How Do Drugs Work?

Question 1

How are drugs distributed throughout the body?

Answer 1

• Blood
• Other Bodily Fluids

Question 2

What happens when drugs arrive to the proper site of action?

Answer 2

They bind to the receptor.

Question 3

Where is the receptor located?

Answer 3

Usually on the outer membrane of the cell.

Question 4

What sometimes happen when a drug molecule binds to a receptor?

Answer 4

Triggers an activation of enzymes located within the cell.

Question 5

Question: What role does absorption play in drug dynamics, and what factors influence it?

Answer 5

Answer: Absorption is dependent on factors such as solubility.

Question 6

Question: In drug distribution, what is the significance of the ratio of bound/free drug?

Answer 6

Answer: The ratio of bound/free drug is important because only free drug can bind to receptors and exert its effect.

Question 7

Question: Why is metabolism necessary for drugs, and what are its primary functions?

Answer 7

Answer: Metabolism is needed for drug inactivation and excretion.

Question 8

Question: What is the most common route for drug excretion?

Answer 8

Answer: Excretion most commonly occurs via urine.

Question 9

Question: In some cases, what can drug binding to receptors trigger within a cell?

Answer 9

Answer: Drug binding to receptors can trigger the activation of enzymes located within the cell.

Question 10

Question: Where are receptors typically located, and what is their structural nature?

Answer 10

Answer: Receptors are typically integral membrane proteins at the plasma membrane, but they can also be found inside the cell.

Question 11

Question: What is the primary function of receptors, and what do they recognize and bind to?

Answer 11

Answer: Receptors recognize and bind to specific chemicals, known as ligands (agonists/antagonists), thereby invoking a biologically relevant response.

Question 12

Question: How can the number of receptors be modulated, and what are the terms for these regulatory processes?

Answer 12

Answer: Receptor numbers can be increased (up-regulation) or decreased (down-regulation). This may occur in response to a chronically low or high concentration of the agonist to optimize sensitivity.

Question 13

Question: What are ligands, and what is their role in biological systems?

Answer 13

Answer: Ligands are chemicals that bind to receptor proteins.

Question 14

Question: Define an agonist and list two important properties associated with it.

Answer 14

Answer: An agonist is a ligand with both affinity (strength of binding to receptor) and efficacy (intrinsic activity, induces a conformational change in the receptor, and activates a response).

Question 15

Question: Explain what affinity refers to in the context of ligands.

Answer 15

Answer: Affinity is the strength of binding between a ligand and a receptor.

Question 16

Question: Define efficacy in the context of agonists, and what does it lead to?

Answer 16

Answer: Efficacy is the ability of an agonist to induce a conformational change in the receptor and activate a response. It leads to the maximum response made by a drug.

Question 17

Question: What is an antagonist, and how does it differ from an agonist in terms of efficacy?

Answer 17

Answer: An antagonist is a ligand that blocks the receptor. It has affinity but lacks efficacy, meaning it does not activate a response.

Question 18

Question: Provide examples of substances that act as antagonists.

Answer 18

Answer: Examples include anti-histamines and beta-blockers.

Question 19

Question: What is down-regulation, and when does it occur?

Answer 19

Answer: Down-regulation occurs in response to a chronically high concentration of ligand. It decreases the sensitivity (desensitizes) of the cell response to frequent or intense stimulation.

Question 20

Question: Define up-regulation and under what conditions it occurs.

Answer 20

Answer: Up-regulation happens when there is chronic stimulation at very low levels of a ligand. It requires increased sensitivity at the receptor level, achieved by increasing the number of receptors.

Question 21

Question: How does down-regulation impact the sensitivity of cellular responses?

Answer 21

Answer: Down-regulation decreases the sensitivity (desensitizes) of the cell response to frequent or intense stimulation, typically in response to a high ligand concentration.

Question 22

Question: What is the purpose of up-regulation, and how does it affect receptor sensitivity?

Answer 22

Answer: Up-regulation occurs to increase sensitivity at the receptor level. Greater numbers of receptors are present to ensure increased sensitivity, especially in response to chronic low-level ligand stimulation.

Question 23

Question: How can aberrant cellular signaling impact biological systems?

Answer 23

Answer: Aberrant cellular signaling can lead to disease processes.

Question 24

Question: What is a common target for many drugs, and why?

Answer 24

Answer: Many drugs are targeted to cellular signaling processes.

Question 25

Question: How does improved knowledge of cellular signaling processes contribute to drug development?

Answer 25

Answer: Improved knowledge of cellular signaling processes continues to identify novel targets for drug design and improved therapy.

Question 26

Question: What does the intracellular signal chemical not do in signal transduction, and what is its alternative name?

Answer 26

Answer: The intercellular signal chemical, also known as the first messenger (ligand), does not enter the cell.

Question 27

Question: What occurs when the signal chemical binds to its receptor in signal transduction?

Answer 27

Answer: Binding of the signal chemical to its receptor initiates a series of chemical changes, including the activation of intracellular second messengers, in the cell.

Question 28

Question: How do the chemical changes initiated by signal transduction alter the cell’s physiology?

Answer 28

Answer: These chemical changes alter the physiology of the cell

Question 29

Question: What is the significance of signal transduction in terms of cellular responses?

Answer 29

Answer: Signal transduction enables amplification of the cellular response.

Question 30

Question: How can drugs influence the effects of signal transduction, and what is the ultimate result?

Answer 30

Answer: Drugs can alter the effects of signal transduction, leading to an alteration in the cellular response.

Question 31

Question: What is one way in which signal transduction can occur, involving ion channels?

Answer 31

Answer: Signal transduction can involve the direct opening of ion channels.

Question 32

Question: How can signal transduction directly activate an enzyme?

Answer 32

Answer: Signal transduction can lead to the direct activation of an enzyme.

Question 33

Question: Describe the process of signal transduction involving indirect activation or inactivation of an enzyme, including the role of a G-protein.

Answer 33

Answer: Indirect activation or inactivation of an enzyme in signal transduction involves a G-protein, acting as a molecular switch. It can also lead to indirect opening or closing of ion channels.

Question 34

Question: Name some intracellular second messengers involved in signal transduction.

Answer 34

Answer: Intracellular second messengers in signal transduction include cyclic nucleotides (e.g., cAMP), inositol trisphosphate (IP3), diacylglycerol (DAG), and calcium ions (Ca2+).

Question 35

Explain this diagram

Answer 35

In this case, the receptor protein is an ion channel, i.e. a protein that forms a pore in the plasma membrane through which a specific type of ion can pass. For example, Na+ channels allow only Na+ to pass. Ion channels are either ‘open’ or ‘closed’ and this is determined by the presence/absence of the specific agonist. Binding of the agonist to its specific receptor-operated ion channel results in a conformational change in the protein, which then opens. Ions then flow through the channel, down their concentration gradient. The distribution of these channels is often specific to certain specialised cell types, especially excitable cells

Remember: Ions flow down concentration gradient.

Question 36

Question: Provide an example of an agonist, specify the receptor it acts on, and describe the effect on the ion channels.

Answer 36

Answer: Acetylcholine acts on nicotinic cholinergic receptors, opening cation channels, mainly Na+.

Question 37

Question: Name an agonist associated with excitatory amino acids, identify the receptor it acts on, and explain its effect on ion channels.

Answer 37

Answer: Glutamate acts on excitatory amino acids receptors, opening Na+ or Ca2+ channels.

Question 38

Question: Identify an agonist related to GABA, specify the receptor it acts on, and describe its impact on ion channels.

Answer 38

Answer: GABA acts on GABAa receptors, opening Cl- channels.

Question 39

Explain the enzyme - linked receptor

Answer 39

Receptors of this type are transmembrane proteins which often possess enzyme activity. They have a ligand binding domain on the outer face of the plasma membrane and a catalytic or enzymatic domain on the inner face of the plasma membrane. Stimulation of this type of receptor by an agonist increases the receptor’s catalytic activity.

One class of these is tyrosine kinase receptors. Activation of the receptor by its agonist causes the transfer of a phosphate group onto specific amino acids (i.e. specific tyrosines) in the receptor itself. This results in the recruitment of proteins from the cytosol, which become ‘scaffolded’ to the receptor. This scaffold transmits the signalling information to the cell.

Question 40

Question: Name a tyrosine kinase receptor associated with epidermal growth, specify its agonist, and mention its effects.

Answer 40

Answer: The tyrosine kinase receptor is EGFR (Epidermal Growth Factor Receptor), and its agonist is epidermal growth factor. It is involved in cell proliferation, differentiation, and cell survival, often associated with cancer.

Question 41

Question: Identify a tyrosine kinase receptor related to platelet-derived growth, name its agonist, and outline its effects

Answer 41

Answer: The tyrosine kinase receptor is PDGFR (Platelet-Derived Growth Factor Receptor), and its agonist is platelet-derived growth factor. It is associated with cell proliferation, differentiation, and development, often linked to cancer.

Question 42

Question: Specify a tyrosine kinase receptor connected to insulin, name its agonist, and describe its effects.

Answer 42

Answer: The tyrosine kinase receptor is the insulin receptor, and its agonist is insulin. It is involved in glucose uptake and is associated with conditions like diabetes.

Question 43

Question: What is Component 1 of G protein-coupled receptor signaling, and how does it relate to specific agonists?

Answer 43

Answer: Each G protein-coupled receptor (GPCR) binds its specific agonist; for example, adrenaline binds to adrenoceptors, and glucagon binds to glucagon receptors.

Question 44

Question: Describe Component 2 of G protein-coupled receptor signaling, focusing on the G-protein as a molecular switch.

Answer 44

Answer: The G-protein acts as a molecular switch, being ON when associated with GTP (guanosine triphosphate) and OFF when associated with GDP (guanosine diphosphate). It is also an enzyme that converts GTP to GDP, turning itself and the system OFF.

Question 45

Question: What is the structural composition of G protein-coupled receptors, and how many times does the polypeptide chain span the lipid bilayer?

Answer 45

Answer: G protein-coupled receptors are made up of a single polypeptide chain that spans through the lipid bilayer seven times, resulting in seven receptors where the ligand binds.

Question 46

Question: Explain the sequence of events when an agonist binds to a G protein-coupled receptor, leading to activation of the G-protein.

Answer 46

Answer: When an agonist binds to the receptor, a conformational change occurs, and the receptor binds to the G-protein. GDP dissociates, and GTP binds, activating the G-protein.

Question 47

Question: How does the G-protein switch off after activation, and what is the role of GTPase in this process?

Answer 47

Answer: The G-protein switches off as GTP is hydrolyzed by GTPase, converting it back to GDP.

Question 48

Question: Name an effector enzyme in GPCR signaling that catalyzes the conversion of ATP to cAMP.

Answer 48

Answer: Adenylyl cyclase is an effector enzyme that catalyzes the conversion of ATP to cAMP (cyclic AMP or cyclic adenosine monophosphate).

Question 49

Question: Identify an effector enzyme in GPCR signaling that cuts the plasma membrane lipid phosphatidylinositol bisphosphate into DAG and IP3.

Answer 49

Phospholipase C is an effector enzyme that cuts the plasma membrane lipid phosphatidylinositol bisphosphate into DAG (diacylglycerol) and IP3 (inositol trisphosphate).

Question 50

Name an effector enzyme in GPCR signaling that breaks down cGMP.

Answer 50

cGMP phosphodiesterase is an effector enzyme that breaks down cGMP (cyclic GMP, cyclic guanosine monophosphate).

Question 51

Question: What role do cAMP, DAG, IP3, and cGMP play in GPCR signaling as ‘second messenger’ molecules?

Answer 51

Answer: cAMP, DAG, IP3, and cGMP are second messenger molecules. They bind to specific target proteins within the cell, such as protein kinases or IP3 receptors, to change the cell’s physiology.

Question 52

How does GPCR signalling work?

Answer 52

Activation: Agonist activation of the receptor induces its 3-dimensional or conformational change, thereby enabling it to interact with a G protein .The G protein loses GDP and gains GTP. Therefore, the G protein becomes switched ON. The activated (GTP-bound) G protein interacts with the effector enzyme and increases its catalytic activity. The effector enzyme produces specific ‘second messenger’ molecules. These alter the biochemical machinery inside the cell by interacting with their specific target molecules), which either phosphorylate other specific proteins or release intracellular stores of Ca2+.

De-activation: The agonist dissociates from the receptor. The G protein’s own GTPase activity converts the bound GTP to GDP and the G protein becomes switched OFF. G protein interaction with the effector enzyme ceases and the effector enzyme activity returns to normal. The ‘second messenger’ molecules are broken down and their target proteins are no longer activated.

Question 53

Question: What is calcium signalling involved in?

Answer 53

• Muscle contraction
• Secretion
• Metabolism
• Neuronal excitability
• Cell proliferation

Question 54

Question: In the context of second messenger roles, what is unique about calcium ions?

Answer 54

Answer: Calcium ions are neither produced nor destroyed; they are moved between compartments.

Question 55

Question: How are the effects of calcium ions as second messengers influenced?

Answer 55

Answer: The effects of calcium ions as second messengers are concentration-dependent.

Question 56

Question: List some actions of calcium ions as second messengers.

Answer 56

Answer: Calcium ions act by activating specific protein kinases, ion channels, and regulating the activity of many enzymes.

Question 57

Question: What is another name for Calcium Release Activated Channels (CRAC), and what is their alternative term?

Answer 57

Answer: CRAC is also known as store-operated Ca2+ channels.

Question 58

Question: What is the role of Ca2+ transporters abbreviated as PMCA in cellular function?

Answer 58

Answer: Ca2+ transporters (PMCA) are responsible for transporting calcium ions across the plasma membrane.

Question 59

Question: Name two types of calcium ion channels based on their mode of operation.

Answer 59

Answer: Voltage-operated channels (VOC) and ligand-gated channels are two types of calcium ion channels.

Question 60

Question: How can Ca2+ channel blockers, such as nifedipine and verapamil, be used to influence physiological processes?

Answer 60

Answer: Ca2+ channel blockers can be used to modulate muscle contraction.

Question 61

Question: Name two types of intracellular calcium ion release channels

Answer 61

Answer: Inositol trisphosphate receptor (IP3R) and Ryanodine receptor are intracellular calcium ion release channels.

Question 62

Question: Where are the trans-membrane proteins of intracellular Ca2+ stores primarily located?

Answer 62

Answer: These proteins are primarily located in intracellular stores such as the endoplasmic reticulum (ER), sarcoplasmic reticulum (SR), and nucleus.

Question 63

Question: What is the functional effect of intracellular calcium ion release channels, and how is this triggered?

Answer 63

Answer: These channels release Ca2+ into the cytosol in response to an increase in intracellular IP3 or Ca2+. The functional effect can include processes like contraction and proliferation.