Anti-infective Pharmacogenomics Flashcards
What are the intrinsic factors that influence variable drug response
Pharmacogenomics
Age (peds/geriatrics)
Gender
Body weight
Concurrent illnesses (renal/ hepatic)
What are the extrinsic factors that influence variable drug response
Concurrent medications (DDI)
alcohol consumption
Adherence
Lifestyle factors (diet, exercise, smoking)
Genetic variability can influence various enzyme that categorized into gene involved in
Pharmacokinetics
Pharmacodynamics
Off target proteins
Pharmacokinetics
Proteins related to pharmacokinetics participate in ADME
Pharmacodynamics
Proteins are directly associated with the drug target such as receptors
Off target proteins
Proteins that are not directly linked to the drugs ADME or primary target yet can influence the drugs response.
Goals of pharmacogenomicics in ID
Improve drug efficacy (optimal dosing)
Minimize risk of adverse effects (avoid drug toxicity)
Predict treatment failure due to anti-infective resistance
PGX does NOT replace therapeutic use T/F
True
What are the two types of genomics in the ID world
Host genomic
Microbial/viral genomics
Host genomics
Genetic predisposition to drug toxicity
Genetic predisposition to significantly change drugs metabolism
Microbial/viral genomics
Rapidly replicated increases probability of mutation and development of drug resistance
What class of antibotic is included in the CPiC medication guidelines
Aminoglycosides
-Amikacin
-Gentamicin
-Plazomicin
-Tobramycin
some gram of positive, mostly gram negative
What is the MOA of aminoglycoside
Disrupt protein synthesis by irreversibly binding to 16s of ribosome complex
What is the adverse effect associated with aminoglycoside? What is the vareient associated if any?
Nephrotoxicity
Ototoxicity
-MTXRNR1 = higher risk
Where does the MT-RNR1 gene reside and also known as ?
Human mitochondrial genome
Mitochondrially encoded 12s ribosomal RNA
Genetic alterations in MTRNR1 gene is associated with
Predisposition to aminoglycoside induced hearing loss
Genetic alteration in MTRN1 causes 12s rRNA subunit protein to more closely resemble the bacterial 16s rRNA subunit —>
Increase aminoglycoside off target binding
MTRNR1 increased risk hearing loss CIPC recommendation
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