biological aspects of drug delivery

Question 1

what is the main pathway for transport around the body

Answer 1

circulatory system

Question 2

what is extravasation

Answer 2

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

Question 3

functions of lymphatic system

Answer 3

-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

Question 4

why are lymphatic capillaries leaky

Answer 4

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

Question 5

how is interstitial fluid formed

Answer 5

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

Question 6

How does lymph collect in lymphatic capillaries

Answer 6

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

Question 7

describe the anatomy of epithelium

Answer 7

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

Question 8

epithelial tissue function

Answer 8

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

Question 9

describe the apical surface in the epithelium

Answer 9

free surface, cilia/microvilli can be present

Question 10

describe the lateral surface in the epithelium

Answer 10

free adjacent cells, cell junctions may be present

Question 11

describe the basal surface in the epithelium

Answer 11

cells adhere to ECM, cell junctions may be present

Question 12

name the 5 main types of cell junctions

Answer 12

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

Question 13

describe each cell junction

Question 14

how can cell junctions effect drug delivery

Answer 14

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

Question 15

describe the structure of the basement membrane

Answer 15

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

Question 16

function of basement membrane

Answer 16

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

Question 17

what is basal lamina and where is it secreted

Answer 17

secreted by epithelial cells, contains protein, glycoproteins, proteoglycans

Question 18

what is reticular lamina

Answer 18

contains proteins secreted by underlying connective tissue

Question 19

2 main types of epithelial tissue

Answer 19

covering/lining, glandular

Question 20

where can covering and lining epithelium be found

Answer 20

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

Question 21

ways to classify covering and lining epithelium

Answer 21

arrangement of cells in layers, cell shape

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

what is the endothelium lining of blood vessels composed of

Answer 24

simple squamous epithelium

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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

Question 27

where are most drugs metabolised

Answer 27

liver

Question 28

what is bioavailability

Answer 28

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

Question 29

what is bioavailable dose

Answer 29

fraction of administered dose of drug that reaches systemic circulation unchanged

Question 30

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

Answer 30

epithelium, basal lamina, endothelium

Question 31

what is paracellular route

Answer 31

between cells, through cell junctions, small contribution to drug absorption passive, requires conc gradient

Question 32

what is transcellular route

Answer 32

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

Question 33

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

Answer 33

folds in villi/microvilli

Question 34

what is the rate limiting step in paracellular absorption

Answer 34

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

Question 35

what can tight junctions be modulated by

Answer 35

permeation enhancers, increases cell membrane permeability and drug bioavailability

Question 36

structure of transcellular absorption

Answer 36

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

Question 37

what is the main function of lipid films

Answer 37

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

Question 38

describe the rate of absorption in passive diffusion

Answer 38

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

Question 39

what does fick's first law of diffusion describe

Answer 39

relationship between diffusion rate and factors that affect diffusion

Question 40

what 3 factors affect the rate of diffusion

Answer 40

surface area of membrane, membrane thickness, concentration difference

Question 41

what does fick's first law state

Answer 41

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

Question 42

describe the rate of absorption in carrier mediated uptake

Answer 42

rapid increase then plateaus, plateaus when carrier proteins become saturated

Question 43

types of carrier mediated uptake

Answer 43

active transport and facilitated diffusion, useful for hydrophilic molecules

Question 44

adaptation for carrier mediated uptake

Answer 44

lots of embedded membrane proteins to aid transport

Question 45

what is symport and antiport

Answer 45

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

Question 46

problems with carrier mediated transport

Answer 46

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

Question 47

name 3 types of vesicular uptake/endocytosis

Answer 47

phagocytosis, pinocytosis, receptor-mediated endocytosis

Question 48

what is phagocytosis

Answer 48

engulfment of particles, immune system, vesicle around foreign cells

Question 49

what is pinocytosis

Answer 49

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

Question 50

what is receptor-mediated endocytosis

Answer 50

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

Question 51

what is endocytosis

Answer 51

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

Question 52

describe what happens in lymphatic uptake

Answer 52

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

Question 53

what happens in the mucosal cell in lymphatic uptake

Answer 53

triglycerides reassembled and combined with cholesterol to form chylomicrons

Question 54

describe the two ways fat is absorbed

Answer 54

short/medium= taken up through epithelium, endothelium, circulatory system, portal vein, liver long chain= triglycerides>chylomicrons>lymph vessels, packaging idk

Question 55

problems/considerations with lymphatic uptake

Answer 55

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

Question 56

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

Answer 56

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

Question 57

list the types of drug uptake routes

Answer 57

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