Pharmacodynamics - Target Tissue Receptors

Question 1

affinity

Answer 1

• the amount of attraction between a drug and a receptor
• related to the drug amount that is required to bind to the unoccupied receptors
• drugs with a high affinity binds readily easily to open receptors even if the concentration of the drug is relatively low

Question 2

What are the three kinds of surface receptors?

Answer 2

• ion channels
• enzymes (start chain of reaction)
• G proteins / regulatory proteins

Question 3

What is an example of surface receptors that act as ion channels

Answer 3

• Acetylcholine (ACh) post synaptic membrane of neuromuscular junction
• GABA ion channel complex for neruonal membranes in the CNS

Question 4

Whats an example of a surface receptor linked directly to an enzyme

Answer 4

• tyrosine kinase protein for insulin and other growth factors

Question 5

Explain and give an example of surface receptors linked to regulatory proteins

Answer 5

• drug binds and links to G protien (activated by the binding of guanine nucleotides)
• called G-protien coupled receptors
• drug acts as a first messenger and intracellular pathway is second messenger

Ex; cAMP

Question 6

What are common types of intracellular recptors/drugs for for these receptors

Answer 6

• receptors are specific for certain endogenous hormones and hormone-like drugs (steroids and thyroid compounds)

Question 7

What factors impact drug-receptor interactions?

Answer 7

• drugs size and shape relative to binding site
• electrostatic attraction between drug and receptor

Question 8

Allosteric modulators

Answer 8

• receptors may exit in variable affinity states depending on the influence of local regulators (allosteric modulators)
• these increase or decrease affinity for a drug by binding to another site on the receptor

Question 9

What other factor besides allosteric modulators impact affinity

Answer 9

lipid membrane fluidity and organization

Question 10

selective

Answer 10

drug that only affects one type of cell or tissue and produces a specific physiological response

drug selectivity is a relative term bc no drug produces only one effect

related closely to subtypes of receptors based on structural differences (so we can develop drugs that will affect only one receptor subtype and produce selevtive effects and limit side effects)

Question 11

Describe the dose-response curve

Answer 11

• response is typically proportional to the number of receptors occupied by the drug,
• not a linear relationship bc threshold and ceiling effect

Question 12

agonist vs antagonist

Answer 12

• agonist; 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

Answer 13

• competitive; whoever has the higher concnetration (antagonist or agonists) will win receptor spot
• noncompetitive; antagonist forms a permanent bond with receptor and the agonist can’t compete for that spot no matter how high the concentration (terminated only with normal protein turnover so the effect tends to remain long)

Question 14

Partial Agonist

Answer 14

• drugs when they do not evoke a max response compared to a strong agonist
• does not completely activate the receptor after it binds
• but it is not due to decreased drug-receptor affinity

Question 15

Mixed agonist-antagonist

Answer 15

agents that stimulate certain receptor subtypes while simultaneously blocking the effects of endogenous substances on other receptor subtypes

AKA acting as agonist on one tissue and antagonist on another tissue

promoting estrogen for bone but preventing growth on breast tissue (cancer) SERMs

Question 16

Inverse agonist

Answer 16

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

Question 17

Receptor Regulation

Answer 17

a prolonged increase in the stimulation of various receptors will lead to a decrease in receptor function

and decreased stimulation will lead to an increase in receptor numbers or sensitivity

Question 18

desensitization

Answer 18

a fairly brief and transient decrease in responsiveness

associated with phosphorylation

brief response goes back to normal

decrease in respnse (may take longer once binded) whereas downregulation is decrease in actual number of receptors)

Question 19

Receptor internalization

Answer 19

receptors are withdrawn from the cell membrane by endocytosis

brief response goes back to normal

Question 20

Down regulation

Answer 20

more prolonged slower process

number of available receptors is diminished

possibly due to prolonged exposure of the aginost causing removal of receptors OR decreased receptor synthesis

Question 21

What are receptor supersensitivity examples

Answer 21

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

denervation supersensitivity - is when an area becomes overly sensitive after nerve damage, due to the body’s attempt to compensate for the loss of nerve function