Section 1 Flashcards
What is pharmacology?
The study of drugs
what is pharmacodynamics?
drug effects
textbook:
the study of the detailed** mechanism of action** by which the drugs produce their pharmacologic effects.
Describe the important characteristics of a
receptor.
its binding ability, change its shape to get signal into cell and push cell to have response.
Describe the relationship between [drug], binding
to receptors and effect using a dose-response curve
on a dose response curve, the effect is the y axis and the log dose is the x axis.
compare & contrast potency and efficacy
potency is: compares the concentrations of drugs needed to get 50% of maximal effect (EC50)
efficacy is: the measure of maximal effect, you can have full and partial agonists.
What is a receptor?
something that has the affinity to bind to drugs and cause an effect.
They are macromolecules that are oftem membrane bound proteins.
High affinity
low amount of drug needed
slower ending of effect (binds tightly to receptor and is slower to end)
compare & contrast agonists and antagonists
agonists have an effect. Antagonists bind to the receptor but have no effect (on the receptor, they have an effect on the agonist). They block the effect of the agonist and shifts the dose-response curve of an agonist to the right (this is the effect of the antagonist).
an antagonist would make a flat line. antagonism is competitive.
This is how reversals work*
what does a drug as an agonist do?
activates the receptor
What law does binding follow?
The law of mass action
How do you describe the drug receptor complex?
the disociation constant (Kd) is equal to the product of the concentrations of the ligand and protein divided by the concentration of the protein ligand complex once equilibrium is reached.
Kd tells how much drug to give, small Kd less drugs to give
A drug receptor is a specialized target macromolecule that binds a drug and mediates its pharmacological action. These receptors may be enzymes, nucleic acids, or specialized membrane-bound proteins. The formation of the drug-receptor complex leads to a biological response.
What is Kd?
the measure of the affinity/potency
and it also tells you how much of the drug to give.
also is a rtio of the off rate of receptor binding to the on rate.
really low disociation constant, binds tightly
for the log dose graph
what does the straight part represent?
The straight part runs from 10-90% maximal drug effect. it is 81 fold based off law of mass action (low activity to high activity). 1 drug binding site per receptor.
two binding sites means you get a steeper curve
What is the law of mass action?
In chemistry, the law of mass action is the proposition that the rate of the chemical reaction is directly proportional to the product of the activities or concentrations of the reactants. It explains and predicts behaviors of solutions in dynamic equilibrium
What is the measure of affinity/potency?
the Kd, a smaller Kd is more potent. 50% of rectopr bound at Kd is a measure of potency.
Which is more important? Efficacy or potency?
In general, efficacy is very important. A less potent drug with high efficacy will usually produce better results than a less efficacious drug with high potency.
analgesia
and examples given
the inability to feel pain
buprenorphine: a very potent (partial) agonist at opioid receptors. has high afffinity binding (which means you can give less), binds for a long time, does not give as strong an analgesic effect as morphine.
and morphine: a less potent (full) agonist. has lower affinity binding, binds for a shorter period of time, stronger analgesic affect.
about receptors and signaling
What are the type of receptors?
mentioned in the first lecture
- Ionotropic receptors: ion channels (glutamate, GABA)
- metabotropic receptors: use G-proteins, kinases (autonomic receptors - Beta adrenergic receptors)
- Transcription factors - Alter gene expression (Steroid hormones)
What is the drug receptor complex?
the binding of the drug and its receptor.
drug effects
When does the effect happen?
after signal transduction after the drug receptor complex is made after receptor binding when the drug and recdeptor meet.
describe classes of simple signal transduction
pathways
Neurotransmitters work very rapidly through ion channels: Binding very rapid, fall off receptors very rapidly (msec)
Steroids work very slowly through protein synthesis: Take hours to days to synthesize proteins
Antibodies bind slowly (minutes), come off receptors slowly (days-weeks)
describe three situations where binding of drugs
to receptors is not proportional to drug effect.
Complex interactions:
* 1 Cascades of 2nd messengers
* 2 Spare receptors: Only need to activate a small fraction of receptors to get maximal response (Neuromuscular junction)
Tolerance/desensitization:
* 3 Previous exposure to a drug may cause decreased effects
contrast the effects of competitive and noncompetitive antagonists on the dose-response curve of an agonist
Agonists:
* Bind & activate receptor
* Get a dose-response curve
Antagonists:
* Bind & don’t activate receptor
* Flat dose-response curve by themselves
* Shift the dose-response curve of an agonist
explain the effects of partial agonists, inverse agonists etc. using a receptor model where active and inactive receptors are in equilibrium
partial agonists have a lower efficacy and a smaller curve in comparison to a full agonist and not quite as s-shaped.
inverse agonists
describe how the ED50 may be lower than the Kd for a drug in the case of spare receptors.
When there are spare receptors, you only need to activate a fraction of them to get a maximal response.
define a non-competitive antagonist
a non-competitive antagonist makes the curve smaller
define inverse agonist
an inverse agonist stabilizes inactive agonist, active receptors flicker to inactive and soon you bottom out and response ends.
The dose response curve as a full agonist, partial agonist, antagonist, and inverse agonist
high long curve, shorter curve, flat curve (if by itself), and opposite agonist respectively.
What is the (not so much used) protective index?
TD50/ED50
often used interchangeably with TI
TD: toxic dose
What is the standard safety margin?
- % by which the ED99 must be increased before an LD1 is reached
- (LD1- ED99)/ED99 x 100
Define the therapeutic window
The dose range of a drug that provides safe and effective therapy with minimal adverse effects. Generally, at low concentrations, a drug runs the risk of being ineffective; at high concentrations, the risk of adverse effects is increased.
Also tells you how much of a drug to give.
define tachphylaxis
it is an acute sudden decrease in response to a drug after its administration; i.e. a rapid and short-term onset of drug tolerance. It can occur after an initial dose or after a series of small doses. Increasing the dose of the drug may be able to restore the original response.
an increase in uterine oxytocin receptors in the third trimester of pregnancy, promoting the contraction of the smooth muscle of the uterus is an example of
upregulation
what is endocytosis
the taking in of matter by a living cell by invagination of its membrane to form a vacuole.
what kind of receptors are opioid receptors?
G-protein coupled receptors
the effect of a drug depends on…?
concentration
parenteral
administered or occurring elsewhere in the body than the mouth and alimentary canal.
google definition
Describe the general characteristics/advantages of i.v. bolus
Drug starts in blood & central compartment (well perfused organs)
Drug moves to less perfused organs later
Peripheral compartment
Muscle
Skin
Fat
This redistribution ↓ blood concentrations
Elimination causes subsequent losses
Describe the general characteristics/advantages of iv infusion
a gradual climb of concentration in the blood. after about 4 half lies, concentration will be flat. as you give more of the drug, the rate of elimination gets biggerand eventually measures uptake and create a “steady state” concentration (usually occurs after 4 half lives)
Describe the general characteristics/advantages of subcutaneous
Prompt absorption for aqueous solutions
Slow & sustained for repository
Suitable for some suspensions (can give things you can’t give IV)
Site of some slow-release implants
Don’t give large volumes, irritants
Describe the general characteristics/advantages of intramuscular
Prompt absorption for aqueous solutions
Slow & sustained for repository
Suitable for moderate volumes, some oily vehicles and irritants
IM can hurt, watch for safety with larger animals.
similar whale hump
Describe the general characteristics/advantages of intraperitoneal
Lab animals
very Fast, almost as fast as IV
Don’t use for irritants (keep in mind peritonitis, gonna be irritating)
seemed to never hurt the animal or penetrate organs
Describe the general characteristics/advantages of pulmonary
Gases, nonirritating aqueous drugs (if you have a trach tube in and do not have IV, you can dump down trach tube and sometimes as fast as IV)
careful of aspiration pneumonia
another cool way is intraosseous
Describe the general characteristics/advantages of oral
Absorption variable: Bioavailability (fraction of drug that makes it to the systemic blood), Usually slower onset than IV etc
Often more: Economical (doesn’t have to be safe), Safe, Convenient (Can the owner pill the animal?)
Species variability: Not usually used in ruminants
What should you not give in IV?
oils and suspensions
Describe which processes (uptake, elimination) predominate in regions of a curve describing the blood levels of a single dose of drug given orally.
Same, whale hump.
“for sq, IM, etc”: get a period where absorption predominates then elimination which creates the hump
Describe which processes (uptake, elimination) predominate in regions of a curve describing the blood levels of multiple doses of drug given orally.
Starts leveling out at about four half lives and get a stady state. In multiple doses you get peacks and troughs.
What are some “special sites” for paranetal routes
Mouth: Squirt sedatives etc into cats mouths
Nerve blocks
Epidurals
Joint injections
Skin
Eye drops
Describe the characteristics of a drug that allow it to penetrate a biological membrane/epithelium
if not being transported, lipid soluble can be transported better than polar drugs and, with that being said, uncharged form can move across lipid bilayer.
smaller crosses better than large
surface area: stomach small surface area, small intestines large surface area
transporters: many drugs are not absorbed from the gut using transporters, if they are, polartiy/size of drug may not matter.
transporters throw this all out the window;can absorb any drug with them
Describe how changes in pH affect movements of acidic and basic drugs across membranes
Weak acids are absorbed from acidic environments (Stomach, acidic urine)
Weak bases are absorbed from basic environments
(Small intestine, basic urine)
Define “First pass” effect of the liver on drugs.
The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation.
Define Volume of distribution
Simply defined, the volume of distribution is the volume of plasma that would be necessary to account for the total amount of drug in the patient’s body, if that drug were present throughout the body at the same concentration as found in the plasma.
Be able to define:
Central & peripheral compartments
Central compartment: well perfused, effects are rapid. Peripheral: not well perfused, slower effects. Drug starts in blood & central compartment (well perfused organs). Drug moves to less perfused organs later. Peripheral compartment: Muscle, Skin, Fat. This redistribution ↓ blood concentrations. Elimination causes subsequent losses
Be able to describe the effect of the binding of drugs to plasma proteins on the binding of drugs to receptors.
Albumin and other plasma proteins may bind drugs with a low affinity. Only free drug binds receptors. Both hydrophilic and hydrophobic drugs bind proteins. Liver disease may affect protein levels: Decreased proteins may lead to increased levels of free drugs.
