Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology -- Test #1 > Drug Metabolism > Flashcards

Drug Metabolism Flashcards

1
Q

What is a xenobiotic?

A

A drug or nonessential exogenous compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is oral bioavailability?

A

Fraction of the total dose that reaches systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List factors that may influence bioavailability

A

Solubility
Membrane Permeability
P-gp efflux
First pass metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens in Phase I drug metabolism

A 
Chemical Modification (biotransformation)
Hydroxylation, Oxidation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens in Phase II drug metabolism

A

Conjugation of polar group (acetyl, sulfate, etc.) with drug
Puts a big ass handle on that fucker
More H2O soluble, Deactivates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is bioinactivation?

Example?

A

Making drug metabolites less active or completely inactive.

Ex. Procaine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is Detox?

A

Bioinactivation used to break down a tocin in the body

Example: Chlorpyrifos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Two primary ways that elimination helps you get rid of drugs

A

Decreased lipid solubility to get them out of storage

Increased water solubility for pissing them out

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are prodrugs?

A

Drug metabolites may be more active than the parent compound.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Toxification?

A

Compounds activated to biologically active metabolites that frequently cause adverse effects.

ex. genotoxicity of polyaromatic carbons seen in cigarette smoke.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why are adverse reactions in drug metabolism typically unpredictable?

A

Because people don’t know shit.

Who reacts with metabolites?
Protein Modifications?
Risk factors (esp. genetics?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mechanism of acetaminophen toxicitiy

A

OD –> more N-acetyl-p-benzoquinoneimine
Normally liver glutathiones it up for elimination
Too much –> glutathiones used up, metabolite becomes toxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What typically catalyzes Phase I reactions?

A

CYPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does Cytochrome P450 work?

A 
NADPH gives e- to P450 reductase
Electrons are passed to the P450 heme
Used for (RH +O2 +2H+ --> ROH + h2O)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Other than p450 reductase, who might do electron transfer to P450?

A

Cytochrome b5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CYP2D6*1A. Identify the Family

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

CYP2D6*1A. Identify the Subfamily

A

D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

CYP2D6*1A. Identify the Individual Gene

A

6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

CYP2D6*1A. Identify the Allele

A

1A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

The active site of a CYP contains….

A

an iron-heme cofactor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The iron heme is coordinated to… (3 things)

A
  1. 4 N atomes of the heme
  2. 1 Thiolate Ligand from Cysteine
  3. H2O (when in native state)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why is it called Cytochrome P450

A

Max light absorption is at the SORET PEAK at 450 nm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the heme’s reaction mechanism in P450

Anyone else reading this, please don’t trust it

A

Substrate displaces H2O
Chelation of Iron reduces e-
Highly activated O is held next to substrate and FUCKS SHIT UPPPPPPPPPPP
Water on and Substrate released

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What intrinsic factors determine if and to which extent a group is metabolism.

A

Entering bonding site?
Ligand Bind?
Intrinsic reactivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Three factors that determine binding strength

A

Coordination with heme iron
Hydrophobic contacts with binding site of CYP
Specific Contacts with binding site residues

26
Q

Molecules with nitrogen as ______________ have typically a stronger affinity

A

sixth iron coordinating ligand have typically a stronger affinity to the heme iron than molecules

27
Q

Why does it make sense that Azo antifungals are strong CYP inhibitors

A

they work by shutting down fungi CYPs

Ex. KETOCONAZOLE

28
Q

Why aren’t inhibitors effective against all substrates of a specific CYP?

A

Different binding sites may block different routes in to the reaction center
ex. cimetidine blocks warfarin, not ibuprofen

29
Q

What occurs in mechanism-based inhibition/suicide inhibition

A

Metabolism of substrate generates reactive metabolite that irreversibly interacts with the heme or residues in the binding site

30
Q

What is induction?

A

Increase in the rate of metabolism of a drug (caused by increased expression of CYP genes)
Ex. Rifampin acts as an inducer with ketoconazole
erythromycin induces Gleevec

31
Q

Drug he said he has “repeatedly told us about” that acts as an inhibitor of CYPs

A

ketoconazole

32
Q

How do limited #s of triggers allow for so many different types of CYP induction?

A

Dimerization with many different types of nuclear receptors

33
Q

Give an example of induction leading to toxicity

A

Polycyclic aromatic hydrocarbons trigger AhR/Arnt dimer to promote CYP1A1
CYP1A1 turns PAH into reactive epoxides, causing toxicitiy

34
Q

Cooperativity

A

One drug increases the metabolism of the second drug

Ex. Dapsone increases Flurbiprofen metabolism

35
Q

When drug-drug interactions happen…..

A

efficiency/toxicity of a drug is altered by the co-administration of another drug/food

36
Q

Do people ever do drug-drug interactions intentionally

A

Lopinavir + Ritonavir

Ritonavir inhibits CYP3A4, Lop is a substrate. This keeps Lopinavir in action for longer

37
Q

Example of a Food-Drug interaction

A

Felodipine (Ca Channel Agonist) + Grape Juice

GJ inhibits CYP3A4

38
Q

Tell me something about CYP1A1/2 binding

A

Planar binding site
Narrow pocket
Planar Aromatic Compounds
BENZOPYRENE

39
Q

CYP 1A2 Substrates

A

Caffeine
Clozapine
Propanolol
Tacrine

40
Q

CYP 1A2 Inhibitors

A

Fluvoxamine

Ciprofloxacin

41
Q

CYP2 important targets

A

nicotine, clozapine, buproprion, omeprazole, diazepam

42
Q

CYP2C9 substrates…

A

Sulphonylureas
S-warfarin
NSAID
Angiotensin II blockers

43
Q

CYP2C9 inhibitors…

A

Fluconazole

Amiodarone

44
Q

CYP2D6 metabolizes…

A

lipophilic amines…

propanolol, haloperidol, sertraline, codeine, etc.

45
Q

What helps make CYP3A4 so active?

A

Its got a big ass active site that can let lots of stuff of different shapes and sizes in

46
Q

Examples of major CYP3A4 substrates

A 
Acetomenophen
Amiodarone
Buspirone
Colchicine
Estradiol
Lidocaine
47
Q

Non-CYP Phase I enzymes?

A 
Flavin containing monooxygenase
Alcohol dehydrogenase
Monoamine oxidase 
Esterase/Amidase
Epoxide hydrolase
48
Q

T or F. Phase II reactions can only act to bio-inactivate and detoxify compounds.

A

F.

Phase II rxns can be used for bioactivation or toxification

49
Q

The most dominant phase II enzymes

A

UDP-glucuronosyl transferases

50
Q

Why are UGTs such a big fuckin deal

A
  • Liver has a shit ton of glucose and uridine triphosphate, allows reaction to go to UDPGA
  • Many fxnal groups can for glucaronide conjugates
51
Q

What helps UGT and P450 interact for frequently.

A

They are co-localized on the endoplasmic reticulum

Metabolized without a long path btw rxns

52
Q

What is SULT?

A

Sulfotransferases. a Phase II for steroids, catecholamine NTs, phenolic drugs

53
Q

Cause of Gray baby syndrome

A

Chloramphenicol IV administered to newborns with immature UGT system

54
Q

Common concerns with CYP activity in pre-natal and newborns

A

Expression is different before and after birth

Some syps have extrememly varied profiles after birth

55
Q

Only defense against xenobiotics in fetal circulation

A

P-gp efflux pumps

56
Q

Unique drug metabolism scenarios for the elderly

A

drug-drug interactions
Reduced first-pass metabolism
Less phase 1 rxns
decreased renal excretion

57
Q

Diseases that may influence drug metabolism

A

Acute/Chronic Liver disease
Alcoholic Hepatitis
Alcoholic Cirrhosis
Cardiac disease decreases blood flow to the liver

58
Q

Three types of drug metabolizers

A

Poor metabolizers
Extensive metabolizers
Ultra metabolizers

59
Q

The name Katie will use for her first born of either gender

A

Sparteine

60
Q

Consequences of being a poor metabolizer

A

Higher chance of drug-drug interactions/adverse effects

slower prodrug activation

61
Q

Consequences of being an ultrarapid metabolizer

A

Faster drug elimination

Greater potential for toxic metabolites.

Pharmacology -- Test #1 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions