Pharmacokinetics

Question 1

What is ADME?

Answer 1

Absorption
Distribution
Metabolism
Exceretion

Question 2

Absorption is …

Answer 2

The process of medicine moving from administration site to systemic circulation

Question 3

Bioavailability

Answer 3

The amount of medicine that is passed into systemic circulation after administration

Question 4

Bioequivalence

Answer 4

The principle that one drug produces a similar effect when compared to another drug, without causing clinical problems. Compares drugs bioavailability of drugs in the same class with same active ingredient

Question 5

What are time critical drugs?

Answer 5

Drugs which have a narrow therapeutic window

Question 6

Branded vs Non branded medicines?

Answer 6

Same active ingredient
Bioavailability +/- 5%
Everything else can be different

Question 7

Drug plasma concentration

Answer 7

Amount of drug within the plasma concentration of blood

Question 8

Why does IV have a higher bioavailability?

Answer 8

Goes straight into systemic circulation

Question 9

Why is there a delay in peak plasma concentration in oral medicine administration?

Answer 9

The medicine must be absorbed through the GI tract before entering systemic circulation

Question 10

First pass metabolism

Answer 10

Defence mechanism of the liver to remove toxins or drugs absorbed by GI tract by hepatic portal vein. Therefore only part of the drug reacts systemic circulation.

Question 11

A drug that is more extensively metabolised during first pass metabolism…

Answer 11

Propranolol
Caution: hepatic impairment, increase half life, can increase risk of hepatic encephalopathy

Question 12

Disintegration

Answer 12

The process where tablets break down into smaller particles into liquid medium

Question 13

Dissolution

Answer 13

The small particles dissolve into a solution

Question 14

Diffusion

Answer 14

The net movement of anything from an area of high concentration to low concentration

Question 15

Main absorption site of GI tract

Answer 15

Small intestine
Absorption facilitated by microvilli and rich blood supply

Question 16

Lipophillic

Answer 16

Fat loving

Question 17

Properties for medicines to cross lipid cell membranes

Answer 17

Lipophillic

Question 18

Factors affecting GI absorption

Answer 18

• mesentric/splenic blood flow
• food
• hypovolaemic states
• gastric mobility
• drug formulation, particle size
• physiochemical factors

Question 19

What do these indicate on medicines?
“EC, MR, SR, XL, LA”

Answer 19

Modified/Slow release medications

Question 20

Example of physiochemical drug interactions: (2)

Answer 20

Tetracyclines and calcium: Calcium inhibits tetracyclines effect.

Colestryramine and warfarin: binds to warfarin preventing absorption.

Question 21

Distribution

Answer 21

The movement of drug molecules around the body

Question 22

What factors of systemic circulation affect drug distribution?

Answer 22

• Cardiac output
• Regional blood flow

Warm patients have better drug distribution compared to hypothermic patients.

Question 23

4 compartments of Body Water

Answer 23

• Extracellular fluids
• Interstitial fluids (surrounding cells)
• Intracellular fluids
• Transcellular fluids (CSF, synovial fluid)

Question 24

What drugs are pharmacology active?

Answer 24

Free drugs.
Only free drugs can interact with their site of action and have an effect.

Question 25

Which 2 different ways do drug molecules move around the body?

Answer 25

- Diffusional transfer (short distance molecule by molecule) - Bulk flow transfer (I.e via blood stream)

Question 26

Two major compartments within the body

Answer 26

- Aqueous (water) - Lipid (fat)

Question 27

Factors affecting distribution of drugs within the body (4)

Answer 27

- Molecular size [vancomycin: large, unable to pass GI tract. Ciprofloxacin: small, easy pass via GI tract = 100% bioavailability] - lipophyllic/lipophobic -hydrophilic/hydrophobic - pH and ionisation

Question 28

Lipophillic

Answer 28

Fat loving

Question 29

Lipophobic

Answer 29

Fat hating

Question 30

Hydrophobic

Answer 30

Water hating

Question 31

Hydrophyllic

Answer 31

Water liking

Question 32

Metabolism

Answer 32

Refers to the body’s chemical processes that convert drugs into other substances (metabolites) to facilitate their excretion

Question 33

2 phases of metabolism

Answer 33

Phase 1: carbolic reactions Phase 2: synthetic/anabolic reactions Both phases decrease lipid solubility, therefore more water soluble & increases renal excretion

Question 34

Catabolic reactions (phase 1) (3)

Answer 34

1. Oxidation 2. Reduction 3. Hydrolysis

Question 35

Oxidation

Answer 35

Defined as a process that occurs when atoms or groups of atoms lose electrons

Question 36

Reduction

Answer 36

Refers to the gain of electrons by a molecule.

Question 37

Hydrolysis

Answer 37

Process of breaking down complex molecules into simpler ones. Releases energy in the process

Question 38

Enzymes

Answer 38

Proteins Catalyst to biological reactions (accelerating them) Inhibiting or inducing

Question 39

CYP 1A1 metabolises

Answer 39

Theophylline

Question 40

CYP 1A2 catalyses

Answer 40

Caffeine, paracetamol, theophylline

Question 41

CYP 2C9 catalyses

Answer 41

Ibuprofen, Phenytoin, Warfarin

Question 42

CYP 2C19 catalyses

Answer 42

Omeprazole

Question 43

CYP 2D6 catalyses

Answer 43

Codine, Metoprolol

Question 44

CYP 2E1 catalyses

Answer 44

Ethanol, Eflurane, Halothane

Question 45

CYP 3A4 catalyses

Answer 45

Cyclosporin, Simvastain, Tacrolimus, Atorvastatin

Question 46

Interaction: Clarythromycin and Simvastatin

Answer 46

Clarythromycin increases exposure of Simvastatin, both metabolised by CYP 3A4.

Question 47

Interaction: Clarythromycin and tacrolimus

Answer 47

Clarythromycin increases concentration of Tacrolimus. Taking both increases risk of side effects: renal problems, nervous system disorders, hyperkalemia

Question 48

Substrate

Answer 48

A molecule of which the enzyme acts

Question 49

Ketoconazole inhibits ..

Answer 49

CYP 3A4

Question 50

In the context of enzymes, what is biological variation?

Answer 50

We all express genes differently, therefore we individually vary in the enzymes and quantities we express them in

Question 51

Ethanol is metabolised by… (2)

Answer 51

- CYP 2E1 in liver - Alcohol dehydrogenase

Question 52

Glucuronide formation

Answer 52

Produce so much energy - form bonds with many known/unknown chemicals. Major pathway in drug metabolism Asprin -> salcylic acid -> glucuronide

Question 53

Example of a drug with active metabolites

Answer 53

Morphine

Question 54

Enterohepatic Circulation

Answer 54

Process where drugs eliminated by the liver into the bile, go back to intestine and then reabsorbed back into hepatic portal circulation Liver secretion => billary transport=> intestinal reabsorption=> back to liver

Question 55

Common drugs that go through enteroheptatic recirculation

Answer 55

- cholesterol - progesterone - hydrocortisone

Question 56

Renal excretion penicillins

Answer 56

Nearly completely excreted on first pass

Question 57

Renal excretion of Diazepam

Answer 57

Cleared by kidneys very slowly

Question 58

3 factors in renal excretion

Answer 58

1. Glomerular filtration 2. Active tubular secretion 3. Passive diffusion across the tubular epithelium

Question 59

Glomerular filtration

Answer 59

Process where your kidneys remove excess fluids and waste products Excreted into urine Fat-liking molecules more likely to pass back into blood stream - excreted more slowly

Question 60

How many half lives until a drug is deemed fully excreted

Answer 60

5.5

Question 61

Which drugs do we need to closely monitor with example?

Answer 61

Ones with small therapeutic range - Digoxin - Theophylline - Phenytoin - Warfarin