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Pharmacogenetics in Opioids and NSAIDs- Elchynski

Terms in this set (23)

What was the population characteristics and common comorbidity of pain in the US?
Population C:
-Poverty
-less than high school education
-Public health insurance

Common comorbidity;
-Anxiety and depression\
What are the outpatient medications used as pharmacotherapy for pain management?
-Acetaminophen
-NSAIDs
-Antidepressants
-Anticonvulsants
-Topical analgesics
-Opioids
What are the genes of interest for Opioids and NSAIDs?
Opioids:
-CYP2D6
-CYP2B6
-OPRM1
-COMT

NSAIDS:
-CYP2C9
-CYP2C8
Complete each
Codeine--(CYP2D6)-->
Tramadol--(CYP2D6)-->
Oxycodone--(CYP2D6)-->
Hydrocodone--(CYP2D6)-->
1. Morphine
2. O-desmethyl-tramadol (M1)
3. Hydromorphone
4. Oxymorphone
Which are strong inhibitors (ASx0) and which are moderate inhibitors (ASx0.5)?
-Arbiraterone
-Buproprion
-Fluoxetine
-Duloxetine
-Quinidine
-Terbinafine
-Cinacalcet
-Lorcaserin
-Paroxetine
-Mirabegron
Strong: Bupropion, fluoxetine, paroxetine, quinidine, terbinafine
Moderate: Abiraterone, cinacalcet, duloxetine, lorcaserin, mirabegron
What are the CPIC guidelines for Codeine with phenotype CYP2D6 ultrarapid metabolizer and poor metabolizer?
UM: AS=>2.25; Increase formation of morphine leading to higher risk of toxicity (Implications); Avoid codeine use b/c of potential for toxicity. If needed, consider a non-tramadol opioid (recommendation), Classification of recommendation= Strong

PM: AS=0; Greatly reduced morphine formation leading to diminished analgesia, avoid codeine use b/c of possibility of diminished analgesia. If opioid use is warranted, consider a non-tramadol opioid., Classification= Strong
What are the CPIC guidelines for Codeine with phenotype CYP2D6 normal and intermediate metabolizer.
NM: AS= 1.25<x<2.25; Expected morphine formation (implications); Use codeine label recommended age-specific or weight-specific dosing (recommendations), Classification = Strong

IM: As=0<x<1.25; Reduce morphine formation, Use codeine label recommended dosing; If no response and opioid use is warranted, consider non-tramadol opioid; Classification=Moderate
What are the CPIC guidelines for Tramadol for phenotype CYP2D6 ultrarapid and poor metabolizer?
UM: AS= >2.25; Increased formation of O-desmethyltramadol leading to higher risk of toxicity; Avoid tramadol use b/x of potential for toxicity. If opioid use is warranted, consider non-codeine opioid; Classification=Strong

PM: AS=0; Greatly reduced O-desmethyltramadol formation leading to diminished analgesia; Avoid tramadol use b/c of diminished analgesia. If use is warranted, consider non-codeine opioid; Classification=Strong
What is the CPIC guideline for Hydrocodone for the phenotype CYP2D6 ultrarapid metabolizer?
AS= >2.25; Minimal evidence for pharmacokinetic or clinical effect; No recommendation b/c of minimal evidence regarding adverse events of analgesia; Classification= No recommendation
CYP2B6 is highly or lowly polymorphic, and it is a poor metabolizer in what biogeographical groups?
Highly; -AA/Afro-caribbean -Asian-European-Latino-Near Eastern-Oceanian-Sub Saharan African
What is described below:
- Opioid receptor that is a target for opioids
-rs1799971
-200+ variants
OPRM (µ-opioid receptor µ1)
rs1799971 is most widely studied in OPRM1. It has a --(reduced or increased?)-- expression of the receptor (OPRM1). A small --(increase or decrease?---- in analgesia &/---(increase or decrease) in morphine requirements. --T or F-- it is also clinically actionable in dose reductions.
Reduced; Decrease; Increase; False, the dose is too small to be clinically actionable
What is described below:
-Enzyme that regulates catecholamine concentrations
-rs4680
COMT (Catechol-O-methyltransferase)
rs4680 is the most widely studied in COMT. It has a __to__ fold lower activity for methylation of dopamine. ---(increased or decreased?)--- catecholamines available in patients w/ variants (data does conflict if this is clinically actionable).
3-4; increased
List the indications and common uses for NSAIDs.
Indications:
-Antipyretic
-Anti inflammatory
-Analgesic

Common Uses:
-Muscle pain
-Migraines/headaches
-Gout
-Fever
-Arthritis
-Patent ductus arteriosus (PDA)
What were the PGx guidance Non-selective NSAIDs from this lecture?
Flurbiprofen
Ibuprofen
Meloxicam
Piroxicam
What non-selective NSAIDs don't have a pediatric dosing?
Diflunisal
Ketoprofen
Nabumetone
Flurbiprofen
Mefenamic Acid
List five non-selective NSAIDS that have pediatric dosing available.
Diclofenac
Etodolac
Ibuprofen
Indomethacin
Ketorolac
Meloxicam
Naproxen
Oxaprozin
Piroxicam
Sulindac
Tolmetin
What are the COX-2 selective NSAIDs, and tell whether they are PGx guidance and have a pediatric dosing available?
Celecoxib; Has PGx guidance but no pediatric dosing
Match the characteristics with the common side effect (gastrointestinal, renal, cardiovascular, hematological) (all characteristics are not listed):
1. Inhibition of prostaglandins responsible for protecting gastric mucosa
2.Antiplatelet effect and more prominent for those taking nonselective NSAIDs
3. COX-2 selective cause an imbalance between thromboxane A2 and prostaglandin I2 subsequently causing atherosclerosis and thrombosis
4. Example complications include fluid retention, __ papillary necrosis, and interstitial nephritis.
5. Increased risk of damage if patient has prior history of peptic ulcers, but a decreased risk of side effects in COX-2 selective agents.
6. Up to 5% of regular users experience hypertension and up to 1% heart failure
7. Increased risk if history of GI bleeding and disease states that affect platelet activity (ex. von Willebrand)
Gastrointestinal: 1, 5
Renal:4
Cardiovascular:3,6
Hematological:2,7
What are the inhibitors of CYP2C9?
Amiodarone and Fluconazole
What are the inducers of CYP2C9?
Rifampin
Carbamazepine
Aprepitant
What is the activity score of each phenotype:

CYP2C93/3
CYP2C91/3
CYP2C91/1
PM
IM
NM
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