Module 3 Lecture 1 Drugs and NT

Question 1

What is a drug?

Answer 1

Any substance that affects or changes biological functioning. Therapeutic drugs are used to correct physiological function. Restoration.

Question 2

How would you correct a function that isn’t stimulated enough on its own?

Answer 2

You would use a drug that acts as an agonist to enhance cellular activity.

Question 3

How would correct a biological function where the system is working overtime? HINT: Inhibit

Answer 3

You would use a drug that acts as an antagonist to block cellular activity.

Question 4

How do you determine if a drug is sufficient or unsafe?

Answer 4

You use ADME to determine what effects the drug has on the system.

Question 5

What are the target for drugs?

Answer 5

Receptors. They can be enzymes, membrane receptors, transporters, ion channels. Enzymes act as pro drugs.

Question 6

What are pharmacodynamics?

Answer 6

Quantitative relationship between the drug and the effect when the drug binds to its receptor. What does the drug do to the body. CONCENTRATION vs. EFFECT.

Question 7

What are pharamcokinetics?

Answer 7

Refers to drug elimination and how the concentration of the drug falls over time through metabolization and excretion. What the body does to the drug.

Question 8

How can you administer drugs for absorption?

Answer 8

Oral: absorption through the GI track. Goes through first pass elimination.

Intravenous (IV): bypasses the GI track and goes directly into circulation.

Question 9

What is first pass elimination?

Answer 9

The process the drug goes through before it reaches circulation. It is largely reduced through metabolization in the liver.

GI track -> portal system -> liver -> liver breaks down the drug before circulation

Question 10

How do drugs affect changes in the brain?

Answer 10

It needs to get through the blood brain barrier. The BBB protects the brain through its tight junction of endothelial cells. Endothelium cells have transporter protein on them and are selective about what they allow through.

Oxygen and CO2 are lipid soluble and can dissolve in fat or nonpolar substances.

Question 11

Where else do we get BBB crossing?

Answer 11

At the chorid plexus where cerebrospinal fluid is produced.

Question 12

How could you circumvent the BBB?

Answer 12

Intrathecal administration (spinal cord). At the bottom of spinal cord, the space is much thinner.

Question 13

What kind of property does a drug need to have to cross the BBB?

Answer 13

It needs to be lipophilic (fat affinity) or use a hitchhiking transporter.

Question 14

What are the properties of lipophilic drugs?

Answer 14

They are non polar molecules that can penetrate through the endothelial cells and cross the BBB.

Question 15

How does hitchhiking work?

Answer 15

Use a transporter that already exists. Since DA cannot cross BBB, the precursor LDOPA hitchhikes on LAT-1 that is on the the BBB. LDOPA is absorbed and gets converted into dopamine.

Question 16

What is the volume of distribution?

Answer 16

How is the drug evenly distributed in the body compared to the plasma. Example: person who is mostly muscle takes a drug that is concentrated in muscle. Therefore, the patient gets a higher dosage. A person with more fat will need higher dosage, as the drug will be accumulated in fat cells before it can reach the brain.

Question 17

What is biotransformation?

Answer 17

Taking the drug from being non polar to polar, inactive metabolites for excretion. The drug needs to become hydrophilic.

Question 18

What are the two phases of biotransformation?

Answer 18

Functionalization: requires Cytochrome P450 (CYP P450) enzyme that does a number of reaction to turn the drug polar and inactive. BBB also has CYP P450 in the choroid plexus. Takes drug and kicks it out of the brain.

Conjugation: attaches a flag to the drug to make it more polar and water soluble. Enzymes also found on the choroid plexus where they remove the drug from the CSF.

Question 19

Describe clearance.

Answer 19

The effectiveness of how the drug is moved out of the body. Clearance = Rate of elimination/plasma of concentration. Clearance works to prevent build up and keeps drug at a study state.

Question 20

Describe rate of elimination

Answer 20

Rate of elimination = CL x Drug concentration, Rate of elimination increases with the drug concentration.

Question 21

What is the therapeutic index?

Answer 21

Ratio between the amount of the drug we need to be effective compared to the level at which the drug is toxic. Effective and toxic dose.

Question 22

What happens to NT before action potential?

Answer 22

They are synthesized and stored in synaptic vesicles.

Question 23

How do you reach steady state?

Answer 23

When the total rate of elimination= rate of drug infusion and drug levels stop rising.

Question 24

How do we get dopamine?

Answer 24

Tyrosine -> LDOPA -> DA

This has similar pathway as Noradrenaline, both start with tyrosine.

Question 25

What is half life?

Answer 25

The time it takes for the drug to go from 100% to 50%.

Question 26

What is first order kinetics?

Answer 26

The more drug concentration increases, the rate of elimination also increases.

Question 27

How are NT transported through membranes?

Answer 27

Through different transporters that are passive, primary, active, and secondary active.

Question 28

Describe types passive transport.

Answer 28

Passive Transport: moves with the flow from high concentration to low concentration.

Facilitated Transport: needs a transport protein, still moving from high -> low concentration. No energy required. The protein flips to the inside.

Question 29

Describe types of active transport.

Answer 29

When molecules need to move against its concentration gradient.

Primary: Grab drug from outside, Uses ATP -> ADP, and flips to the other intracellular.

Secondary (most common):
Symporter uses electrochemical gradient of Na+ to move the molecule. Stored energy responsible for this movement. Anti moves in 2 separate directions.

Question 30

What happens with prodrugs?

Answer 30

They become activated using CYP P450 systems.