Intro Flashcards
how do drugs impact rehab?
response to exercise patient's pain perception participation and motivation in rehab interactions with modalities side effects screening understanding of current medical management in inter-professional care
what is a drug
-types of drugs
any non-nutrient chemical which has a physiological effect on the body types -natural -semi-synthetic -synthetic
what is pharmacotherapeutics
-subcategories
the use of specific drugs to prevent, treat, or diagnose a disease
subcategories
-pharmacokinetics
-pharmacodynamics
what is pharmacokinetics
-areas of interest
study of how the body processes a drug areas of interest -administration -absorption -distribution -elimination
what is pharmacodynamics
-types of effects
analysis of drug mechanism and effects
types of effects
-systemic
-cellular
- azine
- use
- example
antipsychotics, neuroleptic, antiemetic
phenothiazine
- azole
- use
- example
antifungal
miconazole
- azapam
- use
- example
antianxiety drugs
barbital/-bital
- use
- example
barbiturate sedative hypnotics
phenobarbital
- caine
- use
- example
local anesthetics
lidocaine
- cillin
- use
- example
antibiotics
penicillin
- cycline
- use
- example
antibiotic protein synthesis inhibitor
tetracycline
- mycin, -micin
- use
- example
aminoglycoside inhibiting antibiotic
erythromycin
- navir, -vir
- use
- example
antiviral (protease inhibitor)
saquinavir
- olol
- use
- example
beta-adrenengic blocker
propanolol
- oxin
- use
- example
cardiac glycosides
digoxin
- ine
- use
- example
stimulants
caffeine
- pril
- use
- example
ACE inhibitor
ramipril
- statin
- use
- example
HMG-CoA reductace inhibitors
lovastatin
OTC pros and cons
pros -lower drug doses -increased availability/access -less expensive cons -possible interactions with prescription medications -may delay use of more effective medications or treatments -adverse effects
when determining the dosage of a drug, what is the overall consideration?
concentration must be large enough to produce a beneficial response without being toxic
dose-response curves: threshold dose and ceiling effects (maximal efficacy)
threshold dose
-where response begins and increases in magnitude until a response plateau is reached
ceiling effect
-point at which there is no further response
dose-response concepts: efficacy vs. potency
efficacy
-dosage ranges over which the drug has desired effect
-magnitude of response increases as dosage increases (up to some maximum effect)
potency
-threshold dose that produces a given response
-higher potency means less of the compound is required to produce a given response
-lower threshold dose = greater potency
quantal dose-response curve
% of the population who exhibit a specific response relative to the dose of the drug
looks at variations in drug responses due to individual differences within the clinical population
therapeutic index
- what is it
- equation
calculated value to indicate drug sfaety
TI = TD50/ED50
median effective dose
- abbreviation
- what is it
ED50
dose at which 50% of the population respond to a drug in a specified manner (response)
median toxic dose
- abbreviation
- what is it
TD50
dose at which 50% of the population exhibits the adverse effect/response
median lethal dose
- abbreviation
- what is it
LD50
dose that causes death in 50% of the animals studied
FDA drug approval process
-general characteristics of the process
clinical testing phases: 0-IV
7-9 years (about 1 billion dollars total cost)
fast track exists for life-threatening conditions or approval of a new indication for a known drug
clinical testing phases
0: pre-clinical testing: lab animals I: clinical testing: healthy subjects 2: limited target population 3: large target population new drug approval IV: monitor general population
a drug is placed into a category or “schedule” based on…
potential for abuse
schedule I
- abuse potential
- legal use
- example
potential -highest legal use -restricted to approved research or therapeutic use in very limited # of patients example -medical marijuana -cocaine
schedule II
- abuse potential
- legal use
- example
potential -high legal use -specific therapeutic purposes w/ prescription example -opoids: morphine
schedule III
- abuse potential
- legal use
- example
potential
-mild-moderate possible physical/psychologic dependence
legal use
-specific therapeutic purposes w/ prescription
example
-certain opoids: codeine combos; anabolic steroids
schedule IV
- abuse potential
- legal use
- example
potential
-limited possible physical/psychologic dependence
legal use
-specific therapeutic purposes w/ prescription
example
-anti-anxiety drugs; other depressants and stimulants
schedule V
- abuse potential
- legal use
- example
potential -lowest relative abuse potential legal use -OTC example -cough medications; anti-diarrheal medications
areas to look at involving pharmacodynamics
potency efficacy therapeutic effect side effects receptors
what is efficacy
drug’s ability to produce a desired response
which route of administration does phonophoresis and iontophoresis
transdermal
enteral
- characteristics
- absorbed by…
- drug must have…
usually oral easiest for self-administration generally safe, controlled entry to system absorbed by small intestine drug must have high lipid solubility
enteral
-first pass effect
metabolism/destruction of drug molecule in liver before reaching its site of action
parenteral
-characteristics
bypass the GI system
more direct route to target site
more predictable quantity
not subject to “first pass effect”
bioavailability
- what is it
- depends on…
% of drug administered that reaches the bloodstream
depends on
-route of administration and the drug’s ability to cross membrane barriers
-extent of first pass metabolism
why is the SI the primary location of drug absorption
surface area
which drugs are absorbed out of the stomach
weak acids
which drugs are absorbed out of the SI (duodenum)
weak bases
bioavailability factors
body membrane structure and function
drug movement across membrane barriers
active transport
factors that affect distribution
tissue permeability
blood flow
plasma protein binding
subcellular protein binding
serum protein binding
drugs will sometime attach to plasma proteins
proteins allow the drug to stay in the blood, but a drug that is bound to plasma protein cannot leave the blood to distribute into tissues and is inactive
drug that is unbound (free) may distribute from blood to tissues and is active
volume of distribution (Vd)
-what is it
amount of drug administered / concentration of drug in plasma
if Vd... -equals total amount of body water -greater than total amount of body water -less than total amount of body water slides 80-83
equal
-uniform body distribution
greater than
-drug is being concentrated in the tissues
less than
-drug is being retained in the bloodstream (due to plasma protein binding for example)
when does apparent volume of distribution come into play?
when there is some material that absorbs the drug and prevents it from showing up when you try and check the Vd
primary sites of drug storage
-what type of drugs are stored in each?
adipose tissue -primary site; ex: anesthetics bone -toxic agents; ex: lead muscle -long-term storage; ex: anti-malarials organs -often liver and kidneys; ex: anti-microbials
other (new) drug delivery examples
controlled release
implanted reservoir
targeted cell and tissue delivery
controlled release
- benefits
- examples
decreases the number of doses/day sustains dose throughout night examples -beta blockers -analgesics -Parkinson's drugs
implanted reservoir
- locations
- examples of drugs
locations -abdomen -spinal cord examples -muscle relaxers -analgesics -anesthetics -hormones
trageted cell and tissue delivery
- function
- examples
attaching antibodies to drugs
examples
-Brentuximab vedotin for Hodgkin Lymphoma
drug elimination
-what are mechanisms for doing this?
biotransformation
excretion
combination
-of the above 2
biotransformation
- aka
- what is it
aka metabolism
chemical altering of a drug to a metabolite via enzymes to deactivate that drug
excretion
- what is it
- common methods
excreting the active form of a drug
methods
-liver to SI via bile duct
-through kidneys
biotransformation-cellular mechanisms
oxidation
reduction
hydrolysis
conjugation
drug metabolism
- where
- how
- other factors
where -primary location: liver -lungs, kidneys, GI, skin how -biotransformation other factors -tissue/organ damage -metabolic inhibitors -enzyme induction
competitive inhibition of metabolism
inhibition of the enzyme that metabolizes drug B, by drug A, decreases the metabolism of drug B
if drug A forms a covalent bond with the enzyme, then you have to wait for the cell to make more enzymes for drug B to have effect
induction of metabolism
induction of the enzyme that metabolizes drug B, by drug A, increases the metabolism of drug B by increasing the enzyme quantity
factors affecting excretion
reabsorption polarity of metabolite ionized=polar polar drugs tend to be excreted non-polar drugs tend to be reabsorbed into body versus being excreted
drug elimination rates
-two key ideas
clearance
half-life
clearance (CL)
- what is it
- equation
- dependent on…
- what is systemic CL
the ability of one organ or all organs to clear a drug
CL = Q x ((Ci-Co/Ci))
dependent on organ ability to extract drug from plasma and perfusion
systemic CL
-sum of individual organ CLs
CL factors
blood flow to organ (Q)
extraction ratio - the fraction of drug removed from the plasma as it passes through the organ (Ci-Co)
concentration
half-life
duration of activity of the compound in the body
the amount of time required for 50% of the drug remaining in the body to be eliminated
a function of both clearance and volume of distribution
dosing schedules
-2 types
continuous administration
interval administration
continuous administration
matching the rate of administration with the rate of drug elimination (clearance) once the desired plasma concentration in achieved
after 5 half-lives of a drug you will reach a steady state
interval administration
dosage is adjusted to provide an average plasma concentration over the dosing period dosing interval (time in hours) will affect size of dosage need to maintain same relative plasma concentration
what is a receptor
a cellular component where a drug binds and initiates a chain of biochemical events
surface receptors
- location
- responsive to…
- recognize and effect change by…
located on outer cell membrane responsive to amino acid peptides, or amine compounds recognize and effect change by -ion channel/membrane permeability -enzymatic effects -regulatory protein links
surface mechanisms
receptor + ion channels
enzymes + receptors
regulatory proteins + receptors
receptor + ion channels
ACh example
-ACh binds to receptor which activates opening pore in membrane allowing sodium in
enzymes + receptors
protein tyrosine kinases
-outer surface stimulation activates inner surface wall enzymatic process
regulatory proteins + receptors
proteins are located on inner surface of membrane
G-proteins when stimulated then activates enzymes or Ion channels
2nd messenger system
intracellular receptors
- location
- examples
- generally control…
located at cytoplasm and nucleus
a specific interaction mechanism for hormones
examples: thyroid hormones; steroids
generally control gene expression when activate
drug-receptor interactions
-successful binding is affected by…
drug size
drug shape/fit: key-lock analogy
affinity
presence of allosteric modulators
affinity
electrostatic attraction between a drug and receptor
related to the drug amount required to bind to the unoccupied receptors (if affinity is low, higher concentrations may be needed)
what are allosteric modulators
local modulators that affect affinity of receptor portion of bond
drug selectivity
a drug affects only one type of cell or tissue and produces a specific physiologic response
dose response
- what is it
- can also be affected by
response is essentially proportion to the number of receptors occupied by the drug not always a linear relationship can be affected by -affinity -receptor signal transmission
what is an agonist
-what is a partial agonist
drug capable of binding to a receptor and activating change in the cell’s function
has both affinity and efficacy
partial agonists
-create a less than optimal response even though they are capable of occupying receptors
what is an antagonist
- example
- competitve vs irreversible
drug capable of binding to a receptor but unable to create change in the receptor cell’s function
has affinity, but not activity
occupy valuable receptor site thereby “blocking” agonists from binding
example: beta blockers
competitve or irreversible
competitve antagonists can be displaced with higher concentrations of a drug agonist, but irreversible antagonists form permanent bonds that prevent agonists from binding
receptor regulation
a prolonged increase in receptor stimulation will result in a decrease in receptor function (due to agonists)
a decrease in receptor stimulation will result in an increase in receptor numbers or sensitivity (due to antagonists)
