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Flashcards in Pharm Exam 1 Deck (45):
1

1 potent inhibitor of OAT?
* Why is it given w/cidefovir? (explain)

Probenecid
- Given w/cidefovir to protect from otherwise severe renal toxicity by blocking uptake into the proximal tubules (from the blood)

2

3 Drugs transported by OAT?

Ci-Me-N
- Cidefovir
- Methotrexate
- NSAIDs

3

1 drug class transported by OATP?

Statins

4

1 potent inhibitor of OATP?
* If given w/statins, where would it inhibit the uptake of statins and what would this cause?

Cyclosporin
- Inhibits statin uptake from blood to liver, increasing toxicity risk and decrease statin efficacy

5

4 Drugs transported by OCT?

Ci-Ci, pro met
- Cisplatin
- Cimetidine
- Procainamide
- Metformin

6

2 Drugs transported by P-gp/MDR-1?

- Digoxin
- Loperamide

7

1 potent inhibitor of P-gp/MDR-1?

Cyclosporin

8

St. John's Wort and rifampin induce which transporter protein type?

P-gp/MDR-1?

9

1 drug class transported by BCRP?

Statins

10

3 endogenous substrates of MRP?

- Glutathione
- Glucuronide
- Sulfate-conjugates

11

What drugs induce expression of CYP450 enzymes?

Phen-Phen rifles St. John’s glowing pink cars.

- Phenytoin
- Phenobarbitol
- Rifampin
- St. John's wort
- Glucocorticoids
- Pioglitazone
- Carbamazepine

12

What drugs inhibit expression of CYP450 enzymes?

Eric’s red grape kept its clear fluid

- Erythromycin
- Ritonavir
- Grapefruit juice (enterocytes, NOT liver)
- Ketoconazole
- Itraconazole
- Clarithromycin
- Fluconazole

13

E.g. of drug class that may compete for protein binding and increase the unbound fraction of other drugs?

Sulfanomides

14

2 drugs eliminated by zero-order kinetics?

- Phenytoin
- Alcohol

15

3 types of rxns involved in phase I rxns?

- Oxidation (CYP450)
- Reduction
- Hydrolysis

16

3 most common CYP450 enzyme subfamilies?

- 3A
- 2C
- 2D

17

What classes of biochemical binding-site interactions are irreversible inhibitors of CYP3A4? (1). Reversible? (2)

- REVERSIBLE: Competitive or allosteric
- IRREVERSIBLE: Suicide inhibitor (covalent binding)

18

Is gray baby syndrome related to phase 1 or 2 enzymes? (Excess or deficiency?)
- What drug leads to it?

- Phase 2 deficiency
- Chloramphenicol
(results in circulatory collapse and cyanosis)

19

Chemicals in cigarette smoke, charbroiled food and cruciferous vegetables all induce CYP___.

1A2

20

Chronic alcohol induces expression of CYP___

2E1

21

Substrate specificity for OAT?

Broad range of low MW substrates

22

Substrate specificity for OATP?

Broad range of substrates; Amphipathic Anions, MW > 350 Da

23

Most drug interactions mediated by OCT/MATE are caused by what drug?
- How? (what organ)

Cimetidine
- Prevents renal elimination of other OCT-dependent drugs

24

What 2 channels does cyclosporin inhibit?

OATP and P-gp/MDR-1

25

What 2 channels transport statins?

- OATP (influx)
- BCRP (efflux)

26

What drug is given w/cisplatin to avoid nephrotoxicity?

Cimetidine.

27

Substrate specificity for P-gp/MDR-1?

- Broad substrate specificity, typically bulky hydrophobic structures with neutral/positive charge

28

Would tumor cells upregulate or downregulate p-gp/MDR-1? Why?

Tumor cells often upregulate expression of P-gp/MDR1 to promote efflux of anti-cancer drugs

29

Of the transporters mentioned, which one is not present at the apical gut lumen?

OAT

30

Name the 3 most common CYP polymorphic genes.

CYP2D6, 2C9 and 2C19

31

Which of the CYP proteins is linked to warfarin inactivation of the active metabolite, S-warfarin?

CYP2C9

32

How does VCORC1 relate to warfarin?
What does VCORC1 do
What would happen with a mutation in VCORC1?

- Warfarin nlly inhibits VCORC1
- VCORC1 leads to formation of active clotting factor
- VCORC1 mutation = warfarin resistance = low anticoagulation (need higher dose)

33

What are the 3 non-pharmacological means of antagonizing drug effects?

1. Chemical antagonism (e.g. chelation)
2. Physiologic antagonism (use of opposing pw's)
3. Biologic antagonism (1 drug effects metab/PK of another)

34

How is 95% of acetaminophen metabolized?
What about the other 5%?
Why is high dose dangerous?
* Treatment with what drug will elevate glutathione levels and shunt back to normal pw?

- 95% is conjugated and eliminated
- 5% converted to NAPQI, which can be conjugated
- High dose shunts pw to NAPQI -> hepatotoxicity
- N-acetyl cysteine

35

Explain (in small amount of detail) the 5 parts of pre-clinical trials.
1) What 2 doses must be determined?

1. Safety pharmacology (no effect dose + LD50)
2. Toxicology
3. PK testing (ADME)
4. Drug interactions (CYP450, xporters)
5. Chemical/pharmacological devo (stable? reproducible?)

36

When does the FDA perform a review in the making of a new drug?

- Reviews investigational new drug application (INDA)
- Meets b/w phase II and III of clinical trials (to be sure it's safe for larger pop.)
- Reviews new drug application (NDA)

37

What are the 3 things an IND application must have?

1. Animal pharm and toxicology data
2. Manufacturing info
3. Clinical protocols/investigator info

- Shows drug is reasonably safe and allows drug to be shipped across state lines

38

1. Purposes of phase I trial?
2. Trial design?

1. Is it safe/tolerable; PK
2. Open label w/escalating dose

39

1. Purposes of phase II trial?
2. Trial design?

1. Does it work in actual pts? Dosing; Efficacy; safety
2. Single/double-blind

40

Purposes of phase III trial?
Trial design?

1. Does it work in large pt population? Efficacy + safety
2. Double-blind

41

What 4 things must be labeled on drug packaging?

1. Dosage
2. Adverse reactions
3. Contraindications
4. Special warnings/precautions

42

Define the 3 classes of drug recall.

Class I: Reasonable probability that use of drug will cause serious adverse health consequences or death (e.g. microbial contamination)

Class II: Use of drug will cause temporary adverse health consequences, although probability of serious health consequences is remote

Class III: Use of drug is unlikely to cause adverse health consequences (e.g. quantity packaging error)

43

What can happen when loperamide is given concurrently w/cyclosporin?

P-gp/MDR-1 receptors can be inhibited by cyclosporin, allowing loperamide to cross BBB can cause respiratory depression.

44

Which protein transporter class has specificity that overlaps with CYP3A4?

P-gp/MDR-1

45

In what phase of clinical trials of "proof of concept" established?

Phase II