2 years
29
Important physiological parameters for neonates regarding drug absorption?
1) -saliva 2) -stomach capcity 3) -si length 4) -GET 5) +pH
30
impact on cholesterol concentration to diffusion
+TC = -diffusion
31
how are dosage forms classified?
``` MARS physical state point of application delivery mode tech of release ```
32
what drug properties are modified in modified release systems?
1) time course | 2) location of release
33
what polymers are used for enteric coating?
1) CAP -- cellulose acetate phthalate 2) PVAP -- Polyvinyl acetate phthalate 3) HPMCP -- Hydroxypropylmethylcellulose phthalate 4) PMACM -- polymethacrylic acid co-methacrylates
34
describe phthalate group
C1 -- COOH | C2 -- ketone + R
35
describe the ionizable group pKa of effective ec's?
pKa 3-6
36
how long is the GET?
0 - 3 hours
37
what affects GET?
1) fats & large chunks extend | small particles don't extend
38
What is the rate limiting step in absorption?
GET
39
Food's effect on GET & AUC?
food delays but does not decrease AUC
40
Rate out equation?
R = (k_e)(V_d)(C_d)
41
describe the order of elimination?
first
42
What are the properties of desirable drug candidates for ER?
APCESS 1) moderate elim rate 2) permeable (1 or 2) 3) wide window of absorption 4) small 5) safe (dose dumping) 6) chronic disease
43
FDA approval criteria for ER?
DERC approves ER at FDA 1) Dose dumper (no!) 2) ER claim met 3) reproducible 4) conventional therapeutic concentration
44
What ER systems provide 0-order release?
1) reservoir diffusion | 2) osmotic pump
45
RLS in reservoir diffusion?
diffusion thru membrane
46
Why is reservoir diffusion 0-order?
C1 high & constant = Cs | C2 low & negligible
47
RLS in matrix diffusion?
diffusion thru matrix
48
How is rate of matrix diffusion described?
square-root-time equation
49
What affects release rate in dissolution systems?
rate of polymer dissolution - - thickness - - solubility (length)
50
What are the 2 types of reservoir dissolution systems?
Spansule caps: rapid + SR blend | Contac caps: bead coating combos
51
osmotic pressure eqn
``` (pi) = CRT C = molarity, R = gas k, T = temp in K ```
52
RLS in osmotic systems?
water diffusion | size of orifice
53
mechanism of L-OROS & purpose
push from all sides -- hydrophobic, liquid drugs
54
mechanism & purpose of OROS tri-layer
separated components & viscosities -- release rate altered at different times
55
charge of polymer in ion exchange?
negative
56
how is release rate influenced in ion-exchange?
1) polymer excipient size 2) pKa & solubilities of polymer & drug 3) drug-polymer charge ratios
57
concerns in ion-exchange?
multi-valent cations (higher affinity)
58
2 stages in muco-adhesive dosage forms?
contact & consolidation
59
What happens in the contact stage of muco-adhesion?
surface properties of adhesive attracted to mucin | hydrophilicity, H-bonding, charge, size/flexibility
60
What are the types of gastro-retentive systems?
1) muco-adhesion | 2) floatation
61
requirements for mucoadhesive sytems?
only 24 hours with slow release
62
Concerns with floatation systems?
1) best with full stomach | 2) dose-dumping upon deflation
63
4 major regions of the oral cavity?
1) hard palate 2) gingival 3) SL 4) buccal
64
area of mucosa in oral cavity
100 cm2
65
buccal turnover
5-7 day
66
SL turnover
20 days
67
hard palate turnover
24 days
68
describe gingival turnover
??? -- diet related
69
3 types of oral cavity mucosa & proportions
1) 60% lining 2) 25% masticatory 3) 15% specialized
70
describe relative keratinization of mucosa types in oral cavity
lining < specialized < masticatory lining sucks meat
71
blood flow in gingival mucosa?
20 mL/min/100g
72
how does blood supply of oral cavity relate to GI?
GI has 4x more blood supply
73
pH of saliva
5.8 - 7.6
74
volume of saliva at one time
1-2 mL
75
saliva production in volume / day
1 L /day
76
what is the purpose of mucin in the oral cavity?
lubrication & hydration (not a barrier to absorption)
77
What approaches are used to enhance absorption in the oral cavity?
1) Class 1 or 2 2) Modify membrane for Pe limited (III) 3) Improve contact time
78
What modifications are used to increase absorption in the transcellular route in the oral cavity?
increase D == surfactants, organic co-solvents
79
What modifications are used to increase absorption in the paracellular route in the oral cavity?
increase pore size -- Ca-ion chelators
80
Optimal drug properties for oral cavity admin?
soluble, non-irritating
81
directions for effervescent buccal tab?
dissolve over 15-25 min, rinse after 30 mins
82
how does effervescent buccal tab improve AUC?
increased solubility (acidic local environment due to CO2 production)
83
directions for lozenge (troche)
place between teeth & cheek
84
Directions for the oravig buccal tablet
hold in place for 30 seconds with "L" toward lip | this one was 12 hour-release miconazole
85
What are criteria for bioadhesive systems?
PELT 1) permeable 2) exit (no binding with adhesive polymer) 3) lo dose -- less than 25-50 mg 4) t1/2 = 2-8h
86
3 types of bioadhesive sytems?
1) bi-directional 2) uni-directional 3) dual-rate bidirectional
87
Describe the composition of conventional bioadhesive tablet?
conventional tablet with adhesive coating
88
Describe composition of compressed bioadhesive tablet?
tablet contains adhesive polymer as eroding matrix
89
Describe oral patch composition?
reservoir + membrane + adhesive + impermeable backing < 1.6 cm2
90
directions for oral bioadhesive patch?
seat patch for 30 seconds, alternate sides with consecutive applications
91
What is the RLS in gums?
drug release (not absorption)
92
directions for nicotine gum?
chew, park, repeat for 30 mins
93
nicotine properties (pKa, -philicity, miscibility)
pKa = 6.6 (unionized in saliva) | oily but still miscible with saliva
94
Components of gums
``` Decoy FAGS D: drug stabilizer F: filler A: active ingredient G: gum base S: sweetener ```
95
What bases are used for gums, and which is preferred?
preferred for better control: Polyvinyl acetate (PVA) | also polyisobutylene
96
Describe release of nicotine?
ion exchange resin (BH+ held to negative (COO-) polymer, replaced by Na or K)
97
advantages for fast-releasing dosage forms
1) compliance -- instant gratification & local/systemic | 2) convenience
98
Types of fast-releasing dosage forms?
ODT | Oral soluble films
99
3 types of ODTs?
1) compressed 2) molded 3) freeze-dried
100
what is RLS for ODTs?
absorption ...not release
101
considerations for oral soluble films?
1) solubility -- give with saliva-stimulating agent?
102
directions for oral soluble films?
wash hands & dry immediately place on tongue SWALLOW AFTER 20 SECONDS wash hands again --avoid food, liquids ok after 5 mins
103
define suppository?
solid, bullet-shaped mass of drug with a base of either cocoa butter or hi-mw-PEG manufactured by casting
104
Advantages of rectal admin for systemic therapy?
``` Drug-in-butt stability (DIBS) D -- dysphagia/retaining I -- irritation B -- bypass S -- stability ```
105
disadvantages of rectal admin?
1) poor acceptance 2) variable bioavailability 3) difficult to titrate dose
106
Function of rectum
continence & defecation (do not interfere with these)
107
what is the distance from anus across stratified squamous epithelium to columnar epithelium?
2.5 cm
108
describe rectal arterial blood supply
superior rectal artery (branch of inferior mesenteric artery)
109
venous return for superior rectal vein?
inferior mesenteric vein --> hepatic portal
110
venous return for middle/inferior rectal veins?
internal iliac --> IVC
111
describe tonicity, volume, & pH of rectal fluids
pH = 7.2 tonicity: isotonic, can deal with slight changes volume = 3mL, can hold 30-60mL additional
112
How much of rectal fluid is mucus?
1 - 2%
113
function of mucus in the rectal cavity
lubricant
114
describe properties of the two suppository vehicles
1) cocoa butter -- melts @ 37C for slow, DR | 2) hi-mw-PEG -- dissolves in fluids
115
describe properties of rectal gels
concentrated solution of hydrophilic polymer | bioadhesive
116
how does suppository manufacture affect absorption?
1) manufactured -- solution incorporated into melted base - - drug moleculary dispersed in rectal cavity 2) compounded -- particles incorporated into melted base - - drug particles dispersed in rectal cavity

Drew 924 (16 decks)

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