Pharmacodynamics

Question 1

Pharmacodynamics

Answer 1

concerted w/ study of biochemical and physiological effects of drugs and their mechanism of action.

Concerned w/ drug concentration (dose) and magnitude of effect

Question 2

Drugs produce their effects by 1)

Answer 2

Interacting with receptors

Question 3

What are examples of a drug interacting w/ receptors?

Answer 3

G-protein coupled receptors (GPCR); G-protein mediate the receptor interaction

Question 4

Drugs produce their effects by 2)

Answer 4

inhibiting enzymes

Question 5

What are ways a drug can inhibit enzymes?

Answer 5

Competitive inhibitor binds to same site;

noncompetitive inhibitor binds to different site on enzyme, alters shape.

Question 6

Drugs produce their effects by 3)

Answer 6

interacting w/ membrane transport proteins

Question 7

What are ways drugs interact w/ membrane transport proteins?

Answer 7

ion channels - drugs bind and directly compete for the receptor and can also bind to a different site (allosteric) that alters ion channels (increae or decrease the flow of ions).

Neurotransmitter transporters - transport neurotransmitters out of the synapse and back to the neuron (reuptake inhibitors)

Question 8

Drugs produce their effects by 4)

Answer 8

Act directly on DNA - bind directly to nucleic acids (anticancer agents)

Question 9

Drugs produce their effects by 5)

Answer 9

act directly on membrane lipids - general anesthetics

Question 10

Receptor-binding affinity

Answer 10

tendency of a drug to combine w/ its receptor - strength of the interaction between a drug and its receptor.

Question 11

How is the affinity of a drug mesured

Answer 11

by its dissociation constant (KD)

Question 12

Signal transduction

Answer 12

describes pathway

• from ligand binding to changes in the receptor
• receptor interaction w/ an effector molecule called second messengers (cyclic AMP, IP3, Diaclyglycerol

This cascade ultimately leads to physiologial effect

Question 13

Efficacy

Answer 13

Ability of drug to initiate a cellular effect (stimulate the receptor and start the signal tranduction pathway)

Question 14

Agonist

Answer 14

drug has both affinity and efficacy (produces response)

Question 15

Antagonist

Answer 15

drug has affinity but lack efficacy (prevents the action of agoinists (ex: anti-histamines)

Question 16

Full agonist

Answer 16

produce the maximal response - increase the rate of signal tranduction when it binds to the receptor

Question 17

Partial agonist

Answer 17

produce a submaximal response - will act as an antagnosit in presence of full agonist due to preventing the full agonist from binding the receptor and exerting maximal effect.

Question 18

Inverse agonist

Answer 18

decreases the rate of signal transduction; works on GABA - inhibitory neurotransmitter that relaxes everything

Question 19

Effects of antagonist

Answer 19

Can prevent the action of agonists, its effects are surmountable if dose of agonist is increased

Question 20

Competitive antagonist vs. noncompetitive antagonist

Answer 20

competitive - bind to the same site as agonist but are reversively bond

noncompetitive - antagonist block the agonist site irreversibly.

Question 21

Receptor regulation

Answer 21

receptors can undergo changes w/ respect to their density (numbers/cell) and their affinity for drugs and other ligands

Question 22

What happens w/ continuous or repeated exposure to an agonist?

Answer 22

can desensitize receptors (effect called dsensitization or tachyphylaxis; rapid rate of tolerance where you don’t get the same effects anymore.

Question 23

Down-regulation

Answer 23

longer-term adaptation in which the number of receptors DECREASE; also responsible for tolerance

Question 24

What can continuous, or repeated exposure to antagonists do?

Answer 24

initially can increase the response of the receptor (super sensitivity)

Question 25

Up-regulation

Answer 25

chronic exposure that results in an INCREASE number of receptors

Question 26

Dose-response relationship

Answer 26

relationship between the concentration of drug at receptor and magnitude of response.

Question 27

Graded dose-response relationship

Answer 27

effect of various drug doses of a drug on an INDIVIDUAL

Question 28

Quantal dose-response relationship

Answer 28

effect of various doses of a drug on a POPULATION of individuals

Question 29

What does graded dose-response illustrate?

Answer 29

The relationship between drug dose, receptor occupancy, and magnitude of the resulting effect.

Question 30

What are 2 important parameters of graded dose-response?

Answer 30

Potency is drug dose that produces 50% of the maximal response (ED50 = median effective dose)
**Largely determined by affinity of drug for receptor

Question 31

Efficacy

Answer 31

maximal response produced by a drug

Question 32

How can quantal relationships be defined?

Answer 32

as either present or not present; can be defined for therapeutic effect and toxic ffects

Question 33

What is TI and CSF? What are they based on?

Answer 33

TI- therapeutic index
CSF - certain safety factor
based on difference between the toxic dose and the therapeutic dose in a population of subjects

Question 34

Therapeutic index - ED50

Answer 34

(median effective dose); produces an effect in 50% of subjects

Question 35

Therepeutic index - LD50

Answer 35

(median lethal dose) produces death in 50% of subjects

Question 36

Therapeutic ratio

Answer 36

between LD50 and ED50 - provides the margin of safety of a drug

Question 37

CSF ratio

Answer 37

LD1 (lethal in 1%) and ED99 (therapeutic effect in 99%) - more realistic estimate of drug safety.

Question 38

Thereapeutic index number

Answer 38

the larger the number, the safer the drug is.

the smaller the number, the more toxic the drug is.

Question 39

Narrow thereapeutic range (index) drugs

Answer 39

containing certain drug substances subject to therapeutic drug concentration or pharmacodynamic MONITORING, and/or where product labeling indicates a narrow therepeutic range designation.

Question 40

Pharmacodynamic response changes in older patients

Answer 40

• Increased sensitivity to CNS effects of benzodiazepines.
• Enhanced response to anticoagulants.
• Reduced response to beta-agonists and antagonists
• Increased risk of tardive dyskinesia w/ antipsychotic ageents (irreversible, parkinson’s symptoms)