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PY366 Type 1 Diabetes > Routes of delivery > Flashcards

Routes of delivery Flashcards

1
Q

why are drugs delivered to the lungs

A
  1. local administration- targets large and small bronchial airways
    - bronchodilators, steroids
  2. systemic- target alveolar region
    - insulin (macromolecule)
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2
Q

what occurs in the nasopharyngeal and tracheobronchial

A

air conduction/conditioning

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3
Q

what occurs in the alveolar

A

gas exchange

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4
Q

what does the pulmonary epithelium in the alveolar region consist of

A
  1. type I pneumocytes
  2. type II pneumocytes
  3. alveolar macrophages
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5
Q

what are the properties of type I pneumocytes

A
  • thin
  • 93% surface area
  • half number of type II
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6
Q

what are the properties of type II pneumocytes

A
  • cuboidal
  • store and secrete surfactant
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7
Q

what are the properties of alveolar macrophages

A
  • 3% of cells
  • phagocytic cells which scavenge and transport particulate matter to lymph nodes and mucociliary escalator
  • antigen presenting cells and recruit lymphocytes to lung
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8
Q

what are the barriers in delivering to the lung

A
  1. reaching site of absorption
  2. being absorbed
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9
Q

what factors affect reaching the site of absorption

A
  1. aerodynamic particle size of aerosol
  2. stability of formulation in aerosol generation process
  3. sufficient and reproducible deposition
  4. filters- mucociliary clearance
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10
Q

what factors affect the drug being absorbed at the site of absorption

A
  1. alveolar lining fluid
  2. macrophages
  3. absorptive epithelium
  4. basement membranes
  5. enzymes
  6. disease
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11
Q

what are the major clinical issues affecting treatment via lungs

A
  1. drug formulation and stability
  2. drug safety
  3. dosing issues- reaching site of absorption
  4. absorbed proportion of deposited drug- getting into bloodstream
  5. safety and efficacy of additives
  6. pharmacokinetics
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12
Q

what are the parameters affecting particle deposition in the lungs

A
  1. aerodynamic particle behaviour- size, density, shape
  2. breathing pattern- inhaled volume, flow rate of inhalation, breathe holding
  3. time of aerosol pulse injection into breathing cycle
  4. airway anatomy and morphometry of patient
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13
Q

what is meant by aerodynamic particle diameter

A

the diameter of a sphere with a density of 1gcm-3 that has the same aerodynamic behaviour as the particle which shall be characterised

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14
Q

describe the relationship between aerodynamic diameter and geometric diameter in a water droplet vs in large porous particles

A

water droplet, aerodynamic diameter= geometric diameter
large porous particles, aerodynamic diameter< geometric diameter

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15
Q

what are the 3 types of aerodynamic particle behaviour

A
  1. brownian diffusion- particles <0.5 microns
    - not significant for inhaled drugs
  2. gravitational sedimentation- particles >0.5 microns
  3. inertial impaction- particles >3 micron
    - prevents aerosol particles entering the lungs
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16
Q

what does residence time depend on

A
  • air flow rate
  • inhaled and exhaled volume
  • end inspiratory breathe hold of the patient
17
Q

what are the 2 types of breathing patterns

A
  1. fast inhalation- enhanced deposition by impaction in nose and trachea
    - poor penetration into deep lung
  2. slow inhalation- particles up to 10um can enter lung but variable
    - decreased variability if particles 1-3um
    - if too small then exhaled
18
Q

what is meant by aerosol bolus

A
  • pulse of aerosol sandwiched in clean air
  • time of injection into inhalation manouvre can influence site of deposition
  • early in cycle, deeper lung penetration
  • exploited in breath actuated MDIs and dry powder inhalers
  • used by AERx device
19
Q

what occurs after deposition

A
  1. mucus barrier- dissolution, diffusion
  2. mucociliary clearance- ends at terminal bronchioles
  3. alveolar clearance- uptake by alveolar macrophages
20
Q

what are the advantages of lung delivery over oral route

A
  1. less harsh environment
  2. avoids first pass intestinal and hepatic metabolism
21
Q

what are the disadvantages of pulmonary route for systemic delivery

A
  1. poor access
  2. devices difficult to use
  3. poor reproducibility
  4. mucociliary clearance
  5. alveolar macrophages
22
Q

what are the factors affecting systemic pulmonary delivery of insulin

A
  1. drug factors- peptide hormone, large molecule molecular weight
  2. biopharmaceutical factors- not absorbed after oral administration
  3. therapeutic factors- aim to mimic insulin secretion by normal pancreas
23
Q

name examples of inhaled insulin devices

A

Exubera, afrezza, AERx

24
Q

what are the requirements for inhaled insulin

A
  1. particle size range 1-3 um- to aid alveolar deposition
  2. good inhalation technique and device- release of insulin in early part of slow inhalation
  3. reproducible dose- to avoid hyper/hypoglycaemia
25
Q

what is afrezza and how is it used

A
  1. lyophilised rapid acting inhaled insulin
  2. technosphere particles
  3. taken at beginning of each meal and used in combination with a long acting injected insulin
  4. not recommended for treatment of diabetic ketoacidosis or patients who smoke
  5. no propellant or power source
  6. 1 chamber
26
Q

what are the properties of technosphere particles

A
  • FDKP
  • high internal porosity
  • high surface area
  • high adsorption of insulin
27
Q

what are the requirements of an inhaled insulin device

A
  1. portable
  2. convenient to use
  3. give reproducible delivery to lower airways where absorption is good
  4. avoid delivering insulin too fast
28
Q

describe the properties of Exubera

A
  1. lyophilised regular insulin in blister packets
  2. no propellant or power source
  3. 2 chambers
  4. release unit to be changed biweekly
  5. upper chamber and mouthpiece to be washed weekly
29
Q

What is the AERx insulin diabetes management system

A
  1. phase III trials
  2. microprocessor controlled
  3. liquid insulin delivered under pressure
  4. breath check system
  5. chaser volume of fresh air
  6. 1-10 units can be delivered
  7. 1 AERx unit= 1 IU insulin sc
  8. electronic download capability- monitors dosing, frequency of use and breathing pattern
30
Q

what is the main difference between Exubera and Afrezza

A

exubera is inhaled regular insulin, whereas afrezza is a monomer

PY366 Type 1 Diabetes (12 decks)

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