Pharmacology

prescription drugs
Over the counter medications
Brand name (patented) drug vs generic drugs

FDA
online
chemistry, pharmacokinetics, indication, mechanism, side effects, toxicity, contraindications, dosage, information for special populations
NOT, comparative efficacy

label indication
off label
new data is obtained

how drugs reach targets in the body
what determines the change with time of the concentration at target sites

from administration site into the blood stream

from blood stream into tissues
Cp - concentration in plasma

from body
by metabolism or to other molecules
by excretion in urine, feces, air

through porosites between cells
transport in bulk flow of aqueous fluid

hydrostatic pressure
molecular size
binding to plasma proteins that prevents filtration
tissue porosity

through cell membranes into and out of cells
lipid of plasma membrane
tight junctions, porosity

concentration gradient
MW
Lipophilicity

solubility in lipid relative to water
measured by oil/water parition coefficient
predicts permeation into cells and accumulation in fat

across cell membranes into and out of cells, uses transport proteins

absorption half life - how fast
percent dose absorbed - bioavailability - how much

degradation by enzyms in GI lumen. mucosa, or liver
why some drugs have poor bioavailability through oral route

Vd
Volume of blood into which a drug appears to have distributed
dilutes dose to produce a concentration

clearance
excretion of body or metabolism into another molecule

volume of plasma cleared of compount per unit time by all routes and mechanisms
expressed as ml/min or ml/hr normalized for body weight
sum of renal and non renal clearances
CIt = CIrenal + CInonrenal

inactive
active
toxic

they don’t interact with target

turns into a molecule with similar activity, so eliminated but still has an effect

bad
ex: acetaminophen -> liver toxicity

time to eliminate 50% of drug from plasma
generally independent of dose
slower clearance = longer half life

may be higher at first in order to achieve steady state
or if you need a rapid onset of effect

Receptors
Transporters
Enzymes
DNA
mRNA

Transcription factor
enzyme
Ion channel
G protein coupled

Excessive therapeutic effect
side effects
toxic effect
adverse drug reactions
allergic reactions
Idiosyncratic reactions - not a side effect yet bc it only happens to a few people

ability to produce effects by one mechanism

ability to produce one effect such as the desired therapeutic effect without producig other effects
the most selective drug is the safest one

intensity of the drug measured in relation to its concentration

binding affinity

intensity of a drug increases with its concentration until the Emax is achieved
The concentration that produces 50% of Emax, the EC50 is determined by the drug’s affinity for binding to the target

highest potency

maximum efficacy

agents with affinity for a receptor but without effiacy
bind but has no effect -> inhibitors
like a beta blocker

reversible and competitive
compete for the same binding sites

competes and displaces
potency
EC50
Emax

drug binds a chemical and prevents its action

two agonists produce opposite effects by actions on different receptors

drug acts on same receptor as an agonist and decreases agonist potency or efficacy

potentiation: agent with no efficacy alone increases the potency of an agonist