Pharmacodynamics

Question 1

Pharmacodynamics

Answer 1

Study of how drugs produce their effect on the body

Question 2

2 Main focuses of pharmacodynamics

Answer 2

1) Mechanism of action - how a drug produces its pharmacologic effects
2) Pharmacological effect - anticipated results of a drug’s actions either therapeutic or adverse

Question 3

Drugs cannot create new cellular functions, they can only…

Answer 3

…modify existing ones

Question 4

Physical/chemical mechanisms of drug actions

Answer 4

Some drugs produce responses by altering the cell or its environment WITHOUT interacting with cellular receptors

Question 5

Receptor mechanisms of drug actions

Answer 5

Receptors which bind drugs usually reversibly either mimicking the action of the body’s own regulatory molecule or blocking the action of those regulatory molecules

Question 6

Example of drug that mimics and drug that blocks action of norepi at the heart

Answer 6

Isoproteronol is similar enough to norepi, while b-blockers prevent the action

Question 7

Signal transduction

Answer 7

Process by which a receptor binding a ligand leads to a cascade of biochemical events that results in physiological effect

Question 8

4 basic mechanisms of transmembrane signaling

Answer 8

1) Lipid soluble ligand crosses the membrane and acts on the intracellular receptor
2) Transmembrane receptor proteins that upon binding a ligand intracellular enzymatic activity is activated
3) Ligand gated ion channels opening or closing in result of binding
4) Transmembrane receptor stimulates a G protein that generates a 2ndary messenger (often use cAMP)

Question 9

Example of receptor ion channel system

Answer 9

GABA

Question 10

Example of transmembrane receptor protein system

Answer 10

Insulin binding causes catalytic domain activation of glucose uptake transporters

Question 11

Common 2ndary messenger G protein system

Answer 11

Drug -> receptor -> G protein activates -> adenylate cyclase actiavtion -> conversion of ATP to cAMP -> Kinase activation -> further phosphorylation

Question 12

Common intracellular receptor system

Answer 12

Diffusion of hormone across cell and nuclear membrane -> bidining to a nuclear receptor ->Allows for mRNA synthesis -> protein product

Question 13

Specificity in drug receptor interactions

Answer 13

Ability of a drug to bind to a receptor determined by the shape of the drug relative to the receptor - lock and key concept

Question 14

Selectivity in drug receptor interactions

Answer 14

Refers to ability of drug to affect only one type of cell or tissue and produce a specific physiologic response

Question 15

The less selective a drug is the more likely…

Answer 15

…to see unwanted or negative effects on tissues that we do not want effected

Question 16

Example of drug that is less selective resulting in having multiple unintended consequences

Answer 16

Propranolol acts as a B blocker used to act on B1 and B2 receptors and inhibit effect of norepi on heart, but it is non specific and also has an impact on the lungs as well causing bronchoconstriction and therefore isn’t good to use in patients with asthma or COPD

Question 17

Affinity

Answer 17

Term used to describe amount of attraction between a drug and receptor, high affinity readily binds open receptors even if conc is low, drugs iwth low affinities require a high conc. before receptrs become occupied

Question 18

Efficacy

Answer 18

Relates to ability of drug to produce a pharmacologic response after it has interacted with a receptor

Question 19

Quantifiying effect

Answer 19

Effect (E) is a function of the quantity of the drug receptor complex (DR) and can be expressed as E=a(DR) when a=constant for a given drug and is a partial determinant of whether an effect occurs, experimentally determined and considered a measure of a drug’s intrinsic activity (a=0 in antagonist?)

Question 20

Agonist

Answer 20

Drug that interacts with a receptor and produces a pharmacologic response, once inserted to a suitable receptor drug acts same way normal hormone would, has affinity and efficacy

Question 21

Antagonist

Answer 21

Drug that interacts with a receptor and produces no response, in presence of an antagonist drug, normal response reduced or completely prevented, antagonists have affinity for receptor but lack efficacy

Question 22

Partial agonist

Answer 22

Do not evoke maximal response compared to a strong agonist, efficacy somewhere between a full agonist and full antagonist, have affinity for receptor but often do not activate receptor resulting in decreased efficacy

Question 23

Partial agonist benefits

Answer 23

Can produce adequate effects without excessive side effects in some cases

Question 24

Quantal response

Answer 24

All or none response to a drug and relates to the frequency with which a specified dose of a drug produces a specific response in a population, the smallest amount of drug that produces a quantal response is not the same for all members of a population

Question 25

Graded dose response

Answer 25

As dose administered increases, pharmacologic response increases up to a point (ceiling effect, where the degree of action levels off because every receptor is bound E-max)

Question 26

Potency

Answer 26

The dosage required to achieve a certain degree of pharmacologic effect

Question 27

Chirality/sterioisomerism

Answer 27

Chemical structures that contain an assymetric carbon with all 4 valences utilized by different groups resulting in nonsuperimposible mirror images of each other

Question 28

Determining R or S chirality

Answer 28

Rank the valence groups off the central carbon from highest atomic number to lowest, if it goes clockwise then it is R, if it goes counter it is S

Question 29

Example of how isomers matter

Answer 29

Despite having the same chemical equation, the chirality of S-citalopram and R-citalopram result in S-citalopram being the most selective SSRI to have a therapeutic response while R has no clinical benefits and is not therapeutically active

Question 30

Competitive antagonism

Answer 30

Where antagonists compete with agonists in a reversible ffashion for the same receptor site, whichever drug is in greater conc. typically has predominant effect

Question 31

Noncompetitive antagonism

Answer 31

Relatively rare, when antagonists irrefersibly bind to receptor site therefore inhibitn gthe response to the agonist forming a strong permanent bond to receptor, no matter how much agonist is added can never acheive the same effect as with the agonist alone

Question 32

Physiologic antagonism

Answer 32

A drug acting on a different receptor than another physiologically decreasing the effect of others

Question 33

Why are physiologic antagonists less preferable to receptor specific antagonists?

Answer 33

Physiologic antagonists work on different receptors, they produce effects that are harder to control than the effects of a receptor specific antagonist

Question 34

Antagonism by neutralization

Answer 34

finish it!

Question 35

Therepeutic index

Answer 35

Describes relative safety of a drug expressed in a radion LD50/ED50

Question 36

LD50

Answer 36

Lethal dose that will kill 50% of animals given drug

Question 37

ED50

Answer 37

Effective dose that will produce therapeutic effect in 50% of animals given the drug

Question 38

The greater the TI, the _____. The closer the TI is to 1, the ______

Answer 38

the safer the drug, greater potential danger to the patient

Question 39

Down regulation

Answer 39

Desensitization - if receptors are continually stimulated as is the case with chronic use of certain drugs, their responsiveness may decrease as a result of decrease in # of receptors or changing responsiveness to existing receptors

Question 40

Up regulation

Answer 40

Supersensitivity - prolonged decrease in stimulation of receptors can result in functional increase in receptor sensitivity, may occur with chronic use of receptor antagonist drugs, results in creased production of receptors

Question 41

Why is up regulation dangerous?

Answer 41

If an individual suddenly stops taking a blocker, then they are hypersensitive, need to take time to ween off and have receptors return to normal levels

Question 42

Pharmacodynamic tolerance

Answer 42

When the MEC of a drug becomes abnormally high, thought to be due to down regulation

Question 43

Metabolic tolerance

Answer 43

Tolerance resulting from accelerated drug metabolism, brought about by the ability of some drugs to induce synthesis of drug metabolizing enzymes, does not change level of drug needed to elicit a response, increased dosage to achieve the same response not a higher one

Question 44

Tachyphylaxis

Answer 44

Form of tolerance defined as a reduction in drug responsiveness over a very short period of time (sets it apart from others), NOT a common form of drug tolerance

Question 45

Example of tachyphylaxis

Answer 45

Nitroglycerin response lost within 24 hours when administered transdermally, must take a break to replenish supply at night

Question 46

Placebo

Answer 46

Preparation that is devoid of intrinsic pharmacologic activity, any response is solely the patient’s psychologic reaction and not to direct physiologic or biochemical action of the placebo itself

Question 47

With all medications, some fraction of total response is a result of the…

Answer 47

…placebo effect

Question 48

Placebo response positive and negatives

Answer 48

• If a patient is convinced a medication will be effective, placebo will promote recovery
• If a patient is convinced a medication will be innefective/harmful, placebo will detract from progress