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Pharmacogenetics Exam 1 > Pharmacodynamics and Genetics > Flashcards

Pharmacodynamics and Genetics Flashcards

1
Q

PK Factors ADME lead to

A

Inactivation, activation or change in bioavailability which leads to no response or a response

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2
Q

PD Factors lead to

A

Enzymes, receptors, or transporter changes which leads to toxicity or no toxicity

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3
Q

GPCR Targets/Drugs

A

B-adrenergic receptors (beta-blockers)
Serotonin (antipsychotic/antidepressants)
Mu-opioid receptor (analgesics)

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4
Q

Transportor and Ion channels targets/drugs

A

Sodium & potassium (anti-arrhythmics)

Serotonin

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5
Q

Nuclear Hormone Receptors targets and drug

A

Estrogen (hormone)
Androgen (hormone)
Glucocorticoid

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6
Q

Enzymes targets and drugs

A

ACE (ACEI)

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7
Q

Effects of polymorphisms can be seen?

A

Binding sites
Signal transduction
Biologic (adaptive) response (tolerance)

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8
Q

Beta agonists do?

A

Reactive airway disease; target Beta 2 receptors

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9
Q

Beta blockers do?

A

CV disease; target Beta 1 receptors

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10
Q

B2 adrenergic receptor polymorphisms?

A

12 SNPs –> 5 AA changes

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11
Q

Clinical implications of B2 adrenergic polymorphs

A 
Enhance receptor down regulation (tolerance- 50%)
Resistant to down regulation (maintain efficacy - 25%)
Reduced affinity (decreased efficacy- 6%)
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12
Q

Asthma Therapy

A

Montelukast
Zafirieukast
Zileuton
Pranleukast

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13
Q

Arachidonic acid is converted to?

A

Leukotrienes (high inflammation) via 5-lipoxygenase)

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14
Q

Decrease expression in promoter region?

A

Less response to leukotriene inhibitors –> disease is not mediated by leukotrienes

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15
Q

Increased expression in promoter region?

A

More responsive to leukotriene inhibitors –> leukotrienes have a major role in disease

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16
Q

Genetic polymorphisms in 5-lipoxygenase is most likely to affect:
A. Risk of agranulocytosis from clozapine
B. Response to beta-agonists therapy
C. Response to clozapine
D. Response to leukotriene inhibitors

A

D. Response to leukotriene inhibitors

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17
Q

Serotonin is implicated in?

A 
Depression
Anxiety
OCD
Psychosis
Eating disorders
Substance abuse
Dependence
18
Q

Clozapine is used in?

A

Schizophrenia 50% response rate

19
Q

Cloazpine side effects?

A

Agranulocytosis
Seizures
Myocarditis

20
Q

Polymorph of importance?

A

Tyr/Tyr: drugs almost never work but they have bad side effects

21
Q

Avoiding Clozapine in patients with Tyr/Tyr means?

A

Limit unnecessary drug exposure and risk of sever toxicities

Selection of alternative therapy that is more effective

22
Q

Do you genotype with clozapine?

A

YES

23
Q

Clinical relevance of Opioid Receptors

A

Pain therapy

Substance abuse

24
Q

Toxicity with Opioid Receptors?

A

N/V
Respiratory depression
Constipation

25
Q

Opioid mutation

A

Mutation in the receptor at the receptor → decreased binding affinity → efficacy decreases and less side effects
— requires higher doses

26
Q

CYP2D6

A

codeine –> morphine

27
Q

Ultra metabolizers lead to

A

toxicity

28
Q

Poor metabolizers lead to

A

Decreased efficacy

29
Q

Which patient would have the least analgesic effects with codeine?

a. CYP2D6 extensive metabolizer and mu-opioid receptor mutation
b. CYP2D6 poor metabolizer and mu-opioid receptor mutation
c. CYP2D6 poor metabolizer and mu-opioid receptor wildtype
d. DYP3D6 extensive metabolizer and mu-opiod receptor wildtype
A

b. CYP2D6 poor metabolizer and mu-opioid receptor mutation

30
Q

Genotype in Codeine?

A

No because you can just slowly titrate up and avoid ADRs

31
Q

Risk Factors for QT prolongation

A 
Female
Concomitant meds (also affect QT like calrithro or compete for metabolism)
Hereditary LQTS (mutation in ion channels
32
Q

LQTS Genetics affect

A

Potassium and sodium ion transporters

33
Q

Therapeutic consideration with LQTS

A

K supplementation and K channel openers as well as Na channel openers

34
Q

Abacavir Hypersensitivity

A

NRTI in HIV

5-7% hypersensitivity reaction

35
Q

HLA-B genetics

A

MHC Class I

Presents the peptide to the immune cells

36
Q

Define Haptenation

A

Drug has to complex with an endogenous protein → when the two get together and gets processed is now immuno-reactive

37
Q

Abacavir Genotype and Reaction

A

HLAB*5701

Fatal

38
Q

Carbamazepine Genotype and Reaction

A

HLAB*1502
SJS
Toxic –> fatal

39
Q

Allopurinol Genotype and Reaction

A

HLAB*5801

Rash

40
Q

Abacavir has a black box warning for?

A

Genotyping before use

41
Q

Carbamazepine has a FDA alert for?

A

Genotyping because of SJS

Pharmacogenetics Exam 1 (7 decks)

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