Block 3 Week 1

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What is pharmacokinetics?

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1

What is pharmacokinetics?

what the body does to the drug

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2

What is pharmacodynamics?

what the drug does to the body

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3

What does ADME stand for in pharmacokinetics?

A-absorption D-distribution M-metabolism E-excretion

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4

what route of administration is the most convenient

oral

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5

what are the functions of the GI system

-digestion of food -absorption of nutrients and drugs -elimination

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6

why can insulin not be administered orally

the chemical and mechanical breakdown means the protein would be digested so it would not perform its function

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7

why can't monoclonal antibodies be administered through oral administration

Proteins are large molecules so it is difficult for molecules to diffuse into the blood Whereas if it is administered intravenously then the monoclonal antibodies enters the blood stream straight away Proteins would also be digested

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8

What is the oral cavity?

mouth

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9

What is the role of the esophagus?

transport food from mouth to stomach

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10

what is the role of the stomach in digestion

secretion of gastric juices for chemical digestion mechanical break up of food mixing food and the gastric juices

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11

what is the difference between a drug and a medicine

drug is the actual drug compound and medicine is how the drug is formulated

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12

what is peristalsis

the involuntary constriction and relaxation of the muscles of the intestine or another canal, creating wave-like movements that push the contents of the canal forward.

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13

what is the role of surface mucus cells

secrete bicarbonate and gastric mucus

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14

what is gastric mucus

glycoprotein which lubricates stomach lining and protects wall from HCl

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15

what is the role of parietal cells

produce HCl and castle intrinsic factor

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16

what is castle intrinsic factor

necessary for absorption of vitamin B-12

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17

what is the role of chief cells

secrete pepsinogen and gastric lipase

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18

what is pepsinogen

turns into pepsin by the action of HCl

  • pepsin hydrolyses secondary and tertiary polypeptides

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19

what gastric lipase

digestive enzymes breaking down the short and medium chains fats

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20

what effects gastric emptying

volume of meal kcal contents fat content protein content liquid/ solid state

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21

why is the small intestine a major site of absorption of different nutrients

large surface area exposure to enzymes and solubilises secretion from liver and pancreas

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22

where is the major site of absorption of orally administered drugs

the small intestine

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23

the small intestine is the site of first pass metabolism which enzyme is this via

CYP3A4

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24

what comprises of the mucosa in the small intestine

epithelium + connective tissue with blood and lymphatic vessels; submucosa + serosa

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25

how is the surface area if the small intestine so large

has villi + micro villi is highly convoluted

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26

why is a large surface area needed for drug absorption

allow time for drugs to be absorbed by passive diffusion, enterocytes contain metabolic enzymes

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27

What is coeliac disease?

A chronic inflammatory response to the protein gliadin a component of gluten

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28

what is the role of liver

main site of metabolism of xenobiotics secretes bile

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29

What does the pancreas secrete?

proteolytic enzymes - trypsin and chymotrypsin for protein digestion lipase for digestion of lipids bicarbonate for stomach acid neutralising

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30

where does the majority of digestion of carbohydrates occur

in small intestine

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31

what are micelles formation used

transport of lipids

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32

compared to the small intestine the absorption of drugs in the large intestine is _____________

minimal

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33

What occurs in the large intestine?

reabsorption of water, vitamins, electrolytes

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34

what is the distal intestine

the colon

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35

the colon has a large number of bacteria why

they contribute to normal digestion - ferment carbs and protein escaping digestion in absorbable energy able to metabolise some drugs into other xenobiotics

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36

What are xenobiotics?

foreign chemicals that the body does not produce

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37

what are the characteristics of molecules

ionisation solubility pKa polymerisation colour taste chemical stability

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38

what is solubility

equilibrium between a solid and a solution

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39

what are the characteristics of materials

melting and boiling point particle size surface area adsorption absorption crystallinity composition purity colour viscosity taste physical stability

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40

how to molecules turn into materials

materials are made of molecules which come together and interact

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41

what does colour difference of medicines depend on

electron cloud of molecule

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42

adsorption and absorption are both sorption process what does this

a substance (sorbate) is captured by another substance (sorbent) in a condensed state (solid/ liquid)

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43

what is the boundary between two phases called?

interface

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44

which interaction is weaker: gas and liquid or liquid

gas and liquid

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45

what does an imbalance of forces give rise to

surface tension

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46

why is the force surface tension applied

to resist an external force due to cohesive nature of water molecules

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47

why do liquids see a decrease in surface tension when temperature increases

water molecules are more free to move so surface tension decreases

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48

what are surfactants

surface acting agents used to reduce surface tension

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49

chemical enhancer are used to interact with ___________, swell stratum cornteum, reduce surface tension and improve penetration of drugs

keratin

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50

What is the stratum corneum?

outermost layer of epidermis

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51

what has the highest surface tension of all pharmaceutical liquids

water

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52

what effect do organic impurities have the surface tension

they decrease the surface tension

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53

What is wetability?

the extent to which solid comes in contact with a liquid

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54

why is surface tension affected with solids

molecules are held more rigidly

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55

why does shape affect surface tension of a solid

shape is affected by crystallisation, milling which means different rough surfaces and spreading abilities

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56

why does orientation of crystals affect surface tension

different chemical groups will be on surface

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57

what is contact angle

how interfacial tension for S/L interface is determined

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58

how is the tendency of liquid to spread estimated

magnitude of contact angle

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59

when the size of the contact angle is greater than 90 degrees what does this suggest

a surfactant needs to be added

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60

hydrophobic drugs require wetting agents. what are wetting agents

used to lower the surface tension between solid drugs and vehicle to favour suspension of the solid

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61

does this relate to absorption or adsorption: accumulation of particles throughout another surface

absorption

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62

does this relate to absorption or adsorption: accumulation of particles onto a surface/ interface

adsorption

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63

does this relate to absorption or adsorption: bulk phenomenon

absorption

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64

does this relate to absorption or adsorption: surface phenomenon

adsorption

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65

is absorption exo or endothermic

endothermic

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66

is adsorption exo or endothermic

exothermic

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67

does temperature affect absorption

no

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68

what effect does temperature have on adsorption

favoured by lowering temperature

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69

does this relate to absorption or adsorption: occurs at a uniform rate

absorption

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70

does this relate to absorption or adsorption: rate steadily increases until it reaches equilibrium

adsorption

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71

does this relate to absorption or adsorption: concentration eventually becomes the same throughout the material

absorption

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72

does this relate to absorption or adsorption: surface concentration differs from internal concentration

adsorption

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73

what the two types of adsorption

physisorption and chemisorption

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74

What are the characteristic of physisorption?

adsorbate held on absorbent via weak intermolecular forces reversible forms multilayers low enthalpy of adsorption

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75

what are characteristics chemisorption

highly specific - chemical bonding between adsorbent and adsorbate irreversible forms monolayer high enthalpy

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76

what attapulgite

magnesium aluminium phyllosilicate it is used to remove toxins in stomach

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77

what factors affect adsorption

pH of solution solubility of adsorbate temperature surface area of absorbent

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78

What is solubility?

composition of a saturated solution in terms of a designated solute in a designated solvent is the solubility

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79

what does solubility of a drug depend on?

absorption rate dose formulated volume of solvent present

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80

How can solubility be increased?

changing the chemistry or preparing a salt formation

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81

what are ways of measuring solubility

gravimetrically UV - vis spectroscopy HPLC assay

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82

what are some pre-formulation considerations

  • is solubility high enough for an solid oral dosage?

  • is the GI absorption high enough for oral delivery?

  • is solubility in water high enough to make solution for injection?

  • can a safe co-solvent be used? is it safe for use in children? can pH be increased or decreased without causing precipitation?

  • is pH appropriate for eyedrops? is drug more soluble in water than in oil?

  • will it diffuse through membranes?

  • if does not partition in oil are there active transporter membranes?

  • is it stable enough for formulation are there toxic decomposition products?

  • can it be packaged to increase stability?

  • can it be stored at low temperatures?

  • what is the anticipated shelf life and is it sufficient to transport a chain?

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83

why is it a good question if pH is appropriate for eyedrops?

as it must be isotonic and sterile

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84

if a drug has a very high log P what does this mean about formulation

cannot be used to make an injection with water as it will not dissolve. oils can be used for injection but not intravenously

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85

what is dimerisation

reaction with another molecule

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86

how would you increase the dissolution rate?

decrease the size of the particle which increases the surface area

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87

what is the melting point

where solids and liquids are in equilibrium and physical properties are the same

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88

What is hygroscopicity?

ability of a material to take water up from the environment

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89

What is viscosity?

resistance to flow

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90

if a material has high viscosity what does it mean about its fluidity

it has low fluidity

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91

why is it important injectables have a low viscosity

so they are able to fit through very small opening of the syringe

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92

what is powder

a colloid of solid and gas with very high concentration of solid particles

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93

how is shear stress derived

derived by the force applied to layer divided by its surface

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94

when do Newtonian fluids move more

when force is applied

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95

What is a boundry layer?

where the velocity of the material closer to the surface is lower than further away from the surface. molecules experience drag forces due to friction aim for smallest boundary layer possible

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96

what is laminar flow?

when all layers flow in the same direction and has the highest mass transfer.

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97

what is turbulent flow

when molecules don't travel parallel to each other

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98

what are the advantages of plastic flow

high viscosity means solid particles remain suspended once taken out of bottle it can be shaken to overcome yield stress and suspension will flow freely

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99

disadvantages of plastic flow?

in injectable is a draw back as have to exert a high force to eject the medication from the syringe which can cause the formulation to heat up which could decompose thermocline drugs

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100

sheet thinning is also known as what?

pseudo plastic flow

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