Lecture 8

Question 1

What are the two theories that we use to describe drug receptor interactions?

Answer 1

1. the simple occupancy theory

2. the modified occupancy theory

Question 2

What is the simple occupancy theory?

Answer 2

• the intensity of the drugs response is proportional to the number of receptors occupied
• the maximal response occurs when all the receptors are occupied
• implies that two drugs that act at the same receptor should produce the same effect (not true!)

Question 3

What is the modified occupancy theory?

Answer 3

• intensity of a drugs response is proportional to the number of receptors occupied
• two drugs occupying the same receptor can have different binding strengths (affinity)
• two drugs occupying the same receptor can have different abilities to activate the receptor (intrinsic activity)

Question 4

Affinity

Answer 4

• the attraction that a drug has for its receptor
• drugs with high affinity are highly attracted to their receptor (even at low concentration)
• low affinity = weakly attracted to receptor = bind ineffectively even at high concentration
• affinity is the primary determinant of a drugs potency (high affinity = high potency)

Question 5

Intrinsic activity

Answer 5

• ability of a drug to activate the receptor
• high intrinsic activity cause intense receptor activation
• high intrinsic activity have high maximal efficacy

Question 6

3 Classifications of drug receptor interactions

Answer 6

1. agonist
2. antagonist
3. partial agonist

Question 7

Agonists

Answer 7

• a molecule that activates the receptor it binds to
• target to mimic the action of the bodys endogenous molecules
• have both affinity and intrinsic activity
• does not always increase a physiological response, may increase or decrease physiological response depending on which receptor is activated
• some can bind to different receptors = can have different effects depending on dose (ex dopamine)

Question 8

Antagonists

Answer 8

• bind receptors but do not activate them
• have affinity but no intrinsic activity
• can prevent the binding of endogenous molecules and other agonists causing profound pharmacological effects (dependent on the presence pf an agonist)
• can be used to treat drug overdoses

Question 9

Examples of antagonist drugs

Answer 9

• beta blockers: binding of endogenous epinephrine to beta 1 receptors in the heart; slows beating of the heart
• antihistamines: block binding of histamine to H1 histamine receptors int he nasal mucosa; prevents symptoms of allergy
• gastric acid reducers: block the binding of histamine H2 histamine receptors in the gut; decreases gastric acid secretion
• opioid receptor blockers: block the binding of opioids to opiate receptors; useful for treating opiate overdose

Question 10

types of antagonists

Answer 10

1. competitive
2. irreversible
3. allosteric

Question 11

Competitive antagonists

Answer 11

• compete for binding with an agonist at the same binding site: highest affinity wins
• reversible binding
• if affinity is equal, one with the highest concentration will win
• effect of antagonist can be overcome by increasing the concentration of the agonist bc its reversible

Question 12

Irreversible Antagonist

Answer 12

• bind the same receptor site at the agonist
• irreversible & non-competitive
• decreases the maximal response the agonist may have
• cannot be overcome by increasing the dose of agonist
• lasts until the receptor is replaced
• seldom used in therapeutics

Question 13

Allosteric Antagonists

Answer 13

• bind to a different site on the receptor than the agonist does resulting in changes to the conformation of the receptor such that the agonist can no longer bind
• reversible but not competitive bc they bind to different sites on the receptor
• cannot be overcome but increasing agonist dose
• these decrease the maximal response the agonist may elicit

Question 14

What are partial agonists?

Answer 14

• agonists with minimal or moderate intrinsic activity
• able to act as antagonists by causing minimal/moderate activation of the receptor while also blocking binding by full agonist

Question 15

Regulation of cell surface receptor expression

Answer 15

• # of receptors not constant and can change with exposure to drugs
• action of drugs depends on the receptor being present on the cell surface

Question 16

What is drug tolerance

Answer 16

• continual exposure to a drug may = decreased response

Question 17

3 types of drug tolerance

Answer 17

1. desensitization
2. metabolic tolerance
3. tachyphylaxis

Question 18

Desensitization

Answer 18

continuous exposure causes the receptor to internalize into the cell or be destroyed
- result: decrease in cell surface receptor expression and decreased drug effects

Question 19

Metabolic tolerance

Answer 19

• continuous exposure results in induction of drug metabolizing enzymes= a decrease in the the plasma concentration fo the drug

Question 20

Tachyphylaxis

Answer 20

• rapid decrease in the response to a drug

- some drugs require a free period between administrations to prevent this

Question 21

Receptor Upregulation

Answer 21

• continuous exposure to an antagonist the opposite effect of tolerance
• cell becomes hypersensitive or supersensitive
• occurs bc the cell synthesizes more receptors which = increases response to drug