7.4 Pharmacokinetics Part 2

Question 1

What is the Steady State?

Answer 1

1) The point in a consistent dosing regimen where serum levels are no longer changing.
2) Time to steady state is a function of the drug’s elimination half-life.
3) Loading doses can can decrease the time needed to achieve steady state.

Question 2

How many half lives does it take to reach steady state?

Answer 2

4 half lives

Question 3

What do loading doses do?

Answer 3

-They are larger initial doses to get to the steady state quicker. Then only smaller doses are needed to maintain steady state level.

Question 4

What is Phase 1 of drug liver metabolism?

Answer 4

Involves cytochrome p450 (CYP) liver enzyme system

Question 5

What are the two most common drug metabolizing CYP?

Answer 5

CYP 34A and CYP 3A5

Question 6

When do you draw a peak level?

Answer 6

30 minutes after the drug dose is infused.

Question 7

What type of relationship does the half life and clearance rate have?

Answer 7

• Inverse relationship.

- Clearance time up, half life down

Question 8

If a drug has a 8 hour half life how long will it take to reach a steady state?

Answer 8

32 hours

Question 9

What is Phase 2 of the drug liver metabolism?

Answer 9

• Conjugation step (with glucuronic acid, sulfate)
• Uridine 5’-diphosphat-glucuronosyl transferases are the most dominant enzymes in phase 2.
• Conjugation of drug with glucuronic acid is most common reaction.

Question 10

What is a prodrug?

Answer 10

• Is an inactive parent drug which requires bio-activation.
• Toxification: toxic metabolite formed from parent drug
• A biologically inactive compound that can be metabolized in the body to produce a drug.

Question 11

Does the liver have to be involved in the creation of all prodrugs?

Answer 11

Prodrug activation does not have to involve the liver.

Question 12

What are the 4 possible outcome of liver drug metabolism.

Answer 12

1) Chemical alteration.
2) Bioactivation
3) Toxification
4) Elimination
- Drug metabolism is the process by which drug molecules are chemically ale red, usually to more polar metabolites that exhibit increased water solubility to allow elimination in urine or bile and or increased access to execratory transporters.
- Metabolism: active metabolites can be formed both parent drug and metabolite active, prodrug is an inactive parent drug which requires bioactivation, toxification (toxic metabolite formed from parent drug)

Question 13

What is an inducer?

Answer 13

A drug that speeds up the metabolism of other drugs.

Question 14

What is enterohepatic recycling?

Answer 14

• It can prolong drug duration of action
• Drugs eliminate in the bile are available for absorption in the GI tract. This re-entry into the body after elimination via the bile results in the recycling of drug and prolongs the time required for the rig to be irreversibly eliminated from the body.

Question 15

Role of Kidney in Drug elimination, Drug Out?

Answer 15

• Filtration at glomerulus

- Renal tubular secretion

Question 16

Role of kidney in drug elimination, drug in?

Answer 16

• Renal tubular reabsorption

- pH effect and ion trapping= therapeutically change ruing pH to alter drug ionization and lipid solubility.

Question 17

What does the kidneys do during aspirin overdose?

Answer 17

Increases urine pH to increase secretion of aspirin in an overdose situation

Question 18

How do histamines initiate effects?

Answer 18

• Histamine initiates its effects by stimulating the cel membrane.
• Mast cells release histamine after binding to IgE and antigen.

Question 19

What are the four different Histamine receptors?

Answer 19

H1R, H2R, H3R, H4R

Question 20

What are the two main histamine drug targets?

Answer 20

H1 and H2 to stop major biological effects such as acute allergic responses.

Question 21

What drug is the choice for emergency treatment of severe allergic reactions?

Answer 21

-Epinephrine

Question 22

What care two clinical advantages that loratadine and fexofenadine have over diphenhydramine?

Answer 22

• CNS depression-sedation (mainly with first generation agents)
• Anticholinergic Effects (mainly with first generation agents)
• Loratadine and fexofenadine are 2nd generation drugs and are basically “non-drowsy” and have a low incidence of anticholinergic effects. These drugs have a decreased ability to cross into the CNS (this explains the “non-drowsy”)

Question 23

Describe the anticholinergic effects from diphenhydramine?

Answer 23

1) Dry mouth
2) Confusion memory loss
3) Constipation
4) Blurred vision
5) Confusion memory loss