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540 drug delivery > Exam 2 review > Flashcards

Exam 2 review Flashcards

1
Q

Percutaneous absorption: trans follicular route

A

-dissolution of drug in vehicle
-diffusion to skin surface
-partitioning into sebum
-diffusion through lipids in sebaceous pore
-partitioning into viable epidermis
-diffusion through cellular mass of epidermis
-fibrous mass of upper dermis
-capillary uptake and systemic dilution

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2
Q

Percutaneous absorption: trans epidermal route

A

-dissolution of drug in vehicle
-diffusion to skin surface
-partitioning into STRATUM CORNEUM
-diffusion through PROTEIN LIPID MATRIX OF STRATUM CORNEUM
-partitioning into viable epidermis
-diffusion through cellular mass of epidermis
-fibrous mass of upper dermis
-capillary uptake and systemic dilution

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3
Q

paste

A

powder and ointment

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4
Q

absorption base

A

ointment and emulsifier

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5
Q

w/o ointment

A

ointment, emulsifiers, little water

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6
Q

w/o cream

A

-water, oitment, emulsifier in equalish amounts

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7
Q

o/w cream

A

-mostly water, oilment, emulsifier

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8
Q

o/w lotion

A

water, little oitment, emulsifier

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9
Q

soak

A

water

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10
Q

lotion(shake)

A

roughly half water and half powder

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11
Q

Layers of skin

A

-epidermis
-dermis
-subcutaneous layer

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12
Q

How thick is skin

A

0.5-6 mm

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13
Q

components of dermis

A

-connective tissue
-blood vessel
-nerves
-hair follicles

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14
Q

Sebum

A

-sticky oil that acts as a barrier against water loss
-antibacterial
-antifungal

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15
Q

Advantages of topical formulations

A

-high frug conc at application site
-low first pass effect
-low risk of systemic side effects
-easy to use
-self administration
-many OTCs
-non-invasive

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16
Q

Disadvantages of topical formulations

A

-poor adherence
-limited contact time
-messy
-small amount can be absorbed systemically
-skin irritation
-SENSITIZATION
-special packaging to measure dose

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17
Q

advantages of hydrocarbons

A

-emollient
-occlusive
-cheap
-non irritating
-insoluble in water
-not water washable
-anhydrous

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18
Q

disadvantages of hydrocarbons

A

-will not absorb water
-greasy
-insoluble in water
-not water washable
-anhydrous

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19
Q

examples of hydrocarbons

A

-white petrolatum
-white ointment
-vegetable shortening
-Vaseline

“heavy duty”

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20
Q

advantages of anhydrous bases

A

-absorb water
-emollient
-occlusive
-insoluble in water
-not water washable
-anhydrous

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21
Q

disadvantages of anhydrous bases

A

-greasy
-may be sensitizing
-compatibility problems
-insoluble in water
-not water washable
-anhydrous

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22
Q

examples of anhydrous bases

A

-lanolin
-aquaphor
-aquabase
-polysorb
-hydrophilic petrolatum

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23
Q

Advantages of w/o emulsion absorption

A

-absorb water: limited
-emollient
-occlusive

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24
Q

disadvantages of w/o emulsion absorption

A

-greasy
-sensitizing
-compatibility
-stability or microbial problems

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25
Q

examples of w/o emulsion absoption

A

-hydrous lanolin
-cold cream
-Eucerin
-hydrocream
-Rose water ointment

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26
Q

advantages of o/w emulsion (water removable)

A

-absorb water
-non greasy
-insoluble in water
-water washable
-contains water

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27
Q

disadvantages of o/w emulsion (water removable)

A

-less emollient
-non occlusive
-compatibility probs
-stability issues
-may dry out
-insoluble in water
-water washable
-contains water

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28
Q

examples of water removable bases (o/w emulsion)

A

-Vanishing Cream
-Dermabase®
-Velvachol®
-Unibase®
-Hydrophilic Ointment

USED FOR WEEPING LESIONS/OOZING WOUNDS

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29
Q

topical local delivery forms

A

-ointments
-creams

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30
Q

topical systemic delivery forms

A

-transdermal patch

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31
Q

true or false: drug absorption is slowed by stratum corneum

A

true

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32
Q

drug absorption through sweat pore

A

-low surface are
-slowed fir hydrophillic drugs

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33
Q

drug absorption through SC

A

-high surface area
-hydrophobic drugs slowed

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34
Q

drug absorption through hair follicle

A

-low surface area
-hydrophillic drugs are slowed

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35
Q

Stratum corneum (SC)

A

-major barrier for drug absorption
-layer of dead skin cells about 0.1 mm thick
-tightly packed, flat, dead skin cells
-no nucleus

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36
Q

Desquamation

A

-process by which epithelial “brick wall” is maintained at constant thickness
-turnover takes 21-28 days

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37
Q

What equation is used to calculte drug absorption across SC

A

Fick’s First law

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38
Q

Fick’s first law

A

dM/dt = (DK A* ΔC) / h

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39
Q

How do drugs cross the SC?

A

-intercellular route
-has to travel in the spaces between dead cells

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40
Q

Penetration enhancers for SC

A

-water
-helps separate hydrocarbon chains
-loosening=more permeable

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41
Q

true or false: Approximately 20% of water present in the body is accumulated in the skin, with 60–70% of this amount being accumulated in the dermis.

A

true

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42
Q

What factors affect drug absorption?

A

-O/W partition coefficient of drug
-size and charge
-contact time
-drug concentration
-surface area
-penetration enhancer

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43
Q

Pysiological factors that affect topical drug absorption

A

-anatomic site
-skin hydration: increase
-skin metabolism: decrease
-shedding: increase
-temperature: increase
-burn: increase
-eczema: increase

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44
Q

Neonates skin

A

-first 4 weeks of life
-thin skin
-pH 6.2-7.5
-susceptible to infection

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45
Q

pre term infants skin

A

-poor skin barrier function
-susceptible to infection

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46
Q

true or false: it is impossible to overdose on topical medications

A

False, drug absorption is just slow

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47
Q

Elderly skin

A

-thin
-dry
-increased pigmentation
-photo damage
-wrinkles
-Immunocompromised

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48
Q

transdermal drug delivery profile

A

-infusion like
-steady increase and platues

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49
Q

advantages of transdermal drug delivery

A

-bypass first pass effect
-reduce side effects
-reduce inter and intra patient variability
-increased patient complience
-self admin
-easy to apply

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50
Q

Disadvantages of transdermal

A

-lipophillic drugs with low MW
-potent drugs
-dhort half life
-irritation from adhesive
-Erythema: skin redness
-itching
-edema
-lag time to reach steady state
-skin damage: elderly

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51
Q

Components of a transdermal patch

A

-backing layer
-drug reservoir
-rate controlling membrane
-adhesive

Sometimes 2 and 3 combined

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52
Q

transdermal patch: couseling

A

-clean non hairy site
-site rotation
-apply firmly
-remove old patch
-excess drug in patched
-disposal methods
-avoid high heat

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53
Q

suggested sites for birth control patch

A

-abdomen
-butt
-shoulder
-upper arm

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54
Q

maximizing transdermal drug delivery: passive

A

-ALL METHODS TO MODIFY SC
-hydration
-chemical enhancers
-thermal passive

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55
Q

maximizing transdermal drug delivery: mechanical SC poration methods

A

-microstructure array
-SC removal
-high velocity particles/liquids

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56
Q

maximizing transdermal drug delivery: Electronically driven SC poration methods

A

-sonophoresis
-Ionophoresis
-Electroporation
-thermal poration
-radio frequency poration

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57
Q

Penetration enhancer for transdermal drugs

A

-Oleic acid
-increase spacing because of kinked cis structure

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58
Q

Iontophoresis

A

-drives drug across skin through hair follicles and sweat glands
-uses electric current
-charge repulsion, electro-osmosis
-local dermal anesthesia, corticosteroids, and GlucoWatch
-useful for PROTEIN/PEPTIDE DRUGS

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59
Q

routes of transdermal drug delivery

A

-diffusion
-iontophoresis
-electroporation
-microneedles

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60
Q

Advantages of vaginal drugs

A

-high conc at application site
-no first pass effect
-reduce side effects
-patient compliance
-non invasive
-easy to use
-self administration
-many OTCs

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61
Q

disadvantages of vaginal drugs

A

-only few drugs
-gender specific
-patient compliance
-irritation
-low residence time
-frequent application
-exposure to male sexual partner
-variability in drug absorption

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62
Q

common causes of vaginal infections

A

-fungi
-virus: HIV, HPV
-Protozoa
-Bacteria

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63
Q

rugae

A

fold, ridges and bumps in vagina

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64
Q

drug absorption in the vagina

A

-rich blood supply
-lymphatic vessels
-BP pushes fluid through intercellular gaps between epithelia cells(transudation)

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65
Q

Skin is vagina

A

-stratified squamous epithelium: 25 layers, regenerate 3-5 days
-thick lamina propria: collagen and elastin, nerve supply
-Fibrous layer adds strength and binds surrounding tissue

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66
Q

vaginal physiological considerations

A

-vaginal fluids: drug dissolution
-pH: drug ionization
-enzyme activity: drug stability
-transport routes: drug absorption
-mentural cycle

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67
Q

true or false: absorption can change depending on menstrual cycle

A

-true
-higher during diestrus

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68
Q

Cyclic changes in vaginal epithelium

A

-hydrophilic drugs: increased absorption during luteal phase

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69
Q

Vaginal formulation factors

A

-ease of administration
-drug release
-drug and excipient conc
-area of contact
-residence time

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70
Q

vaginal semi solids

A

-gels and creams
-inexpensive, prolonged resisdence
-messy, frequent use, hard to remove

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71
Q

Vaginal tabs

A

-ease of insertion
-more expensive, frequent applications, spreadability

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72
Q

vaginal suppositories

A

-easy to insert
-frequents, poor retention, spread ability
-can accommodate drugs in soln, emulsion, or susp.

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73
Q

controlled release forms: vaginal

A

-microspheres and rings
-expensive
-high tech

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74
Q

vaginal rings components

A

-made of silicon rubber and ethylene-vinyl acetate (EVA)

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75
Q

Benefits of vaginal ring

A

-30+ days
-increased pt compliance
-easy to use
-high and low dose
-requires dexterity to insert

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76
Q

vaginal dryness treatment

A

-estrogen replacement therapy
-oral tab and transdermal patch

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77
Q

Vaginal estrogen

A

-cream: daily for 2 weeks
-tab: daily for 2 weeks
-gel
-suppositories
-avoid first pass

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78
Q

vaginal dryness couseling

A

-bedtime
-delay intercourse
-avoid tampons
-oil based cream and suppositories weaken condoms and diaphragms

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79
Q

advantages of rectal delivery

A

-self admin
-unconscious or vomiting pts
-avoid 1st pass
-prevent and treat N/V
-useful if oral route is restricted
-localized drug delivery
-reduced systemic effects

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80
Q

Disadvantages of rectal route

A

-poor acceptance and compliance
-erratic absorption
-1st pass effect if placed too high in rectum
-may expel
-can leak
-not for immunocompromised
-mucosal irritation

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81
Q

rectum anatomy

A

-end of the large intestine that attaches the colon to the anus
-12-15 cm
-holds stool
-static environment
-no microvilla
-mucous volume= 1.2-3 ml
-pH=7
-highly vascularized

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82
Q

Hemorrhoids

A

-swollen blood vessels in and around anus and rectum
-treat with hydrocortisone acetate creams and ointments
-hydrocortisone acetate suppository

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83
Q

Constipation

A

-difficult bowel movements
-Glycerin suppository: promotes bowel movement, local irritation via dehydration, hyperosmotic

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84
Q

5-aminosalicylic acid (5-ASA)

A

-for ulcerative colitis
-extent of disease impacts formulation choice

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85
Q

Oral 5-aminosalicylic acid (5-ASA)

A

-release in the distal/terminal ileum or colon
-extensive disease

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86
Q

Liquid Enema: 5-aminosalicylic acid (5-ASA)

A

-may reach the splenic flexure
-do not frequently concentrate in the rectum

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87
Q

Suppositories: 5-aminosalicylic acid (5-ASA)

A

reach upper rectum
-15-20 cm beyond anal verge

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88
Q

Suppositories for drug delivery

A

-act as a protectant for local tissue
-carry drug for local OR systemic action
-avoid cutting

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89
Q

size and shape of rectal suppositories

A

-cylindrical or conical
-tapered
-2 grams
-1-1.5 inches long
-infant suppositories 1 g

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90
Q

Requirements of suppository bases

A

-nontoxic
-nonirritating
-inert
-compatible with med
-formed by compression or molding
-dissolve in presence of mucous or melt at 37 C

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91
Q

Suppository fatty bases

A

-melt base
-cocoa butter and synthetic substitutes

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92
Q

Suppository dissolvable bases

A

-water soluble/miscible base
-glycerinated gelatin
-PEG

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93
Q

PEG

A

-good substitute for fatty bases that melt in warm climates
-PEG supp. must be moistened to reduce hydroscopicity and local irritation
-hyperosmotic, dehydrates, and is used for constipation

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94
Q

fatty base drug release

A

-contains hydrophilic drugs: salt form releases faster
-melts
-spreads

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95
Q

dissolve base drug release

A

-hydrophobic and hydrophilic have same rate of release
-dissolves
-diffuses

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96
Q

Rectal drug absorption

A

-15 min-6 hour
-liquids absorb faster than suppositories
-prolong duration of effect
-peak blood levels vary
-bioavailability less than oral due to less surface area
-erratic absorption

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97
Q

Diazepam rectal vs nasal

A

-BIOAVAILABILITY OF
NASAL FORMULATIONS
RELATIVE TO RECTAL
DIAZEPAM WAS IN THE
RANGE OF 70–90%,
ALBEIT WITH HIGH
VARIABILITY.

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98
Q

true or false: rectal delivery is unsafe for newborns and children

A

False
-many rectal drug available for children

99
Q

Bisacodyl suppository

A

-10 mg
-OTC laxative
-effective in 15-60 minutes
-pediatric

100
Q

Artesunate suppository

A

-for children with severe malaria
-risk of premature expulsion
premature patients: caution for tissue tearing and infection
-lower psychological and social barriers in emergency

101
Q

purpose of immunization

A

-protect against disease after exposure

102
Q

immunization timing

A

-immunize before exposure
-childhood and adult schedules published annually

103
Q

ideal vaccine

A

-induce immune response in all
-no adverse effects
-cheap to make
-not temp sensitive

104
Q

passive immunization

A

-transfer of immunity from one person to another
-through IG or blood
-maternal antibodies: transfer accross placenta 3rd trimester
-temporary but immediate protection

105
Q

maternal antibody transfer

A

-IgG transport last 2 months of pregnancy
-protect infant from infection during first months of life

106
Q

Immunizations given in pregnancy

A

-tetanus
-influenza
-pertussis
-RSV

107
Q

active immunity

A

-stimulate host to produce a protective response to a pathogen
-natural infection or immunization
-relies on immunologic memory

108
Q

IgA

A

in secretions

109
Q

IgE

A

-involved in allergy and anaphylaxis
-parasites

110
Q

IgG

A

-large amounts in serum
-major antibody of secondary response

111
Q

IgM

A

predominant early antibody

112
Q

Secondary antibody response

A

-no maturation of IgM response
-antibodies respond quicker after secondary exposure: higher affinity, quick, longer, higher conc, mostly IgG

113
Q

Phase 1

A

-follows IND
-small group tests in healthy volunteers
-goal is safety, tolerability and preliminary
immunogenicity involving different doses and different
immunization schedules
-8-12 months

114
Q

Phase 2 studies

A

-larger number of volunteers(50-500)
-low risk and high risk
-goal: generate safety data, refine dose and immunization schedule, vaccine formulation, lot consistency
-18-24 months

115
Q

Phase 3 study

A

-Blinded, randomized, controlled clinical trial
-Many participants(1000+)
-vaccine efficacy and safety
-leads to licensure application

116
Q

How do we develop immunity?

A

1) virus enters body
2) virus enters cell
3)fuses with vesicles and RNA is released
4) virus assembly
5)virus release
6)Immune response

117
Q

Live attenuated vaccine

A

-contain live organism
-limited replication in host
-immune response without causing disease

118
Q

examples of live attenuated vaccines

A

-MMR
-varicella
-rotavirus
-nasal influenza
-oral polio
-typhoid
-yellow fever

119
Q

Issues with live vaccines

A

-single dose to produce long lasting immunity
-timing
-contraindicated in pregnancy, immunosuppressed

120
Q

whole, inactivated vaccines

A

-grown in culture
-exposed to heat/chemicals to inactivate
-sometimes purified to contain only portion needed to induce immunity

121
Q

examples of whole, inactivated vaccines

A

-hepatitis
-polio
-rabies

122
Q

issues with inactivated vaccines

A

-multiple doses needed to produce immunity
-booster doses
-minimal interference from circulating antibody

123
Q

Fractional vaccines

A

-portion of pathogen that induces protective immunity
-reduces adverse effects associated with vaccine administration: soreness, redness, systemic reactions

124
Q

examples of fractional vaccines

A

-polysaccharides vaccines
-recombinant DNA vaccines
-toxoids
-flu
-acellular pertussis

125
Q

Polysaccharide vaccines

A

-long chains of sugar molecules fro bacterial capsule
-stimulate B cells without T helper cells
-ineffective in children <2
-no booster
-response is IgM

126
Q

example of polysaccharide vaccine

A

pneumococcal)PPSV23)

127
Q

conjugate vaccines

A

-polysaccharide linked to protein making it a more potent vaccine
-conjugation overcomes the disadvantages of polysaccharide vaccines: elicit memory response, disease in infants

128
Q

examples of conjugate vaccines

A

Hib
PCV15, PCV20
meningococcal

129
Q

recombinant DNA technology

A

-insert antigen gene into microorganism: yeast or bacteria
-Microorganism produces antigenic protein
-Antigenic protein harvested and purified for use as vaccine

130
Q

recombinant DNA vaccines advantages

A

large amount of pure antigen

131
Q

recombinant DNA vaccines disadvantages

A

expensive

132
Q

examples of recombinant DNA vaccines

A

-Hep B
-HPV
-Influenza(Flublok)
-Recomb. Zoster
-Novavax COVID-19
-RSV

133
Q

Toxoids

A

-inactivated bacterial toxins
-immune response to toxin produced by infecting bacteria

134
Q

examples of toxoids

A

-tetanus
-diphtheria

135
Q

nucleic acid vaccines

A

-immune response to the protein encoded by plasmid DNA or mRNA
-induces cell mediated and antibody responses
-gene for pathogen taken up by host cell

136
Q

Nucleic acid vaccine characteristics

A

-Easy to manufacture
-cheap
-many trials: prophylaxis, therapeutic
-long lasting immunity

137
Q

mRNA vaccines

A

-mRNA in lipid coat enters cell
-translated into viral protein
-immune system recognizes viral protein
-mounts immune response
-easy and cheap to make
-easy to modify

138
Q

nucleic acid vaccine advantages

A

-cell mediated and antibody response
-pure
-no infectious risk
-easy and inexpensive to produce

139
Q

nucleic acid vaccines candidates

A

Hep C
hepers simplex virus
-human immunodeficiency virus
-parasites
-cancer
-Sars-CoV-2

140
Q

recombinant viral vector vaccines

A

-live vaccine engineered into carriers or vectors of antigens from other pathogens
-advantage of live vaccine
-may induce immune response to vector and target pathogen

141
Q

True or false: pre existing immunity may limit effectiveness of nucleic acid vaccines

A

False
-limit effectiveness of recombinant viral vector vaccines

142
Q

viral vector vaccine

A

-ebola
-parts of virus DNA are put in carrier
-like the spike protein

143
Q

adjuvants

A

-Substance that enhances the immune response to the
antigen with which it is mixed
* Aluminum-containing materials primary adjuvant in
U.S.
* MF59 contains squalene (oil in water adjuvant)
[influenza vaccine] and AS01 contains saponin

144
Q

adjuvants mechanism

A

-mechanism for improvement of immune response not completely determined: make antigen less soluble, enhance immune stimulatory signals, cause inflammatory response

145
Q

Vaccine preparation

A

-vaccine prepared at time of administration: draw from vial, reconstitutes, needle on prefilled syringe
-pre filling is discouraged: use manufacturer prefilled syringes

146
Q

IM admin

A

-deltoid: adults and children
-anterolateral aspect of the thigh for infants
-Needle size
* Adults 1 to 1 ½ inches; 22-25 gauge
* Infants and children 5/8 to 1 ¼ inch; 22-25 gauge

147
Q

SubQ admin

A

-over tricepts: adults
-anterolateral aspect of thigh: infants
-pinch tissue
-45 degree angle
-5/5 inch, 23-25 G

148
Q

Oral admin

A

-oral or mucosal pathogens
-live attenuated vaccines
-IgA production

149
Q

Oral vaccine on a film

A

-attenuated virus on methylcellulose combined with sugar and surfactant
-easy to package and transport
-film dissolves in mouth

150
Q

edible vaccines

A

-transgenic plants
-oral admin
-cheap
-rapid upscale of production
-minimize storage problems

151
Q

mucosal admin

A

-antigen delivered to mucosal surface
-Nasal
-Oral
-Vagina or rectal
-IgA production

152
Q

Nasal influenza vaccine

A

-live attenuated flu sprayed onto nasal mucosa
-immune response at site of pathogen entry

153
Q

transdermal immunization

A

-needle free delivery
-patch application

154
Q

Topical admin

A

-investigational delivery systems

155
Q

Skin immune system

A

-barrier stratum corneum
-Langerhans celss

156
Q

Intradermal vaccine admin

A

-Dermis and epidermis are rich in antigen presenting cells
* More efficient immune response with smaller amounts of
vaccine antigen

157
Q

intradermal vaccine administration: advantages

A

-small volume
-often equivalent response as IM

158
Q

intradermal vaccine administration: disadvantages

A

-single dose vial used as multidose
-off label use of vaccines
-may need vaccine reformulation

159
Q

Intradermal vaccine possibilities

A

-mpox, rabies, flu
-yellow fever and inactivated polio
-

160
Q

critical issue with vaccines

A

-exposure to temps outside recommended ranges can reduce potency
-errors cost $$$$
-loss of patient confidence

161
Q

cold chain

A

The cold chain is
interconnected with refrigeration equipment that allows vaccines
to be stored at recommended temperatures to maintain their
potency

162
Q

vaccine storage equipmant

A

-stand alone freezers and refrigerators
-refrigerator compartment can be used for vaccine storge
-water jugs
-keep vaccines away from freezer
-use only for biologics

163
Q

refrigerator temperatures

A

-between 35-46 C
-2-8 C
-Average 40 F (5 C)

164
Q

Freezer storage temps

A

-stand alone freezer
–frost free/automatic defrost cycle
- -58-5 F
- -50- -15 C

165
Q

monitoring temperature

A

-twice daily recording
-digital thermometers
-alarms when closed
-notification sent to email or cell phone

166
Q

Thermometers

A

-calibrated
-biosafe glycol encased probe

167
Q

temperature excursions

A

-do NOT discard
-separate/ from other inventory
-call manufacture or health department for guidance

168
Q

Clinical immunization program plans

A

-designated and individual and back up
-written plan for odering and deliveries
-emergency back up written plan

169
Q

Global immunization issues

A

-vaccine integrity
-formulation tricks: dried nucleic acids in a sugar matrix, molecular ensilication

170
Q

RTS,S vaccine for malaria

A

-targets circumsporozoite
protein on sporozoite surface
3 doses 1 month aparts

171
Q

R21/Matrix M vaccine

A

-Targets plasmodium sporozoite
-3 doses with 4th dose one year later

172
Q

vaccine cost consideration

A

-cost is only 1 component
-program start up costs: fridge, training
-administration costs: time to administer, outreach

173
Q

RSV vaccines

A

-Pfizer bivalent RSVpreF (Abrysvo)
* GSK adjuvanted RSVpreF3 (Arexvy)
* Single dose
-give in pregnancy 32-36 weeks

174
Q

RSV vaccine adverse effects

A

-injection site reactions
-arthralgia, myalgia, fatigue, headache
-Guillain Barre syndrome

175
Q

Nirsevimab for infants

A

-long acting monoclonal antibody with efficacy to prevent RSV
-administer just prior to RSV season

176
Q

What is a biofilm?

A

-phenotypic diversity
-aggregates
-various substrate utilization
-low metabolism
0low motility
-high attachment
0antibiotic resistant

177
Q

-Biofilms

A

are sophisticated
communities of matrix-encased,
surface attached bacteria

178
Q

hydrated structures

A

-contain water channels to allow nutrients and oxygen diffusion

179
Q

Biofilm-Associated Infections

A

-65% of all bacterial infections are associated with biofilms
-Catheter, prostetic valve, pacemaker…

180
Q

How do biofilms increase risk of infections?

A
  • Bacteria that attach to a surface and grow as a biofilm are protected
    from killing by innate host defenses and antimicrobial agents
    -poor antibiotic penetration
    -decreased cell replication
    -efflux and inactivation
181
Q

Small colony variants (SCVs)

A

-* Non-pigmented, non-haemolytic colonies
-COMMONLY found in biofilms
-slow growing: nutrient deficient bacteria=poor antibiotic activity

182
Q

common organisms in biofilms

A

-Coagulasee-negative staphylococcus spp
-Staphylococcus aureus
-Gram negative bacilli: E coli
-CANDIDA ALBICANS

183
Q

clinical implications of biofilms

A

-attachment and growth: persistant infections and metastatic spread
-involved in prostetic material and native tissue infections
-biofilms are less suseptible to antimicrobials

184
Q

BAD BUGS NO DRUGS: No ESK(C)APE

A

-Enterococcus faecium
-Staph. aureus
-Klebsiella pneumoniae and Clostridiodes difficile
-Acinetobacter baumanii
-Pseudomonas aeruginosa
-Enterobacter spp and E.Coli

185
Q

How do biofilms affect drug delivery?

A

-formulation
-pharmacokinetics
-polymers/coatings
-Stability
-Application
-Drug carriers

186
Q

Surface properties that increase biofilm adhesion

A

-positive charge
-rough
-low topography
-stiff

187
Q

Surface properties that decrease biofilm adhesion

A

-negative charge
-smooth
=soft
-high topography

188
Q

Drug formulation for biofilms

A

-deliver antimicrobials to site of infection
-oral therapy
0IV therapy
-embedding/coating device with antimicrobials
-localized therapy: topical antiseptics, beads, spacers, cements

189
Q

Central Venous Catheters and Infection Risk

A

-common
-Staphylococcus aureus and Staphylococcus
epidermidis
-

190
Q

Short term CVC

A

-majority of all catheter related bloodstream infections

191
Q

Peripherally inserted central catheter

A

-alternative to other catheters
-similiar infection risk to CVCs in ICU

192
Q

Long term CVC

A

-surgically implanted
-prolonged chemotherapy
-home infusion
-hemodialysis

193
Q

focus of preventative stratagies for catheter infections

A

-catheter hubs
-insertion site

194
Q

True or false: removing catheters is a method recommended by CDC to prevent antibiotic resistance

A

True.

195
Q

treatment approah of CRBSI

A

-prevention: infection control practices, topical antiseptics, antibiotic coated devices
-systemic and local therapy: IV therapy, antibiotic locks and washes

196
Q

Combination therapy: killing biofilms

A

-improves killing of biofilms
-bacteriocidal regardless of biofilm formation
-Vanco+Rifammpin
-Vanco+Tigecycline

197
Q

Antimicrobial properties for biofilm delivery

A

-penetration
-molecular size
0diffusion
-activity
-stability
-release from delivery mechanism

198
Q

Guidelines to prevent catheter related infections

A

-sterile barrier
-2% chlorohexidine prep
-avoid routine replacement
-antiseptic impregnates CVCs

199
Q

Guidelines to treat catheter related infections

A

-IV vanco for empiracal therapy
-avoid IV/PO linezolid for empiracal therapy

200
Q

non-gram positive coverage

A
201
Q

antibiotic locks

A

–catherter salvage
-if can’t be used, IV antibiotics

202
Q

Formulation of antibiotic lock solutions

A

-ethanol: antiseptic
-anticoagulant: heparin, sodium citrate, EDTA
-antibiotic: dose several times higher than organism suppressibility]

203
Q

Catheter Associated Urinary tract infections(CAUTI)

A

-WTF
-Why the foley?

204
Q

Drug Delivery for CA-UTI Prophylaxis

A

-systemic antimicrobial NOT reccomended
-catheter irrigation NOT routinly used
-Antimicrobial coated catheters

205
Q

Drug Delivery for CA-UTI Treatment

A

Systemic antimicrobials is recommended for most
symptomatic patients

206
Q

host and antibiotic resistance

A

-host contributes to antibiotic resistance in PJI
-Daptomycin (DAP) resistance may occur in the absence of DAP
exposures

207
Q

antibiotics in bone cement

A

-high doses increase rate and extent of release
-lasts 20 days
-high dose=unstable bone cement

208
Q

Preventative Measures For
Device-Related Infections

A

-optimize bundles
-patient screening and decolonization
-Impregnated devices: silver, chlorohexidine, minocycline coating
-antibiotic beads, cements, spacers
-novel materials

209
Q

Nebulizer

A

-air jet
-long inhalation times
-cleaning times
-frequent administration

210
Q

pressurized metered dose

A

-propellant
-efficacy is less than 60%

211
Q

dry powder inhaler

A

-dry powder
-small device
-high effort to be efficient

212
Q

Alveoli

A

site of gas exchange

213
Q

key features of airways

A

-Generations
-decrease with diameter and length
-geometrically increasing number
-dramatic increase in surface area

214
Q

epithlia in bronchi

A

-mucus
-cillia
-ciliated columnar cells
goblet cell: secretes mucus

215
Q

epithlia in bronchiole

A

-ciliated cuboidal cells
-shorter epithelim
-less mucus

216
Q

lung mucus

A

-trap pathogens, irritants
-transport out of lungs

217
Q

mucociliary escalatory

A

-cilia act like wave
-propel mucus and debris
-cough or sneeze out secretions
-hypozia, cigarette smoke, degydration slow dowsn

218
Q

Type-I pneumocytes

A

-Broad, thin cells (0.1-0.5 µm dia)
-Cover ~ 95% of alveolar surface
-Short airway-to-blood path length

219
Q

Type-II pneumocytes

A

-cuboidal cells that secrete
pulmonary surfactant
make type 1 cells to help repair epithelium

220
Q

cell types in a respiratory unit

A

-Endothelial cells line capillaries
-Type 1 pneumocytes
-Type 2 Pneumocytes

221
Q

Lung surfactants

A

-secreted by type 2
-decrease surface tension and maintains structure
-lipids, lipoproteins, cholesterol, and surfactant
-surfactant deficiency results in respiratory distress syndrome

222
Q

obstructive diseases

A

-interfere with air flow in or out
-affect large or small airways
-COPD, CF, pneumonia

223
Q

Restictive diseases

A

-interfere witht he expansion of the lungs or the chest wall
-reduced lung volume or lung capacity
-Pulmonary fibrosis, scoliosis, obesity, neuromuscular damage

224
Q

pneumonia

A

Alveoli fill with a thick fluid,
making gas exchange difficult

225
Q

Bronchitis

A

Airways are influenced due to
infection (acute) or due to a
prolonged irritant (chronic).
Coughing brings up mucus.

226
Q

Asthma

A

Airways are inflamed due to
irritation, and bronchioles
constrict due to muscle spasms

227
Q

Emphysema

A

Alveoli burst and fuse into
enlarged air spaces. Surface area
for gas exchange is reduced.

228
Q

Cystic fibrosis

A

-autosomal recessive mutation in CFTR gene
-regulates transport of Na and Cl across epithelium
-produces thick, sticky mucus
-trap bacteria
-repeated infections
-lung damage and premature death

229
Q

Factors affecting residence time in the airways

A

Mucus barrier
2. Mucociliary clearance
3. Alveolar clearance (Macrophages)

230
Q

Factors affecting absorption & metabolism of drugs

A
  1. Surface area and blood supply
  2. Absorption barrier thickness
  3. Membrane permeability
  4. Metabolism and enzymatic activity
231
Q

Mucus barrier

A

-dissolution: limited by viscosity
-diffusion: thickness, size of drug

232
Q

factors affecting drug delivery: pharmaceutical

A

-particle diameter: 3-5 um for tracheobronchial region, <3 um for alveolar region
-particle characteristics
-aerosol stability
-aerosol velocity

233
Q

Respirable fraction

A

% drug present in aerosol particles <5 μm in size

234
Q

Aerodynamic diameter

A

diameter of spherical particle with unit
density that settles as same rate as particle in question

235
Q

Mass median aerodynamic diameter (MMAD):

A

diameter at
which 50% of particles are larger and 50% are smaller

236
Q

Geometric standard deviation (GSD)

A

ratio of diameters
corresponding to 84% and 50% on the cumulative frequency
curve
-

237
Q

factors affecting drug delivery: physiological

A

-particle diameter
-characteristics
-gravity
-inertial impaction
-breathing pattern

238
Q

Conventional nebulizers

A

aerosol generated at constant
rate whether patient inhaling or
exhaling

239
Q

Breath-enhanced nebulizers

A

direct inhaled air within the
nebulizer à produce increased
volume of aerosol during the
inhalation phase.

240
Q

Dosimetric nebulizers

A

release aerosol only during
inhalation phase.

241
Q

improve poorly soluble drugs

A

-prodrug

242
Q

improving peptides/proteins

A

-conjugation to polymers like polyethylene glycol to prevent protease digestion

243
Q

excipients for inhalations

A

-Lactose, glucose, mannitol prevent aggregation
* Phospholipids increase dissolution
* Bile salts increase permeability (change mucus properties, open
tight junctions but can be toxic)
* Cyclodextrins – most promising to increase solubility, also non-toxic

244
Q
A

540 drug delivery (2 decks)

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