Pharmacology

Question 1

Pharmacokinetics vs pharmacodynamics

Answer 1

Kinetics: what the body does to the drug
Dynamics: what the drug does to the body

Question 2

Pharmacokinetics is all about the…

Answer 2

PLASMA CONCENTRATION

Question 3

Pharmacodynamics is all about the…

Answer 3

RECEPTORS

Question 4

Pharmacokinetics ADME

Answer 4

Movement of drugs in the body!
Absorption, distribution, metabolism, excretion/elmination

Question 5

Majority of drugs are what size?

Answer 5

Molecular weight between 100-1000

Question 6

SMALL molecules as drugs

Answer 6

Low molecular weight, less than 1000
Chemical synthesis
Linear structure
ORAL usually
Metabolized
SHORT half lives, daily administration, short acting
On and off target toxicity

Question 7

LARGE molecules as drugs

Answer 7

High molecular weight
Biosynthesis
Complex tertiary or quaternary structure
Parenteral only, IV
Degraded/catabolized
Longer half lives (days/weeks)
Intermittent administration, longer acting
On target toxicity

Question 8

brand name vs generic

Answer 8

1. Drug given chemical name
2. Given code name or short version
3. When approved by FDA, a generic name is applied
4. When drug is patented, a brand name is developed
5. When off patent, other manufacturers can sell under generic name or own brand name

Question 9

Are OTC and prescription both FDA regulated?

Answer 9

YES!

Question 10

Supplements

Answer 10

Do not have to prove efficacy, do not have to prove safety, cannot be sold to treat/address disease, only regulated POST marketing

DRUGS :regulated pre and post marketing, prove safety and efficacy

Question 11

Drug targets (receptors)

Answer 11

1. Regulatory proteins: growth factor receptors, hormone receptors, neurotransmitter proteins
2. Enzymes: dihydrofolat reductase, HMG-CoA
3. Transport proteins: Na/K ATPase, serotonin reuptake, ion channels
4. Structural proteins: tubulin

Question 12

Graded Dose-response relationship

Answer 12

Concentration or dose of drug vs. % of MAXIMUM effect
Linear: hyperbolic
Log: sigmoid

EC50 or ED50=EFFECTIVE concentration or dose required to produce HALF the maximum effect
EMAX: EFFICACY

Question 13

Efficacy

Answer 13

The ability of a drug to bind a receptor and generate an effect: reflects intrinsic activity of a drug or HOW WELL a drug generates an effect—how well does the drug work?

Defined by the maximum effect a drug can produce
Drugs may have SAME ED50, but DIFFERENT MAXIMAL EFFECT

Question 14

Potency

Answer 14

Relative concentration of drug required to produce a given effect (ED50), how STRONG a drug is

Multiple drugs may have same max efficacy, but some may be more POTENT

Question 15

Goal in administering drugs is?

Answer 15

Obtain drug concentration in THERAPEUTIC RANGE

Question 16

Degree of safety of drug

Answer 16

Depends on adequate separation between doses that produce therapeutic effects (ED50) and undesirable effects (LD50)

Question 17

Therapeutic index (TI)

Answer 17

LD50/ED50

SHould be GREATER than 1 and BIGGER IS BETTER
Ideally, greater than 10!!
Importance is separation of therapeutic benefit and toxic doses in individuals

Question 18

Margin of safety

Answer 18

MI
LD1/ED99
More CONSERVATIVE comparing the extremes of the dose response curves to indicate any overlap

Should be greater than 1, bigger is better

Question 19

Drug receptors

Answer 19

Macromolecule that drugs interact with to modify or produce physiologic effect

They have endogenous ligand that modulate physiologic effects
Some drugs have NO RECEPTORS: MANNITOL, just draws water into kidney tubule

Question 20

Effectors

Answer 20

Component that accomplishes biological effect after receptor is activated
“Second messengers” or “signaling pathways” , they are coupled to receptor

Sometime they are part of receptor
They can greatly amplify the signal from receptor !!!! They can also prolong effect of the drug after drug LEAVES RECEPTOR

Question 21

AGonist vs antagonist

Answer 21

Agonist: drug that binds to receptor and activates it
Antagonist: drug that binds to receptor but does not activate it and PREVENTS activation by agonist

Question 22

Competitive antagonist

Answer 22

Can be overcome by INCREASING AGONIST concentration

Question 23

Irreversible antagonist/noncompetitive

Answer 23

CANNOT be overcome by increasing agonist concentration

Does not produce an effect on its own, so has Affinty but NO EFFICACY
Prevents endogenous ligand from binding
Leads to reduced number of receptors available for ligand to bind
Affects the efficacy of the endogenous ligand, can’t work as well

Question 24

Physiologic antagonist

Answer 24

Drug that counters the effects of another drug by inning to a different receptor and causing apposing effects

Question 25

Chemical inhibitor

Answer 25

Drug that causes effects by binding to another agonist: chelates of heavy metals, anti acids, antibodies that bind to growth factors

Question 26

Agonist binding site vs allosteric site

Answer 26

1. Drug can bind receptor at agonist binding site (receptor site) to initiate signaling pathway 2. Drug can bind at allosteric/modulatory sites: binds to receptor no does not interfere with agonist binding but modulates activity of agonist!!!

Question 27

FULL agonist

Answer 27

Produces the SAME maximal effect as the endogenous ligand, efficacy is 100% for both Binding activates receptors signaling pathway CAN differ in POTENCY but NOT EFFICACY *smaller EC50, higher potency

Question 28

Competitive Antagonist

Answer 28

Freely binds and dissociates from the receptor Does NOT produce effect on its ow so has affinity but NO EFFICACY Competes with endogenous ligand for binding CAN be overcome by large amount of endogenous ligand, so REVERSIBLE Affects the POTENCY of the endogenous ligand (unlike irreversible that affects the efficacy )

Question 29

Mechanisms of desensitization and tachyphylaxis

Answer 29

1. Changes in receptor function 2. Changes in available receptor numbers 3. Exhausting mediators 4. Induced drug metabolism 5. Physiologic compensation

Question 30

Allosteric modulators

Answer 30

Modify function by binding at site OTHER than active site No effect on their own POSITIVE modulators can increase potency or efficacy of endogenous ligand: agonists NEGATIVE modulators can decrease potency or efficacy of the endogenous ligand: inverse agonists

Question 31

Partial agonist

Answer 31

Has a little bit of activity on its own (even when Receptors are bound!) so on its own is a partial agonist. BUT when combined with a full agonist, it acts as an ANTAGONIST: competes with full agonist for same binding site

Question 32

Inverse agonist

Answer 32

Inhibits the basal constitutive activity o receptors

Question 33

Partial (mixed agonist)

Answer 33

Produces sub-maximal effect as compared to endogenous ligand, efficacy is less than 100% Binding does NOT fully activate receptors signaling pathway so efficacy is reduced

Question 34

Specialized receptor: enzyme

Answer 34

Common mechanism by which drugs act Decrease or stops the conversion of endogenous substrate into the product !! Competitive, noncompetitive, uncompetitive, irreversible

Question 35

Prodrug

Answer 35

Inactive form of drug that binds the active site of the target enzyme and is activated by the enzyme

Question 36

P-glycoproteins

Answer 36

P-gp or mdr or abac1: PROTECTIVE function by transporting substrates that enter cells either back where they came from or into the adjacent elmination site to prevent accumulation of a substrate Mdr: multi drug resistance found to make some tumors resistant to multiple different classes of drugs Enterocyte: back into intestinal lumen hepatocytes: into biliary canaliculi

Question 37

How to interfere with function of transporters?

Answer 37

Inhibit transporter function with drugs Prevent transporter function….mutation !

Question 38

Dogs with non-functional P-gp

Answer 38

Frameshift mutation of mdr-1 results inn stop codons and truncated protein that is NOT FUNCTIONAL These drugs are sensitive to many drugs that are p-gp substrates Macrocyclic lactose, loperamide, acepromazine, anti-neoplasticism Combining pgp inhibitor with a substrate can elevate concentrations of either drug in tissues that pgp normally protects Be careful when administering higher doses of macrocyclic lactones and consider breed !! Be careful when combining drugs that are substrates and inhibitors: ex is ketoconazole and ivermectin