0509 - Molecular aspects of Drug Action - CS

Question 1

List possible drug targets (broad categories, not specific) (5)

Answer 1

-Receptors (types 1-4)-Ion channels-Enzymes-Transporters-Exceptions

Question 2

List and briefly describe two general mechanisms by which a drug that targets receptors could work

Answer 2

1. Agonist - keeps the receptor in an active state2. Antagonist - inhibits the action of an agonist but has no effect if agonist is absent

Question 3

List and briefly describe two general mechanisms by which a drug that targets ion channels could work

Answer 3

1. Blockers - drug block permeation through the ion channel2. Modulators - drug can either increase or decrease the probability that the ion channels will open

Question 4

List and briefly describe three mechanisms by which a drug that targets enzymes could work

Answer 4

1. Inhibitor - drug inactivates the enzyme (eg by causing the enzyme to be phosphorylated or undergo a conformational change)2. False substrate - drug reacts with the enzyme in place of the substrate with which the enzyme is designed to react. An abnormal metabolite may be produced by this reaction3. Pro-drug - drug is given in an inactive form. It reacts with an enzyme which then produces the active form of the drug

Question 5

List and briefly describe two mechanisms by which a drug that targets transporters could work

Answer 5

1. Inhibitor - drug reacts with some part of the transporter protein or complex which blocks the transporter and stops the substrate from being able to be transported across the membrane2. False substrate - drug is able to be transported across the membrane by the transporter in place of the usual substrate

Question 6

List and briefly describe four mechanisms for drugs that targets has some OTHER mechanism that does not involve receptors, ion channels, transporters or enzymes

Answer 6

1. Microtubule inhibitor - eg colchicine used for gout stops neutrophils from being able to migrate to joints via microtubules2. DNA structure modifying agents - eg cisplatin for cancer treatment causes intrastrand linking and cross linking of DNA3. Osmotic diuretics - eg mannitol increases urine osmolarity which results in water and salt being drawn into the urine, reducing blood volume and increasing urine volume4. Antacids - neutralises stomach acid

Question 7

List four types of receptors that can be targeted by drugs

Answer 7

Type 1 - ligand gated ion channelsType 2 - G-protein - coupled receptorsType 3 - Kinase-linked (& related) receptorsType 4 - Nuclear receptors

Question 8

Briefly describe possible mechanisms for a drug that targets type 1 receptors

Answer 8

Type 1 receptor = ligand-gated ion channel in cell membrane (controls entry of a particular ion into the cell).Gate may be induced to open or close - increases or decreases permeability for whatever that channel can allow through. May have an excitatory, inhibitory or modulatory effect depending on the type of ion channel targeted and the site to which it binds to that ion-channel receptor.Agonist: binds to receptor causing channel to openAntagonist: Binds to receptor and stops agonist from binding (stops channel from opening)

Question 9

Briefly describe possible mechanisms for a drug that targets type 2 receptors

Answer 9

Type 2 receptor = G-protein coupled receptor. Most abundant class of receptor in the body. Drug binds to receptor on the cell membrane which leads to release of Gprotein into the cell and then sets off a cascade of reactions inside the cell.Can lead to different effects depending on the particular receptor being stimulated.Eg 1. G-protein can interact with an ion channel making it more or less likely to open.Eg 2. G-protein can activate or inhibit an enzyme inside the cell which might increase the production of second messengers such as cAMP or IP3 which sets off other changes inside the cell.

Question 10

Why might selectivity be an important feature of a drug?

Answer 10

Can target a more specific effect and minimise unwanted side effects. eg beta receptors are found in cardiac tissue. There are different types of beta receptors (beta-1, beta-2 etc). A drug that activates both can cause tachycardia and heart pounding (unwanted side effects) in addition to bronchodilation. A drug that targets only beta-2 receptors can cause bronchodilation without side effects.

Question 11

Briefly describe a possible mechanism for a drug that targets type 3 receptors

Answer 11

Type 3 = Kinase-linked (& related) receptors. Have a transmembrane signalling mechanism.Receptor is a protein that crosses the membrane. Drug binds to a site on the receptor on the outside of the membrane and activates the receptor (eg by causing a conformational change). This then sets of a reaction or series of reactions inside the cell

Question 12

Briefly describe a possible mechanism for a drug that targets type 4 receptors

Answer 12

Type 4 = nuclear receptorsEG. drug may be lipo-phillic (soluble in fat) and therefore able to diffuse directly through the membrane into the cytoplasm and bind to and activate a receptor inside the cell such as a transcription factor. Together the drug and the receptor form an activated receptor complex and enter the nucleus of the cell and lead to the transcription of DNA and ultimately protein synthesis. Requires minutes to hours or days for response to be complete. Response may continue after concentration of compound reduces to zero.