Pharmacology

Question 1

Define pharmacokinetics and pharmacodynamics

Answer 1

Pharmacokinectics is what the body does to the drug; the study of how the drug is administered, absorbed, distributed, biotransformed, and excreted. Determines how much/how often you can administer drug. Determines when therapeutic plasma conc. reached and when this value can be measured.

Pharmacodynamics is what the drug does to the body. The study of the time to onset, magnitude, duration/mechanisms of drug effects. Determines what drug class and how much of a drug you can prescribe. Sets the therapeutic/toxic ranges.

Question 2

What drug class is –mab?

Answer 2

monoclonal antibody

Question 3

What drug class is –ximab?

Answer 3

chimeric (mouse-human) monoclonal antibody

Question 4

What drug class is -zumab?

Answer 4

humanized monoclonal antibody; i.e. mouse component only 10% or less

Question 5

What drug class is -umab?

Answer 5

human monoclonal antibody

Question 6

what drug class is -cept?

Answer 6

receptor-antibody fusion protein that mimics an immunoglobin.

Question 7

Explain the bioequivalence of generic drugs

Answer 7

Whether or not the generic drug gets into the blood stream to the same extent and as fast as the brand-name drug.

Question 8

Explain the bioequivalence of biosimilar drugs

Answer 8

Whether or not a biosimilar drug has the same exact structure as the original biologic.

Question 9

What is the difference between drug selectivity and specificity?

Answer 9

A drug is specific when it has only 1 effect on all biological systems. Very few drugs are specific.

Drugs that are selective will exhibit activity at more than 1 receptor site of at high enough concentration. Most drugs are selective.

Question 10

At what dose of a selective drug will it exhibit specific activity?

Answer 10

There is NO specific dose for a selective drug. Varying doses may be more selective for one effect or another, but a selective drug is never specific.

Question 11

Describe the phases of drug development

Answer 11

Basic research phase: includes synthesis, examination and screening.

Drug development phase:

• Preclinical tests: animal models
• Clinical Phase I, II, III: human

Introduction/Registration phase: includes post-marketing surveillance

Only 1 out of every 10,000-25,000 drugs make it to market.

Question 12

How does the FDA communicate w/ Physicians?

Answer 12

Primary method is product labeling on drugs. Includes info on the efficacy and safety of the drug, but only for indications approved by the FDA.

Can also access the FDA Drug Approval Package online which details ALL studies done with the drug, avoids publication bias where only “good” studies are talked about, includes raw data which is put through analysis by statistician for verifications.

Question 13

What is “off-label” prescribing/use of a drug and how is the safety/efficacy of off-label use addressed by the FDA and drug companies?

Answer 13

Off-label use of a drug is when the drug is used for something the FDA has not approved it for. The FDA is silent about off-label uses of drugs. So physicians won’t know whether a drug is truly safe/effective for an off-label use. The FDA does not regulate physician prescribing, so if you rx a drug for an off-label use, you are on your own.

Drug companies cannot advertise off-label uses, but can tell you about them if you directly ask. Drug companies can hand you journal articles about off-label uses now.

Question 14

What is drug potency? What does it look like on a graded Log-Dose response curve?

Answer 14

The amount (dose) of a drug needed to cause the same effect as compared to another drug. That is to say that if drug A achieves an ED50 at 40 mg and drug B at 60 mg, drug A has a higher potency (ED50 represents a 50% response).

On a graded Log-Dose curve, find ED50 on the y-axis and follow to the right comparing at what dose various drugs achieve ED50. similar to Km

Question 15

What is drug efficacy? What does it look like on a graded Log-Dose response curve?

Answer 15

The maximal effect produced by a drug; efficacy has nothing to do w/ potency. That is that two drugs with different potencies can have the same efficacy. Efficacy is more important than potency.

On a graded log-dose response curve, efficacy is the maximum response seen on the curve. Similar to Vmax.

Question 16

What is drug slope on a graded log-dose response curve?

Answer 16

The steepness by which response changes with respect to changes in dose. Ideally want a drug to have a more shallow slope, because if a small change in dosage corresponded to a large response and there are adverse effects, would want to minimize this.

Question 17

What is drug variation?

Answer 17

differences between individual samples.

Question 18

What is an agonist?

Answer 18

An agent that activates a receptor and its associated effector system.

Question 19

What is a partial agonist?

Answer 19

A drug that exhibits an efficacy less than 1 (full agonist have efficacy =1) but less than 0 (antagonist have efficacy = 0). Partial agonists have same binding affinity as full agonists, but when used together with an agonist a partial agonist will decrease the net response. That is, partial agonists can be used to reduce endogenous activity.

Question 20

Explain the differences in efficacy between partial and full agonists and what the other contributing factors are.

Answer 20

While a full agonist has greater efficacy than a partial agonist, in theory, the efficiency of drug-receptor coupling determines the actual efficacy of a drug.

A full agonist with “inefficient coupling” to its receptor may require higher stimulus to achieve a given response. Whereas a partial agonist with highly “efficient coupling” may have an actual efficacy that is equal to a full agonist.

Question 21

What is an inverse agonist?

Answer 21

A drug that binds to a receptor and inhibit constitutive activity of the receptor by exhibiting negative intrinsic activity. Example: if a receptors basal activity was 50% and a full agonist boosted this activity to 75%, then an inverse agonist would decrease the activity to 25%. Different from an antagonist.

Question 22

What is an antagonist?

Answer 22

An agent that prevents/blocks a receptor and its effector system from performing its action. Alone, an antagonist does nothing.

Question 23

What is a competitive antagonist?

Answer 23

A antagonist that can be overcome by increasing conc. of agonist. Dose response curves are shifted to the right. Maximum efficacy remains the same, though affinity of an added agonist for its receptor appears to be decreased.

Question 24

What is noncompetitive antagonism?

Answer 24

An antagonist where inhibition cannot be overcome by increasing conc. of the agonist. No right-shift of curve seen, but affinity of agonist for receptor remains the same. Also max effectiveness will decrease.

Question 25

What is chemical antagonism?

Answer 25

When one drug interacts with another to prevent its action. Ex. chelation of lead to prevent toxicity. Or, interaction of N-acetylcysteine w/ reactive electrophiles to prevent toxicity as w/ acetaminophen.

Question 26

What is physical antagonism?

Answer 26

When a drug counteracts the effects of another drug, by binding to a different receptor and causing opposite effects. Example: glucocorticoids can increase blood sugar. While insulin is administered to decrease blood sugar. These two act via different receptor systems.

Question 27

What are spare receptors?

Answer 27

Are added receptors to a membrane that increase sensitivity to a drug. By increasing receptors in a membrane that are specific for a drug, you can give less drug and still get to same desired response.

Question 28

What is KD?

Answer 28

KD or Kd, is the concentration of agonist needed to bind 50% of target receptors. Represents affinity of an agonist for its receptor.

Question 29

What is ED50 or EC50?

Answer 29

Both are the same. Dose at which a drug has a 50% response.

Question 30

What is Quantal Log-Dose Response?

Answer 30

Shows the frequency/cumulative frequency of a given response within a population at different dose concentrations. The slope of a quantal log-dose response is an indicator of variability of the population.

Question 31

What is therapeutic index?

Answer 31

The ratio of TD50:ED50, comparing dose at which 50% of individuals saw toxicity to the dose at which 50% of responding individuals saw a therapeutic effect. Want a HIGH ratio, signifies high therapeutic effect and low toxicity.

Question 32

What is desensitization? Compare homologous and heterologous desensitization.

Answer 32

Desensitization is the diminished response of a receptor (diminished signal) to an agonist. Homologous desensitization is when only the signal from the stimulated receptor is attenuated. Can be due to covalent modification, receptor destruction, or receptor relocation within the cell.

Heterologous desensitization is when multiple receptors (targeted by different drugs) with a common effector pathway may be less effective only when 1 is stimulated.