PHM203 (ID) - Pharmacogenomics, Nanomedicine, UTI, Antivirals, IAI, Osteomyelitis, Travel Medicine, Meningitis And Encephalitis, STI, Opportunistic
Infections, Endocarditis, HIV - Final Review: Qs & As
Tips For The Final:
Found that knowing pathophysiology helped a lot with the second portion of the course, since these infections came from your own body (IE, OM, IAI, meningitis). Therefore if you knew the source of infection, and you knew the bacteria which inhabit that area of the body, you can figure out the necessary empiric therapy.Other than that, know the spectrum!!!What is the function of HLA-B? Right Ans - Helps the immune system *distinguish* the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.Which genotype is associated with increased risk of hypersensitivity reaction
with *abacavir*? Right Ans - *HLA-B57:01* genotype.
In one study, 94.4% of HSR cases were HLA-B57:01 carriers (patients with at
least one B57:01 allele).
It is thought that abacavir may enhance quantity and quality of self-peptide
binding to B57:01.
When is screening for HLA-B57:01 allele recommended? Right Ans - 1.
Prior to *initiating* therapy with abacavir.
2. Prior to *re-intiation* of abacavir in patients of unknown HLA-B57:01
status who have previously tolerated abacavir therapy.If patient is showing signs and symptoms of hypersensitivity reaction (HSR) with abacavir, can they be rechallenged? Right Ans - No. Same as any other true allergy.Which HLA-B genotype is associated with increased risk of *SJS/TEN with
allopurinol*? Right Ans - HLA-B*58:01 1 / 4
Which HLA-B genotype is associated with increased risk of *SJS/TEN with
carbamazepine/phenytoin*? Right Ans - HLA-B*15:02
FDA/CPIC recommend that at-risk populations (Asians, particularly Han
Chinese) be screened for HLA-B15:02 allele prior to starting carbamazepine.
True or false: HLA-B*15:02 carriers should also avoid use of oxcarbazepine or phenytoin. Right Ans - True.IFNL4 rs12979860 genotype is associated with treatment failure for chronic hepatitis C with which drug? Right Ans - Pegylated interferon alpha and ribavirin (PegIFN/R).Homozygous carriers had higher rates of treatment failure compared to heterozygous carriers.What was found in the SPRINT in ADVANCE trials with IFNL4 rs12979860 genotypes (PegIFN/R non-responders)? Right Ans - For HepC patients, PegIFN/R non-responders had lower cure rates for HepC if PegIFN/R was included in their drug regimen (the *non-responders were associated with development of drug resistance*)
True or false: >90% of the population have at least one genetic variation in
proteins responsible for drug metabolism and drug transport. Right Ans - True.And majority of population has an actionable variant (at least one genetic variance in a drug which is commonly used.What is the purpose of the Clinical Pharmacogenetics Implementation Consortium (CPIC)? Right Ans - Provides guidelines to enable translation of genetic test results into *actionable prescribing decisions* for specific drugs.Designed to help clinicians understand *how available genetic test results should be used* to optimize drug therapy, rather than whether tests should be ordered.What is the pharmacist's role in pharmacogenomics? Right Ans - 1.Identifications of patients which may benefit from PGx testing. 2 / 4
- Interpretation of information (clinically relevant or not).
- Guiding dialog with physicians and assistance in optimizing patient therapy.
- Patient education.
- Assistance in establishing drug and dosage "guidelines" for genotype
populations.
List pros and cons of parenteral administration. Right Ans - Pros:
- accurate dosing
- administration to unconscious/uncooperative pts
- rapid onset
- long-term dosing
- polypharmacy
- minimal concentration fluctuations
Cons:
- difficult to reverse administration
- great demands on the quality of the product
- sterility
- endotoxins
- composition
- cost
- Buffer
- Active pharmaceutical ingredient
- Preservative
- Tonicity agent
- Components necessary to stabilize the solution
What are components of a parenteral solution? Right Ans - - Vehicle (usually water)
Must be sterile!!!!Why is there a limit on the particulate matter for parenteral solutions?Right Ans - If there are more particles than the stated limits, the solution will have precipitate.What is nano-medicine? Right Ans - Pharmaceutical design which packages 'difficult' drugs (low solubility, low permeability) into container with one or more dimension less than 1 micrometer. 3 / 4
Everything in nano-medicines is more complex than aqueous, solution-based parenteral solutions.Describe class I-IV of the toxicological classification of nano delivery systems.
Right Ans - Class I: size above 100nm, biodegradable.
Class II: size above 100nm, non-biodegradable.
Class III: size below 100nm, biodegradable.
Class IV: size below 100nm, non-biodegradable.
List different types of liposomes. Right Ans - - Conventional liposome
- Theranostic liposome
- Ligand-targeted liposome
- PEG liposome (*PEG can help evade immune system*)
- Characterized based on lamella (each layer of bilayer is called a lamella).
How can you sterilize liposomes? Right Ans - Filtration (0.22 micrometre filter).Can't use steam/heat or irradiation for liposomes.How does one characterize liposomes based on its morphology? Right Ans
True or false: liposome can have a very large total charge. Right Ans - True.In a 100nm diameter liposome, there are ~80 000 lipid molecules per liposome.Many of the lipids used in liposomes are charged (only non-charged one is
DOPE).
Describe the general method of preparing liposomes. Right Ans - - Pour lipids into an organic solvent
- Freeze dry the mixture
- Add aqueous solution which contains water-soluble drugs
- Agitate container to form the liposomes
- Separate from organic phase to get final product
- / 4
Which 3 methods of characterizing liposomes were discussed in class?Right Ans - 1. Morphology of liposome (lamellarity)