L5-Pharmacokinetics (Part 2)

Question 1

How are most drugs eliminated from the body?

Answer 1

Most drugs are eliminated via urine, either unchanged or as polar metabolites. Other routes include elimination through bile, lungs, sweat, and milk.

Question 2

Why are lipophilic drugs not efficiently eliminated by the kidneys?

Answer 2

Lipophilic drugs are not efficiently eliminated by the kidneys because they can passively diffuse back into the bloodstream. These drugs must first be metabolized into more polar compounds to be efficiently excreted.

Question 3

What is drug metabolism?

Answer 3

Drug metabolism is the enzymatic conversion of a drug into a different chemical entity, often a more polar metabolite. This can either result in an active metabolite or a toxic compound.

Question 4

Where does drug metabolism primarily occur?

Answer 4

Drug metabolism primarily occurs in the liver, facilitated by enzymes, most notably cytochrome P450.

Question 5

What are the two phases of drug metabolism?

Answer 5

• Phase 1
• Phase 2

Question 6

What’s Phase 1?

Answer 6

Involves reactions that introduce reactive groups (e.g., hydroxyl) into the drug molecule, often catalyzed by cytochrome P450 enzymes.

Question 7

What’s Phase 2?

Answer 7

Involves conjugation of the drug (or Phase I metabolites) with substituents such as glucuronide, catalyzed by enzymes like UDP-glucuronyl transferase, making the drug more water-soluble and ready for excretion.

Question 8

What role does the cytochrome P450 system play in drug metabolism?

Answer 8

Cytochrome P450 enzymes introduce reactive groups into drugs during Phase I metabolism, preparing them for further modifications in Phase II. This system is responsible for the oxidative metabolism of many drugs.

Question 9

What is the final product of the P450 pathway, and how is it excreted?

Answer 9

The final product is a hydroxylated drug (DOH), which becomes a target for Phase II reactions that attach substituents like glucuronide, forming an inactive, excretable compound.

Question 10

What are the main cytochrome P450 enzyme families involved in drug metabolism?

Answer 10

The main P450 enzyme families are CYP1, CYP2, and CYP3. Each family has multiple subclasses that metabolize different drugs.

Question 11

Can you provide examples of drugs metabolized by different P450 isoenzymes?

Answer 11

• CYP1A1
• CYP1A2
• CYP2C9
• CYP3A4/5

Question 12

CYP1A1

Answer 12

Metabolizes theophyline

Question 13

CYP1A2

Answer 13

Metabolizes caffeine, paracetamol, and theophyline.

Question 14

CYP2C9

Answer 14

Metabolizes ibuprofen, warfin, and phenytoin

Question 15

CYP3A4/5

Answer 15

Metabolizes ciclosporin, losartan, and nifedipine

Question 16

What factors cause variations in P450 enzyme activity?

Answer 16

-Genetic Polymorphisms
- Environmental factors

Question 17

Genetic Polymorphisms

Answer 17

Individuals have genetic variations that affect how they metabolize certain drugs.

Question 18

Environmental Factors in P450 enzyme activites

Answer 18

Diet and exposure to substances can influence P450 activity. For example, grapefruit juice inhibits drug metabolism, while cigarette smoke and Brussels sprouts induce P450 enzymes.

Question 19

How can drug metabolism change the properties of a drug?

Answer 19

• Convert active drugs into inactive forms.
• Convert inactive prodrugs into active drugs or toxic substances.
• Produce metabolites that have different pharmacological effects from the parent drug.

Question 20

Provide an example of a drug with different metabolite effects.

Answer 20

Aspirin inhibits platelet function and has anti-inflammatory properties. After being hydrolyzed to salicylic acid, it retains anti-inflammatory activity but loses its antiplatelet effect.

Question 21

What is the primary route of drug and metabolite elimination?

Answer 21

The primary route of elimination is through renal excretion (urine). About 20% of drugs cross the glomerular filter, while 80% are actively transported from peritubular capillaries to the tubules.

Question 22

Why are lipid-soluble drugs not efficiently excreted in the urine?

Answer 22

Lipid-soluble drugs are passively reabsorbed by diffusion across the tubules back into the bloodstream, meaning they require metabolic conversion to polar forms for efficient excretion.

Question 23

How does urine pH affect drug elimination?

Answer 23

• Alkaline urine: Increases the excretion of acidic drugs.
• Acidic urine: Increases the excretion of basic drugs.

Changes in urine pH can also affect drug response and plasma concentration.

Question 24

What is a pharmacokinetic plot?

Answer 24

A pharmacokinetic plot represents the plasma concentration of a drug over time, reflecting its absorption, distribution, metabolism, and excretion.

Question 25

What is the half-life of a drug?

Answer 25

The half-life of a drug is the time it takes for 50% of the drug to be eliminated from the body. It depends on the drug itself, not on the administered dose.

Question 26

What is toxicokinetic?

Answer 26

Toxicokinetic follows the same principles as pharmacokinetics but focuses on the movement of toxic substances through the body, including their absorption, distribution, metabolism, and excretion.

Question 27

How are lipophilic toxicants handled by the body?

Answer 27

Lipophilic toxicants, such as pesticides, are slowly excreted because they accumulate in fat. Some toxicants also have a high affinity for specific tissues, such as the liver and kidneys, where metallothionein’s hold heavy metals like cadmium and zinc.

Question 28

Can some toxicants be used therapeutically?

Answer 28

Yes, some toxic substances can be therapeutic at low doses.

Question 29

Examples for toxicants being used as therapeutics:

Answer 29

• Botulinum toxin (BOTOX)
• Ivermectin

Question 30

Botulinum toxin (BOTOX)

Answer 30

Used cosmetically.

Question 31

Ivermectin

Answer 31

Used as an antiparasitic drug