Section 1

Question 1

What is pharmacology?

Answer 1

The study of drugs

Question 2

what is pharmacodynamics?

Answer 2

drug effects

textbook:
the study of the detailed** mechanism of action** by which the drugs produce their pharmacologic effects.

Question 3

Describe the important characteristics of a
receptor.

Answer 3

its binding ability, change its shape to get signal into cell and push cell to have response.

Question 4

Describe the relationship between [drug], binding
to receptors and effect using a dose-response curve

Answer 4

on a dose response curve, the effect is the y axis and the log dose is the x axis.

Question 5

compare & contrast potency and efficacy

Answer 5

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.

Question 6

What is a receptor?

Answer 6

something that has the affinity to bind to drugs and cause an effect.

They are macromolecules that are oftem membrane bound proteins.

Question 7

High affinity

Answer 7

low amount of drug needed
slower ending of effect (binds tightly to receptor and is slower to end)

Question 8

compare & contrast agonists and antagonists

Answer 8

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*

Question 9

what does a drug as an agonist do?

Answer 9

activates the receptor

Question 10

What law does binding follow?

Answer 10

The law of mass action

Question 11

How do you describe the drug receptor complex?

Answer 11

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.

Question 12

What is Kd?

Answer 12

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

Question 13

for the log dose graph

what does the straight part represent?

Answer 13

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

Question 14

What is the law of mass action?

Answer 14

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

Question 15

What is the measure of affinity/potency?

Answer 15

the Kd, a smaller Kd is more potent. 50% of rectopr bound at Kd is a measure of potency.

Question 16

Which is more important? Efficacy or potency?

Answer 16

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.

Question 17

analgesia

and examples given

Answer 17

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.

Question 18

about receptors and signaling

What are the type of receptors?

mentioned in the first lecture

Answer 18

• Ionotropic receptors: ion channels (glutamate, GABA)
• metabotropic receptors: use G-proteins, kinases (autonomic receptors - Beta adrenergic receptors)
• Transcription factors - Alter gene expression (Steroid hormones)

Question 19

What is the drug receptor complex?

Answer 19

the binding of the drug and its receptor.

Question 20

drug effects

When does the effect happen?

Answer 20

after signal transduction after the drug receptor complex is made after receptor binding when the drug and recdeptor meet.

Question 21

describe classes of simple signal transduction
pathways

Answer 21

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)

Question 22

describe three situations where binding of drugs
to receptors is not proportional to drug effect.

Answer 22

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

Question 23

contrast the effects of competitive and noncompetitive antagonists on the dose-response curve of an agonist

Answer 23

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

Question 24

explain the effects of partial agonists, inverse agonists etc. using a receptor model where active and inactive receptors are in equilibrium

Answer 24

partial agonists have a lower efficacy and a smaller curve in comparison to a full agonist and not quite as s-shaped.

inverse agonists

Question 25

describe how the ED50 may be lower than the Kd for a drug in the case of spare receptors.

Answer 25

When there are spare receptors, you only need to activate a fraction of them to get a maximal response.

Question 26

define a non-competitive antagonist

Answer 26

a non-competitive antagonist makes the curve smaller

Question 27

define inverse agonist

Answer 27

an inverse agonist stabilizes inactive agonist, active receptors flicker to inactive and soon you bottom out and response ends.

Question 28

The dose response curve as a full agonist, partial agonist, antagonist, and inverse agonist

Answer 28

high long curve, shorter curve, flat curve (if by itself), and opposite agonist respectively.

Question 29

What is the (not so much used) protective index?

Answer 29

TD50/ED50
often used interchangeably with TI

TD: toxic dose

Question 30

What is the standard safety margin?

Answer 30

• % by which the ED99 must be increased before an LD1 is reached
• (LD1- ED99)/ED99 x 100

Question 31

Define the therapeutic window

Answer 31

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.

Question 32

define tachphylaxis

Answer 32

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.

Question 33

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

Answer 33

upregulation

Question 34

what is endocytosis

Answer 34

the taking in of matter by a living cell by invagination of its membrane to form a vacuole.

Question 35

what kind of receptors are opioid receptors?

Answer 35

G-protein coupled receptors

Question 36

the effect of a drug depends on…?

Answer 36

concentration

Question 37

parenteral

Answer 37

administered or occurring elsewhere in the body than the mouth and alimentary canal.

google definition

Question 38

Describe the general characteristics/advantages of i.v. bolus

Answer 38

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

Question 39

Describe the general characteristics/advantages of iv infusion

Answer 39

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)

Question 40

Describe the general characteristics/advantages of subcutaneous

Answer 40

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

Question 41

Describe the general characteristics/advantages of intramuscular

Answer 41

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

Question 42

Describe the general characteristics/advantages of intraperitoneal

Answer 42

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

Question 43

Describe the general characteristics/advantages of pulmonary

Answer 43

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

Question 44

Describe the general characteristics/advantages of oral

Answer 44

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

Question 45

What should you not give in IV?

Answer 45

oils and suspensions

Question 46

Describe which processes (uptake, elimination) predominate in regions of a curve describing the blood levels of a single dose of drug given orally.

Answer 46

Same, whale hump.
“for sq, IM, etc”: get a period where absorption predominates then elimination which creates the hump

Question 47

Describe which processes (uptake, elimination) predominate in regions of a curve describing the blood levels of multiple doses of drug given orally.

Answer 47

Starts leveling out at about four half lives and get a stady state. In multiple doses you get peacks and troughs.

Question 48

What are some “special sites” for paranetal routes

Answer 48

Mouth: Squirt sedatives etc into cats mouths
Nerve blocks
Epidurals
Joint injections
Skin
Eye drops

Question 49

Describe the characteristics of a drug that allow it to penetrate a biological membrane/epithelium

Answer 49

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

Question 50

Describe how changes in pH affect movements of acidic and basic drugs across membranes

Answer 50

Weak acids are absorbed from acidic environments (Stomach, acidic urine)
Weak bases are absorbed from basic environments
(Small intestine, basic urine)

Question 51

Define “First pass” effect of the liver on drugs.

Answer 51

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.

Question 52

Define Volume of distribution

Answer 52

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.

Question 53

Be able to define:
Central & peripheral compartments

Answer 53

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

Question 54

Be able to describe the effect of the binding of drugs to plasma proteins on the binding of drugs to receptors.

Answer 54

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.