Brainscape's Knowledge GenomeTM

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


See full index

Med Chem Test 4 > Drug Metabolism Factors > Flashcards

Drug Metabolism Factors Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

What are the pharmacodynamics internal factors that affect drug metabolism?

A

Dose (overdosing)
Route of administration
Distribution (protein/tissue)

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

What are the physiological internal factors?

A 
Tissue DME's 
Disease
Age
Gender
Genetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the external or environmental factors that affect drug metabolism?

A

Nutritional Status

Induction/Inhibition of drug metabolism enzymes.

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

How can dose affect drug metabolism?

A

Overdosing can overwhelm DMEs capacities and toxicity can ensue.

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

What is an example of toxicity caused by overdosing?

A

APAP toxicity.

Glucuronidation and Sulfation are overwhelmed and thus CYP450 creates N-Acetylparabenzoquinoeimine (NAPQ1)

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

What are the different routes of administration?

A

Instillation, aerosol, oral(inhaler), sublingual, transdermal patch, topical, intramuscular, ear instillation, subcutaneous, intravenous, and suppository.

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

Oral route is susceptible to what?

A

1st pass effect

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

What is the 1st pass effect?

A

Pre-systemic metabolism.

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

Where does the 1st pass effect occur?

A

Gut wall; small intestine (bacterial enzymes); liver; lung.q

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

What are examples of drugs with significant 1st pass effect?

A

Isoproterenol, lidocaine, nitroglyercin.

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

How is isoproterenol affected by the 1st pass effect?

A

Intestinal wall Sulfation.

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

How is lidocaine affected by the 1st pass effect?

A

Ineffective by mouth

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

How is nitroglyercin affected by the 1st pass effect?

A

It can only be administered buccally.

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

What factors affect distribution?

A

Serum protein binding, tissue binding, and transporters.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

In serum protein binding the bound drug is active or inactive?

A

Inactive

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

When binding sites are saturated what happens to the free drug?

A

There is more of it.

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

What does the amount of free drug affect?

A

pharmacological effects and elimination

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

Protein binding ______ metabolism and _______drug half life.

A

Protein binding decreases metabolism and increases drug half life.

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

What are examples of drugs that bind to serum proteins?

A

Warfarin, NSAIDs, Sulfonamides; Sulfonylureas; Depakene; Nifedipine; Prazosin; Diphenhydramine

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

Weak acids bind to what serum protein?

A

albumin

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

Weak bases bind to what serum protein?

A

alpha-1 acid glycoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are other serum binding proteins?

A

lipoproteins, globulins (alpha, beta, and gamma)

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

What does tissue drug binding involve?

A

Non-specific binding to proteins and lipids.

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

Tissue binding increases what?

A

Drug concentration in tissue.

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

ABC transporters determine what?

A

oral bioavailability
cellular accumulation
excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the transporter proteins?

A

usually influx/efflux transporters.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What tissue specific enzymes are expressed in the skeletal muscle?

A

CYP2C9, MAO-A, MAO-B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What tissues are the MAO-A AND THE MAO-B not expressed in?

A

the skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What enzymes are expressed in almost every tissue except skeletal muscle?

A

CYP2D6
CYP2E1
CYP3A4
CYP3A5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What disease states effect drug metabolism?

A

Liver diseases, Cardiac diseases, diabetes, inflammation/infection, thyroid disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How does liver disease effect drug metabolism?

A

decreases it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How does cardiac disease affect drug metabolism?

A

decreases it due to reduced liver blood flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How does diabetes affect drug metabolism?

A

???

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How does inflammation/infection affect drug metabolism?

A

decreases it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How does thyroid disease affect drug metabolism?

A

increases protein synthesis in hyperthoidism and therefore has elevated drug metabolism enzyme activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

For acute/chronic liver disease the effects on drug metabolism are…

A

not always predictable but if a drug must be metabolized by the liver before elimination it will have an effect. Toxicity due to over dose is common.

37
Q

Why does age impact drug metabolism?

A

Hepatic plus-hepatic enzyme maturation (some fetal hepatic enzymes disappear or decrease after birth and some appear right after birth or later in life)
hepatic blood flow
liver weight

38
Q

What enzyme has a late appearance in life?

A

CYP1A2

39
Q

When do CYP450s form in the fetus?

A

Earlier in gestation then Phase II

40
Q

What are common drug metabolism enzymes in the fetus?

A

CYP1A
CYP3A7
SULTs

41
Q

Is phase 1 or 2 more common in drug metabolism in a fetus?

A

Phase 1

42
Q

Are fetuses more or less susceptible to toxicity?

A

More

43
Q

What enzymes do neonates have a low concentration of?

A

UGT

They have inadequate (UGT1A1) conjugation of bilirubin which leads to jaundice or hyperbilirubinemia.

44
Q

What drugs should you avoid with neonate?

A

Ones that require Glucuronidation for elimination.

45
Q

What drugs may cause gray baby syndrome?

A

Chloramphenicol and omeprazole because of the inability to conjugate due to the high SULTS capacity.

46
Q

How does age affect drug metabolism?

A

Changed body mass/composition.
Overall slow metabolic activity
Susceptible to toxicity

47
Q

How does the changed body mass/composition affect drug metabolism?

A

Less metabolic activity (Less metabolic activity)

Alterations to pharmacokinetics (less excretion, less liver blood flow, less renal filtration rates)

48
Q

Sex hormones stimulate the release of what?

A

GH by pituitary gland

49
Q

GH are release less frequently in males or females?

A

males
Androgens increase metabolism
Estrogen decreases metabolism

50
Q

What are some drugs that sex differences affect?

A

Nicotine, Aspirin, Alcohol, Propranolol, diazepam, etc…

51
Q

How do stress hormones affect DM?

A

Increased glucocorticoid levels induce DME expression.

52
Q

How does pregnancy affect DME?

A

Increased sex hormones, fetus metabolic activity, increased plasma volume, increased liver blood flow, increased glomerular filtration, increased 2D6, increased 3A4, increased UGT

53
Q

What enzymes have DME Polymorphism?

A

CYP2A6, 2C9, 2C19, 2D6

54
Q

CYP2D6 can be what?

A

Poor metabolizers, PM
Intermediate metabolizers, IM
Ultra-rapid Metabolizers, UM
Extensive Metabolizers, EM

55
Q

Which population has ALDH polymorphisms?

A

Japanese and Chinese have a flushing response due to inactive hepatic ALDH1

56
Q

What population has NAT polymorphisms?

A

Caucasians with slow acetylators and rapid acetylators

57
Q

What population has CYP2C19?

A

20 percent of Asians

3 percent of Caucasians

58
Q

EM and PM DME phenotypes are similar to Drug Induction and Inhibition, respectively. T/F

A

True

59
Q

Cats have _____ but lack ____ and vice versa for Pigs?

A

SULTs

UGTs

60
Q

Humans have _____ CYP2D isoform but ______ have six.

A

one

rats

61
Q

How does nutritional status affect drug metabolism?

A

Carbohydrate impact is mixed
Decreased lipid and protein intact can decrease microsomal drug metabolizing activity. Lead to slow and erratic GI absorption.
Vitamins and minerals may be needed in Phase 1 oxidations.
Malnutrition may decrease clearance and increase toxicity.

62
Q

What drugs causes a reduced or delay by food?

A

Reduced or delayed. Ex: Ampicillin, Aspirin, Atneolol, Azithromycin, Captopril; Cefaclor; Cefixime; Cephalexin.

63
Q

What drugs increase absorption with food?

A

Ketoconazole, lithium, lovastatin, metoprolol, nitrofurantoin, propranolol, propoxyphene

64
Q

What are PAHs and how do they affect drug metabolism?

A

smoked foods, cigarettes smoke, etc.
Increase CYP1A2 activity.
CYP1A2 convers PAHs into carcinogens implicated in lung/colon cancers…slow process.

65
Q

Where do indoles come from and what do they do?

A

They come from vegetables (cabbage).

Upregulate CYP1A

66
Q

Where do Isothyocyanates come from and what do they do?

A

Come from vegetables (watercress)

Inhibit CYP2E1

67
Q

Where do Oragnosulfur compounds come from and what do they do?

A

Come from garlic
Inhibit CYP2E1
Induce CYP1A, CYP3A and Phase II enzymes

68
Q

What does grape fruit juice do?

A

Decreases CYP3A activity.

69
Q

Where does Tyramine come from and what does it do?

A

Smoked, aged or pickled meat/fish/sauerkraut/cheesed, etc

High tyramine blood levels can disrupt endogenous catecholamine metabolism. Outcome: fatal hypertension.

70
Q

What are factors that induce or inhibit drug metabolism enzymes?

A

Exposure to…
DME inducing/inhibiting drugs
contaminants/pollutants in air, food, and water
non-contaminants in air, food (preservatives), and water

71
Q

Enzyme induction does what to enzymatic levels and activity?

A

Increases

72
Q

Enzyme induction does what to transcription and translation?

A

increases

73
Q

Enzyme induction does what to protein degradation?

A

Decreases

74
Q

Generally, induction does what to…
DME activity
drug blood levels
Duration of action

A

DME activity increases
drug blood levels decrease
Duration of action decreases

75
Q

What are common inducing agents?

A 
Nevirapine
Efavirenz
Ritonavir
Rifampin
Rifabutin
Phenobarbital
Carbamazepine
Phenytoin
Ehtanol
St. John's Wort
76
Q

What is Cyclosporin A and what happens when 3A4 is induced?

A

Cyclosporin A is an immunosuppressant.
It requires 3A4 for its metabolism so when it is induced it causes drug inactivation of Cyclosporin A and thus causes transplant failure.

77
Q

What are some examples of Polycyclic Aromatic Hydrocarbons (PAHs)?

A

Napthalene, Acenaphtlene, Anthracene, 1,6-Dimethylnapthalene, Fluorene, 1-Methylanthracene, Biphenyl, Phenathrene, 9,10-Dimethylanthracene (they all have 2 or more cyclic rings.

78
Q

What to dioxins and PCBs do?

A

Induce enzymes. They look like cyclic rings with Cl’s on them.

79
Q

How long does reversible enzyme inhibition last?

A

2-3 days

80
Q

How long does irreversible enzyme inhibition last?

A

Drug is bound to enzyme for a longer period
Drug or Intermediate or Metabolite complexation with DME
New enzyme has to be formed.

81
Q

What occurs in mechanism-based inactivation of DMEs?

A

Reactive metabolite formed binds to DME and inhibits its activity. They are called suicide substrates.

82
Q

DME inhibition does what to…
Drug activity or toxicity
Drug blood levels
duration of action

A

Increases drug activity or toxicity
Increases drug blood levels
Increases duration of action

83
Q

DME inhibition effects are greater on the liver enzymes or GI enzymes?

A

The effects are greater on the GI enzymes.

84
Q

What are the inhibitors of drug metabolism?

A 
Protease inhibitors
Delavirdine
Efavirenz
Fluconazole
Itraconazole
Ketoconazole
Voriconazole
Isoniazid
Ciprofloxacin
Grapefruit Juice
Clarithromycin
Erythromycin
Diltiazem
Verapamil
Amiodarone
Cimetidine
Omeprazole
Fluoxetine
85
Q

What causes grape fruit juice to inhibit DME?

A

Furocoumarins - mechanism based inhibitors of 3A4

86
Q

What are some potential outcomes of DDIs?

A

Hemorrhage, Hypoglycemia, Immunosupression, CNS depression

87
Q

What factors contribute to drug response variability?

A

Internal & external factors
Genetic Differences in DMEs
DME induction/inhibition (lead to DM related DDIs, Inducers usually increase clearance, Inhibitors usually diminish clearance).

88
Q

What are the internal and external factors?

A

Internal - Dose, Route of administration, Distribution, Nutrition, Disease, Age, Gender & Hormones, Genetics.

External - Exposure to xenobiotics (Inducer/Inhibitor), Diet or food.

Med Chem Test 4 (6 decks)

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