partial agonist
increasing concentrations of agonist will produce an increase in biologic effect up to an intrinsic activity < 1
all receptors bound → activity level < 100%
can be used therapeutically for withdrawal symptoms
ex. methadone
antagonism
binding of a drug to a receptor that does NOT activate the receptor and prevents a response to an agonist
noncompetitive antagonism
block can NOT be overcome by increasing dose of agonist
aka “irreversible antagonist”
no activity
ex. naloxone
competitive antagonism
block can be overcome by increasing the dose of the agonist
agonist can be reversed (usually by flooding with agonists)
pharmacologic antagonism
competitive & noncompetitive antagonism
based on one effect on the same receptor
ex. drug A ↑ HR by binding to receptors in heart, but drug B ↓ HR by blocking drug A from reaching receptors
effect antagonism
2 receptors are working, but the EFFECTS/ACTIONS oppose each other
based on 2 effects on different receptors
ex. drug A ↑ BP in brain, drug B ↓ BP in arm
ligand-gated ion channels
ligand binds to active site → conformational change → drugs can manipulate how long channels stay open
ex. acetylcholine agonist keeps channel open longer
enzymes
proteins that speed up chemical reactions
can cause conformational change by binding 2 molecules together
ex. renin → ANG I → ANG II can be done faster with use of these
oral drugs
most common dosage form
enteral administration
most common route of administration
mouth
enteral administration
thin lining, rich blood supply
sublingual and buccal routes
stomach
enteral administration
medium surface area, rich blood supply, acidic pH
drugs don’t stay here long
small intenstine
enteral administration
huge surface area, rich blood supply, basic pH
rectal
enteral administration
small surface area, rich blood supply, basic pH
inconvenient but advantageous for local activity, if pt is unable to swallow
parenteral administration
advantages:
can be used for drugs that are poorly absorbed
provide an immediate onset of action
provide a longer lasting effect
can concentrate drug at a specific location
provide a more predictable response
provide titratable dosage
disadvantages:
pain
irreversible
extravasation (toxic chemical leak into tissue)/phlebitis (vein inflammation)
not useful for self-admin
contamination/infection
intravenous, intra-arterial, intramuscular, epidural, intrathecal, subcutaneous, intra-articular
types of parenteral administration
skin
topical administration
ointments, creams, patches
local and systemic
eyes
topical administration
drops, ointments
local distribution
ears
topical administration
local distribution
intranasal
topical administration
spray and drops
local and systemic
inhalation
topical administration
local and systemic
local: asthma, COPD
systemic: anesthesia
vaginal
topical administration
local and systemic
mainly local, can be systemic for hormones
disintegration
1st pharmaceutical phase of tablets
tablet hits fluid → breaks into little chunks to increase surface area
dissolution
2nd pharmaceutical phase of tablets
broken into molecules, can be absorbed
dissolved liquid
oral dosage form
ex. elixir, syrup
not convenient compared to tablets
suspensions
oral dosage form
chunks of drug floating in liquid (must shake)
thick, gloopy
powders
oral dosage form
ground up drug
not common, inconvenient
capsules
oral dosage form
gelatin shell containing powder
tablets
oral dosage form
compressed powder (made w/ pressure)
coated tablets
oral dosage form
coating for extended release, easier swallowing, taste
enteric-coating
oral dosage form
specific coating made to survive stomach acid, only dissolves in basic pH
sustained-release
oral dosage form
a short-term drug turned into a longer-lasting drug
dissolved liquid
fastest absorbed oral dosage form
sustained-release
slowest absorbed oral dosage form
rate
_____ of absorption can determine
onset of action
duration of action
intensity of response
variables affecting absorption
nature of absorbing surface
surface area
blood flow to site of administration
pH at the site of absorption
primary method of excretion
kidneys
drug elimination
2 types:
biotransformation
excretion
biotransformation
active drugs transformed into inactive for elimination
hepatic metabolism, tissue enzymes
types of biotransformation
secondary method of excretion
GI tract
absorption phase
absorption rate more than elimination rate
elimination phase
no significant absorption occurs
toxic level
concentration of drug that will predictably cause problems
minimum effective concentration
how much drug in the body before there is an effective concentration
therapeutic range
safe and effective concentration of drugs in the body
onset of action
time for drug to become effective
body weight
variable affecting dose/response
larger doses often given to patients with greater weight or BMI
dependent on where drug is distributed to
age
variable affecting dose/response
altered capacity to metabolize and/or excrete drugs (usually decreased)
most common in very young and very old
gender
variable affecting dose/response
differences in body composition and hormonal activity
genetics
variable affecting dose/response
enzymatic differences can lead to alterations in magnitude or effect
decrease or increase
tolerance
variable affecting dose/response
larger doses must be given to maintain the same effect
commonly seen with opioids
psychological factors/beliefs
variable affecting dose/response
placebo effect
comorbid medical conditions
variable affecting dose/response
can affect all phases of pharmacokinetic and pharmacodynamic response
drug-drug interaction
pharmacological or clinical response to the administration of a drug combination difference from that anticipated from the known effects of the two agents when given alone
synergism
one drug enhances the effect of other drugs
pharmacokinetic
drug interaction in which one drug alters the rate or extent of absorption, distribution, metabolism or excretion of another drug
one drug causes a change in the plasma concentrations of another drug
pharmacodynamic
drug interaction in which one drug induces a change in a pt’s response to a drug without altering the object drug’s kinetics
pharmacological interactions
pharmaceutical
drug interaction that includes physical and chemical incompatibilities
IV admixtures
pts at greatest risk of interactions
pts on multiple medications, multiple prescribers/pharmacies, elderly, obese pts, critically ill pts
object drug
drug for which an effect is altered (increased or decreased)
precipitant drug
drug that provokes an interaction onto an object drug
narrow therapeutic range, steep dose response curve, metabolized by hepatic enzymes, typically used chronically
characteristics of important object drugs
small intestine
primary site of drug absorption
complexation
drugs that form chemical complexes with other agents may lower the rate and extent of drug absorption
ex. divalent and trivalent metal ions; Mg, Ca, Zn, Fe, Al can bind to prescription drugs and prevent absorption
complexation, changes in pH, changes in GI motility
mechanisms of altered absorption
H2 receptor blockers, proton pump inhibitors, antacids
drugs that can change gastric pH (acidic to basic)
ketoconazole, itraconazole, iron supplements
drugs that need an acid pH for dissolution