Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

The study of the biochemical and physiological effects of drugs, as well as their mechanism of action.

Question 2

What are the four main types of protein targets for drug binding?

Answer 2

1. Ion channels
2. Enzymes
3. Transporters (carrier molecules)
4. Receptors.

Question 3

What are ion channels?

Answer 3

Consist of protein molecules designed to:
* form pores that span the membrane,
* switch between open and closed states,
* and allow ion movement through the pore.

Question 4

What governs the rate and direction of ion movement through the pore?

Answer 4

Electrochemical gradient for the particular ion

Question 5

What are the two main types of ion channels?

Answer 5

1. Ligand-gated
2. Voltage-gated

Question 6

What is the function of ligand-gated channels?

Answer 6

ionotropic receptors
* Only open when one or more ligand molecules are bound to the receptor
* Causes a conformational change and allowing ions to flow through.

Fast neurotransmitters act in this way e.g. Acetylcholine

Question 7

What is an example of a drug that targets an enzyme?

Answer 7

Captopril
* Used to treat high blood pressure
* Binds and inhibits angiotensin-converting enzyme (ACE)
(ACE inhibitor)

Question 8

What is the coagulation cascade?

Answer 8

• A series of enzymatic reactions that leads to a blood clot.
• Drugs target various enzymes involved in the cascade to prevent or treat thrombotic disorders.

Question 9

What is the role of transporters in drug binding?

Answer 9

• The transport of ions and small organic molecules across the cell membrane.
• Important for the transport of molecules across the blood-brain-barrier (BBB)

Question 10

What is an example of a drug that targets transporters?

Answer 10

α-methyltryptophan (pharmacological blocker)
* SLC6A14 up regulated several fold in pancreatic cancer cells

• α-methyltryptophan:
  induced amino acid starvation
  &
  Reduced growth and proliferation both in vitro and in vivo.

Question 11

What is an example of a transporter that transports substances such as drugs from the inside of the cell to the outside?

Answer 11

P-glycoprotein (P-gp)
aka Multidrug resistance protein 1 (MDR1)

Question 12

What are receptors and where are they found?

Answer 12

Molecules that are linked to other molecules within the cell and allow for cellular communication.
Found in the:
* Cell membrane,
* Cytosol
* Nucleus.

Question 13

How do drugs interact with receptors?

Answer 13

In the same way that endogenous ligands bind to receptors.
Pharmaceuticals take advantage of receptors already present
Therapeutically useful drugs act on receptors for known endogenous ligands.

Question 14

What is an example of a endogenous ligand-receptor interaction?

Answer 14

• Adrenaline binds to the beta-adrenoceptor
• Activates receptor
• Increase in the force and rate of heartbeat.

Question 15

What is an example of a drug-receptor interaction?

Answer 15

• Propranolol binds to the beta-adrenoceptor
• Blocks adrenaline from binding
• Acts as an antagonist (beta blocker).

Question 16

What is the difference between an agonist and an antagonist?

Answer 16

Agonist
* Binds to a receptor and produces a response,

Antagonist
* Binds to a receptor but does not produce a response.
* Blocks/inibits action of agonist

Question 17

What is a reversible competitive antagonist?

Answer 17

• Competes with an agonist for binding to the same site.
• Increasing conc. of the antagonist progressively inhibit the agonist binding
• High conc. of the agonist can surmount the effect of the antagonist.

Question 18

What is an irreversible antagonist?

Answer 18

• Antagonist binds with covalent bonds to the receptor
• Agonist cannot displace irrevisble antagonist
• Antagonist dissociates very slowly, or not at all, from the receptor
• Leads to reduced maximal binding or occupancy.

Question 19

What is an allosteric antagonist?

Answer 19

• Non-competitive antagonist
• Does not bind to agonist binding site
• Binds to different site

Question 20

Can allosteric antagonists be reversible or irreversible?

Answer 20

• Reversible or irreversible
• Depending on their binding mechanism to the receptor.

Question 21

What is drug specificity?

Answer 21

• The ability of drugs to act selectively on particular cells and tissues.
• Receptors are specific for a particular drug, although a drug may bind to more than one receptor.

Question 22

Example of drug specificity

Answer 22

• Peptide Angiotensin acts strongly on vascular smooth muscle and kidney tubule
• Little effect on other smooth muscle or on intestinal epithelium

Question 23

What is the Law of Mass Action?

Answer 23

Principle proposed by AJ Clark in 1926
States that:
* The rate at which drugs combine with their receptors depends on the concentration of both the drug and receptor.
* The rate of dissociation also depends on the number of drug-receptor complexes formed.

Question 24

What is the distinction between drug binding and receptor activation?

Answer 24

Drug binding
The process by which a drug binds to a receptor
Receptor activation
The response produced by the receptor after binding with the drug.

Question 25

What is the difference between a partial agonist and a full agonis?

Answer 25

Partial agonist
* A drug with intermediate efficacy
* Only trigger a sub-maximal response, even when 100% of the receptors are occupied.

Full agonist
* Has high efficacy
* Can produce a maximal response