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Biopharmaceutics > biological aspects of drug delivery > Flashcards

biological aspects of drug delivery Flashcards

1
Q

what is the main pathway for transport around the body

A

circulatory system

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2
Q

what is extravasation

A

leakage of blood/lymph/any fluid from blood vessel and into surrounding tissue

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3
Q

functions of lymphatic system

A

-drain excess interstitial fluid from tissue spaces
-transport dietary lipids and vitamins absorbed by GI tract
-carry out immune responses against microbes and abnormal cells

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4
Q

why are lymphatic capillaries leaky

A

so interstitial fluid can move in easily, no tight junctions, gaps between cells and overlapping endothelial cells

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5
Q

how is interstitial fluid formed

A

components of blood plasma filter through capillary walls to form interstitial fluid

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6
Q

How does lymph collect in lymphatic capillaries

A

flows up ducts past valves, filtered through lymph nodes, returned to circulation by larger lymphatic vessels/ducts

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7
Q

describe the anatomy of epithelium

A

tissue consisting of cells arranged in sheets, cells closely held together by cell junctions to limit intracellular space between membranes, covers body surface and lines hollow organs

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8
Q

epithelial tissue function

A

selective barrier- limit/aid substance transfer
secretory surface- release products from cells
protective- prevent physical/chemical injury

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9
Q

describe the apical surface in the epithelium

A

free surface, cilia/microvilli can be present

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10
Q

describe the lateral surface in the epithelium

A

free adjacent cells, cell junctions may be present

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11
Q

describe the basal surface in the epithelium

A

cells adhere to ECM, cell junctions may be present

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12
Q

name the 5 main types of cell junctions

A

tight junctions, gap junctions, adherens junctions, desmosomes, hemidesmosomes

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13
Q

describe each cell junction

A
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14
Q

how can cell junctions effect drug delivery

A

can restrict passage of materials between cells
limit materials from lumen passing unrestricted into underlying tissue
block materials from underlying tissue escaping into environment
prevent migration and exchange of membrane proteins
permeable to water

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15
Q

describe the structure of the basement membrane

A

thin extracellular layer below epithelium, 20-25nm thick, meshwork of fibrils

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16
Q

function of basement membrane

A

restricts passage of particles/materials through epithelial, provide support and point of attachment for overlying epithelium tissue

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17
Q

what is basal lamina and where is it secreted

A

secreted by epithelial cells, contains protein, glycoproteins, proteoglycans

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18
Q

what is reticular lamina

A

contains proteins secreted by underlying connective tissue

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19
Q

2 main types of epithelial tissue

A

covering/lining, glandular

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20
Q

where can covering and lining epithelium be found

A

outer covering of skin, internal organs, blood vessel/ducts lining, interiror of respiratory/digestive/reproductive/urinary systems

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21
Q

ways to classify covering and lining epithelium

A

arrangement of cells in layers, cell shape

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22
Q

describe how covering and lining epithelium can be classified according to layers

A

simple- single layer, roles in diffusion/osmosis/filtration/secretion/absorption

pseudostratified- appearance of layers due to uneven distribution of cells, not all cells reach apical surface

stratified- 2 or more cell layers, protects underlying tissue where tearing is common

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23
Q

describe how covering and lining epithelium can be classified according to cell shape

A

squamous cells- flat/thin ‘tiles’, allow rapid passage of substances

cuboidal- cubes/hexagons, may have microvilli, function in absorption/secretion

columnar- tall/thin, protect underlying tissue, apical surface may have cilia/microvilli, specialised for absoroption/secretion

24
Q

what is the endothelium lining of blood vessels composed of

A

simple squamous epithelium

25
Q

name 3 types of capillaries and where each type can be found

A

continuous- endothelial cells form continuous tube with cell junctions, continuous underlying basement membrane, contains many intracellular vesicles
-brains, lungs, muscle

fenestrated- plasma membranes of endothelial cells contains pores
-kidney, villi in small intestine, endocrine gland

sinusoid/discontinuous- large fenestrations present in endothelial cells, large intracellular clefts, incomplete/absent basement membrane
-liver, spleen, anterior pituitary

26
Q

before entering the circulation, name the layers that a drug has to cross

A

epithelia- layer of cells for protection
basal lamina- network of proteins produced by epithelia as a barrier
endothelia- specialised epithelia cells lining blood vessels

27
Q

where are most drugs metabolised

A

liver

28
Q

what is bioavailability

A

amount of an administered dose of drug that reaches systemic circulation intact and rate it occurs

29
Q

what is bioavailable dose

A

fraction of administered dose of drug that reaches systemic circulation unchanged

30
Q

barriers a drug has to pass before entering blood/lymphatic capillaries

A

epithelium, basal lamina, endothelium

31
Q

what is paracellular route

A

between cells, through cell junctions, small contribution to drug absorption

passive, requires conc gradient

32
Q

what is transcellular route

A

across/through cell membrane, mostly diffusion, major contribution to drug absorption

33
Q

how does the small intestine epithelium create a large surface area for absorption

A

folds in villi/microvilli

34
Q

what is the rate limiting step in paracellular absorption

A

transport across tight junctions, number of tight junctions decrease down GI tract

35
Q

what can tight junctions be modulated by

A

permeation enhancers, increases cell membrane permeability and drug bioavailability

36
Q

structure of transcellular absorption

A

materials pass apical membrane, epithelial membrane made of lipids, lipid film acts as aqueous pores

37
Q

what is the main function of lipid films

A

acts as small aqueous pores, provides flow of water through membrane

38
Q

describe the rate of absorption in passive diffusion

A

first order, directly proportional, increased conc of drug in gut will increase rate of absorption in intestinal lumen, drug readily transported away in bloodstream

39
Q

what does fick’s first law of diffusion describe

A

relationship between diffusion rate and factors that affect diffusion

40
Q

what 3 factors affect the rate of diffusion

A

surface area of membrane, membrane thickness, concentration difference

41
Q

what does fick’s first law state

A

rate of diffusion is proportional to surface area and concentration difference and inversely proportional to membrane thickness

rate of diffusion a (SA x conc diff)/thickness

42
Q

describe the rate of absorption in carrier mediated uptake

A

rapid increase then plateaus, plateaus when carrier proteins become saturated

43
Q

types of carrier mediated uptake

A

active transport and facilitated diffusion, useful for hydrophilic molecules

44
Q

adaptation for carrier mediated uptake

A

lots of embedded membrane proteins to aid transport

45
Q

what is symport and antiport

A

symport= movement of 2 molecules in the same direction
antiport= opposite direction

46
Q

problems with carrier mediated transport

A

limited number of carrier proteins per cell, rate plateaus when proteins saturated, some carriers only appear in certain locations, competitive inhibitors

47
Q

name 3 types of vesicular uptake/endocytosis

A

phagocytosis, pinocytosis, receptor-mediated endocytosis

48
Q

what is phagocytosis

A

engulfment of particles, immune system, vesicle around foreign cells

49
Q

what is pinocytosis

A

engulfment of small droplets of extracellular fluid by membrane vesicles, fluid phase endocytosis, forms vacuole, low efficiency

50
Q

what is receptor-mediated endocytosis

A

uses cell surface receptors, binds ligand to form ligand-receptor complexes, conformational changes initiated, invagination of membrane forming coated vesicle

51
Q

what is endocytosis

A

uptake of material in membrane bound vesicles, after uptake vesicle usually transports to other organelles for degradation (eg. lysosomes)

52
Q

describe what happens in lymphatic uptake

A

fats formed into micelles with bile salts, triglycerides break down into glycerol and fatty acids, mucosal cell reassembles triglycerides to combine with cholesterol =chylomicrons, chylomicrons enter lacteals in villi and transported away

53
Q

what happens in the mucosal cell in lymphatic uptake

A

triglycerides reassembled and combined with cholesterol to form chylomicrons

54
Q

describe the two ways fat is absorbed

A

short/medium= taken up through epithelium, endothelium, circulatory system, portal vein, liver

long chain= triglycerides>chylomicrons>lymph vessels, packaging idk

55
Q

problems/considerations with lymphatic uptake

A

not efficient, capillaries have low carrying capacity, lymphatics have lots of fatty material but very slow flow

can double the rate of uptake for very lipophilic drugs

56
Q

why dont all drugs absorb via lymphatic uptake if many are lipophilic

A

flow differences between circulatory and lymphatic system, capillary has fast flow of blood, lymph vessels are slow and no pump, fat content of diet can effect uptake routes of drugs

57
Q

list the types of drug uptake routes

A

transcellular, paracellular, passive diffusion, carrier mediated, vesicular uptake, vascular, lymphatic

Biopharmaceutics (11 decks)

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