Lecture 1

Question 1

What does a drug do?

Answer 1

Interacts with specific macromolecules (binds receptors or target) in order to alter biochemical or biophysical activities

Question 2

What is pharmacodynamics?

Answer 2

The study of the biochemical and physiological effects of drugs and their mechanisms of action on the body

Question 3

What does the study of pharmacodynamics and pharmacokinetics predict and what does this lead to?

Answer 3

Can predict anticipation of adverse effects leading to safe and successful therapy

Question 4

What can cause drugs to vary from patient to patient?

Answer 4

Genetic differences

Question 5

Why study pharmacology?

Answer 5

Leads to druggable discoveries at any point of a mechanism

Question 6

How can we get drugs to intended target tissues?

Answer 6

Immunotherapy by utilizing specific antigens and antibodies

Question 7

What are some cell activities that can be a result of extracellular stimuli by a drug?

Answer 7

Secretion altering biologic function leading to changes in motility, metabolism, endocytosis and proliferation – alter rate or magnitude of response not create new response

Question 8

What is the most important class of drug receptors?

Answer 8

Proteins – including hormones, growth factors, transcription factors, neurotransmitters

Question 9

What is a physiological receptor?

Answer 9

A receptor that normally serves as a receptor for endogenous regulatory ligands

Question 10

What is an agonist?

Answer 10

A drug that binds a physiological receptor and mimics the regulatory effects of the endogenous signaling compounds

Question 11

What is the difference in a primary agonist and an allosteric agonist?

Answer 11

A primary agonist binds to the same recognition site as the endogenous agonist but allosteric agonists bind to a different region on the receptor

Question 12

What are antagonists?

Answer 12

Drugs that block or reduce the action of an agonist which commonly results from competition for same or overlapping receptor site

Question 13

What is another name for agonists and antagonists?

Answer 13

Agonist - activator, antagonist - inhibitor

Question 14

What is chemical antagonism?

Answer 14

Combination with the agonist

Question 15

What is function antagonism?

Answer 15

Indirect inhibition of the cellular or physiological effects of the agonist

Question 16

What are partial agonists?

Answer 16

Agents are only partly as effective as agonists regardless of the concentration employed

Question 17

What would the relationship between an allosteric activator and agonist combination be compared to the agonist alone?

Answer 17

Larger response

Question 18

What would be the relationship between an agonist and competitive inhibitor combination compared to the agonist alone?

Answer 18

Larger dose would be needed to reach same response

Question 19

What would be the relationship between an agonist and allosteric inhibitor be compared to an agonist alone?

Answer 19

A lower response

Question 20

What is coupling?

Answer 20

The transduction process that links drug occupancy of receptors and pharmacologic response

Question 21

What does agonist binding to a receptor induce?

Answer 21

A conformational change – one of the first steps required to produce a pharmacologic response

Question 22

What is affinity?

Answer 22

The strength of the reversible interaction between a drug and its receptor measured by the dissociation constant

Question 23

What determines affinity and intrinsic activity and specificity to a drug?

Answer 23

Chemical structure

Question 24

What is the downside of a drug that acts on a receptor that is widespread throughout the body?

Answer 24

Could lead to widespread effects that could produce serious side effects

Question 25

What are two types of drugs that have discrete modes of action but effects throughout the entire body?

Answer 25

Digoxin which inhibits NaKATPase and Lidocaine which is a Na+ channe l blocker

Question 26

What can chronic administration of a drug cause?

Answer 26

Downregulation or desensitization leading to dose adjustment or sometimes complete tolerance

Question 27

What is tachyphylaxis?

Answer 27

The process by which chronic administration of drugs cause a rapid development of complete tolerance

Question 28

What determines the concentration of drug required to form a significant number of drug-receptor complexes?

Answer 28

The receptor’s affinity for binding a drug and the total number of receptors available

Question 29

What does the effect of an antagonist depend on?

Answer 29

Binding of agonist molecules and blocking their biologic actions

Question 30

What is pharmacological antagonism?

Answer 30

1 receptor where both the agonist and antagonist compete for the same receptor

Question 31

What is physiological antagonism?

Answer 31

2 receptors where 2 agonists bind to two different receptors each eliciting a physiological response - usually opposing each other

Question 32

What is a chemical antagonism? And what is an example?

Answer 32

0 receptors where the antagonist directly interacts with the agonist such as by neutralizing – protamine is an example that neutralizes heparin due to opposing charges making heparin unavailable for blood clotting

Question 33

What do competitive antagonists do?

Answer 33

Act by binding to receptors to prevent agonists from activating but do not themselves activate – strengthened by increasing concentration – can be reversed if there is enough agonists to overcome

Question 34

What do non competitive antagonists do?

Answer 34

They bind to receptor with a covalent bond that is so tight that the receptor is unavailable for binding of agonist and process is irreversible - limits maximum effect of agonist by other spare receptors

Question 35

What is phenoxybenzamine?

Answer 35

An example of an irreversible/noncompetitive antagonist that is used to control hypertension caused by catecholamines released from an adrenal medulla tumor

Question 36

What are allosteric modulators?

Answer 36

Drugs that function as noncompetive antagonists that are reversible in their reactions as they do not bind covalently

Question 37

What is buprenorphine an example of?

Answer 37

A partial agonist of opioid receptors that is safer than morphine because it produces less respiratory depression

Question 38

How do you reverse effects of an irreversible antagonist?

Answer 38

Must use a physiological antagonist to create an opposing effect with different receptors

Question 39

What does an inverse agonist give?

Answer 39

An opposite physiological response of that of the agonist

Question 40

What are the 3 variable involved in drug-receptor interactions?

Answer 40

Dose, effect and time

Question 41

Does an agonist or antagonist exhibit affinity and efficacy?

Answer 41

Agonist - antagonist has affinity only

Question 42

What is potency?

Answer 42

The measure of the amount of drug necessary for a give response – less needed = more potent (but more side effects) - ex dilaudid (hydromophone) much more potent than morphine

Question 43

What are some receptor types for drug action?

Answer 43

GPCRs, ion channels, transporters on cell membrane – leads to second messengers

Question 44

How do GPCR act as a receptor?

Answer 44

Use ACh as ligand to cause muscarinic cholinergic changes – examples of drugs are atropine and montelukast

Question 45

How do ion channels act as receptors?

Answer 45

Ligand or voltage gated using ACh or GABA as a ligand – drugs are nicotine or lidocaine

Question 46

How do nuclear receptors act in drug mechanisms?

Answer 46

Act as steroid or thyroid hormone receptors that use estrogen as a ligand – drugs include estrogen, androgen and cortisol

Question 47

How do trans-membrane enzymes work as receptors in drug mechanisms?

Answer 47

Use RTKs to bind insulin, and growth factors as ligands – drug is herceptin