What are the 4 main reasons to change the route of administration for a pain medication?
If different drug profiles are needed (eg, quick acting or prolonged acting)
To avoid the 1st pass effect
To have efficient, non-invasive delivery
Patient factors (eg, age/dexterity/support)
What is an Abuse-Deterent Formulation (ADFs) of opioids?
A formulation in which the opioid is rendered useless if the tablet/capsule has been tampered with
How much more potent than morphine is fentanyl?
Name 4 ways that a Abuse-Deterent Formulation can be made
Physcial Barrier (gel) --> Solids that become viscous when alcohol is added to extract the drug
Aversion --> Utilizes a noxious powder in the formulation to act as a deterrent
Agonist/Antagonist --> Naltrexone is added to morphine, which if chewed will be released, reducing the euphoria that is gained from the morphine
Pro-Drug --> The active drug is only avaliable once consumed
What type of fentanyl patch is Duragesic?
And what type are the newer generics?
Duragesic --> Reserviour System
Generics --> Simple adhesive-type
How can patches be abused?
Removal of the gel and boiling --> Allows the opioid to be injected or drunk
Chewing of the patch --> Released all 3 days worth via the mucosa
What is the benefit of Fentanyl Citrate?
The most lipophillic IR opioid --> so has a rapid onset of action as can pass through membranes rapidly
Can be used submucoasally as Oral Transmucosal Fentanyl Citrate (OTFC) for BTcP
What is a Copy-Number Variation (CNV)?
Either a gene deletion (loss of function) or gene duplication (increase expression and hyperactivity)
Explain the following..
Germline Genetic Variation
Somatic Genetic Variation
Halpotype --> A group of allelles across several genes on the same chromosome that are close together and so tend to be inherited together
Germline --> Variation of DNA that is present at conception, and so is passed down to offspiring
Somatic --> Changes in DNA that occur spontaneously after conception, and so aren't passed down to offspring
What's the difference between pharmacogenetics and pharmacogenomics?
Pharmacogenetics --> Study of the variability in drug response due to hereditary factors, with focus on a single gene or several genes
Pharmacogenomics --> Whole-genome application of pharmacogenetics
- Genome-wide analysis of the genetic determinants of drug efficacy and toxicity
Define Actionable Genetics
Where we could change therapy due to the genetic variability of patients (18% of US prescriptions)
What are the effects on being either a Poor Metaboliser (PM) or a Ultra Metaboliser (UM)?
PM --> ADRs at normal doses
- No/poor response to drugs that require activation (eg, pro-drugs)
UM --> No/poor repsonse to usual doses (eg, antidepressents)
- Toxicity after pro-drugs (eg, codeine)
What's the difference between a Genotype and a Phenotype?
Genotype --> An individuals full hereditary information ("Born with it")
- Eg, A pair of alleles regarding the CYP2D6 genotype
Phenotype --> The individuals actually expressed properties/oberservable characteristcs (eg, metabolism of tamoxifen)
Why do Poor Metabolisers (PM) get less of a benefit from tamoxifen?
Which class of drugs would be better for them?
As tamoxifen is broken down to more active metabolites....which is a slower process in PMs
They would get better outcomes by taking aromatase inhibitors
Why is genetic testing useful before giving treatment with 6-MP?
As if people have inactive forms of TPMT they cannot break down 6-MP, so the cancer therapy is toxic
Slow metabolisers will therefore need to have lower doses and shorter durations of treatment
What are the 3 criteria needed for a Pharmacogenomic (PGX) test to be done in hospitals?
Analytical Validity --> Ability of a test to measure accuratly and reliably the genotype of interest
Clinical Validity --> The accuracy with which the test can detect the prescence of the target phenotype/disease
Clinical Utility --> Whether use of the test will improve health outcomes, due to the potential risks of the test itself (often money based)
What are the 3 ways that the FDA and EMA support the integration of PGX tests?
Include PGX data in drug labelling
Use PGX data to choose dose regime and identify patients at risk
Use of a PGX label when PGX data is of high importance for treatment outcomes
When can the Cockroft and Gault equation not be used?
When the patient is not in steady state (eg, renal function must be fairly stable)
Extreme muscle mass
Obesity or ascites
When should TBW be used instead of IBW?
In obese patients to ensure they're not under-dosed!
What is the Calvert Equation?