Principles of Pharmacology

Question 1

Define absorption.

Answer 1

Process by which a drug enters the bloodstream from the site of administration.

Question 2

What factors affect distribution?

Answer 2

1. Blood Flow
2. Binding to Plasma Proteins and Tissues
3. Lipophilicity
4. Volume of Distribution

Question 3

Explain the concept of volume of distribution.

Answer 3

When you take a drug, it spreads through your body’s fluids and tissues. The volume of distribution is a measure of how much the drug seems to “spread out” in your body. If the drug stays mostly in the bloodstream, the Vd is small. If it moves into other tissues and organs, the Vd is larger.

A low Vd means the drug mostly stays in the blood (water soluble), while a high Vd means it spreads more into body tissues (fat soluble).

Low Vd: Drug works more quickly in the bloodstream but may be cleared faster.
High Vd: Drug stays longer in the body and can work more slowly but may need a higher dose to be effective.

Doctors use this information to optimize drug therapy, ensuring the drug reaches the right area of the body at the right concentration for the right amount of time.

Question 4

Explain the concept of plasma protein binding.

Answer 4

When a drug enters the bloodstream, some of it binds to plasma proteins in the blood (albumin). This part of the drug that binds to plasma proteins is inactive until it is released from the bloodstream. The free part of the drug that is not attached to the plasma proteins is the active part that can move into tissues and cause effects.

Plasma protein binding acts like a storage system by keeping some of the drug in reserve and slowly releasing it overtime which is helpful in keeping it active in the body for longer.

Higher plasma binding= low Vd because drug mainly stays in the bloodstream
Lower plasma binding= high Vd because it spreads out to tissues

Question 5

What is the purpose of metabolism in the body?

Answer 5

Metabolism breaks down a drug and helps make it easier to remove from the body.

Question 6

What does phase 1 of metabolism involve?

Answer 6

Drug is broken down and its structure is altered with the help of CYP450 enzyme through the process of oxidation, reduction, and hydrolysis. The whole purpose of this is to make the drug more water soluble for excretion.

Question 7

What is oxidation?

Answer 7

An additional oxygen atom is added to the drug’s structure with the help of the CYP450 enzyme to make the drug more water soluble.

Question 8

What is reduction?

Answer 8

Oxygen is either removed from the drug or hydrogen is added to the drug to make it more water soluble.

Question 9

What is hydrolysis?

Answer 9

Water is used to break a chemical bond in the drug, splitting it into smaller parts which makes the drug easier to process and excrete.

Question 10

What does phase 2 of metabolism involve?

Answer 10

The body adds another substance known as glucuronic acid to the drug in a process known as conjugation (attachment). This makes the drug even more water soluble and ready for excretion from the body.

Question 11

What is glucuronidation?

Answer 11

Most common and important conjugation reactions where the drug is combined with glucuronic acid to form water soluble conjugates that are then excreted.

Question 12

Explain the ways that drugs can be renally excreted.

Answer 12

1. Glomerular filtration: Filter system in the kidneys. The blood that flows through the kidneys have small drug molecules that get filtered out of the bloodstream into the urine. If a drug is not bound to proteins in the blood, it can pass through this filter.
2. Proximal tubular secretion: Drugs that are not filtered through the glomerulus can be secreted from the peritubular capillaries. This is an active process of transport for drugs into the urine.

Question 13

What is the first-pass effect associated with absorption?

Answer 13

This only occurs when a drug is taken orally. Oral medications pass through the blood of the digestive system which goes directly to the liver. This means that a portion of the drug is already metabolized before it can enter the bloodstream and reach target tissues.

This means that some drugs need to be given in higher doses when taken orally or given in other forms to bypass direct passage to the liver.

Question 14

What role do inducers of the CYP450 enzyme do to the body?

Answer 14

They induce, or rial up CYP450 enzyme activity which increases metabolism of the initial drug making it less effective because it is broken down and cleared from the body quicker.

Question 15

What are examples of CYP450 enzyme inducers?

Answer 15

1. Rifampin
2. Carbamazepine
3. St. John’s Wort
4. Phenobarbital
5. Phenytoin
   6.Griseofulvin
6. Charcoal broiled food
7. Vegetables like cabbage and broccoli

Question 16

What are examples of CYP450 enzyme inducer drug interactions?

Answer 16

1. Carbamazepine and Cyclosporine
2. Rifampin and Oral Contraceptives

Question 17

What role do inhibitors of the CYP450 enzyme play in the body?

Answer 17

They inhibit CYP450 enzyme activity which slows it down, leading to the drug staying in the body for longer and can lead to side effects and toxicity.

Question 18

What are examples of CYP450 inhibitors?

Answer 18

1. Grapefruit juice
2. Erythromycin
3. Ketoconazole
   4.Ritonavir
   5.Cimetidine
   5.Fluozetine
4. Paroxetine

Question 19

What are examples of CYP450 enzyme inhibitor drug interactions?

Answer 19

1. Cimetidine and Warfarin: Increases risk of hemorrhage
2. Grapefruit juice and Statins: Increase risk of myalgias and GI side effects.

Question 20

What CYP enzyme is associated with genetic polymorphisms?

Answer 20

CYP2D6 (poor metabolizers)

Question 21

What are major hepatotoxic drugs?

Answer 21

1. Tylenol: Long term use can lead to severe liver damage.
2. Isoniazid: Treatment for TB which can cause liver damage in those with liver conditions
3. Methotrexate: Used in autoimmune diseases- with long term use can cause hepatic fibrosis.
4. Amiodarone: Treats arrhythmias in the heart but can cause liver toxicity.
5. Statins

Question 22

What is half-life?

Answer 22

Half-life of a drug is the time required for the concentration of the drug in the plasma to decrease by 50%.

Half-life is dependent on elimination and the Vd of a drug.

Question 23

What is steady state and when is it reached?

Answer 23

Occurs when drug administration= drug elimination so at steady state the drug level in your bloodstream stays constant and the drug has a stable therapeutic effect.
This is reached in 5 half-lives.

Question 24

What is pharmacodynamics?

Answer 24

How the drug interacts with specific receptors in the body.

Question 25

What is affinity?

Answer 25

Strength of the binding relation between a drug and its receptor. This is measured by the equilibrium dissociation constant (Kd).

Question 26

What does a low and high Kd represent?

Answer 26

Low Kd= higher affinity. The drug sticks to strongly to the receptor and doesn’t come off easily which means it has a strong grip.

High Kd= lower affinity. This means that the drug binds loosely and can easily fall off the receptor.

Question 27

What is efficacy?

Answer 27

Maximum effect a drug can produce.

Question 28

Please explain the concept of drug receptor binding.

Answer 28

The strength of the fit between a drug and its receptor is called affinity

Question 28

What is the correlation between up regulation and down regulation?

Answer 28

Antagonists BLOCK receptors so because these receptors do not get activated, the body will UP-REGULATE (increase the number of receptors) to try to catch more signals.

Agonists ACTIVATE receptors a lot, and the body in turn will DOWN-REGULATE (reduce number of receptors) to prevent overstimulation.

Question 28

What is an agonist and give an example.

Answer 28

Drugs that ACTIVATE a receptor. When the drug binds to a receptor, it stimulates a response.

MORPHINE is a complete agonist for opioid receptors in the brain, meaning it binds to these receptors and triggers pain relief.

Question 29

What is a partial agonist and give an example.

Answer 29

A partial agonist activates a receptor but not as fully as an agonist. The drug binds to the receptor but produces a weaker response compared to a full agonist.

BUPRENORPHINE is a partial agonist used in pain management. It provides some pain relief but not as much as a full agonist like morphine.

Question 30

What is an antagonist and give an example.

Answer 30

Drugs that BLOCK receptors, preventing other substances from activating it. The drug binds to the receptor but does NOT trigger a response and instead will also block other drugs from working.

NALAXONE is an antagonist that blocks opioid receptors and is often used to reverse opioid overdoses by stopping the effect of drugs like heroin or morphine.

Question 31

What is a competitive antagonist and give an example.

Answer 31

Drug that competes with an agonist for the same receptor site. The antagonist can be overridden by increasing the dose of the agonist or vice versa.

Narcan (naloxone) works in this way as well by competing with opioids at the same receptor, reversing their effects during an overdose.

Question 32

What is idiosyncrasy?

Answer 32

Unusual or unexpected reaction to a drug that happens in some individuals but not most people.

Question 33

What is tachyphylaxis?

Answer 33

Occurs when a drug becomes less effective after repeated use over a short time, so the body quickly stops responding to it. The body’s receptors get used to the drug and stop reacting, so the drug doesn’t work as well, and you need to take more to get the same effect.