pharmocodynamics target tissue receptors

Question 1

receptors

Answer 1

• component on or within a cell that a substance can bind to
• when drug binds to receptor, it initiates biochemical chain of events
• have a binding site located on outer surface of cell membrane (differeniate and respond to specific substances)
• transmit a message through the cell membrane to cause a change in cell activity
• surface receptors are often transmembrane proteins

Question 2

surface receptors

Answer 2

directly affect cell function in one of these ways
* acts as an **ion channel **and directly altering membrane permeability
* acts enzymatically to directly influence function within cell
* linked to regulatory proteins that control other chemicals and enzymatic processes

Question 3

surface receptors linked directly to ion channels

Answer 3

• receptors becomes an ion pore–> changes the membrane permeability
• ex: ACh receptor
  -postsynaptic membrane of the neuromuscular junction
  -gamma aminobutyric acid (GABA)- benzodiazepine- chloride ion channel complex
  -neuronal membranes in the CNS

Question 4

surface receptors linked directly to enzymes

Answer 4

drugs and endogenous chemicals that bind to receptor site can change the enzyme activity of the intracellular catalytic component
ex: tyrosine kinase protein for insulin and other growth factor

Question 5

surface receptors linked to regulatory (G) protein and the role of the second messenger

Answer 5

• affect cell function by linking to an intracellular intermediate regulatory protein (G proteins), activated by binding guanine nucleotides (called G protein coupled receptors (GPCRs)
• drug may bind to the cell for only a short period but long enough to initiate the interaction of the G protein with the intracellular effector system (sustained influence).

Question 6

What affects a drugs affinity?

Answer 6

• local regulators (allosteric modulators)
• environments (fludity of cell membrane critical to provide suitable environment for receptors to function)

Question 7

drug receptor interactions

Answer 7

• ability depends on the drug’s size and shape relative to the configuration of the receptor’s binding site and electrostatic attraction between the drug and the receptor
• some drugs bind readily to the receptor, some moderately, some very little, or some not at all

Question 8

affinity

Answer 8

• the amount of attraction between a drug and a receptor
• it is related to the drug amt. that is required to bind to unoccupied receptors
• super high vs high vs low affinity
• influenced by local regulators (allosteric modulators) and environments (membrane’s fluidity and organization)

Question 9

functional aspects of drug receptor interactions

Answer 9

• drug selectivity and receptor subtypes
• dose response
• classification of drugs: agonist vs antagonist
• competitive vs noncompetitive antagonists
• partial agonists
• mixed agonist antagonists and inverse agonists

Question 10

Drug selectivity and receptor subtypes

Answer 10

• drug selectivity
• a relative term b/c no drug produces only one effect (all drugs produce some side effects)
• related closely to subtypes of receptors based on structural and functional differences
• a selective drug affects only one type of cell or tissue and products a specific physiological response and fewer side effects than a nonselective drug

Question 11

Dose-Response

Answer 11

• response typically proportional to the number of receptors occupied by the drug (not a linear relationship)
• increasing the dosage beyond the point at which the maximal effect is reached will not produce any further increase in reponse b/c all the receptors are bound by the drug

Question 12

Classification of Drugs: Agonist vs Antagonist

Answer 12

• agonist has both affinity and efficacy
• antagonist has only affinity and it occupies the receptor to “block” the effect of another chemical

Question 13

Competitive vs Noncompetitive Antagonists

Answer 13

Competitive
* vie for the same receptor as agonist
* equal opporunity
* whichever drug concentration is higher, predominant effect
* agonist. can overcome the antagonist
Non-Competitive
* premanent, irreversible bonds
* inability of agonist to compete with the antagonist
* terminated only with normal protein turnover, so the effect tends to remain long

Question 14

Partial Agonists

Answer 14

if
strong agonist = 100% efficacy
And
strong antagonist = 0% efficacy
partial agonist= 1`99% efficacy
* it does not completely activate the receptor after it binds
* it is not caused by decreased drug- receptor affinity

Question 15

Mixed Agonist-Antagonists

Answer 15

• will act as an agonist on one tisssue/ organ
• will act as an antagonist on another tissue/organ
• Ex: selective estrogen receptor modulators can act as an agonist on bone and on antagonist on breast tissues

Question 16

inverse agonist

Answer 16

opposite effect of an agonist on cellular function
-decreased activity where the receptor is too active or overstimulated

Question 17

Receptor Regulation

Answer 17

• overstimulation of postsynaptic receptors by endogenous substances (neurotransmitters, hormones) or by exogenous agonists (drugs) may lead to functional decrease in the appropriate receptor population
• a prolonged decrease in the stimulation of the post synaptic receptors can result in a functional increase in receptor. sensitivity

Question 18

Receptor Desensitization

Answer 18

• brief and transient; return to normal within a few minutes after the agonist is removed
• associated with phosphorylation

Question 19

Down Regulation

Answer 19

• slow and prolonged (remains several days after the agonist is removed)
• increased receptor removal, decreased receptor synthesis or both

Question 20

drug tolerance

Answer 20

• the need to progressively increase the dose to achieve therapeutic effects
• may be due in part to changes in receptor sensitivity and function

Question 21

efficacy

Answer 21

the drug will activate the receptor and change the function of the cell

Question 22

agonist

Answer 22

a drug that can bind to a receptor and initiate a change in the cells function
- both affinity and efficacy

Question 23

antagonist

Answer 23

• only affinity
• the drug will bind to receptor, but it will not cause any direct change in the function of the receptor or cell
• by occupying the receptor, they prevent the agonistic compound from having any effect on cell.
• blockers because ability to block effect of another chemical

Question 24

receptor internalization

Answer 24

receptors are withdrawn from the cell membrane by endocyosis

Question 25

receptor desensitization and down regulation purpose

Answer 25

negative feedback system to prevent overstimulation by an agonist

Question 26

supersensitivity

Answer 26

decreased stimulation results in increase receptor numbers

Question 27

Receptor Supersensitivity

Answer 27

prolonged decrease in stimulation of the post synaptic receptors can result in a functional increase in receptor sensitivity

Question 28

Denervation in PNS (receptor supersensitivity)

Answer 28

• lack of presynaptic neurotransmitter release results in a compensatory increase in postsynaptic receptor numbers on muscle cell

Question 29

(receptor supersensitivity) parkinson disease

Answer 29

• loss of the endogenous neurotransmitter dopamine result in supersensitivity of receptors for that neurotransmitter

Question 30

taking receptor antagonist drugs for prolonged periods (receptor supersensitivity)

Answer 30

the postsynaptic neuron interprets this as the synapse being denervated and responds by maufacturing more receptors