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Drew 924 > Block 1 > Flashcards

Block 1 Flashcards

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
Q

what is the extrusion refelx?

A

only liquids allowed

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26
Q

when does the first tooth appear?

A

6 mos

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27
Q

stomach volume in neonate?

A

10 - 100mL

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28
Q

when do bile salts & phospholipids mature in the neonate

A

1 -2 years

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29
Q

Important physiological parameters for neonates regarding drug absorption?

A

1) -saliva
2) -stomach capcity
3) -si length
4) -GET
5) +pH

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30
Q

impact on cholesterol concentration to diffusion

A

+TC = -diffusion

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31
Q

how are dosage forms classified?

A 
MARS
physical state
point of application
delivery mode
tech of release
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32
Q

what drug properties are modified in modified release systems?

A

1) time course

2) location of release

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33
Q

what polymers are used for enteric coating?

A

1) CAP – cellulose acetate phthalate
2) PVAP – Polyvinyl acetate phthalate
3) HPMCP – Hydroxypropylmethylcellulose phthalate
4) PMACM – polymethacrylic acid co-methacrylates

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34
Q

describe phthalate group

A

C1 – COOH

C2 – ketone + R

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35
Q

describe the ionizable group pKa of effective ec’s?

A

pKa 3-6

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36
Q

how long is the GET?

A

0 - 3 hours

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37
Q

what affects GET?

A

1) fats & large chunks extend

small particles don’t extend

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38
Q

What is the rate limiting step in absorption?

A

GET

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39
Q

Food’s effect on GET & AUC?

A

food delays but does not decrease AUC

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40
Q

Rate out equation?

A

R = (k_e)(V_d)(C_d)

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41
Q

describe the order of elimination?

A

first

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42
Q

What are the properties of desirable drug candidates for ER?

A

APCESS

1) moderate elim rate
2) permeable (1 or 2)
3) wide window of absorption
4) small
5) safe (dose dumping)
6) chronic disease

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43
Q

FDA approval criteria for ER?

A

DERC approves ER at FDA

1) Dose dumper (no!)
2) ER claim met
3) reproducible
4) conventional therapeutic concentration

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44
Q

What ER systems provide 0-order release?

A

1) reservoir diffusion

2) osmotic pump

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45
Q

RLS in reservoir diffusion?

A

diffusion thru membrane

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46
Q

Why is reservoir diffusion 0-order?

A

C1 high & constant = Cs

C2 low & negligible

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47
Q

RLS in matrix diffusion?

A

diffusion thru matrix

48
Q

How is rate of matrix diffusion described?

A

square-root-time equation

49
Q

What affects release rate in dissolution systems?

A

rate of polymer dissolution

    • thickness
    • solubility (length)
50
Q

What are the 2 types of reservoir dissolution systems?

A

Spansule caps: rapid + SR blend

Contac caps: bead coating combos

51
Q

osmotic pressure eqn

A 
(pi) = CRT
C = molarity, R = gas k, T = temp in K
52
Q

RLS in osmotic systems?

A

water diffusion

size of orifice

53
Q

mechanism of L-OROS & purpose

A

push from all sides – hydrophobic, liquid drugs

54
Q

mechanism & purpose of OROS tri-layer

A

separated components & viscosities – release rate altered at different times

55
Q

charge of polymer in ion exchange?

A

negative

56
Q

how is release rate influenced in ion-exchange?

A

1) polymer excipient size
2) pKa & solubilities of polymer & drug
3) drug-polymer charge ratios

57
Q

concerns in ion-exchange?

A

multi-valent cations (higher affinity)

58
Q

2 stages in muco-adhesive dosage forms?

A

contact & consolidation

59
Q

What happens in the contact stage of muco-adhesion?

A

surface properties of adhesive attracted to mucin

hydrophilicity, H-bonding, charge, size/flexibility

60
Q

What are the types of gastro-retentive systems?

A

1) muco-adhesion

2) floatation

61
Q

requirements for mucoadhesive sytems?

A

only 24 hours with slow release

62
Q

Concerns with floatation systems?

A

1) best with full stomach

2) dose-dumping upon deflation

63
Q

4 major regions of the oral cavity?

A

1) hard palate
2) gingival
3) SL
4) buccal

64
Q

area of mucosa in oral cavity

A

100 cm2

65
Q

buccal turnover

A

5-7 day

66
Q

SL turnover

A

20 days

67
Q

hard palate turnover

A

24 days

68
Q

describe gingival turnover

A

??? – diet related

69
Q

3 types of oral cavity mucosa & proportions

A

1) 60% lining
2) 25% masticatory
3) 15% specialized

70
Q

describe relative keratinization of mucosa types in oral cavity

A

lining < specialized < masticatory

lining sucks meat

71
Q

blood flow in gingival mucosa?

A

20 mL/min/100g

72
Q

how does blood supply of oral cavity relate to GI?

A

GI has 4x more blood supply

73
Q

pH of saliva

A

5.8 - 7.6

74
Q

volume of saliva at one time

A

1-2 mL

75
Q

saliva production in volume / day

A

1 L /day

76
Q

what is the purpose of mucin in the oral cavity?

A

lubrication & hydration (not a barrier to absorption)

77
Q

What approaches are used to enhance absorption in the oral cavity?

A

1) Class 1 or 2
2) Modify membrane for Pe limited (III)
3) Improve contact time

78
Q

What modifications are used to increase absorption in the transcellular route in the oral cavity?

A

increase D == surfactants, organic co-solvents

79
Q

What modifications are used to increase absorption in the paracellular route in the oral cavity?

A

increase pore size – Ca-ion chelators

80
Q

Optimal drug properties for oral cavity admin?

A

soluble, non-irritating

81
Q

directions for effervescent buccal tab?

A

dissolve over 15-25 min, rinse after 30 mins

82
Q

how does effervescent buccal tab improve AUC?

A

increased solubility (acidic local environment due to CO2 production)

83
Q

directions for lozenge (troche)

A

place between teeth & cheek

84
Q

Directions for the oravig buccal tablet

A

hold in place for 30 seconds with “L” toward lip

this one was 12 hour-release miconazole

85
Q

What are criteria for bioadhesive systems?

A

PELT

1) permeable
2) exit (no binding with adhesive polymer)
3) lo dose – less than 25-50 mg
4) t1/2 = 2-8h

86
Q

3 types of bioadhesive sytems?

A

1) bi-directional
2) uni-directional
3) dual-rate bidirectional

87
Q

Describe the composition of conventional bioadhesive tablet?

A

conventional tablet with adhesive coating

88
Q

Describe composition of compressed bioadhesive tablet?

A

tablet contains adhesive polymer as eroding matrix

89
Q

Describe oral patch composition?

A

reservoir + membrane + adhesive + impermeable backing

< 1.6 cm2

90
Q

directions for oral bioadhesive patch?

A

seat patch for 30 seconds, alternate sides with consecutive applications

91
Q

What is the RLS in gums?

A

drug release (not absorption)

92
Q

directions for nicotine gum?

A

chew, park, repeat for 30 mins

93
Q

nicotine properties (pKa, -philicity, miscibility)

A

pKa = 6.6 (unionized in saliva)

oily but still miscible with saliva

94
Q

Components of gums

A 
Decoy FAGS
D: drug stabilizer
F: filler
A: active ingredient
G: gum base
S: sweetener
95
Q

What bases are used for gums, and which is preferred?

A

preferred for better control: Polyvinyl acetate (PVA)

also polyisobutylene

96
Q

Describe release of nicotine?

A

ion exchange resin (BH+ held to negative (COO-) polymer, replaced by Na or K)

97
Q

advantages for fast-releasing dosage forms

A

1) compliance – instant gratification & local/systemic

2) convenience

98
Q

Types of fast-releasing dosage forms?

A

ODT

Oral soluble films

99
Q

3 types of ODTs?

A

1) compressed
2) molded
3) freeze-dried

100
Q

what is RLS for ODTs?

A

absorption …not release

101
Q

considerations for oral soluble films?

A

1) solubility – give with saliva-stimulating agent?

102
Q

directions for oral soluble films?

A

wash hands & dry
immediately place on tongue
SWALLOW AFTER 20 SECONDS
wash hands again

–avoid food, liquids ok after 5 mins

103
Q

define suppository?

A

solid, bullet-shaped mass of drug with a base of either cocoa butter or hi-mw-PEG manufactured by casting

104
Q

Advantages of rectal admin for systemic therapy?

A 
Drug-in-butt stability (DIBS)
D -- dysphagia/retaining
I -- irritation
B -- bypass
S -- stability
105
Q

disadvantages of rectal admin?

A

1) poor acceptance
2) variable bioavailability
3) difficult to titrate dose

106
Q

Function of rectum

A

continence & defecation (do not interfere with these)

107
Q

what is the distance from anus across stratified squamous epithelium to columnar epithelium?

A

2.5 cm

108
Q

describe rectal arterial blood supply

A

superior rectal artery (branch of inferior mesenteric artery)

109
Q

venous return for superior rectal vein?

A

inferior mesenteric vein –> hepatic portal

110
Q

venous return for middle/inferior rectal veins?

A

internal iliac –> IVC

111
Q

describe tonicity, volume, & pH of rectal fluids

A

pH = 7.2
tonicity: isotonic, can deal with slight changes
volume = 3mL, can hold 30-60mL additional

112
Q

How much of rectal fluid is mucus?

A

1 - 2%

113
Q

function of mucus in the rectal cavity

A

lubricant

114
Q

describe properties of the two suppository vehicles

A

1) cocoa butter – melts @ 37C for slow, DR

2) hi-mw-PEG – dissolves in fluids

115
Q

describe properties of rectal gels

A

concentrated solution of hydrophilic polymer

bioadhesive

116
Q

how does suppository manufacture affect absorption?

A

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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