#3 Herb-Drug Interactions

Question 1

3 biggest categories of dietary supplements used

Answer 1

1. Sports enhancement (steroids, ephedrine alkaloids)
2. WT loss (silmutramine, ephedrine alkaloids)
3. Sexual enhancement (PDE, inhibitors)

Question 2

Ecstasy enzyme effects

Answer 2

Its metabolite is a VERY POTENT MDI INHIBITOR of 2D6

Question 3

Ecstasy + dextromethorphan

Answer 3

Ecstasy (metabolite) = Very STRONG inhibitor
Dextromethorphan = 2D6 substrate
INCREASES [dextromethorphan] AUC 14-fold

Question 4

Garlic active component

Answer 4

Allin

Question 5

Garlic uses (2)

Answer 5

1. hypercholesterolemia

2. Boost Immune System

Question 6

Garlic enzyme effects

Answer 6

Studies show inconsistent results!

Question 7

Garlic oil + midazolam

Answer 7

Showed no effect

Question 8

Garlic + saquinavir (3A4 substrate)

Answer 8

DECREASED [saquinavir]

= suggests that garlic is INDUCER of 3A4

Question 9

Garlic + docetaxel (3A4 substrate)

Answer 9

INCREASED [docetaxel]

= suggests that garlic is INHIBITOR of 3A4

Question 10

Gingko biloba active components

Answer 10

Flavonoids

Terpenes

Question 11

Gingko biloba use (1)

Answer 11

memory improvement

Question 12

Gingko biloba enzyme effects

Answer 12

Weak INDUCER:

3A4, 2C9, 2C19….though not totally clear

Question 13

Gingko biloba + tolbutamide DDI

Answer 13

Tolbutamide + 2C9 substrate Gingko = 2C9 inducer

DECREASED [tolbutamide]

Question 14

Gingko biloba + midazolam DDI

Answer 14

Studies show inconsistent results

One study showed INCREASED [MDZ]
another showed DECREASED [MDZ]

Question 15

Gingko biloba + omeprazole DDI

Answer 15

DECREASED [omeprazole] d/t gingko’s INDUCTION of both 2C19 and 3A4

Question 16

Goldenseal active components

Answer 16

NTE 2% hydrastine, 2.5% berberine

Question 17

Goldenseal uses (2)

Answer 17

1. Enhance immune system

2. Stimulate digestion

Question 18

Goldenseal Enzyme effects

Hint: Stop killing the seals! There’s only 2,634 seals left in the world

Answer 18

INHIBITS:
2D6
3A4

Question 19

Goldenseal + debrisoquine DDI

Answer 19

Debrisoquine = 2D6 SUBSTRATE
Goldenseal = 2D6 INHIBITOR
=
INCREASED [debrisoquine]

Question 20

Goldenseal + Midazolam DDI

Answer 20

MDZ = 3A4 SUBSTRATE 
Goldenseal = 3A4 INHIBITOR 

=
INCREASED [midazolam]

Question 21

Green tea active component

Answer 21

Catechins

Question 22

Green tea enzyme effects (2)

Answer 22

1. INHIBITS 1A2 (minor pathway for APAP)

2. INHIBITS OATP1A2

Question 23

Green tea + Folic acid DDI

Answer 23

DECREASED folate AUC

Suggests that green tea has some effect on uptake transporters….but could also be some “unstirred water layer osmolality” thing….

Question 24

Green tea + nadolol DDI

Answer 24

Nadolol = taken up by OATP1A2 (aka substrate)
Caused DECREASE AUC of nadolol

Suggest that green tea inhibits uptake transporter OATP1A2, however this transporter is not expressed in the GI…

Question 25

Green tea + drugs with low GI permeability (proposed mechanism)

Answer 25

Green tea affects GI osmolality and fluid volume = affects absorption of these drugs

Question 26

SJW effects on enzymes

Answer 26

INDUCES 3A4 Pgp

Question 27

Milk thistle effects on enzyme

Answer 27

no consistent PK interactions

Question 28

Saw palmetto effects on enzyme

Answer 28

no consistent PK interactions

Question 29

Valerian effects on enzymes

Answer 29

no consistent PK interactions

Question 30

Turmeric effects on enzymes Hint: same as goldenseal

Answer 30

In VITRO INHIBITS 2D6 In VIVO maybe INHIBITS 2D6 & 3A4

Question 31

T/F: | The biggest SAFETY issue for herbal products and dietary supplements is accidental contamination

Answer 31

FALSE | The biggest SAFETY issue DELIBERATE contamination with DRUGS

Question 32

Ecstasy is a [TIME/CONCENTRATION] dependent inhibitor of 2D6

Answer 32

TIME

Question 33

Ecstasy is an INHIBITOR of this enzyme

Answer 33

2D6

Question 34

T/F: | Ecstasy is a mechanism based INHIBITOR of 2D6

Answer 34

TRUE

Question 35

[MEN/WOMEN/NEITHER] were more affected by ecstasy's 2D6 INHIBITION

Answer 35

WOMEN

Question 36

``` Garlic has been shown to have what effect on 3A4? A. Induce B. Inhibit C. NO effect D. all of the above ```

Answer 36

D. all of the above Inhibit = docetaxel Induce = saquinavir NO effect = midazolam/ritonavir So garlic can both induce and inhibit 3A4. The effects are modes and variable and the data is unclear

Question 37

This is the purported active ingredient of garlic

Answer 37

allicin

Question 38

Garlic was shown to have a noticeable effect on [Ritonavir/Midazolam/BOTH/neither]

Answer 38

NEITHER

Question 39

These supplements inhibit platelet aggregation according to the multiple reports of bleeding disorders

Answer 39

Garlic Ginkgo Asian ginseng (Panax)

Question 40

Ginkgo induces this enzyme

Answer 40

2C9

Question 41

What was the effect of Ginkgo with Tolbutamide?

Answer 41

Ginkgo INDUCED tolbutamide CL through 2C9 induction, 29% DECREASE IN AUC

Question 42

Ginkgo [inhibits/induces/either] 3A4

Answer 42

EITHER

Question 43

What was the effect of Ginkgo with MDZ?

Answer 43

Ginkgo INHIBITED MDZ CL through 3A4 = 24.6% INCREASE IN AUC However later is was shown to INDUCE 3A4

Question 44

Ginkgo [inhibits/induces/either] 2C19 (omeprazole)?

Answer 44

INDUCES | Weak 3A4 & 2C19 induction seems to be the most consistent Ginkgo effect

Question 45

Goldenseal [inhibits/induces] 2D6

Answer 45

INHIBITS

Question 46

Goldenseal [inhibits/induces] 3A4

Answer 46

INDUCES

Question 47

Green tea extract lowered levels of this nutrient

Answer 47

Folic acid

Question 48

Caffeine INHIBITS _______ and interferes with the metabolism of this OTC?

Answer 48

1A2 | APAP

Question 49

How does green tea effect Nadolol?

Answer 49

DECREASED | Concentration by 85%

Question 50

Why does green tea decrease nadolol concentrations?

Answer 50

Absorption of LOW permeability drugs depends on the drug concentration gradient, which is in turn influenced by GI fluid volume and osmolality and slows drug absorption

Question 51

Whether or not this supplement affected caffeine levels depended on the brand used

Answer 51

Echinacea