1- Drug-Receptor Interactions

Question 1

What are drug receptors?

Answer 1

they’re macromolecules that, upon binding to a drug, mediate those biochemical and physiologic changes

Question 2

What is that binding site of the drug?

Answer 2

The site on the receptor at which the drug binds

Question 3

How is a drug receptor selective for a certain drug?

Answer 3

The 3-D structure, shape and reactivity of the site, and the inherent shape, structure and reactivity of the drug.

Question 4

What is the affinity for a receptor?

Answer 4

It is the result of chemical interactions between the two molecules and the favorability of this interaction

Question 5

What are covalent interactions?

Answer 5

They are very strong interactions between the drug and the receptor that they are essentially irreversible

Question 6

What must the cell do if a drug binds to a receptor covalently forming an interactive complex?

Answer 6

It must synthesize a new receptor molecule to replace the inactivated protein

Question 7

How strong is ionic bonding?

Answer 7

Stronger than hydrogen bonds but weaker than covalent bonds

Question 8

What is Van der Waal forces?

Answer 8

They provide weak attractive forces for drugs and their receptors

Question 9

Is the interaction between a drug and a receptor the formation of only one type of bond?

Answer 9

No. Rarely is a drug receptor binding caused by a single type of interaction. Essentially multiple week forces comprise the majority of the drug receptor interactions

Question 10

What is the 2 important reasons why enatiomers are important for drug receptor interactions?

Answer 10

Usually one form is a lot stronger than the other form, and sometimes one form is therapeutic and one form is toxic.

Question 11

What is induced fit?

Answer 11

It’s when the binding of a drug to its receptor results in a change in confirmation of the receptor for better binding of the drug.

Question 12

What is a good example of induced fit using an exogenous drug?

Answer 12

Exogenous insulin stimulates the insulin receptors to the same extent despite differences in amino acid sequences

Question 13

Besides a tighter binding of the receptor to the drug induced fit, what other outcome might result?

Answer 13

Binding of the drug might make the receptor more or less functional than normal.

Question 14

How might drug and receptor structures confer specificity on the interactions between drugs and their receptors?

Answer 14

Structure of the receptor determines where the protein is located in relationship to the cellular boundaries such as the plasma membrane

Question 15

How can hydrophilic drugs passed through the Plasma membrane to get to cytoplasmic receptors?

Answer 15

Transmembrane channels

Question 16

How can lipophilic drugs get to their intracellular targets?

Answer 16

Since they are fat-soluble they just pass right through the membrane.

Question 17

What is the relationship between the Restriction of the receptor and side effects?

Answer 17

The more the restricted the receptor is, the more selective the drug is for the receptor and therefore fewer side effects

Question 18

What is an example of a drug that is not very specific and therefore creates large side effects?

Answer 18

Drugs that have a general function such as DNA synthesis are likely to cause significant toxic side effects, Like chemotherapeutics for the treatment of cancer

Question 19

Is a drug more or less selective if the receptor – defector coupling mechanisms differ among various cell types?

Answer 19

More selective

Question 20

What is a partial agonist?

Answer 20

It’s a drug that produces a submaximal response upon binding to their targets

Question 21

What is a competitive antagonist?

Answer 21

They are drugs that directly blocked the binding site of a physiologic agonist

Question 22

What is an inverse agonist?

Answer 22

They’re drugs and that cause constitutively active targets to become inactive

Question 23

What are noncompetitive antagonists?

Answer 23

They are drugs that bind to sites other than where the physiologic agonist binds and thereby prevents the confirmational change required for receptor activation

Question 24

What are ligand gated channels?

Answer 24

They are channels that the conductance is controlled by a ligand binding to the channel

Question 25

What are voltage gated channels?

Answer 25

They are channels in which conductance is regulated by changes in voltage across the membrane

Question 26

What are second messenger regulated channels?

Answer 26

Their channels in which conductance is controlled by ligand binding to plasma membrane receptors that are links to the channel in someway

Question 27

What is a very important ligand gated channel on muscle cells?

Answer 27

Nicotinic acetylcholine receptor

Question 28

What is the mechanism of local anesthetics?

Answer 28

They block voltage gated sodium channels

Question 29

What is the mechanism of action of benzodiazepines?

Answer 29

They inhibit neurotransmission by GABA to increase the conductance of chlorine ions across neuron membranes

Question 30

What is the most abundant class of receptors in human body?

Answer 30

G protein coupled receptors

Question 31

What is the fxn of the α subunit of the G-protein?

Answer 31

Exchange GDP for GTP and activating effectors

Question 32

Give the pathway of activations that occurs during α subunit binding to AC in Gs receptors

Answer 32

Ligand binds --> α subunit diffuses with GTP to adenylyl cyclase (AC) --> AC converts ATP to cAMP --> cAMP activates PKA --> protein phosphorylation

Question 33

Give the pathway of activations that occurs during α subunit binding to PLC in Gq receptors

Answer 33

Ligand binds --> α subunit with GTP binds to PLC --> IP3 and DAG made --> DAG activates PKC --> protein phosphorylation

Question 34

Generally, what is activated with Gs proteins?

Answer 34

Ca++ channels, Adenylyl cyclase

Question 35

Generally, what is activated with Gi proteins?

Answer 35

K+ channels, inhibits AC

Question 36

Generally, what is inhibits with Go proteins?

Answer 36

Ca++ channels

Question 37

Generally, what is activated with Gq proteins?

Answer 37

PLC

Question 38

Where are β1 receptors located?

Answer 38

Heart (SA node and myocardium), adipose tissue

Question 39

What are the effects of β1 activation?

Answer 39

increased HR, contractility of heart, lipolysis

Question 40

Where are the β2 receptors located?

Answer 40

Bronchial smooth muscle, GI, uterus, bladder, liver, and pancreas

Question 41

What are the effects of β2 activation?

Answer 41

Dilation of bronchioles, relaxation of gut, relaxes bladder and uterus, increases gluconeogenesis in liver, stimulates insulin release from pancreas

Question 42

What are the functions of transmembrane receptors with a cytoplasmic enzymatic domain?

Answer 42

transduce and extracellular ligand-binding interaction into an intracellular action through the activation of a linked enzymatic domain

Question 43

What are the main signals that bind to tyrosine kinase receptors?

Answer 43

Hormones and growth factors.

Question 44

What is the main mechanisms of how tyrosine kinase receptors work?

Answer 44

phosphorylation of tyrosine residues on the cytoplasmic tail of the receptor, leading to phosphorylation of a number of cytosolic signaling molecules

Question 45

Since tyrosine kinase receptors play a key role in cell growth/differentiation, mutations could cause what problems?

Answer 45

mutations in these receptors can lead to cancer and uncontrolled cell growth

Question 46

What types of enzymes remove phosphate groups from specific tyrosine residues?

Answer 46

tyrosine phosphatases

Question 47

What type of transmembrane receptors with a cytoplasmic enzymatic domain does TGF-β superfamily use?

Answer 47

Receptor serine/threonine kinases

Question 48

What is required for a ligand to bind to intracellular receptors?

Answer 48

It has to be lipid soluble to cross the plasma membrane

Question 49

Which lipophilic anticoagulant works by binding to enzymes in the cytosol (a type of intracellular R)?

Answer 49

warfarin

Question 50

Steroid hormones typically bind to intracellular receptors in which part of the cell?

Answer 50

Nucleus (they act as transcription factors)

Question 51

Extracellular enzymes have binding sites for drugs where in the body?

Answer 51

Basically anywhere outside the plasma membrane

Question 52

Give an example of an extracellular receptors that is used to lower blood pressure.

Answer 52

ACE Inhibitor drugs lower blood pressure. Angiotensin converting enzyme (ACE) converts angiotensin I --> angiotensin II (vasoconstrictor)

Question 53

Why can many different drugs produce the same effects via second messengers?

Answer 53

Because 2nd messengers provide cells with a set of common points upon which numerous outside stimuli could converge to generate a coordinated cellular effect

Question 54

What is signal integration?

Answer 54

When ligands bind to receptors that have opposite 2nd messenger effects, like activation of Gs receptors (which activates AC) and Gi receptors (which inhibits AC)

Question 55

What is homologous desensitization?

Answer 55

the effects of agonists at only one type of receptor are diminished

Question 56

What is heterologous desensitization?

Answer 56

the effects of agonists at two or more types of receptors are coordinately diminished

Question 57

What typically causes heterologous desensitization?

Answer 57

Caused by drug induced alteration in a common point of convergence in the mechanisms of action of the involved receptors, such as a shared effector molecule

Question 58

What is receptor inactivation?

Answer 58

completely turning off the receptor to stimulation by ligand.

Question 59

How does a receptor get inactivated?

Answer 59

Results from phosphorylation of the receptor

Question 60

What is the refractory of the receptor?

Answer 60

it’s the state following activation in which the receptor requires time before it can be stimulated again

Question 61

What is down-regulation of the receptor?

Answer 61

a molecular mechanism in which the receptor NUMBER can be altered

Question 62

What is the general mechanism of receptor down-regulation?

Answer 62

prolonged receptor stimulation by ligand induces the cell to endocytose and sequester receptors in endocytotic vesicles. Once the stimulus that caused the down-regulation is gone the receptors can be recycled back up to the cell surface to be used again

Question 63

What are 2 classes of drugs that lack receptors?

Answer 63

osmotic diuretics and antacids

Question 64

What is mannitol?

Answer 64

Osmotic diuretic

Question 65

What is the mechanism of action of mannitol?

Answer 65

Secreted into the lumen of the nephron and increases the osmolarity of the urine to such a degree that water is drawn from the peritubular blood into the lumen.

Question 66

What is the mechanism of action of antacids?

Answer 66

Act nonspecifically by absorbing or chemically neutralizing stomach acid