L2 - what is a medicine Flashcards
overview of learning objectives
- drug delivery & absorption
- drugs, medicines, dosage forms & drug delivery systems
- medicines development pipeline
- role of science in medicines
- biopharmaceutics
- pharmacokinetics
- pharmacodynamics
- ADME
- plasma conc of drug vs time profiles
- how pharmaceutical sciences allow right medicine to be given to right patient at right dose at right time
what is drug absorption?
uptake of NON-metabolised drug, after it is released from its formulation, from the site of delivery to the systematic circulation
routes of delivery
- oral
- injections
- topical
- transdermal
- pulmonary
- nasal
- buccal
- sublingual
- ocular
- otic
- rectal
- vaginal
types of injections
intravenous, intramuscular, subcutaneous (into fatty tissue under skin), intradermal (into the layers of the skin)
what is topical and transdermal?
topical - creams + ointments to skin
transdermal - drugs across the skin to systemic circulation (e.g patches)
what is pulmonary?
inhalation into lungs (inhalers)
what is buccal and sublingual?
buccal - cheeks
sublingual - under the tongue
what is ocular and otic?
ocular - eye
otic - ear
what does drug delivery involve
drug has to cross a biological barrier
what route of delivery does not have an absorption process?
IV administration
define biopharmaceutics
getting the right DRUG to the right PLACE at the right DOSE at the right RATE. this optimises drug delivery.
so it tries to maximises biological effect by taking into account physicochemical properties of the drug, physical properties of delivery ssytem + physiological propeties of delivery route
what does ADME stand for?
absorption, distribution, metabolism, excretion
what is a drug?
the active pharmaceutical ingredient - chemical in medicine responsible for therapeutic effect
what is a medicine?
the API + the excipients
what is a dosage form?
physical form (solid, semi-solid, liquids, gases) in which medicine is produced and administered. it will include the drug + excipients that help deliver the medication effectively
examples of dosage forms
- tablets
- capsules
- liquids
- topicals
- inhalers
what is a tablet?
solid form that is swallowed
what is a capsule?
containers (usually gelatin) with medicine inside
what are liquids?
solutions, suspensions or emulsions taken orally or injected
3 things you must consider in the design of a dosage form
- physicochemical properties of the drug
- biopharmaceutical considerations, e.g how administration route effects rate + extent of absorption into systemic circulation
- therapeutic considerations of the disease state + the patient so you can find out best dosage form, route of administration, duration of action + dose frequency
time of onset of action of intravenous injections
seconds
time of onset of action of intramuscular + subcutaneous injections, buccal tablets, areosols, gases
minutes
time of onset of action of short term depot injections, solutions, suspensions, powders, granules, capsules, tablets, modified release tablets
minutes to hours
time of onset of action of enteric coated formualtions
several hours
time of onset of action of depot injections, implants
days to weeks
time of onset of action of topical preparations
varies
what is the drug delivery system (DDS)?
method or process of administering a pharmaceutical compound to give a therapeutic effect. it focuses on the tech used to deliver the drug to the target site in the body.
4 examples of drug delivery systems
- controlled release systems
- transdermal patches
- injectable systems
- nanoparticles + liposomes
medicine development pipeline
- drug discovery
- preclinical studies
- clinical studies
- FDA regulatory approval
- postmarketing monitoring
mean cost of getting new molecular entity (NME) to market
£1billion
clinical trial pipeline
- phase 0: lab studies on cells
- phase 1: give treatment to healthy ppl
- phase 2: give it to those with condition
- phase 3: see if treatment is better than what we already have via comparisons
overview of drug absorption in GI tract
- oral dosage form is swallow, enters stomach
- if medicine has enteric coating which prevents it from being dissolved in the stomach
- so dosage form passes into small intestine
- no enteric coating = dosage form starts dissolving + released in stomach and passes into intestine
describe blood supply to GI tract
superior mesenteric veins coat small intestine and ascending colon which take blood that has absorbed contents of intestine and empty blood into portal vein.
transverse and descending empty into inferior mesenteric vein.
all go into portal vein, which goes into liver, to the heart, to systemic circulation, where it will diffuse into tissues + have its intended biological effect at intended site
what is the liver the site of?
site of detoxification in body, where drugs are metabolised into metabolites. most excretion occurs from the kidenys.
in depth explanation of how drugs are absorbed in GI tract
- solid dosage form has to break apart and go into solution, giving particles which dissolve, giving a solution of drug molecules
- drug can now be absorbed across the gut epithelium into the blood which empties into liver
how can digestive / bacterial enzymes affect drug absorption in GI tract?
- digestive could break down drug
- bacterial can metabolise drug if drug is a substrate of these enzymes
how can pH affect drug absorption in GI tract?
affect ionisation of drug
how can the presence of food affect drug absorption in GI tract?
acts as physical barrier, makes contents of GI tract more viscous so hinders diffusion of drug, drug molecules can interact with components of drug stopping them from being absorbed
how can the first line of defence affect drug absorption in GI tract?
- acidic environment in stomach may cause break down
- eflux pumps protects body from toxic molecules, so drug may be absorbed and enter blood and cells, but these pumps (e.g P-gp) will pump the drug back out again
how can metabolic enzymes affect drug absorption in GI tract?
can metabolise + inactive drug (e.g cyp3a)
other factors affecting absorption of small drugs
- effect of pH on ionisation + solubility of drug
- H-bonding
- size
- lipophilicity
- villi + microvilli increasing sa
paracellular pathway
between cells, very difficult due to tight junctions
passive diffusion - transcellular pathway
drug must enter lipid membrane of cell and pass out of it into the cell on the other side, diffuse through the cell, through lipid membrane and into the blood and then into liver
what does lipinski’s rule of 5 help do?
predict oral absorption of drugs
do you want drug to be ionised or unionised to be absorbed?
unionised
pharmaceutics vs biopharmaceutics
pharmaceutics - science of making medicines
biopharmaceutics - study of interaction of medicine with biological system, allowing optimisation of drug delivery system
what is bioavailability?
measure of the quantity of drug which reaches its site of action + rate at which it gets there
equation to find net oral bioavailability (F)
F = Fa x Fg x Fh
Fa= fraction absorbed
Fg = fraction escaping GI metabolism
Fh = fraction escaping hepatic (liver) metabolism
note: some metabolites may be more active than parent drug
you can have an active or inactive metabolite
how can you measure bioavailability?
finding drug conc in systemic circulation + looking and blood, serum or plasma.
might not be good for routes other than oral or injection
what is pharmacokinetics?
what body does to drug.
conc of drug in serum overtime. as drug is absorbed conc goes up. as drug is excreted conc goes down.
what is pharmacodynamics?
what drug does to the body.
once drug is in systemic circulation + has reached target site, it carries out its biological effect. so as drug conc increases the effect/ response increases.
PK - PD modelling
how the response of the drug changes over time.
plasma concentration vs time profile (oral administration)
when we measure conc of drug in plasma.
- lag time = when drug is released from oral dosage form before its absorbed
- increase in conc of drug in plasma until it reaches c max conc
- Tmax is the time at which the maximum conc occurs
- minimum toxic conc (MTC) = want drug to stay below this conc
- minimum effective concentration (MEC) = want drug levels to stay above this otherwise will not have biological effect
- between MTC and MEC is the therapeutic range: where drug has intended biological effect
- duration of action where drug is in therapeutic range
- auc = area under curve which is a measure of bioavailability of drug, can compare auc of diff dosage forms to see bioavailability.
