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Biopharmaceutics > other types of delivery- lungs and parenteral and rectal/vaginal > Flashcards

other types of delivery- lungs and parenteral and rectal/vaginal Flashcards

1
Q

two types of drug inhalation applications

A

local delivery and systemic delivery

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2
Q

example of local delivery

A

bronchodilators, antibiotics

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3
Q

example of systemic delivery

A

insulin, other peptides/proteins, opioids, antimigraine drugs

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4
Q

advantages of local action

A

direct access to site of disease, rapid action, avoids GI tract and first pass hepatic metabolism, lower dose, less side effects

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5
Q

advantages of systemic action

A

avoids GI tract and first pass hepatic metabolism, non invasive, no needles, high bioavailability, rapid absorption, rapid action

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6
Q

3 types of inhalers

A

nebuliser, pressurised metered dose inhalers (pMDI), dry powder inhaler (DPI)

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7
Q

what is an aerosol

A

dispersion of solid particles or liquid droplets in a gas

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8
Q

describe the anatomy of the lungs

A

upper airways and lower airways/alveoli, air velocity and diameter decreases going down, surface area increases going down

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9
Q

function of upper airways

A

conducting zone, filter and condition inspired air

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10
Q

function of lower airways and alveoli

A

respiratory zone, gas exchange

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11
Q

2 blood circulation systems

A

bronchial and pulmonary circulation

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12
Q

describe the bronchial circulation

A

part of systemic circulation, supplies conducting zone, high pressure system, 1% cardiac output

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13
Q

describe pulmonary circulation

A

derives from pulmonary artery, part of respiratory zone, low pressure system, 100% cardiac output, capillaries in close contact with alveolar epithelium

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14
Q

name 3 types of epithelia and examples

A

pseudostratified- basal, non/ciliated, goblet cells

cuboidal- ciliated and clara cells

squamous- type 1/2 pneumocytes

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15
Q

what protects the alveolar epithelium

A

alveolar macrophages

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16
Q

describe the alveolar epithelium

A

more than 95% of total lung surface area, protected by alveolar macrophages, very thin, contains type 1 and 2 pneumocytes

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17
Q

what are pneumocytes

A

alveolar cells found on surface of alveoli in lungs

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18
Q

describe type 1 pneumocytes

A

extended and thin cytoplasm with protuberant nucleus (bulging out/on surface) , 95% of alveolar surface area, provides short diffusing pathway to bloodstream

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19
Q

describe type 2 pneumocytes

A

cuboidal cells, 5% of alveolar surface area, synthesizes lung surfactant

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20
Q

describe the lung lining fluid system

A

airway to viscoelastic mucus layer

alveoli to aqueous fluid coated by lung surfactant

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21
Q

what is the airway to viscoelastic mucus layer composed of

A

water and glycoproteins

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22
Q

describe the two phases of lung liniging fluid

A

upper- viscous gel layer
lower- less viscous, in contact with epithelium

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23
Q

what is the the function of airway to viscoelastic mucus layer

A

protects epithelium from dehydration, inhaled particles, microbiological infection

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24
Q

describe the alveoli to aqueous fluid coated by lung surfactant layer

A

isotonic, pH 6.8, contains most of plasma proteins in low conc, contains macrophages

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25
Q

what is lung surfactant synthesised by

A

type 2 pneumocytes

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26
Q

describe lung surfactant

A

one molecule thick layer, 90% phospholipids and 10% proteins

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27
Q

main function of lung surfactant

A

decrease surface tension of alveoli, enhance recognition of foreign particles by macrophages

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28
Q

what does particle deposition in lungs depend on

A

particle properties (shape, charge, size, density), respiratory tract morphology, inhalation technique

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29
Q

3 main mechanisms of particle deposition

A

inertial impaction, sedimentation, diffusion

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30
Q

what is inertial impaction and what causes it

A

particles unable to remain in the streamline when air changes direction due to inertia, particles stick no airway walls, caused by particles with high mass and velocity

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31
Q

where does inertial impaction occur

A

oropharynx and upper airways

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32
Q

where does sedimentation occur

A

lower airways and alveoli

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33
Q

what is sedimentation caused by and what does it depend on

A

particles deposit in respiratory tract due to gravity, depends on residence time in lungs and settling velocity

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34
Q

where does diffusion occur

A

alveoli

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35
Q

what is diffusion favoured by

A

long residence time

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36
Q

what is diffusion in lungs

A

particles <1um are propelled in random directions by collision with gas molecules until they hit a surface

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37
Q

how are patients recommended to inhale and why

A

slow, quiet, deep breath then hold their breath for a few seconds

increases deposition

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38
Q

why does the recommended inhalation technique increase deposition

A

decreases inertial impactions, increases residence time, more time for sedimentation/diffusion/particle growth

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39
Q

why is the efficiency of inhalers poor and explain for each type of inhaler

A

max 20% emitted dose deposit in lungs, due to high impaction in oropharynx

nebuliser- droplets too large
pMDI- particles emitted at high velocity
DPI- high inspiration flow rate needed to aerolize and disaggregate powder

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40
Q

2 ways particles are eliminated

A

mucociliary clearance in tracheo-bronchial tree

alveolar macrophages in alveoli

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41
Q

how does mucociliary clearance in tracheo-bronchial tree eliminate particles

A

particles trapped in mucus are propelled to pharynx by action of cilia and swallowed, rapid mechanism

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42
Q

how does alveolar macrophages in alveoli eliminate particles

A

particles engulfed by macrophages and transported to ciliated region, particle recognition enhanced by lung surfactant, slow mechanism

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43
Q

desrcibe the metabolic activity in lungs

A

all metabolic enzymes found in the liver are present in lungs but in lower amounts, protease in lining fluid, low metabolic activity

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44
Q

what enzyme is present in lining fluid

A

protease, activity balanced by antiproteases

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45
Q

why high and rapid absorption from alveolar region into systemic circulation

A

large SA, thin barrier, high blood flow, no mucus/mucociliary clearance

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46
Q

how does age affect lung deposition

A

lowers lung deposition in children, high impaction in oropharynx, low sedimentation and diffusion, high inspiratory flow if crying

47
Q

how does lung disease affect lung deposition

A

lowers lung deposition in asthma, copd, emphysema, cystic fibrosis

48
Q

how does smoking influence the lungs

A

cilia destroyed, impaired mucociliary clearance, decreased uptake by alveolar macrophages, leaky respiratory epithelium, higher drug absorption

49
Q

what does parenteral delivery mean

A

not via gut, usually injections, directly to bloodstream, avoids 1st pass hepatic metabolism

50
Q

routes of parenteral delivery

A

intravenous, intramuscular, subcutaneous, minor routes (intraarterial, intracardiac…)

51
Q

why is parenteral delivery good

A

.rapid- IV enters plasma immediately and drug dispersed into tissue rapidly
.local/targeted effects
.improved bioavailability- drug wont be absorbed or degraded
.can control drug level
(dose/response relationship)
.can be used for unconscious/uncooperative patients

52
Q

problems/precautions with parenteral delivery

A

air embolism- injection of air bubbles

bleeding- haemophilia (no blood clots)

cost- training and specialised formula

fever- from pyrogens

infiltration/extravasation- local tissue damage

overdose due to rapid onset

particulates- pulmonary embolism

phlebitis- vein irritation

sepsis- sterile practise

thrombosis/blood clot

53
Q

what are pyrogens

A

chemical substance that causes fever

54
Q

what is extravasation

A

leakage of drugs outside of veins and into surrounding tissue

55
Q

considerations to take when using parenteral delivery

A

dosing volume

patient comfort- isotonicity (solution will sting if hyper/hypotonic, may cause phlebitis if enters vein)

drug stability and formulation

convenience for practitioner/patient

drug release and absorption

56
Q

what is phlebitis

A

inflammation of vein near surface of skin

56
Q

why are parenterals not convenient

A

require training for delivery and techniques for safety, labour intensive and costly

56
Q

name 2 improved parenteral forms that can be used by patients themselves at home

A

prefilled syringes, infusion pumps

56
Q

formulation requirements of parenterals

A

sterility bc they bypass infection barriers, isotonic, pH 7.4, most routes only tolerate small volumes so large volumes for IV must be isotonic and isoosmotic, intravenous formulations must be particle free and water miscible

56
Q

name and describe the two forms of parenterals

A

solution dosage forms- drug immediately available for absorption, action determined by site of administration and devices used

dispersed dosage form- onset slower, drug must dissolve into aqueous phase

56
Q

formulation requirements for intravenous formulations

A

particle free and water miscible

57
Q

large volume parenterals for IV must be…

A

isotonic and isoosmotic

57
Q

types of injectables

A

injection- liquid preparations of drug substances/solution

for injection- dry solid in a vehicle

injectable emulsion- liquid preparation of a drug substance dissolved/dispersed in a emulsion medium

injectable suspension- liquid preparation of solid suspended in a suitable liquid medium

for injectable suspension- dry solid that disperses when a vehicle is added idk

57
Q

advantages and disadvantages of intravenous delivery

A

advantage- guaranteed delivery and distribution, immediate effect

disadvantage- requires clinical training, must be sterile, complications, availability of sites (loss of sites in long term treatment), cannot be removed

57
Q

biopharmaceutics of IV route

A

drug injected into vein, passes to heart, passes through pulmonary circulation, heart pumps it around tissues, drug returns to heart through liver, metabolised

58
Q

administration of small volumes in parenteral delivery

A

can be injected directly, slow injection if concentrated, often mixed with LVP

59
Q

how can large volumes be administerd parenterally

A

central venous catheter emptying into subclavian vein, continuous infusion via drip feed or metering pump

59
Q

example of continuous infusion via drip feed/metering pump

A

analgesia, chemotherapy

60
Q

name the pumps that give continuous treatment outside hospital environments or for patient controlled analgesia

A

ambulatory and implantable pumps

61
Q

formulation requirements for small volume parenterals

A

sterile, particle free, pH 3-9 as long as injection is slow/rapidly diluted, cosolvents preservatives are allowed, surfactants can be used to aid solubility

62
Q

formulation requirements for large volume parenterals

A

used for electrolyte balance/parenteral nutrition/plasma replacement, volume >100ml, usually isotonic, preservatives not permitted, cant tolerate large differences for physiological conditions

63
Q

formulation problems in intravenous administration

A

drugs that are hydrophobic enough to cross lipid membranes are poorly water soluble so it must be solubilised for intravenous use, drugs precipitate into small crystals or bind to plasma proteins, causes irritation/phlebitis/embolisms

64
Q

solution to the formulation problems in intravenous administration

A

salts, cosolvents, surfactants, pH control/ionisation, use more sophisticated formulation (eg. emulsions, liposomes, polymer drug conjugates)

65
Q

what happens to particles when injected? (biopharmaceutics of IV particles)

A

particle injected by IV, passes into heart then round pulmonary circulation, particles larger than 5um lodge in pulmonary capillaries, may cause embolisms, smaller particles pass around tissue before reaching liver and spleen, taken up by Kupffer cells in liver and metabolised

66
Q

what cells take up IV particles and where are they

A

Kupffer cells in liver

67
Q

what happens to large IV particles

A

lodge in pulmonary capillaries, causes embolisms

68
Q

what happens to smaller IV particles

A

pass around tissues before reaching liver and spleen

69
Q

what is subcutaneous delivery

A

injections into fatty/connective tussue beneath the skin

70
Q

disadvantages of subcutaneous delivery

A

slower absorption (less well perfused than IM route), slower release, not suitable for irritating formulations

71
Q

what is subcutaneous delivery used for

A

vaccines, some vitamins, most commonly insulin

72
Q

what is intramuscular delivery and some general points

A

injection into muscle tissue

muscle has good blood supply so rapid absorption, can inject solutions/suspensions/depot implants, injection doesnt need to be water miscible, small volume route

73
Q

advantages and disadvantages of intramuscular delivery

A

advantages- rapid absorption into bloodstream, can formulate sustained depots, removable implanted devices

disadvantages- local muscle damage, cant use in cardiac failure, must avoid blood vessel

74
Q

why does intramuscular delivery have rapid absorption

A

muscle has good blood supply

75
Q

why cant intramuscular delivery be used in cardiac failure

A

no muscle perfusion (no blood flow)

76
Q

what is rectal drug delivery

A

dosage forms administered via anus into the rectum/lower colon

77
Q

where is rectal drug delivery administered

A

rectum or lower colon

78
Q

why use rectal drug delivery

A

local and systemic effect

79
Q

types of rectal dosage forms

A

suppositories- solid bullet shape, insert with finger

enemas- liquid in squeeze bag with long insertion tube, 100-150ml

microenemas- liquid/paste in tube similar to superglue, 5-10ml

foams/cream/gel/ointment- rectal admin, use applicator or apply by hand

80
Q

why use rectal route

A

local conditions in rectum/nearby, oral route is unavailable and this is safer than injections, GI surgery/damaged, vomiting episodes, sleeping/unconscious patient, very old/young/mentally disturbed, drugs with extensive first pass metabolism (rectal blood supply doesnt go through liver), convenient night time therapy

81
Q

problems with rectal drug delivery

A

not popular, inconvenient, leakage, proctitis (rectal inflammation) if prolonged administration, bowel movements, unpredictable drug absorption

82
Q

local therapy uses of rectal drug delivery

A

laxative for chronic constipation, bowel evacuation to clear constipation before surgery/endoscopy/radiology, enemas, chronic bowl diseases, inflammation, haemorrhoids

82
Q

what is proctitis

A

rectal inflammation

83
Q

systemic therapy uses of rectal drug delivery

A

pain relief, nausea after chemo, arthritis, seizures, infections

84
Q

what happens to drugs administered high in the rectum

A

drained by superior rectal veins, carried direct to liver, subject to metabolism

85
Q

what happens to drugs administered low in rectum

A

delivered systemically by inferior rectal vein before passing through liver, not subject to metabolism

86
Q

process of rectal delivery

A
  1. rectal area (high and low rectum stuff)
  2. rectal absorption of drugs
  3. retention time of dose form
87
Q

rectal processing of drugs

A

absorption across mucosal epithelium, no villi, lymphatic absorption takes place, rectal veins bypass liver but lower colon veins dont, 50% dose bypass liver on 1st pass

88
Q

rectal absorption of drugs

A

can be slow and incomplete, influenced by position of dosage form, reduced by faecal matter, depend in disease state and retention time

89
Q

what reduces rectal absorption of drugs

A

faecal matter

90
Q

retention time of rectal drugs

A

disease state can alter toilet frequency, diarrhoea- shorter and constipation longer, drugs can affect muscles, irritant drugs can stimulate evacuation like in laxatives

91
Q

requirements for formulation design of rectal route drugs

A

must release drug, spread across epithelium, non irritant, neutral pH 7 secretions of mucin, rectal environment has little buffering capacity to help drugs ionise

92
Q

different type of formulation designs of rectal drugs

A

liquids- immediately available but leak

pastes/suspensions- retained better

foams- rapid knock down and spreading

tablets- bad, little water for disintegration

suppositories- melt at body temp, can give prolonged action if melt slowly, viscous and retained

93
Q

common bases for suppositories in rectal drug delivery

A

hydrophobic wax fats, witepsols, hydrophilic waxes, macrogols, gelatin, glycerogelatin

94
Q

problems with drug release in rectal delivery

A

drug cant retain in base, drugs can reduce melting point/viscosity, surfactants can irritate, different charges on gelatin, ionic binding of oppositely charged drugs, hydrophobic bases release ionised drugs but hydrophilic bases release hydrophobic drugs

95
Q

why use drug delivery to vagina

A

local condition treatment like infections/dryness/irritation/contraception/labour

rarely used

96
Q

methods of administrating into vagina

A

pessaries- wax based suppositories/compressed tablets, inserted high up with stick

gel/foam/cream- administered with syringe applicator

topical creams/ointments- external/internal around vulva

douches- liquid for washing out

sponges/rings- specialised purposes

97
Q

physiology of vaginal mucosa

A

not ciliated, epidermal thickness dependent on cycle of circulating oestrogen and progesterone in menstrual cycle, up to 24 cell layers thick in early cycle, good blood supply, epidermis supported on layer of elastic fibres and underlying muscle

98
Q

physiology of vaginal secretions

A

normal 3-4g per hour, main source is cervix, blood vessels in vaginal walls and glands at vaginal entrance, viscosity changes with hormonal cycle, vagina has its on microorganisms that maintain healthy environment

99
Q

effects of age on vaginal physiology and consequences

A

prepuberty- thin mucosal epithelium, pH ~5

post menopause/after hysterectomy- oestrogen deficient, thin epidermis (4 layers instead of 24), reduced elasticity and vascularisation, reduced secretions and glycogen

consequences- prone to dryness/irritation/infection

100
Q

formulation design of vaginal delivered drugs

A

non irritating, non drying, high patient acceptability (no vaginal leakage, no stains on underwear, discreet, comfortable), compatible with environment as changing pH/microflora can cause pathogens to grow, restoring acidic pH can fix infections, must not interfere with sexual activity

101
Q

formulation designs for vaginal drug delivery for treating dryness

A

hormone replacement therapy eg. oral oestrogen replacement

102
Q

formulation designs for vaginal drug delivery for contraception

A

sponge soaked in spermicide

103
Q

what can vaginal therapy be used for

A

infections, STDs, induction of labour and abortion, spermicide, vaginal dryness

Biopharmaceutics (11 decks)

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