University of Nizwa

College of Pharmacy and Nursing

School of Pharmacy

CHEM440: Pharmaceutical and Medicinal Chemistry I

Spring 2014

Assignment III

Multiple choice questions

1. Irreversible enzyme inhibition involve formation of

A. Hydrogen bond

B. Dipole –dipole bond

C. Electrostatic bond

D. Covalent bond

2. True statement regarding inverse agonist is

A. Binds to the receptor and causes intended action

B. Binds to the receptor and causes opposite action

C. Binds to the receptor and causes no action

D. Binds to the receptor and causes submaximal action

3. A partial agonist has

A. High affinity but low intrinsic activity

B. High affinity but no intrinsic activity

C. Low affinity but high intrinsic activity

D. Low affinity and low intrinsic activity

4. Pick out the answer which is the most appropriate to the term “receptor”

A. All types of ion channels modulated by a drug

B. Enzymes of oxidizing-reducing reactions activated by a drug

C. Active macromolecular interacting with drug to elicit its specific effect

D. All types of macromolecule carriers activated by a drug

5. An agonist is a substance that:

A. Interacts with the receptor without producing any effect

B. Interacts with the receptor producing various effects

C. Increases concentration of another substance to produce effect

D. Interacts with plasma proteins and doesn’t produce any effect

6. If an agonist can produce maximal effects and has high efficacy it’s called:

A. Partial agonist

B. Antagonist

C. Agonist-antagonist

D. Full agonist

7. If an agonist can produce submaximal effects and has moderate efficacy it’s called:

A. Partial agonist

B. Antagonist

C. Agonist-antagonist

D. Full agonist

8. An antagonist is a substance that:

A. Binds to the receptors and initiates changes in cell function, producing maximal effect

B. Binds to the receptors and initiates changes in cell function, producing submaximal effect

C. Interacts with plasma proteins and doesn’t produce any effect

D. Binds to the receptors without directly altering their functions

9. A competitive antagonist is a substance that:

A. Interacts with receptors and produces submaximal effect

B. Binds to the same receptor site and progressively inhibits the agonist response

C. Binds to the nonspecific sites of tissue

D. Binds to one receptor subtype as an agonist and to another as an antagonist

10. The substance binding to one receptor subtype as an agonist and to another as an antagonist is called:

A. Competitive antagonist

B. Irreversible antagonist

C. Agonist-antagonist

D. Partial agonist

11. Irreversible interaction of an antagonist with a receptor is due to:

A. Ionic bonds

B. Hydrogen bonds

C. Covalent bonds

D. All of the above

12. Major mechanism of transport of drugs across biological membranes is by

A. Passive diffusion

B. Facilitated diffusion

C. Active transport

D. Endocytosis

13. Active transport and passive transport differ in that active transport requires

A. Water

B. Carrier protein

C. Energy

D. Concentrated solute

14. What is implied by the term active transport?

A. Transport of drugs through a membrane by means of diffusion

B. Transport without energy consumption

C. Engulf of drug by a cell membrane with a new vesicle formation

D. Transport against concentration gradient

15. The type of membrane transport that uses ion gradients as the energy source is:

A. facilitated diffusion

B. primary active transport.

C. secondary active transport.

D. simple diffusion

16. Symporter is a membrane transporter that transports

A. A single molecule in extracellular direction

B. A single molecule in intracellular direction

C. Two molecules in the same direction

D. Two molecules in opposite directions

17. Which of the following is antiport transporter?

A. Sodium-glucose transporter

B. Na+-K+ ATPase transporter

C. Glucose transporter

D. H+-lactose permease transporter

18. An example of transporter that efflux organic substances from the cell is

A. Organic anion transporter

B. Organic cation transporter

C. Multidrug resistance protein

D. Organic anion transporting peptide

19. Which of the following transporters can reduce fetal drug exposure?

A. P- glycoprotein

B. Adenylate cyclase

C. Serotonin/Na+ symporter

D. Na+/K+ - ATPase

20. Inhibitors of Nav will lead to

A. Hyperpolarization and inhibitory effect

B. Depolarization and excitatory effect

C. Neurotransmitters reuptake and metabolism

D. cAMP hydrolysis and a resting state

21. A voltage gated ion channel composed of 24 transmembrane a- helices in a single peptide chain is

A. Sodium channel

B. ATP-dependent K+ channel

C. Two-pore tandem K+ channel

D. Kv1 potassium channel

22. The low voltage calcium channel is

A. N-type

B. P-type

C. T-type

D. L-type

23. Which of the following potassium channels is coupled to M2 and M3 muscarinic acetylcholine receptors?

A. Voltage gated potassium channel

B. Voltage and G-protein gated potassium channel

C. Voltage and potassium activated potassium channel

D. ATP-dependent potassium channel

24. Physiological activity of KATP openers is

A. Membrane hyperpolarization and closing of Cav channel

B. Membrane depolarization and closing of Cav channel

C. Stimulation of M2 and M3 muscarinic receptors

D. Destimulation of M2 and M3 muscarinic receptors

25. The general anesthetics ketamine and pheyclidine exert their effect via Glutamate – activated receptors. Their action is happening by

A. Agonizing the Glutamate – activated receptors

B. Antagonizing the Glutamate – activated receptors

C. opening the voltage gated sodium channel

D. blocking the voltage gated sodium channel

26. The cationinc Cys-loop receptors superfamily include

A. Nicotinic acetylcholine receptors and Strychnine gylycine receptors

B. Nicotinic acetylcholine receptors and GABA-A receptors

C. Nicotinic acetylcholine receptors and serotonergic 5-HT3 receptors

D. Nicotinic acetylcholine receptors and NMDA receptors

27. Compounds that are agonizing the GABA-A receptors will show neuronal

A. Inhibitory affect

B. Excitatory effect

C. Resting state

D. Mixed inhibitory/excitatory effect

28. Another name for G-protein coupled receptors is

A. Heptahelical receptors

B. Pentameric receptors

C. GMP receptors

D. P-glycoproteins

29. True about G protein coupled receptors is

A. G proteins bind to hormones on the cell surface

B. All subunits alpha, beta and gamma should bind to each other for G proteins to act

C. G proteins act as inhibitory and excitatory because of difference in alpha subunit

D. G protein is bound to GTP in resting state

30. An examples of GPCR is

A. 5HT-3 serotonin receptor

B. NMDA receptor

C. Nicotinic receptor

D. Mu opioid receptor

31. If there is a Gs alpha subunit gain-of-function mutation, this results in

A. Decreased cAMP

B. Decreased IP3

C. Increased GTPase activity

D. Increased cAMP

32. Compounds activating Gi will lead to

A. Phosphorylation of protein kinase A

B. Phosphorylation of protein kinase C

C. inhibition of adenylate cyclase

D. activation of adenylate cyclase

33. Activation of PIP2 through GPCR will lead to

A. inhibition of adenylate cyclase

B. inhibition of guanylate cyclase

C. Phosphorylation of protein kinase A

D. Phosphorylation of protein kinase C

34. Action of alpha subunit of G-protein is

A. Binding of agonist

B. Conversion of GDP to GTP

C. Breakdown of GTP to GDP

D. Internalization of receptors

35. All known effects of cAMP in eukaryotic cells results from

A. Activation of the catalytic unit of adenylate cyclase

B. Activation of synthetase

C. Activation of protein kinase

D. Phosphorylation of G protein

36. Fastest acting receptor/ transduction mechanism is

A. Adenylyl cyclase – cyclic AMP pathway

B. Phospholipase C-IP3: DAG pathway

C. Intrinsic ion channel operation

D. Nuclear receptors

37. Which of the following does not act as second messenger?

A. Cyclic AMP

B. Inositol trisphosphate

C. Diacylglycerol

D. G proteins

38. the second messenger of G-protein-coupled (metabotropic) receptor:

A. Adenylyl cyclase

B. Sodium ions

C. Phospholipase C

D. cAMP

39. Tick the substance which changes the activity of an effector element but doesn’t belong to second messengers:

A. cAMP

B. cGMP

C. G–protein

D. Calcium ions

40. The increase of second messengers’ (cAMP, cGMP, Ca2+ etc.) concentration leads to:

A. Inhibition of intracellular protein kinases and protein phosphorylation

B. Proteinkinases activation and protein phosphorylation

C. Blocking of interaction between a receptor and an effector

D. Antagonism with endogenous ligands

Short answer Questions

1. Each of the following drug molecules interacts with a different biological target and elicits a unique pharmacologic response. For each of the three molecules, list the types of binding interactions that are possible with a target for drug action. For each type of binding interaction, provide one example of amino acid that could participate in that interaction.

2. Suggest where the compound A would form (a) strong bonds and (b) weak bonds with a receptor.The receptor and compound A are drawn to the same scale. Compound A approaches the receptor site from in front of the paper

3. One method that might enhance efficacy of anti-HIV is to increase their concentration in the plasma and Cerebrospinal fluid (CSF). Based on your knowledge on membrane transporters briefly discuss how this could be achieved.

4. Explain the meaning of the terms (a) ligand, (b) agonist, (c) antagonist, (d) secondary messengers in the context of medicinal chemistry.

5. Distinguish between competitive and non-competitive antagonists.

6. What are the four main types of molecular drug targets?

7. What are the two types of membrane transport proteins? Give one example from each type

8. Why evaluate transporters in drug development?

9. Compare and contrast symport and antiport. Which term best describes the transport system mediated by the Na+/K+ ATPase?

10. Distinguish between simple diffusion (SD), facilitated diffusion (FD), and active transport (AT) across a membrane for the following questions (more than one may be true).

a. Which processes are energy dependent?

b. Which processes need some kind of carrier protein(s)?

c. Which processes can be saturated by substrate?

d. Which processes can establish a concentration gradient?

11. Explain why nonpolar compounds are generally able to diffuse across biological membranes without the aid of a specific transport system.

12. Briefly discuss the mechanism in receptor signal transduction

13. Outline how cAMP is generated within a cell by the action of a G-protein.

14. Draw structural formulae for (a) DAG and (b) IP3. What is the cellular function of these compounds?