Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SOM 2 > pulmonary and intranasal administration > Flashcards

pulmonary and intranasal administration Flashcards

1
Q

what factors affect deposition?

A
  • Environmental humidity
  • chemical composition
  • solvent evaporation
  • aerosol velocity
  • respiratory tract physiology
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

why does environmental humidity affect deposition?

A

the lungs have a higher humidity so condensation of water on particle surface will occur as particles move to high humidity
water-soluble particles will also grow in size and affect where deposition occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how do hydrophobic and hydrophilic particles differ with deposition in the body?

A

hydrophobic particles will sit on the water surface

hydrophilic will solublise in the humid environment of the lungs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

why does solvent evaporation affect deposition?

A

important for pMDI devices
- the propellant in these devices mean a large size droplet will have not enough time for propellant evaporation and this impact where it deposits
it will most likely deposit in the back of the throat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

why does chemical composition affect deposition?

A

pMDI drug suspensions can have physical instability such as flocculation, bulk separation, irreversible aggregation
this increases suspended particles size’ and where they are released so could be deposited in the wrong part of the lung or the throat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

why does aerosol velocity affect deposition?

A

there is a high initial velocity of aerosol leaving the inhaler
- they have an increased momentum and will evaporate quicker
can cause them to deposit ay back of the throat as they cant change direction to go back into the lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

why does respiratory tract physiology affect deposition?

A

anatomical and physiological differences influence deposition;

  • age
  • gender
  • body size
  • ethnicity
  • lung state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what methods can improve deposition?

A
  1. Spacer devices
    - reduces droplet velocity and allows propellant evaporation
  2. breath-actuated pMDI devices
    - device first at correct points of inspiratory cycle
  3. breathing patterns
    - slow, deep inhalation followed by breath-hold
    - breath holding allows deposition by diffusion and sedimentation to occur
    - allows greater peripheral distribution of particles to occur and and increase inhalation flow rate increases deposition
    - too rapid can cause back of the throat deposition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how can you assess deposition?

A

using gamma scintigraphy

  • measures deposition in lung, stomach etc.
  • krypton gas used and radio labelled with technetium 99m
  • can use MSLI, NGI, TSI, ACI to measure particle size used and clinical performance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are dis/advantages of the pulmonary route?

A 
\+ non-invasive and easily accessible 
\+ can give low doses as had rapid uptake and OoA
\+ lower proteolytic activity than GI 
\+ avoids first pass metabolism 
- poor reproducibility 
- ability of lung macrophages to engulf particles 
- inefficiency of drug delivery devices 
- metabolic capacity of lungs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what delivery method do most devices aim for?

A

pulmonary drug delivery as it allows delivery to the central regions of the lung
new delivery devices are needed for systemic delivery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

why should you use nasal administration?

A

it has quick systemic absorption so get to the brain quicker

  • convenient
  • useful area for absorption
  • good systemic blood flow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what kind of nasal preparations can you get?

A

you can get preparation used for nasal mucosa e.g. antibiotics, antihistamines
can be administered as in solution form in drops or sprays
can get suspensions, gels, ointments, creams and dry powders can also be used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the limitations to nasal delivery?

A
  • many drugs aren’t absorbed
  • can have nasal irritation
  • some drugs might undergo nasal metabolism
  • the lack of aqueous solubility might be a problem
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are the functions of the nose?

A

it is a sensory organ so detects olfactory stimuli

  • > filters against airborne particles
  • > generates turbulent flow
  • > chemical sensor for environmental irritants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how does nasal deposition occur?

A

initial removal is by the nasal hairs
then further deposition occurs by inertial impaction; for particles >1mm
- optimum particle size is 10mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the primary site of deposition and absorption?

A
  • the respiratory epithelium

has columnar cells that are ciliated and goblet and basal cells that secrete mucus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what factors can affect absorption?

A
  • foreign materials trapped in viscous mucous
  • much moved from nasal cavity to nasopharynx via mucociliary transport
  • epithelium is an extra barrier to absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how can you improve nasal absorption?

A
  • increase nasal residence time
  • enhance nasal absorption
  • modify drug structure to change physiochemical properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are physicochemical factors and what effect do they have on nasal absorption?

A
  1. effect of size and MW
    - > amount of drug absorbed is inversely proportional to the MW
    - >important for absorption of small hydrophilic drugs
    - >absorption occurs through aqueous channels between cells
  2. effect of pH and partition coefficient
    - > most drugs can be ionised
    - > partition coefficient depends on environmental pH
    - > depends on degree of ionisation ; hydrophilic drugs use aqueous channels
  3. effect of lipophilicity
    - higher lipophilicity means faster absorption
    - drug must be ionised to be absorbed effectively
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how can you increase residence time?

A
  1. apply the drug to the anterior part of the nasal cavity ; depends on drug delivery system
    - metered- dose pumps have greatest control of direction and drops are inaccurate and too rapid
  2. reduce rate of clearance
    - use microsphere technology
    - use gel formulation to increase viscosity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how can you enhance nasal absorption?

A
  1. absorption enhancers; alters epithelial cell structure to increase rate
    - > disrupts membranes, inhibits enzymes and opens tight junctions
  2. surfactants; but can cause mucosal damage
  3. bile salts are more effective and less damage but can damage epithelial cells
  4. phosphatidylcholine can enhance absorption without causing damage; can carry the drug across membrane with them
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how could you modify drug structure for better delivery and absorption?

A
  1. alter the solubility or partition coefficient; salt formation or changing substituent groups
  2. use cyclodextrins ; increases drug bioavailability by increasing aqueous solubility
  3. use pro-drug technology
    - > add bio-cleavage group to drug
    - has better absorption properties
    - metabolised to active drugs in nasal epithelium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what route is most beneficial for systemic therapy?

A

nasal route may be advantageous for systemic delivery of drugs that are:
- subject to significant gut wall and first pass metabolism
- possess poor stability in GI tract fluids
- polar compounds exhibiting poor oral absorption
has a rapid systemic effect

25
Q

what is dis/advantages of nasal administration of protein and peptides?

A

+ easily accessible route
+ fast uptake
+ lower proteolytic activity than GI tract
+ avoids first pass
- low bioavailability
peptides are hydrophobic with a high charge density and large MW
aqueous solubility lowest at isoelectric point

26
Q

how can you increase absorption of proteins and peptides

A

co-adminster protease inhibitors

  • use absorption enhancers
  • use mucoadhesives; prolongs presence of peptides at absorption surface
27
Q

why should you use pulmonary administration?

A
  • rapid onset of action
  • smaller doses needed
  • avoids first pass metabolism
  • useful is drug is rapidly metabolised or has poor oral absorption
28
Q

what type of drugs can be administered through pulmonary delivery?

A
  1. bronchodilators
  2. corticosteroids
  3. anti-allergy
  4. mucloytics
  5. anti-infectives
  6. oxygen
  7. inhalation anaesthetics
29
Q

what are the respiratory systems three regions?

A
  • nasopharynx region; nose, mouth, pharynx, larynx
  • tracheobronchial region; trachea, bronchi, bronchioles
  • pulmonary region; respiratory bronchioles, alveoli
30
Q

how must pulmonary drug devices deliver the drug? and what are the three types of devices?

A
  • must deliver the drug as an aerosol ; dispersion of a solid or liquid in a gas

three types of devices:

  1. nebuliser
  2. pressure- metered dose inhaler (pMDI)
  3. dry powder inhalers (DPI)
31
Q

what are nebuliser?

A

simple method of producing an aerosol

  • can deliver large volumes of drug solutions/suspensions
  • allows drug admin during normal tidal breathing ; large % of dose is lost
  • can be affected by surface tension, pH, viscosity, ionic strength
32
Q

how does an air jet nebuliser work?

A
  • works using Bernoulli principle
  • > compressed air carries liquid medication through a narrow at high velocity, then hits baffle making it an aerosol that patient inhales
33
Q

how does an ultrasonic nebuliser work?

A
  • a transducer generates an ultrasonic wave which vibrates a diaphragm at high frequency that has contact with liquid medication
  • the high frequency converts liquid -> vapour mist
  • carrier gas enters and carries droplet to mouth piece
    high frequency -> smaller droplets
34
Q

what are the dis/advantages of a nebuliser?

A

+ can aerosolise most liquid medications
+ large dose delivery
- expensive and time consuming
- majority of drug doesn’t reach lung; stays in nebuliser or goes into the environment; approx 10% hits lugs

35
Q

what are dry powder inhalers?

A

they deliver a metered quantity of powder

    • they are breath ‘actuated’
  • > powder dispensed in a stream of air and patient draws it in with their own inspiratory effect
  • no coordination needed for activation and inhalation
  • need effort to liberate and disaggregate the powder particles
  • size of particles matter for deposition
36
Q

what is a single dose DPI? name some examples of these?

A

e. g Spinhaler, Rotahaler, Cyclohaler, Aerohaler
- drug plus lactose in gelatin capsules
- capsules are individually loaded into the DPI by patient
- priming device pierces the capsule and inhaled air flow disperse powder of capsule

37
Q

what is a multi dose DPI? name some examples of these?

A

e. g DIskhaler
- drug + lactose filled into SEALED aluminium foil blisters with four or eight blister per disc
- disc is loaded into device by patient
e. g Accuhaler
- 60 drug filled blisters on a coiled foil strip in the device

38
Q

what is a Reservoir DPI? name some examples of these?

A

Turbohaler

  • powder drug contained in a storage reservoir in the base of the device
  • twisting the base dispenses a metered dose into the dosing chamber
  • can have unto 200 doses
  • better lung deposition
39
Q

what are the dis/advantages of a DPI?

A

+ propellant and excipient free
+ dont need coordination for inhalation and actuation
+ high protection against humidity
- patient must provide energy source
- dose dependant on inspiratory effect
- operation varies between product and not suitable for all drug types

40
Q

what are pMDI’s?

A

this is when the drug is dissolved/suspended in one or more liquefied propellant gases

  • have excipients e.g. surfactants or co-solvents
  • it is a pressured canister with metering valve in a plastic container
  • has propellant for liquid formation to go through narrow nozzle at high velocity
41
Q

what are some pMDI propellants used?

A

usually chlorofluorocarbons (CFC)
- non toxic, non reactive and non flammable
- do have an unpleasant taste and react with ozone
now using hydrofluroralkanes (HFA)
- no ozone depletion

42
Q

what are dis/advantages of pMDIs?

A

+ energy source for drug delivery
+ dose delivered is independent of patient inhalation
+ device operations similar
+ high humidity and contamination protection
+ portable, compact, inexpensive and multiple dosing
- patient needs coordiantion
- droplets leave at high velocity so can have oropharyngeal inhalation
- replacing CFC with HFA can lead to redness/itchiness at back of throat and impact swallowing

43
Q

what is the most important physical property for pulmonary deposition? what does this depend on?

A

the aerodynamic diameter ; the diameter of a unit density sphere which settles with the same velocity as particle

  • depends on particle shape, size and density
  • you want a mono disperse system
  • GSD decides degree of polydispersity ; mono disperse GSD= 1
44
Q

depending on particle size, where is the site of deposition?

A 
> 10um = in throat
5-10um = upper airways
2-5 um= in lower airways 
0.5-2 um = in alveolar region 
< 0.5um = exhaled without deposition 
<0.1 um = in alveolar region
45
Q

where are most beta2 receptors and M3 receptors located?

A

in the pulmonary region and tracheobronchial region respectively
with lower particle size, we get deposition in the pulmonary region so better response

46
Q

what mechanisms are there for deposition?

A
  1. inertial impaction
  2. gravitational sedimentation
  3. brownian diffusion

can have interception or electrostatic attraction

47
Q

what is inertial impaction?

A

the particle is carried in aerosol stream; has its own momentum
aerosol stream meets an obstacle or bend the gas flow direction changes
- inertial force of particle resists change in direction
- particle can continue original flow or impact on surface of obstacle

48
Q

how does particle being large effect inertial impaction?

A

for large particles they will usually deposit in upper respiratory tract
- have less contribution to therapeutic effect

49
Q

what is gravitational sedimentation?

A

sedimentation of particles occur due to gravitational force action

  • rate of sedimentation is determined by Stokes’ Law ; directly proportional to particle density and diameter 2
  • happens in small bronchi, bronchioles, alveolar region
  • medium particles of 1-5 um
50
Q

what is brownian diffusion?

A

particles smaller than 0.5um are to small for impaction or sedimentation
they are bombard by surrounding molecules in RT
they move to low concentration areas e.g. airways walls
- get knocked around until they eventually stick

51
Q

when does interception occur?

A

when dimensions of particle are similar to the airway diameter
particle edge makes contact with airway surface and particle is trapped
not important for spherical particles only elongated

52
Q

when does electrostatic attraction occur?

A

this is when charged particles can be formed during generation of an aerosol

  • induces opposite charge on walls of airways
  • leads to increased deposition due to electrostatic attraction between opposite charges
53
Q

what are the barriers to absorption?

A
  • rate of absorption of hydrophobic drugs depend on partition coefficient
  • high Log P and hydrophobicity means higher absorption
  • hydrophilic drugs are poorly absorbed through pores
  • smaller MW means better absorption
  • formulation; solution drug/droplet will have rapid absorption
54
Q

what are some physiological barriers that prevent drug reaching target site?

A
  • mucus layer
  • mucocilary escalator
  • macrophage and other cells
  • enzymes
  • alveolar epithelium
55
Q

how does mucus layer act as a barrier to absorption?

A
  • covers walls of RT
  • first barrier
  • composition and thickness vary along RT
  • is mainly water with mucin, carbs, lipid and surfactant
  • dissolution of particle depends on composition of mucus layer at deposition site
56
Q

how does mucociliary escalator act as a barrier to absorption?

A
  • self cleaning mechanism
  • uses cilia and mucus
  • coordinated movement of cilia propels mucus towards pharynx to be swallowed
  • protects bodies against foreign bodies
57
Q

how does macrophages act as a barrier to absorption?

A
  • they wander throughout lung
  • they can rapidly ingest particles and molecules in solution
  • granulocytes migrate to airways ; phagocytose materials and release proteases
  • lymphocytes respond to antigenic material ; sensitise lung to future doses
58
Q

how does alveolar epithelium act as a barrier to absorption?

A
  • tightly knit barrier
    huge SA
  • transport across this is by:
    1. intracellular tight junctions; solutes, ions, fluids
    2. membrane pores; fluid and macromolecules
    3. vesicles; fluid and macromolecules
59
Q

how does enzymes act as a barrier to absorption?

A

can have Phase I oxidation enzymes; reduction and hydrolysis metabolism
or Phase II conjugation reactions
- these Phase II can add sulfur groups onto the drug making it -ve

SOM 2 (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions