Block 3 Week 1

What is pharmacokinetics?

What is pharmacokinetics?

what the body does to the drug

What is pharmacodynamics?

what the drug does to the body

What does ADME stand for in pharmacokinetics?

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

what route of administration is the most convenient

oral

what are the functions of the GI system

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

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

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

What is the oral cavity?

mouth

What is the role of the esophagus?

transport food from mouth to stomach

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

what is the difference between a drug and a medicine

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

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.

what is the role of surface mucus cells

secrete bicarbonate and gastric mucus

what is gastric mucus

glycoprotein which lubricates stomach lining and protects wall from HCl

what is the role of parietal cells

produce HCl and castle intrinsic factor

what is castle intrinsic factor

necessary for absorption of vitamin B-12

what is the role of chief cells

secrete pepsinogen and gastric lipase

what is pepsinogen

turns into pepsin by the action of HCl

• pepsin hydrolyses secondary and tertiary polypeptides

what gastric lipase

digestive enzymes breaking down the short and medium chains fats

what effects gastric emptying

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

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

where is the major site of absorption of orally administered drugs

the small intestine

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

CYP3A4

what comprises of the mucosa in the small intestine

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

how is the surface area if the small intestine so large

has villi + micro villi is highly convoluted

why is a large surface area needed for drug absorption

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

What is coeliac disease?

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

what is the role of liver

main site of metabolism of xenobiotics secretes bile

What does the pancreas secrete?

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

where does the majority of digestion of carbohydrates occur

in small intestine

what are micelles formation used

transport of lipids

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

minimal

What occurs in the large intestine?

reabsorption of water, vitamins, electrolytes

what is the distal intestine

the colon

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

What are xenobiotics?

foreign chemicals that the body does not produce

what are the characteristics of molecules

ionisation solubility pKa polymerisation colour taste chemical stability

what is solubility

equilibrium between a solid and a solution

what are the characteristics of materials

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

how to molecules turn into materials

materials are made of molecules which come together and interact

what does colour difference of medicines depend on

electron cloud of molecule

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)

what is the boundary between two phases called?

interface

which interaction is weaker: gas and liquid or liquid

gas and liquid

what does an imbalance of forces give rise to

surface tension

why is the force surface tension applied

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

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

water molecules are more free to move so surface tension decreases

what are surfactants

surface acting agents used to reduce surface tension

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

keratin

What is the stratum corneum?

outermost layer of epidermis

what has the highest surface tension of all pharmaceutical liquids

water

what effect do organic impurities have the surface tension

they decrease the surface tension

What is wetability?

the extent to which solid comes in contact with a liquid

why is surface tension affected with solids

molecules are held more rigidly

why does shape affect surface tension of a solid

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

why does orientation of crystals affect surface tension

different chemical groups will be on surface

what is contact angle

how interfacial tension for S/L interface is determined

how is the tendency of liquid to spread estimated

magnitude of contact angle

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

a surfactant needs to be added

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

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

absorption

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

adsorption

does this relate to absorption or adsorption: bulk phenomenon

absorption

does this relate to absorption or adsorption: surface phenomenon

adsorption

is absorption exo or endothermic

endothermic

is adsorption exo or endothermic

exothermic

does temperature affect absorption

no

what effect does temperature have on adsorption

favoured by lowering temperature

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

absorption

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

adsorption

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

absorption

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

adsorption

what the two types of adsorption

physisorption and chemisorption

What are the characteristic of physisorption?

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

what are characteristics chemisorption

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

what attapulgite

magnesium aluminium phyllosilicate it is used to remove toxins in stomach

what factors affect adsorption

pH of solution solubility of adsorbate temperature surface area of absorbent

What is solubility?

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

what does solubility of a drug depend on?

absorption rate dose formulated volume of solvent present

How can solubility be increased?

changing the chemistry or preparing a salt formation

what are ways of measuring solubility

gravimetrically UV - vis spectroscopy HPLC assay

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?

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

as it must be isotonic and sterile

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

what is dimerisation

reaction with another molecule

how would you increase the dissolution rate?

decrease the size of the particle which increases the surface area

what is the melting point

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

What is hygroscopicity?

ability of a material to take water up from the environment

What is viscosity?

resistance to flow

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

it has low fluidity

why is it important injectables have a low viscosity

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

what is powder

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

how is shear stress derived

derived by the force applied to layer divided by its surface

when do Newtonian fluids move more

when force is applied

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

what is laminar flow?

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

what is turbulent flow

when molecules don't travel parallel to each other

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

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

sheet thinning is also known as what?

pseudo plastic flow