Exam 2 review Flashcards
(244 cards)
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
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
3
Q
paste
A
powder and ointment
4
Q
absorption base
A
ointment and emulsifier
5
Q
w/o ointment
A
ointment, emulsifiers, little water
6
Q
w/o cream
A
-water, oitment, emulsifier in equalish amounts
7
Q
o/w cream
A
-mostly water, oilment, emulsifier
8
Q
o/w lotion
A
water, little oitment, emulsifier
9
Q
soak
A
water
10
Q
lotion(shake)
A
roughly half water and half powder
11
Q
Layers of skin
A
-epidermis
-dermis
-subcutaneous layer
12
Q
How thick is skin
A
0.5-6 mm
13
Q
components of dermis
A
-connective tissue
-blood vessel
-nerves
-hair follicles
14
Q
Sebum
A
-sticky oil that acts as a barrier against water loss
-antibacterial
-antifungal
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
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
17
Q
advantages of hydrocarbons
A
-emollient
-occlusive
-cheap
-non irritating
-insoluble in water
-not water washable
-anhydrous
18
Q
disadvantages of hydrocarbons
A
-will not absorb water
-greasy
-insoluble in water
-not water washable
-anhydrous
19
Q
examples of hydrocarbons
A
-white petrolatum
-white ointment
-vegetable shortening
-Vaseline
“heavy duty”
20
Q
advantages of anhydrous bases
A
-absorb water
-emollient
-occlusive
-insoluble in water
-not water washable
-anhydrous
21
Q
disadvantages of anhydrous bases
A
-greasy
-may be sensitizing
-compatibility problems
-insoluble in water
-not water washable
-anhydrous
22
Q
examples of anhydrous bases
A
-lanolin
-aquaphor
-aquabase
-polysorb
-hydrophilic petrolatum
23
Q
Advantages of w/o emulsion absorption
A
-absorb water: limited
-emollient
-occlusive
24
Q
disadvantages of w/o emulsion absorption
A
-greasy
-sensitizing
-compatibility
-stability or microbial problems
25
examples of w/o emulsion absoption
-hydrous lanolin
-cold cream
-Eucerin
-hydrocream
-Rose water ointment
26
advantages of o/w emulsion (water removable)
-absorb water
-non greasy
-insoluble in water
-water washable
-contains water
27
disadvantages of o/w emulsion (water removable)
-less emollient
-non occlusive
-compatibility probs
-stability issues
-may dry out
-insoluble in water
-water washable
-contains water
28
examples of water removable bases (o/w emulsion)
-Vanishing Cream
-Dermabase®
-Velvachol®
-Unibase®
-Hydrophilic Ointment
USED FOR WEEPING LESIONS/OOZING WOUNDS
29
topical local delivery forms
-ointments
-creams
30
topical systemic delivery forms
-transdermal patch
31
true or false: drug absorption is slowed by stratum corneum
true
32
drug absorption through sweat pore
-low surface are
-slowed fir hydrophillic drugs
33
drug absorption through SC
-high surface area
-hydrophobic drugs slowed
34
drug absorption through hair follicle
-low surface area
-hydrophillic drugs are slowed
35
Stratum corneum (SC)
-major barrier for drug absorption
-layer of dead skin cells about 0.1 mm thick
-tightly packed, flat, dead skin cells
-no nucleus
36
Desquamation
-process by which epithelial "brick wall" is maintained at constant thickness
-turnover takes 21-28 days
37
What equation is used to calculte drug absorption across SC
Fick's First law
38
Fick's first law
dM/dt = (D*K* A* ΔC) / h
39
How do drugs cross the SC?
-intercellular route
-has to travel in the spaces between dead cells
40
Penetration enhancers for SC
-water
-helps separate hydrocarbon chains
-loosening=more permeable
41
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.
true
42
What factors affect drug absorption?
-O/W partition coefficient of drug
-size and charge
-contact time
-drug concentration
-surface area
-penetration enhancer
43
Pysiological factors that affect topical drug absorption
-anatomic site
-skin hydration: increase
-skin metabolism: decrease
-shedding: increase
-temperature: increase
-burn: increase
-eczema: increase
44
Neonates skin
-first 4 weeks of life
-thin skin
-pH 6.2-7.5
-susceptible to infection
45
pre term infants skin
-poor skin barrier function
-susceptible to infection
46
true or false: it is impossible to overdose on topical medications
False, drug absorption is just slow
47
Elderly skin
-thin
-dry
-increased pigmentation
-photo damage
-wrinkles
-Immunocompromised
48
transdermal drug delivery profile
-infusion like
-steady increase and platues
49
advantages of transdermal drug delivery
-bypass first pass effect
-reduce side effects
-reduce inter and intra patient variability
-increased patient complience
-self admin
-easy to apply
50
Disadvantages of transdermal
-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
51
Components of a transdermal patch
-backing layer
-drug reservoir
-rate controlling membrane
-adhesive
Sometimes 2 and 3 combined
52
transdermal patch: couseling
-clean non hairy site
-site rotation
-apply firmly
-remove old patch
-excess drug in patched
-disposal methods
-avoid high heat
53
suggested sites for birth control patch
-abdomen
-butt
-shoulder
-upper arm
54
maximizing transdermal drug delivery: passive
-ALL METHODS TO MODIFY SC
-hydration
-chemical enhancers
-thermal passive
55
maximizing transdermal drug delivery: mechanical SC poration methods
-microstructure array
-SC removal
-high velocity particles/liquids
56
maximizing transdermal drug delivery: Electronically driven SC poration methods
-sonophoresis
-Ionophoresis
-Electroporation
-thermal poration
-radio frequency poration
57
Penetration enhancer for transdermal drugs
-Oleic acid
-increase spacing because of kinked cis structure
58
Iontophoresis
-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
59
routes of transdermal drug delivery
-diffusion
-iontophoresis
-electroporation
-microneedles
60
Advantages of vaginal drugs
-high conc at application site
-no first pass effect
-reduce side effects
-patient compliance
-non invasive
-easy to use
-self administration
-many OTCs
61
disadvantages of vaginal drugs
-only few drugs
-gender specific
-patient compliance
-irritation
-low residence time
-frequent application
-exposure to male sexual partner
-variability in drug absorption
62
common causes of vaginal infections
-fungi
-virus: HIV, HPV
-Protozoa
-Bacteria
63
rugae
fold, ridges and bumps in vagina
64
drug absorption in the vagina
-rich blood supply
-lymphatic vessels
-BP pushes fluid through intercellular gaps between epithelia cells(transudation)
65
Skin is vagina
-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
66
vaginal physiological considerations
-vaginal fluids: drug dissolution
-pH: drug ionization
-enzyme activity: drug stability
-transport routes: drug absorption
-mentural cycle
67
true or false: absorption can change depending on menstrual cycle
-true
-higher during diestrus
68
Cyclic changes in vaginal epithelium
-hydrophilic drugs: increased absorption during luteal phase
69
Vaginal formulation factors
-ease of administration
-drug release
-drug and excipient conc
-area of contact
-residence time
70
vaginal semi solids
-gels and creams
-inexpensive, prolonged resisdence
-messy, frequent use, hard to remove
71
Vaginal tabs
-ease of insertion
-more expensive, frequent applications, spreadability
72
vaginal suppositories
-easy to insert
-frequents, poor retention, spread ability
-can accommodate drugs in soln, emulsion, or susp.
73
controlled release forms: vaginal
-microspheres and rings
-expensive
-high tech
74
vaginal rings components
-made of silicon rubber and ethylene-vinyl acetate (EVA)
75
Benefits of vaginal ring
-30+ days
-increased pt compliance
-easy to use
-high and low dose
-requires dexterity to insert
76
vaginal dryness treatment
-estrogen replacement therapy
-oral tab and transdermal patch
77
Vaginal estrogen
-cream: daily for 2 weeks
-tab: daily for 2 weeks
-gel
-suppositories
-avoid first pass
78
vaginal dryness couseling
-bedtime
-delay intercourse
-avoid tampons
-oil based cream and suppositories weaken condoms and diaphragms
79
advantages of rectal delivery
-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
80
Disadvantages of rectal route
-poor acceptance and compliance
-erratic absorption
-1st pass effect if placed too high in rectum
-may expel
-can leak
-not for immunocompromised
-mucosal irritation
81
rectum anatomy
-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
82
Hemorrhoids
-swollen blood vessels in and around anus and rectum
-treat with hydrocortisone acetate creams and ointments
-hydrocortisone acetate suppository
83
Constipation
-difficult bowel movements
-Glycerin suppository: promotes bowel movement, local irritation via dehydration, hyperosmotic
84
5-aminosalicylic acid (5-ASA)
-for ulcerative colitis
-extent of disease impacts formulation choice
85
Oral 5-aminosalicylic acid (5-ASA)
-release in the distal/terminal ileum or colon
-extensive disease
86
Liquid Enema: 5-aminosalicylic acid (5-ASA)
-may reach the splenic flexure
-do not frequently concentrate in the rectum
87
Suppositories: 5-aminosalicylic acid (5-ASA)
reach upper rectum
-15-20 cm beyond anal verge
88
Suppositories for drug delivery
-act as a protectant for local tissue
-carry drug for local OR systemic action
-avoid cutting
89
size and shape of rectal suppositories
-cylindrical or conical
-tapered
-2 grams
-1-1.5 inches long
-infant suppositories 1 g
90
Requirements of suppository bases
-nontoxic
-nonirritating
-inert
-compatible with med
-formed by compression or molding
-dissolve in presence of mucous or melt at 37 C
91
Suppository fatty bases
-melt base
-cocoa butter and synthetic substitutes
92
Suppository dissolvable bases
-water soluble/miscible base
-glycerinated gelatin
-PEG
93
PEG
-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
94
fatty base drug release
-contains hydrophilic drugs: salt form releases faster
-melts
-spreads
95
dissolve base drug release
-hydrophobic and hydrophilic have same rate of release
-dissolves
-diffuses
96
Rectal drug absorption
-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
97
Diazepam rectal vs nasal
-BIOAVAILABILITY OF
NASAL FORMULATIONS
RELATIVE TO RECTAL
DIAZEPAM WAS IN THE
RANGE OF 70–90%,
ALBEIT WITH HIGH
VARIABILITY.
98
true or false: rectal delivery is unsafe for newborns and children
False
-many rectal drug available for children
99
Bisacodyl suppository
-10 mg
-OTC laxative
-effective in 15-60 minutes
-pediatric
100
Artesunate suppository
-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
purpose of immunization
-protect against disease after exposure
102
immunization timing
-immunize before exposure
-childhood and adult schedules published annually
103
ideal vaccine
-induce immune response in all
-no adverse effects
-cheap to make
-not temp sensitive
104
passive immunization
-transfer of immunity from one person to another
-through IG or blood
-maternal antibodies: transfer accross placenta 3rd trimester
-temporary but immediate protection
105
maternal antibody transfer
-IgG transport last 2 months of pregnancy
-protect infant from infection during first months of life
106
Immunizations given in pregnancy
-tetanus
-influenza
-pertussis
-RSV
107
active immunity
-stimulate host to produce a protective response to a pathogen
-natural infection or immunization
-relies on immunologic memory
108
IgA
in secretions
109
IgE
-involved in allergy and anaphylaxis
-parasites
110
IgG
-large amounts in serum
-major antibody of secondary response
111
IgM
predominant early antibody
112
Secondary antibody response
-no maturation of IgM response
-antibodies respond quicker after secondary exposure: higher affinity, quick, longer, higher conc, mostly IgG
113
Phase 1
-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
Phase 2 studies
-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
Phase 3 study
-Blinded, randomized, controlled clinical trial
-Many participants(1000+)
-vaccine efficacy and safety
-leads to licensure application
116
How do we develop immunity?
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
Live attenuated vaccine
-contain live organism
-limited replication in host
-immune response without causing disease
118
examples of live attenuated vaccines
-MMR
-varicella
-rotavirus
-nasal influenza
-oral polio
-typhoid
-yellow fever
119
Issues with live vaccines
-single dose to produce long lasting immunity
-timing
-contraindicated in pregnancy, immunosuppressed
120
whole, inactivated vaccines
-grown in culture
-exposed to heat/chemicals to inactivate
-sometimes purified to contain only portion needed to induce immunity
121
examples of whole, inactivated vaccines
-hepatitis
-polio
-rabies
122
issues with inactivated vaccines
-multiple doses needed to produce immunity
-booster doses
-minimal interference from circulating antibody
123
Fractional vaccines
-portion of pathogen that induces protective immunity
-reduces adverse effects associated with vaccine administration: soreness, redness, systemic reactions
124
examples of fractional vaccines
-polysaccharides vaccines
-recombinant DNA vaccines
-toxoids
-flu
-acellular pertussis
125
Polysaccharide vaccines
-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
example of polysaccharide vaccine
pneumococcal)PPSV23)
127
conjugate vaccines
-polysaccharide linked to protein making it a more potent vaccine
-conjugation overcomes the disadvantages of polysaccharide vaccines: elicit memory response, disease in infants
128
examples of conjugate vaccines
Hib
PCV15, PCV20
meningococcal
129
recombinant DNA technology
-insert antigen gene into microorganism: yeast or bacteria
-Microorganism produces antigenic protein
-Antigenic protein harvested and purified for use as vaccine
130
recombinant DNA vaccines advantages
large amount of pure antigen
131
recombinant DNA vaccines disadvantages
expensive
132
examples of recombinant DNA vaccines
-Hep B
-HPV
-Influenza(Flublok)
-Recomb. Zoster
-Novavax COVID-19
-RSV
133
Toxoids
-inactivated bacterial toxins
-immune response to toxin produced by infecting bacteria
134
examples of toxoids
-tetanus
-diphtheria
135
nucleic acid vaccines
-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
Nucleic acid vaccine characteristics
-Easy to manufacture
-cheap
-many trials: prophylaxis, therapeutic
-long lasting immunity
137
mRNA vaccines
-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
nucleic acid vaccine advantages
-cell mediated and antibody response
-pure
-no infectious risk
-easy and inexpensive to produce
139
nucleic acid vaccines candidates
Hep C
hepers simplex virus
-human immunodeficiency virus
-parasites
-cancer
-Sars-CoV-2
140
recombinant viral vector vaccines
-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
True or false: pre existing immunity may limit effectiveness of nucleic acid vaccines
False
-limit effectiveness of recombinant viral vector vaccines
142
viral vector vaccine
-ebola
-parts of virus DNA are put in carrier
-like the spike protein
143
adjuvants
-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
adjuvants mechanism
-mechanism for improvement of immune response not completely determined: make antigen less soluble, enhance immune stimulatory signals, cause inflammatory response
145
Vaccine preparation
-vaccine prepared at time of administration: draw from vial, reconstitutes, needle on prefilled syringe
-pre filling is discouraged: use manufacturer prefilled syringes
146
IM admin
-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
SubQ admin
-over tricepts: adults
-anterolateral aspect of thigh: infants
-pinch tissue
-45 degree angle
-5/5 inch, 23-25 G
148
Oral admin
-oral or mucosal pathogens
-live attenuated vaccines
-IgA production
149
Oral vaccine on a film
-attenuated virus on methylcellulose combined with sugar and surfactant
-easy to package and transport
-film dissolves in mouth
150
edible vaccines
-transgenic plants
-oral admin
-cheap
-rapid upscale of production
-minimize storage problems
151
mucosal admin
-antigen delivered to mucosal surface
-Nasal
-Oral
-Vagina or rectal
-IgA production
152
Nasal influenza vaccine
-live attenuated flu sprayed onto nasal mucosa
-immune response at site of pathogen entry
153
transdermal immunization
-needle free delivery
-patch application
154
Topical admin
-investigational delivery systems
155
Skin immune system
-barrier stratum corneum
-Langerhans celss
156
Intradermal vaccine admin
-Dermis and epidermis are rich in antigen presenting cells
* More efficient immune response with smaller amounts of
vaccine antigen
157
intradermal vaccine administration: advantages
-small volume
-often equivalent response as IM
158
intradermal vaccine administration: disadvantages
-single dose vial used as multidose
-off label use of vaccines
-may need vaccine reformulation
159
Intradermal vaccine possibilities
-mpox, rabies, flu
-yellow fever and inactivated polio
-
160
critical issue with vaccines
-exposure to temps outside recommended ranges can reduce potency
-errors cost $$$$
-loss of patient confidence
161
cold chain
The cold chain is
interconnected with refrigeration equipment that allows vaccines
to be stored at recommended temperatures to maintain their
potency
162
vaccine storage equipmant
-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
refrigerator temperatures
-between 35-46 C
-2-8 C
-Average 40 F (5 C)
164
Freezer storage temps
-stand alone freezer
--frost free/automatic defrost cycle
- -58-5 F
- -50- -15 C
165
monitoring temperature
-twice daily recording
-digital thermometers
-alarms when closed
-notification sent to email or cell phone
166
Thermometers
-calibrated
-biosafe glycol encased probe
167
temperature excursions
-do NOT discard
-separate/ from other inventory
-call manufacture or health department for guidance
168
Clinical immunization program plans
-designated and individual and back up
-written plan for odering and deliveries
-emergency back up written plan
169
Global immunization issues
-vaccine integrity
-formulation tricks: dried nucleic acids in a sugar matrix, molecular ensilication
170
RTS,S vaccine for malaria
-targets circumsporozoite
protein on sporozoite surface
3 doses 1 month aparts
171
R21/Matrix M vaccine
-Targets plasmodium sporozoite
-3 doses with 4th dose one year later
172
vaccine cost consideration
-cost is only 1 component
-program start up costs: fridge, training
-administration costs: time to administer, outreach
173
RSV vaccines
-Pfizer bivalent RSVpreF (Abrysvo)
* GSK adjuvanted RSVpreF3 (Arexvy)
* Single dose
-give in pregnancy 32-36 weeks
174
RSV vaccine adverse effects
-injection site reactions
-arthralgia, myalgia, fatigue, headache
-Guillain Barre syndrome
175
Nirsevimab for infants
-long acting monoclonal antibody with efficacy to prevent RSV
-administer just prior to RSV season
176
What is a biofilm?
-phenotypic diversity
-aggregates
-various substrate utilization
-low metabolism
0low motility
-high attachment
0antibiotic resistant
177
-Biofilms
are sophisticated
communities of matrix-encased,
surface attached bacteria
178
hydrated structures
-contain water channels to allow nutrients and oxygen diffusion
179
Biofilm-Associated Infections
-65% of all bacterial infections are associated with biofilms
-Catheter, prostetic valve, pacemaker...
180
How do biofilms increase risk of infections?
* 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
Small colony variants (SCVs)
-* Non-pigmented, non-haemolytic colonies
-COMMONLY found in biofilms
-slow growing: nutrient deficient bacteria=poor antibiotic activity
182
common organisms in biofilms
-Coagulasee-negative staphylococcus spp
-Staphylococcus aureus
-Gram negative bacilli: E coli
-CANDIDA ALBICANS
183
clinical implications of biofilms
-attachment and growth: persistant infections and metastatic spread
-involved in prostetic material and native tissue infections
-biofilms are less suseptible to antimicrobials
184
BAD BUGS NO DRUGS: No ESK(C)APE
-Enterococcus faecium
-Staph. aureus
-Klebsiella pneumoniae and Clostridiodes difficile
-Acinetobacter baumanii
-Pseudomonas aeruginosa
-Enterobacter spp and E.Coli
185
How do biofilms affect drug delivery?
-formulation
-pharmacokinetics
-polymers/coatings
-Stability
-Application
-Drug carriers
186
Surface properties that increase biofilm adhesion
-positive charge
-rough
-low topography
-stiff
187
Surface properties that decrease biofilm adhesion
-negative charge
-smooth
=soft
-high topography
188
Drug formulation for biofilms
-deliver antimicrobials to site of infection
-oral therapy
0IV therapy
-embedding/coating device with antimicrobials
-localized therapy: topical antiseptics, beads, spacers, cements
189
Central Venous Catheters and Infection Risk
-common
-Staphylococcus aureus and Staphylococcus
epidermidis
-
190
Short term CVC
-majority of all catheter related bloodstream infections
191
Peripherally inserted central catheter
-alternative to other catheters
-similiar infection risk to CVCs in ICU
192
Long term CVC
-surgically implanted
-prolonged chemotherapy
-home infusion
-hemodialysis
193
focus of preventative stratagies for catheter infections
-catheter hubs
-insertion site
194
True or false: removing catheters is a method recommended by CDC to prevent antibiotic resistance
True.
195
treatment approah of CRBSI
-prevention: infection control practices, topical antiseptics, antibiotic coated devices
-systemic and local therapy: IV therapy, antibiotic locks and washes
196
Combination therapy: killing biofilms
-improves killing of biofilms
-bacteriocidal regardless of biofilm formation
-Vanco+Rifammpin
-Vanco+Tigecycline
197
Antimicrobial properties for biofilm delivery
-penetration
-molecular size
0diffusion
-activity
-stability
-release from delivery mechanism
198
Guidelines to prevent catheter related infections
-sterile barrier
-2% chlorohexidine prep
-avoid routine replacement
-antiseptic impregnates CVCs
199
Guidelines to treat catheter related infections
-IV vanco for empiracal therapy
-avoid IV/PO linezolid for empiracal therapy
200
non-gram positive coverage
-IV 4th gen antibiotics with or without aminoglycosides
-
201
antibiotic locks
--catherter salvage
-if can't be used, IV antibiotics
202
Formulation of antibiotic lock solutions
-ethanol: antiseptic
-anticoagulant: heparin, sodium citrate, EDTA
-antibiotic: dose several times higher than organism suppressibility]
203
Catheter Associated Urinary tract infections(CAUTI)
-WTF
-Why the foley?
204
Drug Delivery for CA-UTI Prophylaxis
-systemic antimicrobial NOT reccomended
-catheter irrigation NOT routinly used
-Antimicrobial coated catheters
205
Drug Delivery for CA-UTI Treatment
Systemic antimicrobials is recommended for most
symptomatic patients
206
host and antibiotic resistance
-host contributes to antibiotic resistance in PJI
-Daptomycin (DAP) resistance may occur in the absence of DAP
exposures
207
antibiotics in bone cement
-high doses increase rate and extent of release
-lasts 20 days
-high dose=unstable bone cement
208
Preventative Measures For
Device-Related Infections
-optimize bundles
-patient screening and decolonization
-Impregnated devices: silver, chlorohexidine, minocycline coating
-antibiotic beads, cements, spacers
-novel materials
209
Nebulizer
-air jet
-long inhalation times
-cleaning times
-frequent administration
210
pressurized metered dose
-propellant
-efficacy is less than 60%
211
dry powder inhaler
-dry powder
-small device
-high effort to be efficient
212
Alveoli
site of gas exchange
213
key features of airways
-Generations
-decrease with diameter and length
-geometrically increasing number
-dramatic increase in surface area
214
epithlia in bronchi
-mucus
-cillia
-ciliated columnar cells
goblet cell: secretes mucus
215
epithlia in bronchiole
-ciliated cuboidal cells
-shorter epithelim
-less mucus
216
lung mucus
-trap pathogens, irritants
-transport out of lungs
217
mucociliary escalatory
-cilia act like wave
-propel mucus and debris
-cough or sneeze out secretions
-hypozia, cigarette smoke, degydration slow dowsn
218
Type-I pneumocytes
-Broad, thin cells (0.1-0.5 µm dia)
-Cover ~ 95% of alveolar surface
-Short airway-to-blood path length
219
Type-II pneumocytes
-cuboidal cells that secrete
pulmonary surfactant
make type 1 cells to help repair epithelium
220
cell types in a respiratory unit
-Endothelial cells line capillaries
-Type 1 pneumocytes
-Type 2 Pneumocytes
221
Lung surfactants
-secreted by type 2
-decrease surface tension and maintains structure
-lipids, lipoproteins, cholesterol, and surfactant
-surfactant deficiency results in respiratory distress syndrome
222
obstructive diseases
-interfere with air flow in or out
-affect large or small airways
-COPD, CF, pneumonia
223
Restictive diseases
-interfere witht he expansion of the lungs or the chest wall
-reduced lung volume or lung capacity
-Pulmonary fibrosis, scoliosis, obesity, neuromuscular damage
224
pneumonia
Alveoli fill with a thick fluid,
making gas exchange difficult
225
Bronchitis
Airways are influenced due to
infection (acute) or due to a
prolonged irritant (chronic).
Coughing brings up mucus.
226
Asthma
Airways are inflamed due to
irritation, and bronchioles
constrict due to muscle spasms
227
Emphysema
Alveoli burst and fuse into
enlarged air spaces. Surface area
for gas exchange is reduced.
228
Cystic fibrosis
-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
Factors affecting residence time in the airways
Mucus barrier
2. Mucociliary clearance
3. Alveolar clearance (Macrophages)
230
Factors affecting absorption & metabolism of drugs
1. Surface area and blood supply
2. Absorption barrier thickness
3. Membrane permeability
4. Metabolism and enzymatic activity
231
Mucus barrier
-dissolution: limited by viscosity
-diffusion: thickness, size of drug
232
factors affecting drug delivery: pharmaceutical
-particle diameter: 3-5 um for tracheobronchial region, <3 um for alveolar region
-particle characteristics
-aerosol stability
-aerosol velocity
233
Respirable fraction
% drug present in aerosol particles <5 μm in size
234
Aerodynamic diameter
diameter of spherical particle with unit
density that settles as same rate as particle in question
235
Mass median aerodynamic diameter (MMAD):
diameter at
which 50% of particles are larger and 50% are smaller
236
Geometric standard deviation (GSD)
ratio of diameters
corresponding to 84% and 50% on the cumulative frequency
curve
-
237
factors affecting drug delivery: physiological
-particle diameter
-characteristics
-gravity
-inertial impaction
-breathing pattern
238
Conventional nebulizers
aerosol generated at constant
rate whether patient inhaling or
exhaling
239
Breath-enhanced nebulizers
direct inhaled air within the
nebulizer à produce increased
volume of aerosol during the
inhalation phase.
240
Dosimetric nebulizers
release aerosol only during
inhalation phase.
241
improve poorly soluble drugs
-prodrug
242
improving peptides/proteins
-conjugation to polymers like polyethylene glycol to prevent protease digestion
243
excipients for inhalations
-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
