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ID > Anti-infective Pharmacogenomics > Flashcards

Anti-infective Pharmacogenomics Flashcards

1
Q

What are the intrinsic factors that influence variable drug response

A

Pharmacogenomics
Age (peds/geriatrics)
Gender
Body weight
Concurrent illnesses (renal/ hepatic)

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2
Q

What are the extrinsic factors that influence variable drug response

A

Concurrent medications (DDI)
alcohol consumption
Adherence
Lifestyle factors (diet, exercise, smoking)

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3
Q

Genetic variability can influence various enzyme that categorized into gene involved in

A

Pharmacokinetics
Pharmacodynamics
Off target proteins

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4
Q

Pharmacokinetics

A

Proteins related to pharmacokinetics participate in ADME

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5
Q

Pharmacodynamics

A

Proteins are directly associated with the drug target such as receptors

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6
Q

Off target proteins

A

Proteins that are not directly linked to the drugs ADME or primary target yet can influence the drugs response.

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7
Q

Goals of pharmacogenomicics in ID

A

Improve drug efficacy (optimal dosing)
Minimize risk of adverse effects (avoid drug toxicity)
Predict treatment failure due to anti-infective resistance

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8
Q

PGX does NOT replace therapeutic use T/F

A

True

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9
Q

What are the two types of genomics in the ID world

A

Host genomic
Microbial/viral genomics

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10
Q

Host genomics

A

Genetic predisposition to drug toxicity

Genetic predisposition to significantly change drugs metabolism

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11
Q

Microbial/viral genomics

A

Rapidly replicated increases probability of mutation and development of drug resistance

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12
Q

What class of antibotic is included in the CPiC medication guidelines

A

Aminoglycosides
-Amikacin
-Gentamicin
-Plazomicin
-Tobramycin

some gram of positive, mostly gram negative

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13
Q

What is the MOA of aminoglycoside

A

Disrupt protein synthesis by irreversibly binding to 16s of ribosome complex

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14
Q

What is the adverse effect associated with aminoglycoside? What is the vareient associated if any?

A

Nephrotoxicity

Ototoxicity
-MTXRNR1 = higher risk

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15
Q

Where does the MT-RNR1 gene reside and also known as ?

A

Human mitochondrial genome

Mitochondrially encoded 12s ribosomal RNA

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16
Q

Genetic alterations in MTRNR1 gene is associated with

A

Predisposition to aminoglycoside induced hearing loss

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17
Q

Genetic alteration in MTRN1 causes 12s rRNA subunit protein to more closely resemble the bacterial 16s rRNA subunit —>

A

Increase aminoglycoside off target binding

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18
Q

MTRNR1 increased risk hearing loss CIPC recommendation

A

Very high risk

Avoid aminoglycoside antibiotics unless the high risk of permanent hearing loss is outweighed by the severity of the infection and lack of saf or effective alternative

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19
Q

MTRNR1 normal risk hearing loss CIPC recommendation

A

Normal risk

Use aminoglycoside antibiotics at standard doses for the shortes feasible course with therapeutic dose monitoring

Evaluate regularly for hearing loss

20
Q

MTRNR1 uncertain risk hearing loss CIPC recommendation

A

Weak or no evidence for MT RNR1

Use aminoglycoside antibiotics at standard doses for the shortes feasible course with therapeutic dose monitoring

Evaluate regularly for hearing loss

21
Q

What should you do if there is no effective alternative to an aminoglycoside antibiotic available

A

Evaluate for hearing loss frequency during therapy

22
Q

What antifungal medication has a CPIC recommendation?

A

Voriconazole

23
Q

Indication of voriconazole and MOA

A

Invasive aspergillosis

It impairs fungal growth and proliferation by weakening the fungal cell membrane

Inhibits CYP450 14 a-demethylase , disrupting estrogterol synthesis in fungi

24
Q

What is the gene of interest for voriconazole for the CIPIC guidelines

A

CYP2C19

25
Q

Voriconazole adverse effects

A

Hepatotoxicity
Neurotoxicity
Visual hallucinations
Encephalopathy
Neuropathy
Photopsia
Rash
Photosensitivity
Periostitis

26
Q

What therapeutic concentration rand of voriconazole should be measured after steady state is achieved?

A

Cmin/ trough

Invasive aspergillosis:1-5 ug/ml

27
Q

Individual that metabolizes voriconazole efficiently are at risk for

A

Treatment failure bc of low trough levels (<0.5) —> sub therapeutic

Extentsiom of hospital stay

28
Q

Individual that are NOT able to metabolizes voriconazole efficiently are at risk for

A

Adverse drug reactions , trough concentration >5-5.5 mg/L —> Supratherapeutic

Hepatotoxicity
Neurotoxicity
Visual hallucinations

29
Q

CYP2C19 ultra rapid metabolized

A

An individual carrying two increased function alleles

30
Q

CYP2C19 rapid metabilzer

A

An individual carrying one normal function allele and one increases function allele

31
Q

CYP2C19 normal metabilizer

A

Individual carrying two normal function alleles

32
Q

CYP2C19 intermediate metabilizer

A

An individual carrying one normal function allele and one no function allele or

one no function allele and one increased function allele

33
Q

CYP2C19 poor metabilizer

A

Carrying two no function allele

34
Q

Voriconazole dosing recommendations for Ultra rapid and rapid metabolizers

A

Consider an alternative antifungal agent not affected by CYP2C19 variations

Isavuconazole
Posaconazole
Liposomal amphotericin B

Potential SUBtheraputic levels

35
Q

Voriconazole dosing recommendations for poor metabolizers

A

Consider an alternative antifungal agent not affected by CYP2C19 variations

Isavuconazole
Posaconazole
Liposomal amphotericin B

Avoid ADR
Potential SUPRAtherapeutic levels

36
Q

What three antiviral medications has CIPIC recommendations

A

Atazanavir (protease inhibitors)*

Abacavir (NRTIs)*

Efavirenz

37
Q

What are we concerned with abacavir and what gene/allele is associated with it?

A

Hypersensitivity reaction

HLAB*57:01

38
Q

What is the sensitivity observed with abacavir associated with

A

Individual gene factors that increase hypersensitivity reactions

HLA-B*7:01

39
Q

What is abacavir’s hypersensitivity associated with

A

Off target effect

40
Q

CPIC recommendation for abacavir who is a carrier of HLA-B*57:01

A

Significantly increased risk of hypersensitivity

Abacavir not recommended

41
Q

CPIC recommendation for abacavir who is a NONcarrier of HLA-B*57:01

A

Low or reduced risk of hypersensitivity

Use abacavir per standard dosing guidelines

42
Q

What is the concern for atazanavir and what is the gene of interest?

A

Hyperbillirubinemia

UGT1A1 (phase ll )

43
Q

What factors increase risk for hyperbilirubinemia

A

Decrease UGTA1A1 production or function

DDI: inhibition of UGT1A1 (ABACTAVIR).

44
Q

What is atazanavir effect?

A

Off target effect

UGT1A1 DOES NOT contribute to metabolism nor PD

45
Q

Recommendation for UGT1A1 for normal/extensive and intermediate metabolizers

A

No need to avoid atazanavir

46
Q

Recommendation for UGT1A1 for poor metabolizers

A

Consider alternative agent particularly where jauis of concern to patient

ID (27 decks)

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