Pharmacokinetics

routes of administration injection

intravenous, intra-arterial, subcutaneous, intramuscular, intrathecal

implanted drug delivery

ROA

Directly into spinal canal

PCA pump

baclofen pump

controlled release preparations

at intervals or slowly to maintain blood levels

targeted drug delivery

monoclonal antibodies - antibodies attack specific tissue (created outside)

viral transport and gene therapy - link drug to modified virus to insert into cell

enzyme activation - drug is activated by enzyme in target tissue or organ

absorption factors related to drug

lipid or water solubility - lipid is easier to get through membrane

molecular or particle size - small enough to get through membrane

Ionization - impacts membrane potential or ion channels opening or not

physical/chemical nature - acidity and basic nature impacts

concentration - gradient flow

dosage form

formulation

absorption factors related to body

surface area

vascularity

pH - acid is easily absorbed in stomach but basic will require more energy(like dissolves like)

presence of other substances

GI motility

functional integrity of absorptive surface

diseases

impact availability of drug and access to membrane

absorption

lipid solubility

membranes that affect absorption and distribution

GI to blood stream

fluid around tissue to cell interior

cell interior to fluid around tissue

kidneys to bloodstream

membranes that affect distribution

cell membranes

capillary walls -

blood brain barrier - glial sheaths, astrocytes covering capillaries with only really tight junctions in between; needs lipid soluble and really small drug to pass thru

placental barrier - not really a barrier because shared nutrients

factors affecting distribution

blood flow

capillary permeability

binding - to plasma proteins meaning can’t leave bloodstream

volume of distribution(Vd)

amount of drug administered/concentration of drug in plasmad

drug storage sites

fat(lipid soluble), bone, muscle, organs

leads to prolonged drug effects, prolonged adverse side effects, organ damage

metabolism/biotransformation

alternate version - metabolite - doesn’t imapct the person; inactive

enzymes present in liver, lungs, kidneys, GI tract, skinf

first pass metabolism

oral; passes through GI tract

lipid-soluble drugs

must be metabolized by liver into water soluble substances to be excreted by kidneys

enzyme

break down/metabolize

types of metabolism

first order kinetics

zero-order kinetics

enzyme induction

first-order kinetics

rate of metabolism and elimination is proportional to drug concentration

zero-order kinetics

constant rate of metabolism regardless of drug conctration

enzyme induction

tolerance

more enzymes to break it down, so need more drug to feel effect

metabolism where and why

cytochrome P450 system - liver enzyme doing metabolism

mostly in liver and GI tract

diversified and nonspecific

metabolites become water-soluble to be excreted

phase I metabolism in liver

oxidation - adding oxygen

reduction - taking oxygen out

hydrolysis - breaking drug down with water as a product

phase II metabolism in liver

conjugation

factors affecting metabolism

genetic)number of enzymes), disease, drug interactions, age, diet, etc.

half life

time it takes for 50% of drug to be eliminated

steady state concentration

amount administered = amount eliminated

takes 5-6 half-lives

determined by dose, dose interval, half-life, other factors

leads to predictable accumulation

Bioavailability

percentage of drug that reaches the bloodstream

intravenous = 100%

oral = 50%

what does absorption depend on

route of administration

drug factors

body factors

routes of administration

enteral - through GI tract(oral, sublingual, rectal)

parenteral - the rest(inhalation, injection, topical, transdermal, vaginal)

Oral

adv: easy, safe, convenient

disadv: limited absorption, first pass liver

analgesics, sedative-hypnotics

sublingual

adv: rapid onset, no first pass inactivation

disadv: must easily absorb into mucosa

ex. nitroglycerin

rectal

adv: alternative to oral, local effect

disadv: incomplete absorption, irritation

laxatives, antiemetics, suppositories

inhalation

adv: rapid onset, respiratory, surface area

disadv: irritation, adminstration, compliance

anesthetics, anti-asthmatics

injection

adv: rapid, direct to bloodstream

disadv: infection, self-administration

insulin, antibiotics, chemo

topical

adv: local effects, easy

disadv: can be absorbed into bloodstream

antibiotics, steroids, nose spray

transdermal patch

adv: steady, prolonged delivery

disadv: limited(lots of layers to go through), drug must m=penetrate skin unchanged

hormones, nicotine, opioid analgesics