PT523 Week 1: Pharmokinetics and Drug Receptors

pharmokinetics

how the body absorbs, distributes, and eliminates drugs

what are the routes of administration?

enteral

parental

what is enteral administration?

administered through the alimentary canal (GI tract)

what is parental administration?

administered by injection (ex. intravenous, intramuscular) or other types of methods

what are the types of enteral administration?

oral

sublingual

buccal

rectal

advantages of oral administration

Easy for self-administration

Controlled entering into system

disadvantages of oral administration

Need to be fairly lipid soluble

May irritate stomach -> N and V

First pass effect: need enough dose to survive liver before hitting target tissue

advantages of sublingual administration

No first pass

Faster effects

Helpful for those with swallowing difficulties

disadvantages of sublingual administration

Limited amounts can be delivered

Drug needs to be able to pass through oral mucosa

advantages of buccal administration

No first pass

Faster effects

Helpful for those with swallowing difficulties

disadvantages of buccal administration

Limited amounts can be delivered

Drug needs to be able to pass through oral mucosa

advantages of rectal administration

Preferable to oral when patient is unconscious or vomiting

disadvantages of rectal administration

Many drugs not absorbed well

what are the types of parental administration?

inhalation

injection

topical

transdermal

advantages of inhalation administration

Large alveolar surface area

Can deliver non-lipid soluble meds

Rapid onset

disadvantages of inhalation administration

Can irritate respiratory tract

Hard to predict how much med is delivered

advantages of injection administration

Direct administration

Rapid onset

Can be local or systemic depending on type of injection (IV, IM, intrathecal, SC, intra-arterial)

disadvantages of injection administration

Can lead to infection

advantages of topical administration

Local skin effects

Easy to administer

disadvantages of topic administration

Can only treat outer layer of skin

If large amounts are applied there is risk for systemic adverse effects

advantages of transdermal administration

Can promote systemic effect without breaking skin

Steady, prolonged drug delivery

disadvantages of transdermal administration

Drug needs to be able to pass through skin

what is the 1st pass effect?

with oral medications, they need to go through the liver

need a higher dose so enough of the drug survives the liver to do its benefits

what is implanted drug delivery?

Surgically implanted

Examples are to deliver drugs into the epidural space such as muscle relaxants around spinal cord

what is targeted drug delivery?

Directed chemo to specific tissues to decrease systemic side effects

Prodrug form that does not become active until it reaches the target tissue

true or false: Just because the drug is in the body does not mean the target site will be reached

true

bioavailability

Bioavailability refers to the extent to which the drug reaches systemic circulation

what does bioavailability depend on?

Route of administration will affect bioavailability

Will also be affected by ability to cross cell membranes

what factors affect drug distribution?

Tissue permeability

Blood flow

Binding to plasma proteins

Binding to subcellular components

how does exercise affect drug delivery?

exercise increases blood flow to an area -> the drug will go more to this area than others

where are drugs stored?

adipose

bone

muscle

organs -> kidney and liver

where are most drugs stored?

adipose

adipose drug storage

Reservoir for lipid soluble drugs

Higher fat content=more chance for storage

bone drug storage

Storage site for heavy metals

how are drugs eliminated?

biotransformation (drug metabolism)

drug excretion

what happens if only drug excretion occurred?

this process through the kidneys is so slow that it would cause toxicity

need biotransformation through the liver too

biotransformation

Drug undergoes a transformation to another form, a metabolite, that has less activity and can be inactive

where does biotransformation occur?

liver

where does drug excretion occur?

kidneys

Secondary organs include lungs and GI tract

when does enzyme induction occur?

prolonged use of drug

what is enzyme induction?

Drug is destroyed more rapidly -> decreased therapeutic effect

May be responsible for tolerance

what do we need to consider with drug excretion?

also need to consider excretion via breast milk in women that are breastfeeding

what are the different elimination rates?

clearance

half life

half life

Amount of time required for 50% of the drug in the body to be eliminated

what can affect drug response and metabolism?

Genetics

Disease

Drug interactions

Diet

Age

Sex

Exercise

Smoking/alcohol

Environmental and occupational exposures

what are the different types of receptors?

surface

intracellular

what are the types of surface receptors?

Linked directly to ion channels -> Drug changes cell membrane permeability

Linked directly to enzymes -> Alter biochemical function within the cell

Linked to regulatory proteins -> G-protein activation alters some part of cell functi

why are receptors important?

Responsible for drug binding -> influences the drug concentration

Determine drug's action

Receptors medicate agonists and antagonists

affinity

does the drug like a certain receptor?

efficacy

how much does the drug activate the receptor and change cell function?

aka does the drug work?

agonist drugs

drug that can bind to a receptor and make a change

antagonist drugs

drug binds, but does not cause a direct change

blocks an effect

selective drugs

affects only one type of cell (ie. cardioselective)

what are the benefits of selective drugs?

less side effects bc it effects less tissue

how does affinity affect dosing?

if a certain drug has a high affinity for a certain receptor, you can give lower doses

if a drug has a low affinity for a certain receptor, need higher dose to get the desired effect

what are competitive antagonists?

Both agonist and antagonist vie for same receptors

Whatever drug occupies more receptors will have the effect

are competitive antagonists reversible?

yes

If the inhibitory affect of the antagonist is too great, and is harmful, large amounts of agonist can be given to counteract

what are non-competitive antagonists?

Form strong and almost permanent bonds to receptors

are non-competitive antagonists reversible?

no; cannot be displaced by agonists

Need to wait for normal receptor turnover for effect to wear off so inhibitory effects could last for several days

how can exercise affect drugs (example of propranolol)?

this drug decreases BP and HR by blocking the effects of natural epinephrine

during exercise, the patient's body is releasing more norepinephrine to combat the effects of exercise

if the pt has not had enough propranolol, the norepinephrine may overcome the drug and propranolol may not be as effective

what are partial agonists?

in between strong antagonists and strong agonists

true or false: partial agonists are less efficacious than strong agonist

true

what is a benefit of partial agonists?

May be more biased towards one target site (more selective) -> less side effects

what is down regulation?

Body starts to get rid of a certain receptor and stops producing new ones

what causes down regulation?

Slow process that occurs with prolonged medication use

what is a drug holiday?

used with down regulation

Some drugs may benefit from "holiday" when drug is stopped, and receptors can replenish

what is pharmodynamics?

analysis of what the drug does to the body

what is a therapeutic index?

indicator of the drugs safety

the higher the TI, the safer the drug